This study aimed to characterize the longitudinal trajectories of depression, anxiety, and poor sleep among MSM newly diagnosed with HIV, and secondarily to explore potential causal relationships of HIV infection on these mental health outcomes. A prospective repeated-measures study was conducted between 2017 and 2020 at Beijing Youan Hospital. Newly diagnosed MSM patients with HIV were consecutively enrolled. Depressive and anxiety symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS), while sleep quality was evaluated with the Pittsburgh Sleep Quality Index (PSQI). Follow-up assessments were performed at 4, 12, and 24 weeks to track longitudinal changes in mental health status. As a complementary approach, Mendelian randomization (MR) analysis was employed to explore potential causal relationships of HIV infection on depression, anxiety, and sleep disturbances. A total of 1,170 MSM newly diagnosed with HIV were enrolled. The prevalence of depression, anxiety, and poor sleep decreased from 26.82

Rheumatoid arthritis (RA) is a chronic autoimmune disease with inflammation-mediated joint damage. Its pathogenesis involves synergistic impairment of multiple physiological balances, including immune cell subset dysregulation, abnormal inflammation, oxidative stress, pathological angiogenesis, bone homeostasis disorder and gut microbiota dysbiosis. Conventional therapies have high costs and adverse effects. Traditional Chinese medicine (TCM) follows a holistic balance-restoring concept and is a promising alternative, with Tripterygium wilfordii, Wutou Decoction and Toddalia asiatica extract as evidence-based representatives. This review summarizes 2020-2025 in vitro and in vivo studies on anti-RA TCM. Its core therapeutic mechanism is multi-target, network-based regulation. It rectifies various pathological imbalances simultaneously: modulating immune cell polarization, rebalancing inflammatory factors, scavenging ROS, inhibiting abnormal angiogenesis, regulating osteoblast-osteoclast crosstalk and reshaping gut microbiota. Single TCM agents act on multiple balance networks, showing complex pharmacological properties. TCM's unique advantage for RA is reestablishing the body's dynamic homeostasis by targeting interconnected pathological balances. Further research is needed to clarify TCM components' synergistic regulatory mechanisms and promote their clinical translation.

OBJECTIVES:Incomplete immune reconstitution (IIR) affects 10-40% of people living with HIV (PLWH) despite suppressive antiretroviral therapy (ART), increasing morbidity and mortality. We investigated whether baseline triglyceride-glucose index (TYG), a marker of insulin resistance, predicts long-term IIR risk in PLWH. METHODS:This multicentre retrospective cohort study analyzed 11076 PLWH from three Chinese HIV centers (2009-2020) using a 4-year landmark design. IIR was defined as CD4 <350 cells/μl after >4 years of ART with sustained virological suppression. Center-stratified Cox models with time-varying effects estimated hazard ratios (HRs) for TYG. RESULTS:Over a median follow-up of 7.74 years, higher baseline TYG was associated with a lower risk of IIR. There was borderline evidence of a stronger inverse association over time (P = 0.080), with the HR decreasing from 0.795 (95% CI: 0.733-0.862) at year 5 to 0.733 (95% CI: 0.639-0.842) at year 10. Results remained robust across sensitivity analyses. The association was more pronounced in younger participants (<60 years), those with better baseline immune status (CD4 ≥200 cells/µl, WHO stage I/II), virological suppression, favorable lipid profiles, and higher hemoglobin levels. CONCLUSIONS:Baseline TYG may aid risk stratification for IIR in PLWH.

Polygonum capitatum (PC) is an ethnomedicine with reported antibacterial and anti-inflammatory activities and has been clinically used in urinary tract infection (UTI)-related disorders. However, its in vivo exposure characteristics and metabolically associated therapeutic mechanisms in acute pyelonephritis (AP) remain insufficiently understood. To address this issue, this study aimed to evaluate the therapeutic effects of PC in an Escherichia coli (E. coli)-induced rat model of AP and to explore constituents and metabolic pathways associated with its activity. Different PC extracts were screened for antibacterial and anti-inflammatory activities, and the 70% ethanol extract was selected for further study. Seven major compounds were quantified by HPLC. In AP rats, the pharmacokinetic profiles of these compounds in plasma and the renal cortex were analyzed by microdialysis-coupled HPLC-MS/MS. Pharmacodynamic evaluation included urinary bacterial load, urinalysis, renal function, inflammatory cytokines, and renal histopathology. Exploratory PK-PD analysis, untargeted renal metabolomics, and targeted metabolomics of the tryptophan-kynurenine (Trp-Kyn) pathway were also performed. The 70% ethanol extract of PC exhibited the strongest antibacterial and anti-inflammatory activities. The total content of seven active compounds was 3.85%, with gallic acid being the predominant compound (3.42%). Pharmacokinetic analysis revealed that gallic acid, protocatechuic acid, methyl gallate, and quercitrin achieved relatively high systemic exposure and renal distribution. In AP rats, the pharmacokinetic profiles of several compounds were altered, with increased plasma exposure of protocatechuic acid, vanillic acid, ethyl gallate, and syringic acid, while protocatechuic acid also showed higher exposure in the renal cortex. PC treatment reduced urinary bacterial load, improved renal function and urinalysis parameters, alleviated histopathological injury, and decreased inflammatory mediator levels, particularly in renal tissue. Exploratory PK-PD correlations were observed between several compounds and selected pharmacodynamic indicators. Metabolomic analysis suggested disturbances in glycerophospholipid metabolism and the Trp-Kyn pathway in AP rats, some of which were partially reversed after PC treatment. PC showed antibacterial and anti-inflammatory effects in AP rats. Gallic acid, protocatechuic acid, methyl gallate, and quercitrin may be candidate constituents associated with the therapeutic effects of PC, while modulation of glycerophospholipid metabolism and the Trp-Kyn pathway may be involved in its action against AP. These findings provide preclinical pharmacological evidence supporting the therapeutic potential of PC in AP.

Background:We compared the effectiveness and safety profiles of doravirine, lamivudine, tenofovir disoproxil fumarate (DOR/3TC/TDF) with bictegravir, emtricitabine, tenofovir alafenamide fumarate (BIC/FTC/TAF) in people with HIV (PWH) who had achieved virological suppression on efavirenz (EFV)-based antiretroviral regimens. Methods:This study was a single-center, real-world, prospective observational cohort study. The main inclusion criteria: PWH aged ≥18 years who had received an EFV-containing regimen for ≥6 months and achieved confirmed virological suppression. Participants were stratified according to clinical decisions to switch to DOR/3TC/TDF or BIC/FTC/TAF. The primary effectiveness end point was the proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48, with a preset 4% noninferiority margin. Results:A total of 349 participants received at least 1 dose of study drugs (142 in DOR group, 207 in BIC group). At 48 weeks, 2 (1.4%) in the DOR group and 1 (0.5%) in the BIC group had HIV-1 RNA ≥50 copies/mL (estimated treatment difference [ETD], 1.0%; 95% CI, -1.6% to 3.7%), establishing noninferiority. In the BIC group, mean CD4 counts decreased significantly by ∼76.5 cells/µL at week 48 (95% CI, -111.801 to -41.218; P < .001) compared with baseline. Over 48 weeks, adverse event rates were comparable between the 2 groups (P = .758). At week 48, the BIC group exhibited a baseline-adjusted mean increase of 0.269 mmol/L in total cholesterol (TC) and 0.171 mmol/L in low-density lipoprotein cholesterol (LDL-C), while the DOR group demonstrated a mean reduction of 0.453 mmol/L in triglycerides (TG), 0.412 mmol/L in TC, and 0.241 mmol/L in LDL-C relative to baseline. All β values for the group-time interaction terms were negative (P < .001). The change in body weight from baseline to week 48 in the DOR group was 1.8 kg lower than that in the BIC group (95% CI, -2.474 to -1.114; P < .001). Conclusions:In previously virologically suppressed PWH on an EFV-based regimen, the switch to DOR/3TC/TDF maintained virological suppression noninferior to that of BIC/FTC/TAF, with favorable metabolic profiles.

Background:Experience with Dolutegravir/Lamivudine (DTG/3TC) for rapid initiation of antiretroviral therapy (ART) in newly diagnosed people living with HIV (PLWH) remains scarce. We conducted a study to evaluate the effectiveness and safety of DTG/3TC for rapid ART. Methods:This retrospective, real-world study was conducted among treatment-naïve PLWH at three centers in Beijing, Nanjing, and Qingdao. Participants were stratified into the rapid group (≤7 days) and the non-rapid group (>7 days) based on the time from HIV diagnosis to ART initiation. The primary endpoint was the rate of virological suppression (VS) at week 48, which was assessed using both intention-to-treat (ITT) and per-protocol (PP) analyses in accordance with the Food and Drug Administration (FDA) Snapshot algorithm. Results:A total of 145 participants were enrolled between February 2022 and October 2023 (57 in the rapid group and 88 in the non-rapid group). The median time for the two groups to ART initiation was 4.0 (3.0, 5.0) and 17.0 (12.3, 25.5) days, respectively (P < 0.001). No significant baseline differences were observed between the two groups. ITT analysis showed that the 48-week VS rates were 93.0% [95% confidence interval (CI): 86.1%-99.8%] in the rapid group and 90.9% (95% CI: 84.8%-97.0%) in the non-rapid group (P = 0.765). Multivariable logistic regression analysis, adjusted for age, baseline CD4 counts, baseline VL, and treatment initiation pattern, confirmed that rapid ART was not significantly associated with VS at week 48 [adjusted odds ratio (OR) = 1.100, 95% CI: 0.291-4.164, P = 0.888]. Subgroup analyses further demonstrated consistent results: no significant differences in VS rates were detected across subgroups (all P > 0.05). The median increases in CD4 counts from baseline at week 48 were 232 and 243 cells/μL in the rapid and non-rapid groups, respectively (P = 0.951). Throughout the 48-week follow-up period, changes in liver function, renal function, and lipid levels from baseline did not differ significantly between the two groups. Conclusion:Our study provides clinical evidence supporting the effectiveness and safety of DTG/3TC for rapid ART in treatment-naïve PLWH, with outcomes comparable to those of non-rapid initiation.

ETHNOPHARMACOLOGICAL RELEVANCE:Psoraleae Fructus (PF) is a commonly used traditional Chinese medicine for treating osteoporosis. Previous studies elucidated the pharmacodynamic basis of its treatment for osteoporosis by analyzing the constituents in the blood, but their distribution in bone tissue was not taken into account, which had certain limitations. AIM OF THE STUDY:This study clarified the pharmacodynamic material basis of PF in the treatment of osteoporosis through a comprehensive analysis of its constituents distributed in plasma and bone tissue, along with the osteogenic activity of constituents distributed in the body. METHODS:This research was founded on a pre-established chemical library of PF. The plasma and bone tissues of rats were harvested, and UFLC-MS was employed to detect the constituents absorbed into the plasma and distributed into the bone tissues. The osteogenic activity of the combined constituents entering the body was investigated using MC3T3-E1 subclone cell. RESULTS:36 constituents absorbed into blood and 42 constituents distributed in bone tissue were identified, furthermore uncovering their plasm pharmacokinetic (PK) and bone tissue distribution (BTD) characteristics. Psoralen (5) and isopsoralen (6) exhibited the highest distribution levels in plasma and bone tissue, reaching 1000 ng/mL and 1000 ng/g. Although the Cmax of psoralenoside (45) and isopsoralenoside (46) in plasm were as high as 2068.86 ng/mL and 7486.24 ng/mL, their Cmax in bone tissue were only 194.91 ng/g and 310.26 ng/g, which was attributed to their characteristics of high polarity and being easily metabolized. Bakuchiol followed closely, with a plasma Cmax of 147.56 ng/mL and bone tissue Cmax of 483.05 ng/g. The coumarin compound psoralidin (4), and the prenylated flavonoid constituents, namely neobavaisoflavone (17), corylifol A (21), bavachin (28), bavachinin (29), and isobavachalcone (41), followed in distribution levels with the plasm Cmax mostly below 10 ng/mL and the bone tissue Cmax at 100-500 ng/mL. The distribution levels of other constituents in the body were mostly below 20 ng/g. The dosage of these constituents were relatively low and they belonged to the derivatives of the main flavonoids. Isopentenyl alterations appeared to enhanced the plasma exposure of the trace constituents. A principal component analysis showed these compounds could be clustered into four types: ''high dosage, high blood drug concentration, and high/medium tissue distribution'', ''high dosage, extremely low blood drug concentration, and medium tissue distribution'', ''high dosage, low blood drug concentration, and medium tissue distribution'', and ''low dosage, low blood drug concentration, and low tissue distribution'' based their dosage, Cmax of PK, Cmax of BTD and apparent volume of distribution. The main constituents of PF had a high/medium distribution in bone tissue. Furthermore, the main constituents were combined based on the distribution amount, and they could significantly increase the ALP activity and the formation of mineralized nodules, upregulate the mRNA expression levels of BSP and OCN. The western blotting suggested the combined constituents activated AKT signaling, along with the accumulation of β-catenin and the upregulation of Runx2. CONCLUSIONS:The above findings suggested that the main constituents distributed in bone tissue enhanced the osteogenic differentiation and mineralization by activating AKT/GSK-3β/β-catenin pathway, indicating them as the pharmacodynamic material basis of PF in the treatment of osteoporosis. Furthermore, this study on PK and BTD analyses of other non-main constituents was also possible to provide extremely crucial reference bases for them at multiple levels, including subsequent research, development, and application.

GK-A is a new compound previously isolated by our research group from TCM Ginkgo Semen, which is traditionally used for relieving cough. Pharmacological results showed that it possessed good antitussive and anti-inflammatory activities, yet its low bioavailability is a significant problem. To search for candidate molecules with strong activity and high bioavailability, this study aimed to achieve this goal through structural modification. To evaluate the effects of different N-substituents in GK-A on the activity of active compounds, the study developed a concise synthetic route for these GK-A derivatives, synthesizing 15 derivatives(compounds 10-24) based on this route. Among these derivatives, compounds 10-21 were new compounds. An in vitro inflammatory model was established by inducing RAW264.7 cells with lipopolysaccharide(LPS). The cytotoxicity of different concentrations of the derivatives on mouse RAW264.7 macrophages was assessed using the CCK-8 assay to determine the appropriate dosing concentration. Nitric oxide(NO) levels in the cell supernatant were measured via the Griess assay, and the expression levels of inflammatory cytokines(interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), and cyclooxygenase-2(COX-2) were detected by enzyme-linked immunosorbent assay(ELISA). The results showed that at a concentration of 100 μmol·L~(-1), all tested compounds significantly inhibited NO expression. Specifically, compounds 13 and 16 markedly reduced the expression levels of TNF-α, IL-6, and COX-2 in the cell supernatant. Compound 14 exhibited a significant inhibitory effect on TNF-α expression, while compound 17 significantly suppressed the expression of IL-6 and COX-2. These findings demonstrated that compounds 13, 14, 16, and 17 possessed promising anti-inflammatory activity in vitro. This discovery provides an experimental basis for screening antitussive drug candidates with high pharmacological activity, good bioavailability, and minimal side effects.

INTRODUCTION:Hybridization is a key evolutionary force that enriches genetic diversity and is associated with metabolic innovation. Lotus (Nelumbo), comprising Asian lotus (N. nucifera) and American lotus (N. lutea), is both a culturally important ornamental and medicinal plant rich in benzylisoquinoline alkaloids (BIAs). However, the genomic and biochemical basis of BIA glycoside biosynthesis remains poorly understood. OBJECTIVES:A high-quality hybrid lotus genome was presented to dissect the formation of benzylisoquinoline alkaloid glycosides and the mechanism underlying their synthesis. METHODS:The chromosomal-level hybrid genome was constructed through PacBio HiFi, ONT Ultra-long, and Hi-C sequencing data combined assembly strategies. The metabolite and enzyme function were assayed by LC-MS. Multi-omics and molecular dynamics simulations (MD) revealed the catalytic mechanism of seven tandemly duplicated UGT75C genes. RESULTS:Here, we present a high-quality haplotype-resolved genome of an Asian-American hybrid lotus (Nn × Nl CB), complemented by new assemblies of one N. lutea and four N. nucifera accessions. Comparative genomics revealed divergence time between the two species and extensive interspecific recombination in hybrids. Metabolite profiling uncovered armepavine-4'-O-glucoside, a novel BIA glycoside preferentially accumulated in cotyledons and hybrid cultivars. Weighted gene co-expression network analysis (WGCNA) and Gene Ontology (GO) analysis identified a cotyledon-specific module enriched in UDP-glycosyltransferases (UGTs). Seven tandemly duplicated UGT75C genes, derived from both parental genomes, were cloned and biochemically characterized. Functional assays demonstrated strict substrate and donor specificity, with NnUGT75C2 exhibiting the highest catalytic efficiency toward armepavine and norarmepavine. MD and MM/PBSA analyses identified key catalytic residues, and site-directed mutagenesis validated E321D as an activity-enhancing substitution. CONCLUSION:Together, these results uncover the genetic and biochemical basis of BIA glycoside biosynthesis in lotus, highlight tandem duplication and hybridization as promoters of chemodiversity, and provide molecular targets for breeding and metabolic engineering of high-value medicinal cultivars.

Traditional Chinese medicine(TCM) preparations in medical institutions(hereinafter referred to as &quot;hospital TCM preparations&quot;) are fixed-formula preparations developed by TCM medical institutions based on clinical needs. Hospital TCM preparations play a significant role in meeting special medication demands, inheriting TCM experience, and promoting new medicine development. With policy support, the development of hospital TCM preparations has surged in recent years, but there are issues such as product homogeneity, insufficient clinical evidence, low conversion rates, and unlabeled uses. This paper systematically analyzed the current development status and existing problems of hospital TCM preparations, combining policy background and practical cases. Then, recommendations were proposed, including refocusing on clinical needs, optimizing dispensing policies, improving conversion mechanisms, and establishing a dynamic exit mechanism, aiming to provide references for the healthy development of hospital TCM preparations.

Background:The single-tablet regimen Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (DOR/3TC/TDF) has been included in international guidelines and recommendations and was approved by China's National Medical Products Administration (NMPA) in early 2021 for adult human immunodeficiency virus (HIV)-1 infections. This study presents real-world results of a retrospective analysis of patients who initiated DOR/3TC/TDF at a Chinese HIV center. Methods:This retrospective analysis was carried out on patients who received DOR/3TC/TDF (initial or switch) at the outpatient clinic of the Infection Center in Beijing Youan Hospital in China. Patients' baseline characteristics, reasons for switching to DOR/3TC/TDF, along with the preliminary clinical, laboratory - based efficacy, safety, and tolerability data, were collected. All evaluations were in strict accordance with the protocols of our center. The statistical analysis was mainly descriptive, aiming to assess the changes in laboratory parameters from the baseline to the data - collection deadline, which was December 31, 2024. Result:From May 16 to October 29, 2024, 205 patients were prescribed DOR/3TC/TDF, either as an initiation or a switch. The cohort consisted mainly of males (96.1%), with a median age of 36.0 (31.0, 41.0) years. By the analysis deadline, the entire group had used DOR/3TC/TDF for 149.0 (90.0, 202.0) days. Among them, 40 patients were treatment-naïve, with a median HIV-1 ribonucleic acid (HIV-1 RNA) of 4.1 (3.7, 4.6) log10 copies/mL. At weeks 12 and 24, 64.5% [95% confidence interval (CI): 45.4, 80.8%] and 91.3% (95% CI: 72.0, 98.9%) of the participants achieved HIV-1 RNA < 50 copies/mL. Subgroup analysis showed that high viral load (VL) (≥105 copies/mL) and low CD4 counts (< 200 cells/μL) at baseline did not affect virological efficacy. The results of immune reconstitution were also satisfactory, with CD4 counts increased from 350 (264, 465) cells/μL at baseline to 541.0 (415.8, 789.5) cells/μL by the end of the follow-up (p > 0.05). 165 patients (80.5%) had treatment experience, and the most common cause for switching was treatment simplification (40%). After the switch, an equally high proportion of patients [97.6% (95% CI: 93.7, 99.3%) vs. 96.4% (95% CI: 92.2, 98.7%)] achieved HIV-1 RNA undetectable or <50 copies/mL (p > 0.05). Compared to baseline, there were no significant changes in liver enzymes and renal function (p > 0.05), while body weight, random blood glucose and blood lipid levels decreased significantly (p < 0.05). Among patients with central nervous system (CNS) symptom, both the Pittsburgh Sleep Quality Index (PSQI) and the Hospital Anxiety and Depression Scale (HADS) scores, as well as the proportion of patients with scores greater than 7 points, decreased significantly post-switch (p < 0.05). Conclusion:We provided an observational report on the effectiveness and safety of the short-term use of DOR/3TC/TDF in routine clinical practice.

Dehydration-responsive element-binding (DREB) transcription factors associated with abiotic stress responses. However, an understanding of the DREB gene family and its functions in drought tolerance in licorice (Glycyrrhiza uralensis) is limited. In this study, 79 GuDREB genes were identified across the licorice genome and divided into six major groups. In addition, we provided information on the phylogenetic relationships, gene structures, conserved motifs, collinear relationships and cis-regulatory elements of GuDREBs. Bioinformatical and gene expression pattern analysis showed that the expression of the GuDREB35 of the A5 group was considerably induced by drought stress. Overexpression of GuDREB35 significantly enhanced drought tolerance and promoted flavonoid accumulation in licorice. Conversely, GuDREB35-RNAi plants exhibit significantly reduced drought resistance and a significant decrease in flavonoid levels. Transcriptomic analysis revealed that the overexpression of GuDREB35 up-regulated the expression of genes involved in antioxidant defense and flavonoid biosynthesis. Protein-DNA interaction studies further confirmed that GuDREB35 directly bound to the promoters of GuBGLU12 and GuOMT1, which are two enzymes in the flavonoid synthesis pathway. Our research demonstrates that GuDREB35 enhances drought stress tolerance by activating antioxidant defense and flavonoid biosynthesis pathways, providing a theoretical foundation for understanding the molecular mechanisms of drought tolerance and developing drought-resistant licorice varieties.

Despite its great potential, the development and implementation of scalable new-to-nature biocatalytic transformations in the chemoenzymatic synthesis of clinically significant pharmaceuticals still present a considerable challenge. We developed a chemoenzymatic synthesis of the very recently developed anti-HIV drug lenacapavir's 5/5/3 fused tricyclic fragment featuring an unusual chiral cyclopropane moiety. Key to this development is a biocatalyst-controlled, fully diastereo- and enantiodivergent cyclopropanation of a highly functionalized vinylpyrazole substrate, granting access to all four possible stereoisomers of lenacapavir cyclopropane. High-throughput experimentation led to the discovery of heme-dependent globins, including nitrous oxide dioxygenase (NOD) and protoglobin (Pgb), as promising cyclopropanation biocatalysts. Directed evolution furnished a highly diastereo- and enantioselective cyclopropanation (up to 99:1 d.r. and 99:1 e.r.). Further developed downstream chemical cyclization afforded the desired lenacapavir 5/5/3 fused tricycle with great stereochemical purity.

Medical and edible plants, such as Perilla frutescens, are widely-utilized, generating significant interest in their edibility and safety. This study addressed necessity for assessment and utilization of perilla leaf resources. It comprehensively examined perilla leaf, encompassing chemical composition, geographical distribution, phenotypic characteristics, metabolic pathways, and exogenous contaminants, with respect to efficacy and safety. The study evaluated effectiveness based on volatile oil content, 15 differential markers for distinguishing chemotypes, origins, and phenotypes, and 19 functional ingredients for their pharmacological activity. Safety assessments indicated perilla ketone posed a potential risk while heavy metal and pesticide residues were within safe limits. 31 indices were utilized to establish an EWTOPSIS model after integrating to the factors screened. It was found that perilla leaves with southern origins, double-sided purple phenotype, and non-perilla ketone chemotypes were likely to be safe and high-quality. These findings provided a theoretical foundation and practical guidance for quality control of medicine-food homologous plants.

Anemarrhenae Rhizoma is bitter,sweet,and cold in nature,and has the effects of clearing heat,dispelling fire,nouris-hing Yin,and moisturizing dryness.It is associated with the lung,stomach,and kidney meridians,and is mainly distributed in the northwestern and northern regions of China.Modern research has shown that Anemarrhenae Rhizoma contains various chemical active constituents,including steroidal saponins,flavonoids,polysaccharides,lignans,volatile oils,and alkaloids.These constituents exhibit pharmacological effects such as anti-tumor,hypoglycemic,anti-inflammatory,and neuroprotective activities.However,there have been few comprehensive summaries of Anemarrhenae Rhizoma in recent years,which has limited its in-depth research and development.The complexity of traditional Chinese medicine constituents,along with their quality and efficacy,is easily influenced by processing,prepa-ration,and the growing environment and resource distribution.This paper summarizes the resources,chemical constituents,and phar-macological effects of Anemarrhenae Rhizoma,and predicts its quality markers(Q-markers)from several aspects,including the speci-ficity of chemical composition,properties related to preparation and active ingredients,measurability of chemical components,com-pounding environment,construction of the ″active ingredient-target″ network pathway,and differences in active ingredient content from different origins and parts.These predicted Q-markers may provide a basis for improving the quality evaluation system of Anemarrhenae Rhizoma.

To promote the development of high-quality Chinese patent medicine (CPM), we previously proposed a quality consistency evaluation (QCE) strategy based on intra-and inter-batch differences. In this study, Ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry and gas chromatography coupled with triple quadrupole mass spectrometry (UPLC/GC-QQQ-MS) were separately developed and applied to determine non-volatile and volatile index components' contents, representing the quality attributes of different raw medicines from Huoxiang Zhengqi Shui (HXZQS). Furthermore, the LPS-induced RAW264.7 cell model was applied to evaluate NO inhibitory activity, which ranged from 24.52% to 76.95%. Then the QCE strategy was applied to distinguish between superior and inferior levels from different manufacturer ' s products based on the consistency of chemical contents and bioactivity. The results showed that intra-batch consistency (11.96% - 47.93%) was better than inter-batch consistency (8.53% - 131.25%), and inter-batch difference was the key factor affecting the quality consistency. The correlation coefficient (0.516) of chemical contents and NO inhibition rate suggested that their consistency basically followed a similar trend. The results were further graded by PCA analysis, where M7, M15, M6, M16, M3, and M5 were the best six manufacturers, and M7 had the highest content. Whereas M12 and M13 had the worst consistency and the lowest content. This study aimed to guide manufacturers to focus on process design and quality control, which not only improves the quality and safety of CPM but also promotes innovation and development of the pharmaceutical industry.

Stilbenoids, a class of compounds with the stilbene skeleton as part of plant secondary metabolism, are renowned for their diverse health benefits. Among them, 2,3,5,4'-Tetrahydroxystilbene-2-O-beta-D-glucoside (THSG), specifically abundant in the famous medicinal plant Pleuropterus multiflorus, exhibits significant pharmacological properties. A selfing progeny of P. multiflorus commercial variety Jinwufugui No.1, which contains high THSG content, was used for genome sequencing. Through the combination of weighted correlation network analysis, genome mining, and enzymatic characterization studies, we identified an unpredicted biosynthetic gene cluster responsible for THSG biosynthesis. This cluster includes a stilbene synthase (PmSTS1), a flavin-containing monooxygenase (PmFMO3), and a UDP-glycosyltransferase (UGT72B90). Our findings suggest this stilbenoid gene cluster is formed by transposable element-mediated gene duplications and neofunctionalization, and regulated by MYB and NAC type transcription factors. Notably, PmFMO3, as the first identified stilbenoid-2-hydroxylase, was confirmed that it can modify the other stilbenoids without the A ring modifications. The novel type of gene cluster, in which FMO serves as the key decorating enzyme, will guide the identification of more biosynthetic gene clusters in plants. In addition, the characterization of PmFMO3 extends our understanding of the FMO gene function in plants, and provides an important catalytic bioparts for the heterologous synthesis of polyhydroxylated stilbenoids. ### Competing Interest Statement The authors have declared no competing interest.

Background: Acute lung injury (ALI) often leads to serious respiratory diseases with high incidence rates and mortality. For centuries, Xiebai San (XBS) has been a classical traditional Chinese medicine (TCM) about respiratory illness such as pneumonia in children. However, the related mechanism of XBS against ALI remains indistinct. Purpose: To reveal specific targets of XBS in lipopolysaccharide (LPS)-induced ALI mice using integrated pharmacology. Study Design: The integrated method was to expound mechanism and targets of XBS inhibited ALI. Methods: The primary components in XBS were identified by ultra high performance liquid chromatography-quadrupole time of flight-mass spectrometry (UHPLC-QTOF-MS). The potential drug targets were established using network pharmacology. The anti-ALI effect of XBS was evaluated in mice. Additionally, therapeutic targets were screened by integrating metabolome and transcriptome and verified in lung tissue. Results: In total, 163 chemical components were identified in XBS, and a network of "3 drugs-18 components-86 targets" for XBS against ALI was constructed. In ALI mice, XBS alleviated lung inflammation by decreasing permeation and expression of neutrophils, tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta ) in bronchoalveolar lavage fluid (BALF), serum, and lung tissue. Next, the transcriptome of lung tissue was analyzed and enriched, indicating the importance of mitogen-activated protein kinase (MAPK), Janus kinase-signal transducer and activator of transcription (JAK-STAT), and others, which was consistent with network pharmacology prediction. Also, western blotting and immunohistochemistry results showed that XBS was against ALI mainly by inhibiting extracellular signal regulated kinase (ERK) and signal transducer and activator of transcription 3 (Stat3) phosphorylation. In addition, the metabolome of lung tissue revealed that XBS mainly regulated pathways involved in arachidonic acid, glycerophospholipid, and tryptophan metabolisms. The expression levels of leukotriene, phosphatidylcholine, kynurenine, and others were also verified.

BACKGROUND Enhancing awareness and use of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) is vital to curb human immunodeficiency virus (HIV) spread. High-risk behaviors prevalent among sexually transmitted infection clinic outpatients underscore the need for increased PrEP/PEP education in this group. AIM To investigate the effects of both onsite and online health education on the knowledge of, and willingness to use, PrEP and PEP among individuals receiving PEP services. METHODS Participants were drawn from a cohort study on PEP service intervention at an STD/AIDS outpatient clinic in designated HIV/AIDS hospitals in Beijing, conducted from January 1 to June 30, 2022. Health education was provided both onsite and online during follow-up. Surveys assessing knowledge of, and willingness to use, PrEP/PEP were administered at baseline and again at 24 wk post-intervention. RESULTS A total of 112 participants were enrolled in the study; 105 completed the follow-up at week 24. The percentage of participants with adequate knowledge of, and willingness to use, PrEP significantly increased from 65.2% and 69.6% at baseline to 83.8% and 82.9% at the end of the intervention (both P < 0.05). Similarly, those with adequate knowledge of, and willingness to use, PEP increased from 74.1% and 77.7% at baseline to 92.4% and 89.5% at week 24 (P < 0.05). Being between 31 years and 40 years of age, having a postgraduate degree or higher, and reporting a monthly expenditure of RMB 5000 or more were found to be significantly associated with knowledge of PrEP and PEP (both P < 0.05). CONCLUSION The findings show that both onsite and online health education significantly improved the knowledge of, and increased willingness to use, PrEP and PEP in individuals utilizing PEP services.