Cervical squamous cell carcinoma (CESC) represents the second most commonly diagnosed malignancy among women worldwide, with substantial incidence and mortality rates, particularly in regions where breast cancer is not predominant. Recent advances in tumor-infiltrating lymphocyte (TIL) therapy have demonstrated promising clinical efficacy in CESC. This study elucidated the role of complement factor D (CFD) in CESC and evaluated its potential as a therapeutic target. Bioinformatic analysis of the GSE39001 dataset revealed significant downregulation of CFD in CESC tissues, a finding subsequently validated in 43 paired tumor and adjacent normal tissue samples. Functional assays demonstrated that CFD overexpression in CESC cell lines (SiHa and C33A) substantially suppressed cell proliferation, viability, and invasion, while concurrently attenuating CD8 + T cell exhaustion. Mechanistically, CFD overexpression upregulated nitric oxide synthase trafficking inducer (NOSTRIN) and suppressed the endothelial nitric oxide synthase (eNOS) signaling pathway, as confirmed through RNA sequencing and co-immunoprecipitation assays. Furthermore, the combination of TIL therapy with CFD overexpression significantly suppressed tumor growth in a PDX model. These findings identify CFD as a potential therapeutic target for CESC and suggest that CFD overexpression may enhance the efficacy of TIL therapy in this malignancy.

ABSTRACT Budesonide is a first‐line inhaled glucocorticoid (ICS) for asthma treatment in adults and children. The purpose of this study was to compare the pharmacokinetics and assess the bioequivalence between two budesonide pressurized metered‐dose inhalers (pMDIs, 200 μg/actuation × 1 actuation) in healthy Chinese subjects. The study was conducted in 32 healthy Chinese subjects using a single‐center, randomized, open‐label, four‐period and crossover design with a 3‐day washout between periods. Blood samples were collected up to 16 h post‐dose. Plasma concentrations of budesonide were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Reference‐scaled average bioequivalence (RSABE) or average bioequivalence (ABE) method was applied to evaluate the bioequivalence, on the basis of the within‐subject standard deviation (SWR) of the reference product (Budiair), and the safety was also assessed. Eventually, 31 subjects completed this study. For the maximum concentration (Cmax) (within‐subject standard deviation, SWR ≥ 0.294), the RSABE method showed a geometric mean ratio (GMR) of 97.13% with a 95% upper confidence bound of < 0. For the area under plasma concentration‐time curve from time zero to the last measurable concentration (AUC0−t) and the area under plasma concentration‐time curve extrapolated to infinity (AUC0−∞) (SWR < 0.294), ABE yielded GMRs of 104.81% and 104.61%, with 90% confidence intervals (CIs) of 99.98%–109.86% and 99.81%–109.63%, respectively. All adverse events (AEs) were mild to moderate and transient, with no serious adverse events (SAEs) reported. The two budesonide pMDIs (200 μg) were bioequivalent and well tolerated in healthy Chinese subjects. Trial Registration: Chinese Clinical Trial Registry, Registration No. CTR20244600; ClinicalTrials.gov identifier: NCT06924190

Essential hypertension is a notable threat for the older (age, >= 65 years) population. However, to the best of our knowledge, a real-world study assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablets in older Chinese patients with essential hypertension has not been performed. Therefore, the present study aimed to evaluate the efficacy and safety of OM-AML tablets in these patients. A total of 463 older Chinese patients with essential hypertension treated with OM-AML (20/5 mg) tablets (Sevikar (R)) were analyzed in a prospective, single-arm, multi-center, real-world study. Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, and at week (W)4 and W8 after OM-AML tablet administration were measured. The mean +/- standard error change of SeSBP/SeDBP was -10.3 +/- 0.8/-4.6 +/- 0.5 and -12.5 +/- 0.8/-5.6 +/- 0.5 mmHg at W4 and W8, respectively. At W4, 74.1 and 26.8% of patients achieved BP target according to the China and American Heart Association (AHA) criteria, while at W8, 78.0 and 38.7% of patients reached these BP targets accordingly. Finally, 76.5 and 80.5% of patients achieved BP response at W4 and W8, respectively. Furthermore, home-measured SeSBP and SeDBP were significantly decreased from W1 to W8 (both P<0.001). Additionally, the satisfaction of both patients and physicians was elevated at W8 compared with at W0 (both P<0.001). The medication possession rate from baseline to W4 and W8 was 95.5 and 92.5%. The most common drug-associated adverse events by system organ classes were nervous system disorder (4.5%), vascular disorder (2.8%), and general disorder and administration site conditions (2.6%), which were generally mild. In conclusion, OM-AML tablets may be considered effective and safe in lowering BP, enabling the achievement of guideline-recommended BP targets in older Chinese patients with essential hypertension.

The rise of digital technologies, including artificial intelligence, big data, cloud computing, the Internet of Things, and virtual reality, has sparked interest in emerging occupations. This study categorizes and defines these evolving roles within the context of the new economy and scrutinizes their development in China and practitioners' job perceptions. Findings indicate: (i) The emerging occupation sectors are experiencing rapid growth, with digitalization identified as a pivotal factor propelling their development. (ii) A pronounced demand exists for social production and life service personnel, accompanied by noteworthy salary variations among emerging occupations in different cities. A salary premium is particularly evident for professional and technical personnel. (iii) Four pathways are identified for enhancing job satisfaction, and six pathways for shaping a positive assessment of job prospects. In contrast to job satisfaction, the pathways influencing practitioners' assessment of job prospects are more intricate, indicative of a lack of confidence among practitioners regarding their future career trajectories. Practitioners with a positive job prospect assessment tend to concentrate in economically developed regions.

Cleaner heating policies aim to reduce air pollution and may bring about health benefits to individuals. Based on a fixed-effect model focusing on Beijing, this study found that after the onset of air pollution, daily clinic visits, hospitalization days, and hospitalization expenses increased several days after the occurrence of air pollution. These hospitalization changes were observed in males and females and three different age groups. A difference-in-differences (DID) model was constructed to identify the influences of cleaner heating policies on health consequences. The study revealed that the policy positively affects health outcomes, with an average decrease of 3.28 thousand clinic visits for all diseases. The total hospitalization days and expenses tend to decrease by 0.22 thousand days and 0.34 million CNY (Chinese Yuan), respectively. Furthermore, implementing the policy significantly reduced the number of daily clinic visits for respiratory diseases, asthma, stroke, diabetes, and chronic obstructive pulmonary diseases (COPDs).

Because the study of national identity allows for the exploration of pathways to promote social cohesion, exploring the important influence of national identity on society has become a focus of researchers' attention. The purpose of this review is to do an examination of curriculum and national identity and to explore the potential for research on the impact of curriculum education on national identity. The paper focuses on assessing the concept of national identity, the educational content of national identity in textbooks, and the relationship between curriculum and the formation of students' national identity. The content of national identity in textbooks has been widely studied, but the mechanisms by which instructional materials influence students' national identity have not been empirically examined. Empirical research on students' national identity perceptions, attitudes, evaluations, emotions, and behaviors from the dimensions of curriculum content, curriculum objectives, instructional design, teaching methods, teacher literacy, and curriculum evaluation are all areas that need to be explored.

There lacks real-world study with a large sample size assessing olmesartan medoxomil-amlodipine besylate (OM-AML) tablet. Therefore, this study aimed to evaluate the efficacy and safety of OM-AML tablet in patients with essential hypertension. Totally, 1341 patients from 36 medical centers with essential hypertension who took OM-AML (20/5 mg) tablet were analyzed in the current prospective, single-arm, multi-center, real-world study (SVK study). Seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) at baseline, week (W)4 and W8 were measured. The mean (±SE) change of SeSBP/SeDBP was -10.8 ± 0.4/-6.6 ± 0.3 mmHg at W4 and -12.7 ± 0.5/-7.6 ± 0.3 mmHg at W8, respectively. At W4, 78.8% and 29.0% patients achieved BP target by China and American Heart Association (AHA) criteria; at W8, 84.7% and 36.5% patients reached blood pressure (BP) target by China and AHA criteria, accordingly. Meanwhile, 80.2% and 86.4% patients achieved BP response at W4 and W8, respectively. Home-measured SeSBP and SeDBP decreased from W1 to W8 (both p < .001). Besides, patients' and physicians' satisfaction were elevated at W8 compared with W0 (both p < .001). The medication possession rate was 94.8% from baseline to W4 and 91.3% from baseline to W8. The most common drug-related adverse events were nervous system disorders (4.6%), vascular disorders (2.6%), and general disorders and administration site conditions (2.3%) by system organ class, which were generally mild and manageable. In conclusion, OM-AML tablet is one of the best antihypertensive agents in patients with essential hypertension.

Abaloparatide (ABL) is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. However, real-world data regarding its long-term safety and tolerability in large sample population are incomplete. We evaluated abaloparatide-associated safety signals by data mining of the FDA pharmacovigilance database. We investigated 33,480(0.14

Objective: To investigate the effect of sugammadex on postoperative nausea and vomiting(PONV) after intracranial aneurysm surgery. Methods: Data from intracranial aneurysms patients who met the inclusion and exclusion criteria and underwent interventional surgery in the Department of Neurosurgery, Peking University International Hospital from January 2020 to March 2021 were prospectively included. According to the random number table method, the patients were divided by 1∶1 into the neostigmine+atropine group (group N) and the sugammadex group (group S). Use an acceleration muscle relaxation monitor for muscle relaxation monitoring, and administer neostigmine+atropine and sugammadex to block residual muscle relaxation drugs after surgery. The incidence rates of PONV and severity, the appearance of anesthesia, and the correlation between PONV and postoperative complications were recorded in both groups during five periods after surgery: 0-0.5 hours (T1),0.5-2.0 hours(T2),2.0-6.0 hours (T3),6.0-12.0 hours (T4) and 12.0-24.0 hours (T5). Group comparisons of quantitative data were performed by the independent sample t-test, and categorical data was performed by the χ2 or rank sum test. Results: A total of 66 patients were included in the study, including 37 males and 29 female, aged (59.3±15.4) years (range: 18 to 77 years). The incidence rates of PONV of 33 patients in group S at different time periods of T1, T2, T3, T4, and T5 after surgery were respectively 27.3%(9/33),30.3%(10/33),12.1%(4/33),3.0%(1/33),0(0/33),and the incidence rates of PONV of 33 patients in the group N at different time periods of T1, T2, T3, T4 and T5 after surgery were respectively 36.4%(12/33),36.4%(12/33),33.3%(11/33),6.1%(2/33) and 0(0/33).The incidence of PONV was lower in the group S only in the T3 period after reversal than in the group N (χ2=4.227, P=0.040).However, there was no statistically significant difference in the incidence of PONV between the two groups of patients in other periods (all P>0.05). The recovery time for spontaneous breathing in patients in group S was (7.7±1.4) minutes, the extubation time was (12.4±5.3) minutes, and the safe exit time for anesthesia recovery was (12.3±3.4) minutes; the N groups were (13.9±2.0) minutes, (18.2±6.0) minutes, and (18.6±5.2) minutes, respectively; three time periods in group S were shorter than those in group N, and the differences were statistically significant (all P<0.05). Analysis of the correlation between incidence and severity of PONV in two groups of patients at different periods and postoperative complications showed that only the severity of PONV in the T3 period of the group N was correlated with the incidence of postoperative complications (χ2=24.786,P<0.01);the incidence and severity of PONV during the T4 period were correlated with the incidence of postoperative complications (all P<0.01). There was a correlation between the incidence and severity of PONV in the T3 and T4 periods of group S and the incidence of postoperative complications (all P<0.01). Conclusion: Sugammadex can be used to reverse muscle relaxation in patients undergoing intracranial aneurysm intervention surgery,and it does not have a significant impact on the incidence of PONV, it can also optimize the quality of anesthesia recovery and reduce the incidence of complications after intracranial aneurysm embolization surgery.

Objective: To construct and analyze the functional network changes of hemi-brain in patients with brain tumor before and after anesthesia by using resting state functional magnetic resonance imaging (rs-fMRI). Methods: A total of 18 right-handed patients were prospectively included (6 males and 12 females). The patients underwent glioma resection in Peking University International Hospital from December 2018 to December 2021, and age ranged from 20 to 65 (45.1±13.6) years, with American Society of Anesthesiologists (ASA) grade of Ⅰ-Ⅱ. MRI scans were performed while the patient was awake and at the depth of surgical anesthesia. The functional network of healthy lateral brain was constructed and analyzed by means of graph theory, and its global and local topological properties were calculated. Global topology attributes included global efficiency (Eg), local efficiency (Eloc), clustering parameters (Cp), length parameter of shortest path (Lp), and small world (SW). Topology attributes of nodes included node degree (ND), node efficiency (NE) and between centrality (BC). The global and nodal topological properties of the hemi-brain network were compared between patients with different hemispherical space occupying under wakefulness and anesthesia. Results: At the awake state, Eloc and Cp in the global topological attributes of hemi-brain network were 0.259±0.007 and 0.197±0.010, respectively, and decreased to 0.242±0.013 and 0.177±0.021, respectively after anesthesia, with statistically significant differences (all P<0.01). The topological attributes of the nodes in hemi-side brain showed that ND, NE and BC were increased in the default mode network-related brain regions, while NE and BC were decreased in the limbic system and subcortical structures. Eloc and Cp were 0.258±0.008 and 0.198±0.008 respectively in the patients with left hemisphere space occupying, and decreased to 0.241±0.011 and 0.177±0.015 respectively after anesthesia, with statistically significant differences (all P<0.01). However, only Eloc decreased in patients with right hemisphere space occupying after anesthesia, and Eloc was 0.260±0.006 and 0.243±0.016 respectively when awake and after anesthesia, with statistically significant differences (P<0.05). The topological attributes of nodes in patients with space occupying in different cerebral hemispheres showed bidirectional changes after anesthesia, and patients with space occupying in the left cerebral hemisphere were more likely to be widely affected after anesthesia. The effects of anesthetic drugs may show hemispheric laterality. If the tumor was in the dominant hemisphere, the compensatory function of the dominant side was more likely to be damaged. Conclusions: During anesthesia-induced loss of consciousness in patients with brain tumors, both the ability to integrate information and the functional connections between local regions are weakened, and some brain regions have functional connection reorganization. The changes of brain network after anesthesia are bidirectional regulation.

Based on real-world case data, this study intends to explore and analyze the impact of rescue conscious sedation (CS) on the clinical outcomes of patients with anterior circulation acute ischemic stroke (AIS) receiving mechanical thrombectomy (MT). This retrospective study enrolled patients with anterior circulation AIS who received MT and were treated with either single local anesthesia (LA) or rescue CS during MT between January 2018 and October 2021. We used univariate and multivariate logistic regression methods to compare the impact of LA and CS on the clinical outcomes of patients with AIS who received MT, including the mRS at 90 days, the incidence of poststroke pneumonia (PSP), the incidence of symptomatic intracranial cerebral hemorrhage (sICH), and the mortality rate. We reviewed 314 patient cases with AIS who received MT. Of all patients, 164 met our search criteria. Eighty-nine patients received LA, and 75 patients received rescue CS. There was no significant difference between the two groups in the 90-day good prognosis (45.3

BackgroundHPV infection is closely related to the occurrence of cervical cancer and has an important adverse effect on human life and health. This study used data from the NHANES 2003–2016 to investigate the relationship between PIR and HPV infection status among Americans aged 20 and older.MethodsThe data for this cross-sectional investigation came from the 2003–2016 National Health and Nutrition Examination Survey (NHANES), which included 9580 women who were 20 years of age or older. The linear and nonlinear correlations between PIR and the presence of HPV infection were investigated using multiple linear regression and smooth curve fitting. The stability of the relationship across groups was examined using subgroup analysis and interaction tests.ResultsThere were 2232 impoverished homes and 2543 rich households among the 9580 adult participants aged 20 and above. PIR (ratio of income to poverty) was found to be significantly inversely related to the presence of HPV infection [0.91 (0.89, 0.94)] after adjusting for all other covariates, and the trend persisted even after categorizing PIR into high- and low-income groups (PIR>4 and PIR<1). In addition, significant negative relationships were discovered in subgroup analyses for women aged 25 to 59 [0.90 (0.88, 0.93)], non-Hispanic whites [0.80 (0.70, 0.92)], non-diabetics [0.91 (0.88, 0.94)], and those who had ever engaged in sex [0.91 (0.89, 0.94)].ConclusionsPIR was highly and negatively correlated with the presence of HPV infection in American women aged 20 and older. The results of this study are of great significance for preventing HPV infection and improving the accuracy of HPV screening.

Takayasu's arteritis (TAK) mainly involves the aorta and its major branches, which is characterized as a chronic, progressive and inflammatory disease. China belongs to one of the regions with a high prevalence of TAK referring to its global distribution. However, it is insufficient for the spread and update of standardized diagnosis and treatment of TAK. Based on the evidence and guidelines from China and other countries, Chinese Rheumatology Association developed the standardized diagnosis and treatment of TAK in China. The purpose is to standardize the methods for diagnosis of TAK, assessment of disease activity and disease severity, strategies of internal treatment and timing of surgical intervention, and further leading to protect the function of important organs and improve the disease prognosis.

颅内黏液样间叶性肿瘤是一种罕见的肿瘤，分子遗传学伴EWSR1与CREB家族基因融合。本文报道1例9岁男性患儿，小脑占位性病变，肿瘤结节状生长，界限清楚，肿瘤细胞椭圆形、梭形或星芒状，疏密不等，大部分呈条索状或疏松网状分布于黏液性间质中，间质内可见“石棉样”纤维，局灶细胞较丰富，呈片状排列。免疫组织化学结果：波形蛋白阳性，结蛋白及CD68部分阳性，上皮细胞膜抗原及CD99弱阳性，胶质纤维酸性蛋白、Olig2、S-100蛋白、平滑肌肌动蛋白、p63、CD34等均阴性，p53野生型表达，热点区Ki-67阳性指数约20%。分子表型：荧光原位杂交检测到EWSR1基因分离，二代测序检测出EWSR1-CREB1及SELENOW-EWSR1融合基因。病理诊断为伴EWSR1-CREB1融合的颅内黏液样间叶性肿瘤。术后7个月，患者状态良好，无复发及转移。诊断时应与脑膜瘤、胶质瘤、伴EWSR1-CREB家族基因融合的其他肿瘤及骨外黏液样软骨肉瘤等形态相似的肿瘤鉴别。

Ischemic stroke (IS), a multifactorial and polygenic disease, is the most common cause of death. This study aimed to determine the roles of MMP8/MMP10 polymorphisms in IS susceptibility in the Chinese Han population.

目的利用meta分析方法评价卒中急性期NIHSS评分与卒中后抑郁（post-stroke depression,PSD）发生的相关性,为临床防治PSD提供证据。方法计算机检索PubMed、中国知网、万方数据知识服务平台及维普数据库,搜集建库至2019年10月有关PSD与神经功能评分关系的病例对照研究,纳入符合标准的文献,由2名研究人员独立筛选文献、提取有效数据资料,并根据纽卡斯尔-渥太华量表进行质量评估。应用ReviewManager5.3软件对各研究中的原始数据进行统计,根据纳入研究的异质性检验结果选用固定效应模型或随机效应模型进行合并效应量分析。结果共纳入15篇文献,共计3050例研究对象,其中PSD组1157例,非PSD组1893例。整体meta分析结果显示:PSD组NIHSS评分高于非PSD组,差异有统计学意义（MD 0.92,95%CI 0.48～1.37,P＜0.01）。亚组分析结果显示:（1）以地域分组,在中国人群中,PSD组NIHSS评分高于非PSD组,差异有统计学意义（MD 0.81,95%CI 0.36～1.27,P＜0.01）;（2）以卒中是否首发分组,首发卒中人群中,PSD组NIHSS评分高于非PSD组,差异有统计学意义（MD 1.24,95%CI 0.82～1.67,P＜0.01）,再发卒中两组间NIHSS评分差异无统计学意义（MD-0.25,95%CI-1.53～1.03,P=0.70）;（3）以卒中类型分组,缺血性卒中PSD组NIHSS评分高于非PSD组,差异有统计学意义（MD 0.83,95%CI 0.38～1.29,P＜0.01）;（4）以PSD诊断时间分组,卒中1个月内诊断PSD的研究中,两组间NIHSS评分差异无统计学意义（MD 0.64,95%CI0.01～1.28,P=0.05）,卒中1个月以上诊断PSD的研究中,PSD组NIHSS评分高于非PSD组,差异有统计学意义（MD1.29,95%CI 0.78～1.81,P＜0.01）;（5）根据NIHSS评估时间分组,在卒中后2周内进行NIHSS测评的研究中,PSD组NIHSS评分高于非PSD组,差异有统计学意义（MD 1.01,95%CI 0.62～1.41,P＜0.01）,在卒中后3～4周进行NIHSS测评的研究中,两组间NIHSS评分差异无统计学意义（MD 1.00,95%CI-0.96～2.96,P=0.32）。结论卒中急性期NIHSS评分与PSD的发生显著相关,NIHSS评分是影响PSD发生的重要危险因素,特别是在中国人群、首发卒中、缺血性卒中、卒中1个月后PSD及卒中发病2周内评估NIHSS的患者人群中。

The degree of forest vegetation restoration and reconstruction and the impact of different afforestation tree species on plant diversity in Mount Tai, China were evaluated.We selected 6 kinds of 50-year-old plantations along Tianwai village, Hongmen, Tianzhu peak and Taohuayuan lines.The results show that: 1) Robinia pseudoacacia plantation has significantly lower tree layer richness, Shannon-Wiener diversity and Simpson diversity than other plantations; Pinus tabulaeformis and larch tree plantations have significantly lower shrub layer Shannon -Wiener and Simpson diversity than other plantations, Pinus tabulaeformis and Pinus densiflora have significantly lower Pielou evenness than the other four plantations; Pinus tabulaeformis plantation and Platycladus orientalis plantation have significantly lower herb layer richness than the other four plantations, while Pinus tabulaeformis plantation has significantly lower Shannon-Wiener diversity and Simpson diversity than the other five plantations.2) Species richness, Shannon-Wiener diversity and Simpson diversity of tree and shrub layers are all presented from highest to lowest in the following order: Mount Meng > Mount Tai > Mount Yi, while Mount Tai plantation has the highest herb layer species richness, Shannon-Wiener diversity and Simpson diversity.These results provide basis for the regulation and prediction of regional forest vegetation restoration and reconstruction in the future.

Objective To observe the effect of Traditional Chinese Medicine (TCM)nursing intervention on vertigo in patients with acute stroke Methods Totally 80 acute stroke patients with vertigo were randomly divided into the observation group and control group, with 40 cases in each group. All patients received routine medication treatment and rehabilitation care. The routine TCM nursing interventions such as acupoint application and auricular point pressing therapy were conducted to relieve the symptom of vertigo among patients in both two groups, and an additional TCM intervention of massage therapy was carried out in the observation group. The intervention effect was evaluated at two weeks after intervention, and patient’s treatment compliance and satisfaction with TCM interventions were investigated. Results The overall effective rate of intervention in the observation group was higher than that in the control group (P<0. 05). Patients in the observation group had higher rate of compliance and higher degree of satisfaction with TCM nursing interventions compared with those in the control group (P<0. 05). Conclusion In addition to the routine TCM nursing, The TCM massage therapy is potentially effective to relieve the vertigo in patients with acute stroke and improve their treatment compliance and degree of satisfaction.

Background& Aims: The Coronavirus Disease 2019 (COVID-19) has become a global epidemic and has caused a lasting and huge loss of life security, economic development and social stability in more than 180 countries around the world. Unfortunately, there is still no specific treatment for COVID-19 till now, therefore, at this point, all potential therapies need to be critically considered. LL-37 is one of the best-studied human antimicrobial peptide (AMPs) that has a broad-spectrum activity against bacteria and viruses. The use of living, genetically modified organisms (GMOs) is an effective approach for delivery of therapeutic proteins. The aim of this study was to determine the safety and efficacy of the Lactococcus lactis which has been genetically modified to produce the therapeutic human antimicrobial peptide LL-37 (herein after referred to cas001) in the patients of COVID-19. Methods: Firstly we constructed genetically modified food-grade probiotic, Lactococcus lactis, with sequence of seven tandem repeats of mature human LL-37 under control of the nisin-inducible nisA promoter to produce the cas001. A total of 20 healthy SD rats, half male and half female (There were five male and five female in the control group, the same in treatment group) were used to observe the acute toxic reaction and death after daily administration of cas001 for three weeks, which helps to provide necessary reference basis for clinical dose selection, verificaition of toxic reaction and possible target organs. According to the estimated clinical dosage of 1 x 108CFU /kg/day, considering the conversion of body surface area, the dose for rats should be multiplied by 6.17 to 6 x 108 CFU/kg/day. We administrated 100 times higher dose at 6 x 1010 CFU/kg/day to rats. In order to investigate the pharmacokinetics of cas001, male SD rats (body weight 250-300g, 1 x 1010 /animal, n=3) were given oral administration of LL-37 bacteria powder. The concentration of LL-37 in the blood before and after gavage was detected by ELISA kit (Hycult biotechnology Cat# HK321). Human clinical study was approved by Ethics committee of Chinese PLA General Hospital (S2020-074-04) and a total of 11 patients with mild symptoms were enrolled in Wuhan hankou hospital and Huoshenshan hospital. They were enrolled voluntarily and all patients signed informed consent. Among them, there were 5 males and 6 females, aged 55 {+/-} 12 (36-70) years old, and the duration from onset to medication enrollment was 35 {+/-} 19 (5-68) days. 6 patients were nucleic acid positive and 5 patients were nucleic acid negative when they were enrolled. All patients received the oral drug cas001 treatment according to requirement(1 x 109 CFU/capsule, 3 capsules/time, three times a day for 3weeks), with an average follow-up time of 33 {+/-} 15 days (see table 1 for the results). Findings: Western blot analysis shows that reasonable amount of LL-37 were induced by different concentrations of nisin, which means we have successfully constructed cas001. In the pre-clinical safety evaluation test, after three weeks administration of cas001, no adverse effects were observed on the rat's body weight, food and water intake, hematological or serum biochemical parameters. The results showed that the LD50 of cas001 was higher than that of the 100 times of the expected clinical dose of 6 x 1010 CFU/day. These results showed that cas001 could be safe in animal experiments. In addition, rat pharmacokinetics results showed that the serum concentration of LL-37 reached peak 2 hours after gavage of cas001 and returned to basal level 6 hours after gavage. During study period, the volunteers did not feel any discomfort while taking the cas001 capsules, and two hours after oral administration, the concentration of LL-37 were increased in healthy volunteers. cas001 shows definite effect in the improvement of gastrointestinal symptoms and is possible to have effects in improving the systemic symptoms and respiratory symptoms and may play a role in the improvement of results of nucleic acid test and lung CT test. 11 patients enrolled showed good compliance, tolerance, subjective feeling and actively interacted with the doctors. None of the patients had any adverse reactions. Conclusions Based on above observations, we conclude here that as an oral anti-viral agent, cas001 displayed good safety profiles. It is very hard to reach conclusion of clinical outcomes related to the cas001, although changes of several symptoms indicate encouraging findings.

Monoterpenes present in the essential oils exhibit anti-inflammatory properties. In this study, we investigated the preventive effect of alpha-pinene (AP), a monoterpene, against isoproterenol (ISO)-induced myocardial infarction and inflammation in Wistar rats. Male Wistar rats were pretreated with AP (50 mg/kg body weight (bw)) administration for 21 days and ISO (85 mg/kg bw) was administered subcutaneously for last two consecutive days (20th day and 21st day). We noticed that there was an increased activity of cardiac marker enzymes in ISO-treated rats. We also observed that elevated levels of lipid peroxidative indices decreased activities of antioxidant status in plasma, erythrocyte, and heart tissue in ISO-induced rats. Furthermore, ISO-treated rats showed an increase in the levels of inflammatory mediators like tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the serum. Besides, we confirmed the upregulated expression of TNF-α, IL-6, and nuclear factor kappa-light-chain-enhancer of activated B cells in ISO-induced rat heart tissue. Conversely, we found that AP pretreatment significantly decreased levels of cardiac markers like serum cardiac troponin T and cardiac troponin I, lipid peroxidative markers, and restored antioxidants status in ISO-treated rats. Besides, AP administration attenuated ISO-induced inflammatory marker expression. The present findings demonstrated that AP significantly protects the myocardium and exerts cardioprotective and anti-inflammatory effects in experimental rats.