BACKGROUND:Pien Tze Huang (PTH), a well-established traditional Chinese medicine compound, has exhibited anti-hepatic fibrosis properties both in vitro and in vivo animal models, but the randomized clinical trials to evaluate anti-hepatic fibrosis efficacy of PTH are deficient. Chronic hepatitis B (CHB) is a leading cause of hepatic fibrosis in China. Although antiviral therapies have demonstrated significant effectiveness in arresting the progression of fibrotic disease, complete regression of established fibrosis is limited to only a subset of treated patients. PURPOSE:To assess the efficacy of PTH in improving hepatic fibrosis in CHB patients. STUDY DESIGN:We conducted a randomized, double-blind, placebo-controlled clinical trial involving 144 CHB patients with hepatic fibrosis. This study was carried out from September 2020 to April 2023. (Clinical Trials Registration: ChiCTR2000035128) METHODS: CHB patients with an Ishak score of 2-5 points were recruited from ten hospitals across China. Participants were randomized in 1:1 ratio to receive either oral PTH (0.6 g per dose, three times/day) or placebo for 48 weeks, in addition to the standard treatment of entecavir (0.5 mg/day). The primary endpoint was the change in Ishak score. Secondary outcomes included changes in Knodell HAI score, liver stiffness measurement, AST- to -platelet ratio index, Fibrosis-4 index and hepatic function indices. RESULTS:Of the 144 randomized patients, 142 patients (71 in the PTH group and 71 in the placebo group) were included in the primary analysis. The PTH group exhibited lower Ishak score compared to the control group (2.37 ± 0.94 vs. 2.87 ± 1.04, F = 6.072, p = 0.015). Notably, in treatment-naive patients, the PTH group showed significant improvement in Ishak score post-treatment compared with the control group (2.13 ± 0.72 vs. 2.74 ± 1.07, F = 6.336, p = 0.014). However, no significant changes were observed in these parameters among patients already receiving antiviral therapy. CONCLUSIONS:The combination of PTH and entecavir demonstrates significant improvement in hepatic fibrosis among CHB patients, especially those who are treatment-naive patients.

Diabetic kidney disease (DKD) is a severe diabetic microvascular complication featured by chronic low-grade inflammation. Roux-en-Y gastric bypass (RYGB) surgery has gained importance as a safe and effective surgery to treat DKD. Bile acids significantly change after RYGB, which brings a series of metabolic benefits, but the relationship with the improvement of DKD is unclear. Therefore, this study performed RYGB surgery on db/db mice to observe the beneficial effects of the surgery on the kidneys and performed bile acid-targeted metabolomics analysis to explore bile acid changes. We found that RYGB significantly reduced albuminuria in db/db mice, improved renal function, reversed renal structural lesions, and attenuated podocyte injury and inflammation. Notably, bile acid metabolomic analysis revealed taurolithocholic acid (TLCA) as the most significantly altered bile acid after RYGB. Furthermore, in vitro and in vivo validation experiments revealed that TLCA supplementation improved renal function and reduced renal inflammatory damage in db/db mice. In addition, TLCA inhibited high glucose-induced inflammatory damage in MPC-5 cells, and its mechanism of action may be related to activating Takeda G protein-coupled receptor 5 (TGR5), inhibiting NF-κB phosphorylation, and thus inhibiting inflammatory response. In conclusion, RYGB may play a protective role in the kidneys of diabetic mice by activating the TLCA/TGR5 pathway.NEW & NOTEWORTHY This study determined that the renal protective effect of Roux-en-Y gastric bypass (RYGB) in db/db mice was associated with elevated serum TLCA. Notably, TLCA supplementation improved renal function and alleviated podocyte inflammatory injury in db/db mice, which was associated with the TGR5/NF-κB pathway.

OBJECTIVE:To investigate the antipyretic effect of early treatment with Traditional Chinese Medicine (TCM) on coronavirus disease 2019 (COVID-19) patients. METHODS:We retrospectively analyzed 369 patients from January 26th, 2020 to April 15th, 2020, who had been diagnosed with COVID-19. Among 92 eligible cases, 45 cases were identified as treatment group Ⅰ ( 45) and 47 cases were identified as treatment group Ⅱ. Patients in the treatment group Ⅰ were treated with TCM herbal decoction within 5 d after admission. Patients in the treatment group Ⅱ were treated with TCM herbal decoction after the 6th admission day. The onset time of antipyretic effect, the antipyretic time, the time of negative oropharyngeal swab nucleic acid conversion, and the changes of cell count in blood routine test were compared. RESULTS:The treatment group I showed shorter average antipyretic duration (4 7 d; <0.05), and shorter average time for polymerase chain reaction (PCR) nucleic acid test results to turn negative (7 11 d; <0.05) than the treatment group II. For patients ( 54) with body temperature>38 ℃, patients in the treatment group I had shorter median onset time of antipyretic effect than those in the treatment group II (3 4 d; <0.05). The absolute lymphocyte (LYMPH) count and absolute eosinophil (EOS) count on the 3rd day after admission and the neutrophil/lymphocyte ratio on the 6th day after admission of patients in the treatment group I were notably different from those in the treatment group II at the same time point (0.05). Based on Spearman's rank correlation analysis, the change of body temperature on the 3rd day after admission was positively correlated with the increase of EOS count and the increase of EOS count and LYMPH counts on the 6th day after admission (0.01). CONCLUSIONS:Early TCM intervention within 5 d after hospital admission shortened the onset time of antipyretic effect and fever duration of COVID-19 patients, reduced the time required for PCR test results to turn negative. Moreover, early TCM intervention also improved the results of inflammatory markers for COVID-19 patients. LYMPH and EOS counts can be used as indicators of TCM antipyretic effect.

The pathology of depression is related to the imbalance of various neurotransmitters. The dorsal raphe nucleus (DRN), the main brain region producing 5-HT, is crucially involved in the pathophysiology of depression. It contains several neuron types, in which GABAergic neurons are activated by stimuli associated with negative experiences and 5-HT neurons are activated by reward signals. However, little is known about its underlying molecular mechanisms. Here, we found that p11, a multifunctional protein associated with depression, was down-regulated by chronic social defeat stress in 5-HTDRN neurons. Knockdown of p11 in DRN induced depression-like behaviors, while its overexpression in 5-HTDRN neurons alleviated depression-like behavior caused by chronic social defeat stress. Further, p11 regulates membrane trafficking of glutamate receptors in 5-HTDRN neurons, suggesting a possible molecular mechanism underlying the participation of p11 in the pathological process of depression. This may facilitate the understanding of the molecular and cellular basis of depression.

新型冠状病毒奥密克戎( Omicron )变异株自2021年11月首次发现并传播以来,增速迅猛,已席卷全球,全球已有100 多个国家和地区发现奥密克戎变异株感染病例.新型冠状病毒肺炎(简称新冠肺炎)疫情发生以来,中医药在防治方面发挥了重要作用.为了有效指导临床防治,世界中医药学会联合会急症专业委员会、中国上海中医药大学急危重症研究所、美国中医药针灸学会组织国内外中医药防控新冠肺炎领域临床一线专家及相关学术机构与组织,在参照中华人民共和国国家卫生健康委员会、国家中医药管理局《新型冠状病毒肺炎诊疗方案(试行第九版)》基础上,结合新型冠状病毒奥密克戎变异株感染防治临床经验,就新型冠状病毒奥密克戎变异株感染中医药防治相关问题展开调研与讨论,并最终形成本共识.6

An estimated 20% of women experience depression at some point during menopause. Hormone replacement therapy (HRT), as the main therapy for depression and other menopausal syndromes, comes with a few undesirable side effects and a potential increase in cancer and cardiovascular risk. Consequently, there is a dire need for the development of new therapies to treat menopausal depression. Oxidative stress combined with the decline in sex hormones might explain the occurrence of psychological symptoms characteristic of menopause. Therefore, antioxidants have been suggested as a promising therapy for aging-associated diseases, such as menopausal depression. As a flavonoid antioxidant, kaempferol might have a potential neuroprotective action. Hence, the study was conducted to assess the potential antidepressant action of kaempferol and clarify the underlying mechanism. The results show that kaempferol has potential beneficial effects on VCD-induced rodent model of menopausal depression and produces antioxidant effects as well as increases the deacetylation of superoxide dismutase 2 (SOD2) and the protein level of Sirtuin3 (Sirt3) in the hippocampus. On the contrary, Sirt3 depletion abrogated the antidepressant- and anxiolytic-like effects as well as antioxidant effects of kaempferol. In conclusion, kaempferol might produce antidepressant effects via upregulating the expression of Sirt3, the major deacetylase in mitochondria, and subsequently activate the mitochondrial antioxidases. These findings shed some light on the use of kaempferol or vegetables and herbs that contain kaempferol as a complementary therapy for menopausal depression.

新冠肺炎自2020年爆发以来,中医药取得举世瞩目的救治效果,在全球疫情防控中发挥着重要作用,获得了 WHO的高度肯定.2021年11月新冠肺炎奥密克戎(Omicron)变异株首次出现并迅速传播,我国吉林、上海先后出现爆发并蔓延全国.为了更加有效应对奥密克戎变异株感染,世界中医药学会联合会急症专业委员会、中华医学会急诊分会中西医结合急救学组、中国医师协会急诊医师分会中西医结合急救医学学组、上海中医药学会急诊分会、上海中医药大学急危重研究所等学术机构组织奥密克戎新冠肺炎变异株一线救治专家,根据上海、吉林等奥密克戎感染地区患者中医临床症候,并结合国家《新型冠状病毒诊疗方案(试行第九版)》,就中成药应用相关问题展开调研与讨论,形成本共识,以期对当下新冠肺炎奥密克戎变异株感染乃至以后疫情防控起到临床指导作用.

BACKGROUND Post-transarterial chemoembolization (TACE) liver failure occurs frequently in hepatocellular carcinoma (HCC) patients. The identification of predictors for post-TACE liver failure is of great importance for clinical decision-making in this population. AIM To investigate the occurrence rate and predictive factors of post-TACE liver failure in this retrospective study to provide clues for decision-making regarding TACE procedures in HCC patients. METHODS The clinical records of HCC patients treated with TACE therapy were reviewed. Baseline clinical characteristics and laboratory parameters of these patients were extracted. Logistic models were used to identify candidates to predict post-TACE liver failure. RESULTS A total of 199 HCC patients were enrolled in this study, and 70 patients (35.2%) developed post-TACE liver failure. Univariate and multivariate logistic models indicated that microspheres plus gelatin embolization and main tumor size > 5 cm were risk predictors for post-TACE liver failure [odds ratio (OR): 4.4, 95% confidence interval (CI): 1.2-16.3, P = 0.027; OR: 2.3, 95%CI: 1.05-5.3, P = 0.039, respectively]. Conversely, HCC patients who underwent tumor resection surgery before the TACE procedure had a lower risk for post-TACE liver failure (OR: 0.4, 95%CI: 0.2-0.95, P = 0.039). CONCLUSION Microspheres plus gelatin embolization and main tumor size might be risk factors for post-TACE liver failure in HCC patients, while prior tumor resection could be a favorable factor reducing the risk of post-TACE liver failure.

The gut microbiota system plays a vital role in liver diseases. This study aimed to address the diversity of gut microbiota and its correlations with clinical parameters in healthy individuals, chronic liver disease (CLD), and hepatocellular carcinoma (HCC) patients. Fecal specimens of nine healthy individuals, 11 CLD, and 21 HCC were collected. The diversity of gut microbiota was examined by PCR and Illumina MiSeq sequencing and analyzed using 16S rRNA gene sequencing database. The correlations between gut microbiota and the clinical parameters of participants were also addressed. Compared to healthy individuals, Firmicutes at a phylum level decreased in CLD and HCC patients and Proteobacteria increased (p < 0.05). The composition of Blautia on a genus level in CLD and HCC patients significantly decreased compared to healthy controls (p < 0.05). Firmicutes composition was negatively associated with age and number of males (p < 0.05) and was positively associated with monocytes, high-density lipoprotein cholesterol (HDL-C), and estimated glomerular filtration rate (eGFR) levels (p < 0.05). At a genus level, Blautia composition was negatively associated with cirrhosis, age, and number of males (p < 0.01), while it was positively associated with red blood cells (RBCs), triglycerides, HDL-C, and lymphocyte levels (p < 0.05). Conclusively, there was a significant compositional difference in gut microbiota in CLD and HCC patients compared with healthy subjects. Firmicutes and Blautia in gut microbiota system lessened in CLD and HCC patients. Clinical biochemical parameters have an impact on the diversity of gut microbiota in liver diseases.

This integrated bioinformatic study aimed to investigate potential prognostic candidates in hepatocellular carcinoma (HCC). In the GSE14520, GSE101685, and The Cancer Genome Atlas (TCGA) datasets, differentially expressed genes (DEGs) were identified and functional pathways of common DEGs were enriched. The least absolute shrinkage and selection operator (LASSO) model was used to screen the potential parameters associated with overall survival (OS) in HCC patients. Metabolic pathways were the most significantly enriched functional pathways of common DEGs in these three datasets. After LASSO model analysis, HMGCS2, UGP2, BCLC staging and TNM staging were screened as potential prognostic candidates for OS in HCC patients in GSE14520. HMGCS2 in the metabolic pathway was significantly downregulated in tumor tissues and peripheral blood mononuclear cells in HCC patients (all p < 0.05). Cox regression model indicated that HMGCS2 might be associate with OS in HCC patients in GSE14520 and in the TCGA (p = 0.029 and p = 0.05, respectively). Kaplan-Meier analysis demonstrated that HMGCS2 downregulation in tumors contributed to an unfavorable OS in HCC patients, both in GSE14520 and in the TCGA (p = 0.0001 and p = 0.0002, respectively). Additionally, HMGCS2 was significantly downregulated in HCC patients with high alpha-fetoprotein (AFP), main tumor size >5 cm, multinodular, advanced tumor staging including BCLC, TNM and CLIP (all p < 0.05). HMGCS2 was involved in metabolic pathways, and downregulated HMGCS2 in tumors was associated with unfavorable OS in HCC patients.

Objective: The role of the complement and coagulation cascades signaling pathway in the pathogenesis of cancers remains uncertain. This study aimed to investigate the associations between enriched differentially expressed genes (DEGs) in this pathway and hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients. Materials and Methods: Clinical and gene expression data of the Gene Expression Omnibus (GEO) series profile GSE14520 were downloaded. The "Limma" package was used to screen the DEGs and the "clusterProfiler" package was used to identify the complement and coagulation cascades pathway and enriched significant genes. Cox regression analysis, the Kaplan-Meier method, and the nomogram model were used to address the correlations between significantly enriched DEGs in the complement and coagulation cascades pathway and HCC survival. Results: A total of 220 HBV-related HCC patients were enrolled in this study. The complement and coagulation cascades pathway was significantly enriched by 37 DEGs (p-value < 0.05 and adjusted p-value < 0.05). Complement 8 beta chain (C8B) expression levels had protective effects on overall survival (OS) and recurrence-free survival (RFS) in HBV-related HCC patients. High levels of C8B contributed to favorable OS and RFS in this population (both p < 0.01), even after adjustment of clinicopathological characteristics including tumor node metastasis (TNM) staging, Barcelona Clinic liver cancer (BCLC) staging, gender, and fibrinogen beta chain (FGB) expression (all p < 0.05). Conclusion: C8B in the complement and coagulation cascades signaling pathway serves as a predictive candidate for survival in HBV-related HCC patients.

Objective. This study is aimed at investigating the enriched functions of polymeric immunoglobulin receptor (PIGR) and its correlations with liver fibrosis stage. Methods. PIGR mRNA expression in normal liver, liver fibrosis, hepatic stellate cells (HSCs), and hepatitis virus infection samples was calculated in Gene Expression Omnibus (GEO) and Oncomine databases. Enrichment analysis of PIGR-related genes was conducted in Metascape and Gene Set Enrichment Analysis (GSEA). Logistic model and ROC curve were performed to evaluate the correlations between pIgR and liver fibrosis. Results. PIGR mRNA was upregulated in advanced liver fibrosis, cirrhosis compared to normal liver (all p<0.05). PIGR mRNA was also overexpressed in activated HSCs compared to senescent HSCs, liver stem/progenitor cells, and reverted HSCs (all p<0.05). Enrichment analysis revealed that PIGR-related genes involved in the defense response to virus and interferon (IFN) signaling. In GEO series, PIGR mRNA was also upregulated by hepatitis virus B, C, D, and E infection (all p<0.05). After adjusting age and gender, multivariate logistic regression models revealed that high PIGR in the liver was a risk factor for liver fibrosis (OR=82.2, p<0.001). The area under curve (AUC), positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of PIGR for liver fibrosis stage >2 were 0.84, 0.86, 0.7, 0.61, and 0.90. Conclusion. PIGR was correlated with liver fibrosis and might involve in hepatitis virus infection and HSC transdifferentiation.

Objective: To observe the early interventions of traditional Chinese Medicine (TCM) on the conversion time of nucleic acid in patients with coronavirus disease 2019 (COVID-19), and find possible underlying mechanisms of action. Methods: A retrospective cohort study was conducted on 300 confirmed COVID-19 patients who were treated with TCM, at a designated hospital in China. The patients were categorized into three groups: TCM1, TCM2 and TCM3, who respectively received TCM interventions within 7, 8-14, and greater than 15 days of hospitalization. Different indicators such as the conversion time of pharyngeal swab nucleic acid, the conversion time of fecal nucleic acid, length of hospital stay, and inflammatory markers (leukocyte count, and lymphocyte count and percentage) were analyzed to observe the impact of early TCM interventions on these groups. Results: The median conversion times of pharyngeal swab nucleic acid in the three groups were 5.5, 7 and 16 d (P < 0.001), with TCM1 and TCM2 being statistically different from TCM3 (P < 0.01). TCM1 (P < 0.05) and TCM3 (P < 0.01) were statistically different from TCM2. The median conversion times of fecal nucleic acid in the three groups were 7, 9 and 17 d (P < 0.001). Conversion times of fecal nucleic acid in TCM1 were statistically different from TCM3 and TCM2 (P < 0.01). The median lengths of hospital stay in the three groups were 13, 16 and 21 d (P < 0.001). TCM1 and TCM2 were statistically different from TCM3 (P < 0.01); TCM1 and TCM3 were statistically different from TCM2 (P < 0.01). Both leucocyte and lymphocyte counts increased gradually with an increase in the length of hospital stay in TCM1 group patients, with a statistically significant difference observed at each time point in the group (P < 0.001). Statistically significant differences in lymphocyte count and percentage in TCM2 (P < 0.001), and in leucocyte count (P = 0.043) and lymphocyte count (P = 0.038) in TCM3 were observed. The comparison among the three groups showed a statistically significant difference in lymphocyte percentage on the third day of admission (P = 0.044). Conclusion: In this study, it was observed that in COVID-19 patients treated with a combination of Chinese and Western medicines, TCM intervention earlier in the hospital stay correlated with faster conversion time of pharyngeal swab and fecal nucleic acid, as well as shorter length of hospital stay, thus helping promote faster recovery of the patient. The underlying mechanism of action may be related to improving inflammation in patients with COVID-19. Please cite this article as: Shi MY, Sun SQ, Zhang W, Zhang X, Xu GH, Chen X, Su ZJ, Song XM, Liu LJ, Zhang YB, Zhang YL, Sun M, Chen Q, Xue Y, Lu H, Yuan WA, Chen XR, Lu YF. Early therapeutic interventions of traditional Chinese medicine in COVID-19 patients: A retrospective cohort study. (C) 2021 Shanghai Changhai Hospital. Published by ELSEVIER B.V. All rights reserved.

APOBEC3 (A3) cytidine deaminases inhibit hepatitis B virus (HBV) infection and play vital roles in maintaining a variety of biochemical processes, including the regulation of protein expression and innate immunity. Emerging evidence indicates that the deaminated deoxycytidine biochemical activity of A3 proteins in single-stranded DNA makes them a double-edged sword. These enzymes can cause cellular genetic mutations at replication forks or within transcription bubbles, depending on the physiological state of the cell and the phase of the cell cycle. Under pathological conditions, aberrant expression of A3 genes with improper deaminase activity regulation may threaten genomic stability and eventually lead to cancer development. This review attempted to summarize the antiviral activities and underlying mechanisms of A3 editing enzymes in HBV infections. Moreover, the correlations between A3 genes and hepatocarcinogenesis were also elucidated.

目的:分析新型冠状病毒肺炎重型患者的临床特征及中医证候信息(包括舌脉象),为中西医结合诊治新冠肺炎重型患者提供临床参考.方法:收集2020年1月23日—2月7日上海市公共卫生中心隔离病房收治的13例新冠肺炎重型患者临床资料,均采取中西医结合治疗,予抗病毒、抗感染、氧疗、调节免疫及营养支持等对症处理,并加用中医药干预,分析其临床特征、中医证候信息等.结果:13例新冠肺炎重型患者均有明确流行病学史;以发热、咳嗽、气促为主要症状,部分有乏力、汗出、纳差等,舌象多见腻苔、舌质红或淡红,脉象多见细、滑、数.从入院到病情加重的平均时间为4.5d.经中西医结合治疗后气促、咳嗽、乏力等主要症状好转,均未向危重型进展,13例均已康复出院,平均住院时间为(23.62±4.92)d,较普通型患者长.结论:需重视新冠肺炎患者入院后症状变化的临床意义.经中西医结合诊治后,可改善患者临床症状,提高重型向普通型转化机率,避免重型向危重型发展.

目的 回顾性观察中西医结合治疗非危重型新型冠状病毒肺炎(简称“新冠肺炎”)患者的临床疗效,并与单纯西医疗法对比.方法 将上海市公共卫生临床中心收治的67例新冠肺炎患者,按照接受疗法的不同分为西医组(18例)和中西医结合组(49例).西医组予氧疗、抗病毒及对症支持治疗,重症患者给予抗炎、调节免疫及丙种球蛋白支持治疗;中西医结合组在西医组治疗基础上,加予中成药或汤药口服治疗.收集并分析两组患者的临床资料,包括一般情况、相关实验室指标、影像学表现、症状信息、中医证候(包括舌象、脉象)信息;观察比较两组患者的临床疗效相关指标,包括退热时间、临床症状积分、CT改善率、危重型转化率、住院时间、总病程.结果 ①西医组和中西医结合组一般情况、相关实验室指标水平、影像学表现比较,差异无统计学意义(P＞0.05).②全部患者均接受抗病毒治疗,西医组27.78％的患者使用抗生素治疗,中西医结合组34.69％的患者使用抗生素治疗.③患者主要表现为发热(71.64％)、咳嗽/干咳(52.24％)、乏力(47.76％)、纳差(35.82％)、咽痛/痒(31.34％)、咳白痰/黄痰(26.87％)、出汗(25.37％)、腹泻(22.39％)、鼻塞(13.43％)、头痛/晕(13.43％);两组间临床症状比较差异无统计学意义(P＞0.05).④中西医结合组中湿毒郁肺证32例,占65.31％;热毒闭肺证17例,占34.69％;患者以舌色红或淡红、舌苔白腻为多见,滑脉多见.⑤与西医组相比,中西医结合组住院天数更短、入院第6天临床症状积分更低(P＜0.05);而两组患者的总病程、退热时间、入院第6天CT改善率比较差异无统计学意义(P＞0.05).⑥观察期间,两组均未出现向危重型转化的病例.结论 中西医结合治疗,在改善新冠肺炎患者主要临床症状以及缩短住院时间方面,显示出较大的优势.

目的:评价解毒逐瘀方灌肠治疗HBV相关慢性急性肝衰竭(HBV-ACLF)的临床疗效.方法:236例HBV-ACLF患者,根据入组时是否采用解毒逐瘀方灌肠分为灌肠组55例和对照组181例.比较两组患者临床特征、灌肠治疗短期疗效及分析影响预后的因素.结果:Kaplan-Meier生存分析显示,灌肠组患者总生存期显著优于对照组(P =0.003),灌肠治疗可显著改善早期HBV-ACLF患者总生存期(P=0.021),但对中晚期HBV-ACLF患者总生存期影响差异无统计意义(P＞0.05).Cox回归分析显示年龄、肝性脑病、白细胞计数、凝血酶原活动度及总胆红素水平是影响HBV-ACLF患者总生存期的危险因素(P＜0.01);肝肾综合征、白细胞计数、凝血酶原活动度及天门冬氨酸氨基转移酶水平为早期HBV-ACLF患者总生存期的危险因素(P＜0.01).结论:解毒逐瘀方灌肠可有效改善早期HBV-ACLF患者的总生存率.

Objective: This report aimed to investigate the potential mechanism of polymeric immunoglobulin receptor (PIGR) in promoting cancer development in hepatocellular carcinoma (HCC). Methods: PIGR expression was investigated in Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) databases. Relationships between PIGR and HCC survival and clinico-pathological features were conducted in TCGA. RNAseq of PIGR overexpression and knockdown samples in Bel-7404 cells were performed for identifying potential mechanisms. Results: PIGR was significantly overexpressed in tumors compared to nontumors and in HCC serum peripheral blood mononuclear cells (PBMC) than in healthy individuals (all p < 0.05). In TCGA, PIGR was highly altered in 14% HCC patients. PIGR upregulation was significantly associated with poor disease-free survival (p < 0.05). More patients recurred/progressed in PIGR altered group compared to unaltered group (p < 0.01). PIGR was significantly higher in HCC patients with incomplete cirrhosis (p < 0.001) and established cirrhosis (p < 0.05). Fewer patients had N0 lymph node stage in PIGR altered group than those in the unaltered group (p < 0.05). PIGR RNAseq revealed that ribosome signaling was the common pathway in PIGR overexpression and PIGR knockdown samples. RNAseq analysis indicated that RPL10, RPL10A, RPL12, RPL19, RPL36, RPL38, RPL41, RPL6, RPL8, RPS12, RPS14, RPS15A, RPS2, RPS27A and RPSA were significantly upregulated in PIGR overexpression group and downregulated in PIGR underexpression group (all p < 0.05). Conclusions: Aberrant PIGR was associated with HCC recurrence, and PIGR stimulated ribosome pathway might be a potential mechanism.

Since the end of 2019, Corona Virus Disease 2019 (COVID-19) has been the cause of a worldwide pandemic. The mental status of patients with COVID-19 who have been quarantined and the interactions between their psychological distress and physiological levels of inflammation have yet to be analyzed. Using a mixed-method triangulation design (QUAN + QUAL), this study investigated and compared the mental status and inflammatory markers of 103 patients who, while hospitalized with mild symptoms, tested positive with COVID-19 and 103 matched controls that were COVID-19 negative. The severity of depression, anxiety, and post-traumatic stress symptoms (PTSS) was measured via an on-line survey. Using a convenience sampling technique, qualitative data were collected until the point of data saturation. In addition, a semi-structured interview was conducted among five patients with COVID-19. Peripheral inflammatory markers were also collected in patients, both at baseline and within +/- three days of completing the on-line survey. Results revealed that COVID-19 patients, when compared to non-COVID controls, manifested higher levels of depression (P < 0.001), anxiety (P < 0.001), and post-traumatic stress symptoms (P < 0.001). A gender effect was observed in the score of "Perceived Helplessness", the subscale of PSS-10, with female patients showing higher scores compared to male patients (Z = 2.56, P = 0.010), female (Z = 2.37, P = 0.018) and male controls (Z = 2.87, P = 0.004). Levels of CRP, a peripheral inflammatory indicator, correlated positively with the PHQ-9 total score (R = 0.37, P = 0.003, Spearman's correlation) of patients who presented symptoms of depression. Moreover, the change of CRP level from baseline inversely correlated with the PHQ-9 total score (R = -0.31, P = 0.002), indicative of improvement of depression symptoms. Qualitative analysis revealed similar results with respect to patient reports of negative feelings, including fear, guilt, and helplessness. Stigma and uncertainty of viral disease progression were two main concerns expressed by COVID-19 patients. Our results indicate that significant psychological distress was experienced by hospitalized COVID-19 patients and that levels of depressive features may be related to the inflammation markers in these patients. Thus, we recommend that necessary measures should be provided to address depression and other psychiatric symptoms for COVID-19 patients and attention should be paid to patient perceived stigma and coping strategies when delivering psychological interventions.