ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

ObjectiveTo explore the syndrome elements and evolving patterns of patients with hepatitis B virus-related acute on chronic liver failure （HBV-ACLF） at different stages. MethodsClinical information of 1,058 hospitalized HBV-ACLF patients， including 618 in the early stage， 355 in the middle stage， and 85 in the late stage， were collected from 18 clinical centers across 12 regions nationwide from January 1， 2012 to February 28， 2015. The “Hepatitis B-related Chronic and Acute Liver Failure Chinese Medicine Clinical Questionnaire” were designed to investigate the basic information of the patients， like the four diagnostic information （including symptoms， tongue， pulse） of traditional Chinese medicine （TCM）， and to count the frequency of the appearance of the four diagnostic information. Factor analysis and cluster analysis were employed to determine and statistically analyze the syndrome elements and patterns of HBV-ACLF patients at different stages. ResultsThere were 76 four diagnostic information from 1058 HBV-ACLF patients， and 53 four diagnostic information with a frequency of occurrence ≥ 5% were used as factor analysis entries， including 36 symptom information， 12 tongue information， and 5 pulse information. Four types of TCM patterns were identified in HBV-ACLF， which were liver-gallbladder damp-heat pattern， qi deficiency and blood stasis pattern， liver-kidney yin deficiency pattern， and spleen-kidney yang-deficiency pattern. In the early stage， heat （39.4%， 359/912） and dampness （27.5%， 251/912） were most common， and the pattern of the disease was dominated by liver-gallbladder damp-heat pattern （74.6%， 461/618）； in the middle stage， dampness （30.2%， 187/619） and blood stasis （20.7%， 128/619） were most common， and the patterns of the disease were dominated by liver-gallbladder damp-heat pattern （53.2%， 189/355）， and qi deficiency and blood stasis pattern （27.6%， 98/355）； and in the late stage， the pattern of the disease was dominated by qi deficiency （26.3%， 40/152） and yin deficiency （20.4%， 31/152）， and the patterns were dominated by qi deficiency and blood stasis pattern （36.5%， 31/85）， and liver-gallbladder damp-heat pattern （25.9%， 22/85）. ConclusionThere are significant differences in the distribution of syndrome elements and patterns at different stages of HBV-ACLF， presenting an overall trend of evolving patterns as "from excess to deficiency， transforming from excess to deficiency"， which is damp-heat → blood stasis → qi-blood yin-yang deficiency.

Objectives: To examine the influence of adjuvant chemotherapy after radical resection on the survival of patients with intrahepatic cholangiocarcinoma(ICC) and to identify patients who may benefit from it. Methods: The clinical and pathological data of 654 patients with ICC diagnosed by postoperative pathology from December 2011 to December 2017 at 13 hospitals in China were collected retrospectively. According to the inclusion and exclusion criteria,455 patients were included in this study,including 69 patients (15.2%) who received adjuvant chemotherapy and 386 patients (84.8%) who did not receive adjuvant chemotherapy. There were 278 males and 177 females,with age of 59 (16) years (M(IQR))(range:23 to 88 years). Propensity score matching (PSM) method was used to balance the difference between adjuvant chemotherapy group and non-adjuvant chemotherapy group. Kaplan-Meier method was used to plot the survival curve,the Log-rank test was used to compare the difference of overall survival(OS) and recurrence free survival(RFS)between the two groups. Univariate analysis was used to determine prognostic factors for OS. Multivariate Cox proportional hazards models were then performed for prognostic factors with P<0.10 to identify potential independent risk factors. The study population were stratified by included study variables and the AJCC staging system,and a subgroup analysis was performed using the Kaplan-Meier method to explore the potential benefit subgroup population of adjuvant chemotherapy. Results: After 1∶1 PSM matching,69 patients were obtained in each group. There was no significant difference in baseline data between the two groups (all P>0.05). After PSM,Cox multivariate analysis showed that lymph node metastasis (HR=3.06,95%CI:1.52 to 6.16,P=0.039),width of resection margin (HR=0.56,95%CI:0.32 to 0.99,P=0.044) and adjuvant chemotherapy (HR=0.51,95%CI:0.29 to 0.91,P=0.022) were independent prognostic factors for OS. Kaplan-Meier analysis showed that the median OS time of adjuvant chemotherapy group was significantly longer than that of non-adjuvant chemotherapy group (P<0.05). There was no significant difference in RFS time between the adjuvant chemotherapy group and the non-adjuvant chemotherapy group (P>0.05). Subgroup analysis showed that,the OS of female patients,without HBV infection,carcinoembryonic antigen<9.6 μg/L,CA19-9≥200 U/ml,intraoperative bleeding<400 ml,tumor diameter>5 cm,microvascular invasion negative,without lymph node metastasis,and AJCC stage Ⅲ patients could benefit from adjuvant chemotherapy (all P<0.05). Conclusion: Adjuvant chemotherapy can prolong the OS of patients with ICC after radical resection,and patients with tumor diameter>5 cm,without lymph node metastasis,AJCC stage Ⅲ,and microvascular invasion negative are more likely to benefit from adjuvant chemotherapy.

Bispecific antibody (BsAb) is a new type of highly effective anti-tumor drug that can specifically bind two antigens or epitopes simultaneously or successively. At present, evantuzumab targeting epidermal growth factor receptor (EGFR) and cMET has been approved for the treatment of EGFR ex20ins in locally advanced or metastatic non-small cell lung cancer (NSCLC) . Inhibitors targeting programmed death-ligand 1 (PD-L1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) , programmed death-1 (PD-1) and CTLA-4, PD-L1 and transforming growth factor-β, PD-1 and vascular endothelial growth factor are applied to NSCLC. The treatment of NSCLC is underway, showing good safety and efficacy. Further exploring the research progress of BsAbs in the treatment of NSCLC will provide a new diagnosis and treatment idea for the clinical treatment of NSCLC.

Triple-negative breast cancer is a subtype of invasive breast cancer, accounting for about 15% of all breast cancers. Its clinical treatment is relatively difficult, prone to recurrence and metastasis, with a short median survival and poor prognosis. Sacituzumab govitecan is the first approved antigen-coupled drug targeting trophoblast surface antigen 2 in the world. It has significant clinical efficacy, high safety and less adverse reactions, which brings new hope to the treatment of triple-negative breast cancer.

We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ ₂) receptor ligands. Two ligands with high σ ₂ receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [¹⁸F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[¹⁸F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ ₂ receptor ligand CM398 led to significant reductions in both brain uptake (29%-54%) and brain-to-blood ratio (60%-88%) of the radioligand in a dose-dependent manner, indicating high and saturable specific binding of [¹⁸F]9 to σ ₂ receptors in the brain. Further, ex vivo autoradiography in male ICR mice demonstrated regionally heterogeneous specific binding of [¹⁸F]9 in the brain that is consistent with the distribution pattern of σ ₂ receptors. Dynamic positron emission tomography imaging confirmed regionally distinct distribution and high levels of specific binding for [¹⁸F]9 in the rat brain, along with appropriate tissue kinetics. Taken together, results from our current study indicated the novel radioligand [¹⁸F]9 as the first highly specific and promising imaging agent for σ ₂ receptors in the brain.

Objective To investigate the association of energy metabolic markers with the risk of spontaneous bacterial peritonitis (SBP) in patients with decompensated hepatitis B virus-related liver cirrhosis (HBV-LC). Methods A retrospective analysis was performed for the clinical data of the patients with decompensated HBV-LC who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from November 2017 to November 2019, and baseline clinical parameters and energy metabolic markers were compared between the patients with SBP and those without SBP within 2 weeks after admission. A multivariate logistic regression analysis was performed to investigate the risk factors for SBP. The t -test was used for comparison of normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between two groups; the Fisher's exact test was used for comparison of categorical data between two groups. The receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic efficiency of the newly established logistic regression model, and with the corresponding point of Youden index as the cut-off value, the DeLong test was used to compare the area under the ROC curve (AUC). Results A total of 50 patients with decompensated HBV-LC were included, among whom 23 (46%) developed SBP within 2 weeks after admission and 27 (54%) had no SBP during hospitalization. Compared with the non-SBP patients, the SBP patients had significantly lower triglyceride, prealbumin, and prothrombin time activity (PTA) and significantly higher international normalization ratio, C-reactive protein (CRP), and Model for End-Stage Liver Disease score (all P < 0.05). Comparison of baseline energy metabolic markers showed that compared with the non-SBP patients, the SBP patients had significantly lower respiratory quotient (RQ) [0.79(0.76-0.86) vs 0.85(0.79-0.91), P =0.041] and carbohydrate oxidation (CHO) rate [20.50%(15.25%-41.05%) vs 41.6%(22.25%-68.05%), P =0.041]. The multivariate logistic regression analysis showed that PTA was an independent risk factor for SBP in the patients with decompensated HBV-LC during hospitalization (odd ratio=0.004, P =0.008), and the regression model established based on the variables including PTA, CRP, RQ, and CHO had an AUC of 85.0% and a cut-off value of 0.60 at the maximum Youden index, with a specificity of 85.19% and a sensitivity of 73.91%, suggesting that this model had a better discriminatory ability than CRP (AUC=74.5%, P =0.049) and procalcitonin (AUC=56.4%, P < 0.01). Conclusion There are significant reductions in the energy metabolic markers RQ and CHO in the patients with decompensated HBV-LC who develop SBP within a short term, and their combination with PTA, CRP, and CHO/RQ ratio can help clinicians identify the patients at a high risk of SBP in the early stage and enhance nutrition support for such patients.

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.
Animals ; Anti-Retroviral Agents/adverse effects* ; Body Weight ; Cardiotoxicity ; Collagen ; Female ; Myocytes, Cardiac/ultrastructure* ; Pregnancy ; Rats ; Rats, Sprague-Dawley

Objective To investigate the risk factors for short-term prognosis in patients with HBV-related acute-on-chronic liver failure (ACLF). Methods A retrospective analysis was performed for the clinical data of 119 patients with HBV-related ACLF who were admitted to Mengchao Hepatobiliary Hospital of Fujian Medical University from October 2019 to October 2020, and according to their survival status on day 90, they were divided into death group and survival group. The patients were given antiviral therapy with entecavir or tenofovir. Related clinical data were collected, including alanine aminotransferase (ALT), aspartate aminotransferase, cholinesterase (ChE), albumin (Alb), cholesterol, alpha-fetoprotein, and HBV DNA at baseline, as well as the incidence rate of important complications. Model for End-Stage Liver Disease (MELD) score was also calculated. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-squared test was used for comparison of categorical data between two groups; a logistic regression analysis was used to investigate the influencing factors for the 90-day prognosis of patients with HBV-related ACLF and establish a new predictive model; the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficiency of the new model in predicting the prognosis of HBV-related ACLF. Results Of all patients, 33 died within 90 days, resulting in a mortality rate of 27.7%. There were significant differences between the survival group and the death group in age, ALT, Alb, ChE, MELD score, and incidence rates of hepatic encephalopathy, primary peritonitis, and hepatorenal syndrome (all P < 0.05). The logistic regression analysis showed that baseline hepatic encephalopathy (odds ratio [ OR ]=10.404, 95% confidence interval [ CI ]: 2.522-42.926, P =0.001), serum Alb at baseline ( OR =0.853, 95% CI : 0.764-0.952, P =0.005), and MELD score at baseline ( OR =1.143, 95% CI : 1.036-1.261, P =0.008) were independent predictive factors for the short-term prognosis of patients with HBV-related ACLF. A new predictive model was established based on the combination of these three indices, and the ROC curve analysis showed that this new model had an area under the curve of 0.833, while MELD score had an area under the ROC curve of 0.672. Conclusion As for the evaluation of the 90-day prognosis of patients with HBV-related ACLF, the new prognostic model established based on hepatic encephalopathy, Alb, and MELD score has a better predictive value than MELD score alone.

Background: Guben Zhike decoction (GBZKD) is derived from the experience of Professor Enxiang Chao, an esteemed master of Chinese medicine, while treating chronic obstructive pulmonary disease (COPD). GBZKD reinforces the healthy qi and consolidates defensive qi. This study explored the efficacy and potential mechanism of action of GBZKD in a COPD mouse model using proteomics.Methods: A COPD mouse model was established through cigarette smoke exposure and intranasal lipopolysaccharide administration. The model was verified through lung function test and lung histo-pathological observation. Label-free quantitative proteomics was used to detect the lung tissue proteins of mice from the GBZKD, COPD, and control groups. Results: GBZKD markedly improved the lung function and associated pathological conditions in the COPD mouse model. Proteomic analysis identified 4316 proteins, of which 3696 were quantitative proteins. We highlighted 287 and 184 proteins with significant regulatory roles in the lung tissues of COPD mice and GBZKD-treated mice, respectively. These proteins participated in multiple functions, including complement/coagulation cascade, immune response, and metabolic pathways. Conclusion: GBZKD exhibits multitarget and multipathway therapeutic effects in a COPD mouse model.