Refractory depression is a drug-resistant subtype of major depressive disorder for which there is a lack of effective and durable treatments.Seroxibine,the active substance in the mushroom Capsicum annuum,is a natural 5-hydroxytryptamine hallucinogen that activates the 5-hydroxytryptamine 2A receptor to mediate multiple aspects of antidepressant effects.In recent years,it has received renewed attention for its outstanding therapeutic effects in the treatment of refractory depression or other psychiatric disorders.Therefore,this paper summarizes the studies on neuroplasticity,brain neural connectivity network,neurotransmitters,immune factors,microbiota-gut-brain axis,and clinical efficacy of seloxipine in domestic and international literature,and explores the possible mechanisms of seloxipine's effect on refractory depression,with a view to providing theoretical basis for the clinical application of this drug.

Objective To retrieve and extract the best evidence for preventing intracranial infections related to ex-ternal cerebrospinal fluid(CSF)drainage,and provide evidence-based support for reducing the incidence of intracra-nial infection caused by external CSF drainage.Methods Evidence-based care issues were determined according to PIPOST,and the best evidence on intracranial infection related to external CSF drainage tube was retrieved from top to bottom.The literature retrieval period was 2013-2023.Quality control of the literatures,as well as extraction and summary of the evidence were carried out by 2 trained graduate students.Results A total of 17 literatures were included in the analysis,including 3 guidelines,5 expert consensus,8 systematic reviews,and 1 randomized con-trolled trial.Management strategies from 3 dimensions(pre-catheterization,in-catheterization and post-catheteriza-tion)were obtained,including 20 pieces of evidence for preventing intracranial infection,such as preparation for ex-ternal CSF drainage tube,precautions during catheterization,and post-catheterization disposal.Conclusion There are differences in the management of external CSF drainage tube in clinical practice.It is necessary to develop uni-fied,standardized,and rational bundle strategies to prevent intracranial infection,so as to reduce the incidence of catheter-related intracranial infection.

Background/Aims: The histological characteristics and natural history of precirrhotic primary biliary cholangitis (PBC) with portal hypertension (PH) are unclear. Our aim was to clarify the prevalence, risk factors, and histological characteristics of precirrhotic PBC patients with PH. Methods: This retrospective study compared the clinical features, histological characteristics, and response to ursodeoxycholic acid (UDCA) between the PH and non-PH groups of precirrhotic PBC patients. Results: Out of 165 precirrhotic PBC patients, 40 (24.2%) also had PH. According to histological stage 1, 2 and 3 disease, 5.3% (1/19), 17.3% (17/98), and 45.8% (22/48) of patients also had PH, respectively. Precirrhotic PBC with PH was significantly positively correlated with bile duct loss, degree of cytokeratin 7 positivity, and degree of fibrosis in the portal area, but significantly negatively correlated with lymphoid follicular aggregation. Compared to the non-PH group, patients in the PH group showed a higher prevalence of obliterative portal venopathy, incomplete septal fibrosis, portal tract abnormalities and non-zonal sinusoidal dilatation (p<0.05). In addition, patients with PH were more likely to present with symptoms of jaundice, ascites, epigastric discomfort, a poorer response to UDCA, and more decompensation events (p<0.05). High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values were risk factors for precirrhotic PBC with PH. Conclusions Approximately 24.2% of precirrhotic PBC patients have PH, which is histologically related to the injury of bile ducts. High alkaline phosphatase levels, low white blood cell counts, high Mayo scores, and high FIB-4 index values are associated with increased risk of precirrhotic PBC with PH.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Objective Based on the incidence and mortality of gastric cancer and the correlation with helicobacter pylori (Hp) infection in Enshi Tujia and Miao Autonomous Prefecture from 2011 to 2020, the prevalence trend of gastric cancer in this decade was analyzed, providing theoretical basis for the prevention and treatment of gastric cancer in Enshi Tujia and Miao Autonomous Prefecture. Methods According to the unified national examination and evaluation standards, 15 tumor registries meeting the requirements were selected in Enshi Tujia and Miao Autonomous Prefecture. The incidence and death data of gastric cancer were collected, and the incidence and death rates were analyzed by gender and age. The normalized incidence rate and Hp positive rate of enshi city, Lichuan city and six counties including Jianshi, Badong, Xuan 'en, Xianfeng, Laifeng and Hefeng were compared. Spearman correlation analysis was used to analyze the correlation between standard incidence rate and Hp positive rate of gastric cancer in each district of Tujia and Miao Autonomous Prefecture of Enshi Prefecture. Results Both male and female had an upward trend. The average rate of standard incidence of gastric cancer in male and female was 4.07% and 4.15%, respectively, and there was no significant difference in the trend of standard incidence rate in different genders (P>0.05). The gross death rates and standardized death were decreased in both male and female. The average decreasing rate of standardized death rate of gastric cancer in males and females was -3.91% and -4.12%, respectively, and there was no significant difference in the trend of standardized death rate in different genders (P>0.05). Overall, the incidence rate in age group 50-80 from 2016 to 2020 was significantly higher than that from 2011 to 2015 (P<0.05). The mortality rate in the 60-80 age group from 2016 to 2020 was significantly lower than that from 2011 to 2015 (P<0.05). The trend of morbidity and mortality in different age groups was consistent in the two periods. There was a positive correlation between the incidence standard rate of gastric cancer and Hp positive rate (r =0.473, P<0.05). Conclusion From 2011 to 2020, the incidence and mortality of gastric cancer in Enshi Tujia and Miao Autonomous Prefecture were both at a high level, with an upward trend and a downward trend. The positive rate of Hp and the new infection rate of Hp in the high incidence area of gastric cancer were higher than those in the low incidence area.

Objective To explore the classification and changes of macrophage subsets in liver transplant rejection.Methods Rat liver transplantation model were established and divided into immune tolerance group(B-B),where the liver of BN rat donors was transplanted to BN rat recipients,and immune rejection group(L-B),in which the liver of Lewis rat donors was transplanted to BN rat recipients.Single-cell RNA sequencing and high-throughput RNA sequencing were used to distinguish the macrophage subsets of rat liver transplantation,and to find differential gene in rejection reactions.Immunohistochemistry was used to determine the changes and distribu-tion of protein expression and cell subsets.Results CD68 positive macrophages were higher in the rejection group than that in the tolerance group(P<0.05),and macrophages could be divided into 9 subsets.During the rejection reaction,the CXC chemokine ligand 9(CXCL9)in the 8th subsets of macrophages was significantly increased,while the gene for white blood cell differentiation antigen 74(CD74)in the 5th subsets was significantly increased(P<0.05).CD74 ranked first in the differential gene synthesis of macrophages during rejection,followed by CXCL9.Compared with the tolerance group,a large number of CD74 positive macrophages were observed in the hepatic portal area of the rejection group,and the infiltration of CD74 positive macrophages in the hepatic sinuses was also significantly increased(P<0.05),while a large number of CXCL9 positive macrophages were observed in the hepatic portal area and hepatic sinuses of the rejection group,especially in the portal area(P<0.05),and CD14 positive cells were significantly increased(P<0.05).Conclusions The CD74 positive macrophage subsets and CXCL9 positive macrophage subsets may be key subgroups in promoting liver transplant rejection,improving the mechanism of macrophage action in liver transplant rejection.

OBJECTIVE: To detect the Epstein-Barr virus (EBV) viral load of children after hematopoietic stem cell transplantation (HSCT) using chip digital PCR (cdPCR). METHODS: The sensitivity of cdPCR was determined using EBV plasmids and the EBV B95-8 strain. The specificity of EBV cdPCR was evaluated using the EBV B95-8 strain and other herpesviruses (herpes simplex virus 1, herpes simplex virus 2, varicella zoster virus, human cytomegalovirus, human herpesvirus 6, and human herpesvirus 7). From May 2019 to September 2020, 64 serum samples of children following HSCT were collected. EBV infection and the viral load of serum samples were detected by cdPCR. The epidemiological characteristics of EBV infections were analyzed in HSCT patients. RESULTS: The limit of detection of EBV cdPCR was 110 copies/mL, and the limit of detection of EBV quantitative PCR was 327 copies/mL for the pUC57-BALF5 plasmid. The result of EBV cdPCR was up to 121 copies/mL in the EBV B95-8 strain, and both were more sensitive than that of quantitative PCR. Using cdPCR, the incidence of EBV infection was 18.75% in 64 children after HSCT. The minimum EBV viral load was 140 copies/mL, and the maximum viral load was 3,209 copies/mL using cdPCR. The average hospital stay of children with EBV infection (184 ± 91 days) was longer than that of children without EBV infection (125 ± 79 days), P = 0.026. CONCLUSION EBV cdPCR had good sensitivity and specificity. The incidence of EBV infection was 18.75% in 64 children after HSCT from May 2019 to September 2020. EBV cdPCR could therefore be a novel method to detect EBV viral load in children after HSCT.
Child ; DNA, Viral/analysis* ; Epstein-Barr Virus Infections/epidemiology* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Herpesvirus 4, Human/genetics* ; Humans ; Real-Time Polymerase Chain Reaction ; Viral Load

Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

Guided by the basic theory of traditional Chinese medicine and using modern scientific methods, Dao-di herbs pharmacology studies the nature, performance, interaction with the body and its clinical application.It is a bridge between the basic research and clinical application of Dao-di herbs. It can objectively describe the law of efficacy of Dao-di herbs, scientifically explain the mechanism of efficacy of Dao-di herbs, explore and establish the standards and methods of Dao-di herbs based on biological effect and clinical efficacy, and provide scientific basis for the special properties, pharmacology and clinical value of Dao-di herbs.Furthermore, we put forward a new idea of building the standard of Dao-di herbs based on the curative effect rather than the origin.The Dao-di herbs standard should come from the systematic research of traditional Dao-di herbs producing areas and form a new characteristic system, through the extraction of environmental, genetic, character, chemical, pharmacological and other characteristics.This standard originates from the tradition, but it is higher than the tradition. It may not have the origin meaning of strict administrative division, but it can better reflect the pharmacological characteristics and excellent clinical value of Dao-di herbs.
China ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional ; Plants, Medicinal/chemistry*

Dao-di herbs is one of the characteristics of traditional Chinese medicine different from other ethnic medicine. Sichuan province is rich in varieties and resources of Dao-di herbs, and its development scale and benefits are not obvious in recent decades due to the lag of standards behind the development of the times and objective needs. From the point of view of the whole process and the whole industrial chain, the significance of standardization system for quality assurance, healthy development of the industry, and development of the industry of Sichuan Dao-di herbs are presented in this paper. At present, Sichuan has made every effort to promote the construction and practice of the standardization system for Sichuan Dao-di herbs, to promote the rapid and high-quality development of Dao-di herbs industry in Sichuan.
China ; Drugs, Chinese Herbal/standards* ; Medicine, Chinese Traditional ; Plants, Medicinal/chemistry*