Objective: To explore the mechanism of Buzhong Yiqi Decoction in modulating macrophage polarization and intervening in autoimmune thyroiditis (AIT) mice. Methods: Using the random number table method, 48 SPF-grade NOD.H-2h4 mice were assigned to the normal, model, low-dose (4.10 g/kg), medium-dose (8.19 g/kg), high-dose group (16.38 g/kg) of Buzhong Yiqi Decoction, and selenium yeast tablet (0.026 mg/kg) groups, with eight mice in each group. All groups, except the normal group, were free to drink high iodine water (0.05% sodium iodide) to prepare AIT mouse models for 8 consecutive weeks. After the modeling was complete, each treatment group was orally administered with the corresponding medication, while the normal and model groups were orally administered with an equal volume of distilled water once a day for 8 consecutive weeks. High-performance liquid chromatography with an oscillometric refractive detector was used to analyze the content of Astragaloside Ⅳ in Buzhong Yiqi Decoction. Hematoxylin and eosin staining was used to observe the pathological morphology of mouse thyroid tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum thyroid peroxidase antibody (TPO-Ab), thyroglobulin antibody (TgAb), interleukin (IL)-6, IL-10, and tumor necrosis factor-α (TNF-α). An immunofluorescence assay was used to detect the positive area percentage of M1 and M2 macrophages in mouse thyroid tissue. Flow cytometry assay was used to detect macrophage polarization in mouse spleen tissue. Real-time fluorescence quantitative PCR was used to detect the mRNA expression of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), nuclear factor kappa B inhibitory protein α (IκBα), and nuclear factor-κB (NF-κB) p65 in mouse spleen tissue. Western blotting was used to detect the expression of the phosphorylated IκBα (p-IκBα), phosphorylated NF-κB p65 (p-NF-κB p65), and NLRP3 protein in mouse spleen tissue. Results: The content of Astragaloside Ⅳ in Buzhong Yiqi Decoction was (7.09±0.06) g/L. Compared to the normal group, significant lymphocyte infiltration was observed in the thyroid tissue of mice in the model group. The levels of serum TPO-Ab, TgAb, IL-6, and TNF-α increased (P<0.05). The positive area percentage of M1 macrophages in thyroid tissue increased (P<0.05). The proportion of M1 macrophages and M1/M2 in spleen tissue increased (P<0.05). The relative expression levels of NF-κB p65 and NLRP3 mRNA in spleen tissue increased (P<0.05). The relative expression of p-IκBα, p-NF-κB p65, and NLRP3 proteins increased (P<0.05). Compared to the model group, the inflammation infiltration degree in the thyroid tissue of mice in each dose group of Buzhong Yiqi Decoction and selenium yeast tablet group was reduced, the serum TPO-Ab, TgAb, IL-6, TNF-α content was decreased, the spleen tissue M1/M2 was reduced, the expression of NF-κB p65 mRNA was reduced, and the relative expression levels of p-IκBα, p-NF-κB p65 protein were reduced (P<0.05). The Buzhong Yiqi Decoction high-dose and selenium yeast tablets groups showed an increase in IL-10 content, an increase in positive area percentage of M2 macrophages in thyroid tissue, an increase in M2 macrophages proportion in spleen tissue, and a decrease in NLRP3 mRNA and protein relative expression levels (P<0.05). Conclusion Buzhong Yiqi Decoction may regulate macrophage polarization by inhibiting the NF-κB/NLRP3 signaling pathway, thus improving the inflammatory damage in mice with AIT.

This article systematically reviews the characteristics and trends of the writing, editing, publication and promotion of physiology textbooks in China from the late 19th century to the present, focusing on the introduction, development and innovation of Chinese physiology textbooks. The development of physiology textbooks in China is divided into four main stages: the introduction and initial development of physiology textbooks from the late 19th century to 1925; the localization and diversification of textbooks from 1926 to 1949, after the establishment of the Chinese Physiological Society; the exploratory phase of textbook construction after the founding of the People's Republic of China from 1949 to 1976; the formation and innovation of the textbook development process from 1977 to the present, following the restoration of the college entrance examination. For each phase, the article not only records the historical development of physiology textbooks, but also analyzes the evolution of their content, writing styles and the interaction with the social and political contexts. The article summarizes the characteristics and experiences of all these four phases. Special attention is given to the comprehensive statistical analysis of physiology textbooks published since the restoration of the college entrance examination and Economic Reform and Opening-up in 1977, revealing the changes in the number, publication trends and academic features of textbooks during this period. Finally, the article presets the future development of physiology textbooks in China, proposing that textbook writing should integrate aspects such as ideological and political education, medical humanities, basic and clinical medicine, health education, scientific research and international exchange and collaboration. The article also advocates for the application of new technologies and methods, such as artificial intelligence, virtual teaching models and knowledge graphs, to support "personalized learning". This research provides a systematic reference for the study of the history of medical education and offers theoretical support for the future innovation of physiology textbook in China.
Humans ; China ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Physiology/education* ; Textbooks as Topic/history*

Hepatobiliary and pancreatic tumors are common types of digestive system disorders， and their complex pathogeneses have led to difficulties in early diagnosis and a high metastasis rate， with persistently high incidence and mortality rates in China， which greatly affects the quality of life and prognosis of patients. Studies have shown that heparanase （HPSE）， as a key effector molecule in matrix remodeling， plays a crucial regulatory role in tumor invasion and metastasis and microenvironment remodeling， and it is significantly associated with clinical prognosis. This article reviews the molecular mechanism of HPSE in hepatobiliary and pancreatic tumors， in order to provide a strong scientific basis for developing diagnostic markers and targeted interventions for hepatobiliary and pancreatic tumors.

Liver diseases are a group of complex clinical conditions caused by various factors and can lead to hepatocyte damage and liver dysfunction， posing a serious threat to human health. The cyclic GMP-AMP synthase （cGAS）-stimulator of interferon genes （STING） signaling pathway plays a key regulatory role in the course of liver diseases and is involved in the development， progression， and treatment of various diseases such as viral hepatitis， nonalcoholic fatty liver disease， liver fibrosis， and liver cancer. This article reviews the regulatory mechanisms of the cGAS-STING signaling pathway in processes such as inflammation， autophagy， antiviral response， and oxidative stress， analyzes its molecular function in liver diseases， and explores its application prospect as a potential target for the treatment of liver diseases， in order to provide a theoretical basis for developing novel therapeutic strategies for liver diseases.

To analyze the prevalence, genomic characteristics and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater, and to provide a reference basis for in-hospital assessment of public health situation and prevention of cross-infection. In March 2023, untreated wastewater in the wastewater treatment station of the Second Affiliated Hospital of Soochow University and wastewater in the U-shaped wastewater pipes of the hand-washing sinks in 26 wards were collected, centrifuged and diluted, and the drug-resistant bacteria were isolated by using LB solid plates containing meropenem (2 μg/ml) for species identification, drug sensitivity analysis, carbapenenase gene PCR detection and whole genome sequencing. The genome sequence was identified for drug resistance genes. Retrospective research was used, combining multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis, to compare their homology with clinical isolates of the same quarter. The results showed that 56 carbapenem-resistant gram-negative bacteria were isolated from hospital wastewater, originating from 13 genera, of which 17 were isolated from the total hospital wastewater, with Aeromonas spp. as the most dominant genus (35.3%, 6/17), and 39 were isolated from the wastewater of 17 wards, with Pseudomonas spp. as the most dominant genus (30.8%, 12/39). All common wastewater isolates from our hospital were multidrug-resistant bacteria, with up to 100% resistant to some second-and third-generation cephalosporins. A total of 8 carbapenemase genes originated from wastewater isolates, including blaKPC, blaNDM, blaIMP, blaVIM, blaIND, blaOXA-58-like, blaOXA-48-like, and blaOXA-427-like. 39 wastewater isolates carried the carbapenemase genes, and the total wastewater of the hospital carried the highest isolation rate of blaKPC-2 bacteria (35.3%, 6/17) and the highest isolation rate of blaIMP-8 bacteria (31.8%, 7/22) were found in the wastewater from 26 wards. 14 wastewater isolates were found to carry both carbapenemase genes, with a total of 6 combinations. A new blaIMP-101 isoform was also identified for the first time. 4 wastewater isolates and 11 clinical isolates were screened for inclusion in the SNP analysis, in which only 15 SNPs differed between the two strains of ST11 Klebsiella pneumoniae of clinical and wastewater origin, which was highly homologous. In conclusion, the presence of multiple multi-drug resistant conditionally pathogenic bacteria in untreated hospital wastewater has the potential risk of spreading drug-resistant genes in the environment. The highly homologous Klebsiella pneumoniae isolated from hospital wastewater and clinics indicates the close association between hospital wastewater and clinical infections. Hospitals need to strengthen the monitoring of drug-resistant bacteria and drug-resistant genes in the wastewater environment, to prevent the widespread dissemination of drug-resistant bacteria and drug-resistant genes in hospital wastewater and to prevent nosocomial infections caused by drug-resistant bacteria in wastewater.

Objective To compare the difference in the efficacies of arthroscopic microfracture operation for talar osteochondral injuries with hyperuricemia and non-hyperuricemia,and to explore the correlation be-tween blood urate level and efficacy.Methods Fifty-three patients with talar osteochondral lesions meeting the inclusion and exclusion criteria from February 2015 to August 2021 were selected as the research subjects and divided into the hyperuricemia group (22 cases) and non-hyperuricemia group (31 cases) according to whether or not the preoperative blood uric acid level exceeding 420 μmol/L.The joint range of motion (ROM),visual analog scale (VAS) score,American Foot and Ankle Surgery Society (AOFAS) score,mag-netic resonance score of cartilage repair tissue (MOCART) score and postoperative satisfaction before and af-ter surgery were compared between the two groups.Results The preoperative blood uric acid level in the hy-peruricemia group was higher than that in non-hyperuricemia group,and the difference was statistically signif-icant[(504.35±86.40)μmol/L vs.(332.56±45.80)μmol/L,P<0.05].The ROM score,VAS score and AOFAS score in postoperative 1 year follow up and last follow up in the two groups were significantly im-proved compared with before operation (P<0.001).The AOFAS scores before operation,in postoperative 1 year and postoperative last follow up in the hyperuricemia group were lower than those in the non-hyperurice-mia group (P<0.05).The VAS scores before operation and postoperative last follow up in the hyperuricemia group were higher than those in the non-hyperuricemia group (P<0.05).The uric acid level was negatively correlated with the postoperative AOFAS score (r2=0.076,P=0.041).The MOCART score in postopera-tive last follow up in the hyperuricemia group was lower than that in the non-hyperuricemia group,and the difference was statistically significant (P<0.05).The cartilage defect repair and filling degree and the fusion of repaired tissue with adjacent cartilage had statistical differences between the hyperuricemia group and non-hyperuricemia group (P<0.05).Conclusion Arthroscopic microfracture operation in treating talar osteo-chondral injuries has good clinical effect,the postoperative clinical effect in the patients with complicating hy-peruricemia is lower than that in the patients with non-hyperuricemia and the blood uric acid level is negative-ly correlated with the AOFAS score after microfracture surgery.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

To analyze the prevalence, genomic characteristics and clinical relevance of carbapenem-resistant bacteria in untreated hospital wastewater, and to provide a reference basis for in-hospital assessment of public health situation and prevention of cross-infection. In March 2023, untreated wastewater in the wastewater treatment station of the Second Affiliated Hospital of Soochow University and wastewater in the U-shaped wastewater pipes of the hand-washing sinks in 26 wards were collected, centrifuged and diluted, and the drug-resistant bacteria were isolated by using LB solid plates containing meropenem (2 μg/ml) for species identification, drug sensitivity analysis, carbapenenase gene PCR detection and whole genome sequencing. The genome sequence was identified for drug resistance genes. Retrospective research was used, combining multilocus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis, to compare their homology with clinical isolates of the same quarter. The results showed that 56 carbapenem-resistant gram-negative bacteria were isolated from hospital wastewater, originating from 13 genera, of which 17 were isolated from the total hospital wastewater, with Aeromonas spp. as the most dominant genus (35.3%, 6/17), and 39 were isolated from the wastewater of 17 wards, with Pseudomonas spp. as the most dominant genus (30.8%, 12/39). All common wastewater isolates from our hospital were multidrug-resistant bacteria, with up to 100% resistant to some second-and third-generation cephalosporins. A total of 8 carbapenemase genes originated from wastewater isolates, including blaKPC, blaNDM, blaIMP, blaVIM, blaIND, blaOXA-58-like, blaOXA-48-like, and blaOXA-427-like. 39 wastewater isolates carried the carbapenemase genes, and the total wastewater of the hospital carried the highest isolation rate of blaKPC-2 bacteria (35.3%, 6/17) and the highest isolation rate of blaIMP-8 bacteria (31.8%, 7/22) were found in the wastewater from 26 wards. 14 wastewater isolates were found to carry both carbapenemase genes, with a total of 6 combinations. A new blaIMP-101 isoform was also identified for the first time. 4 wastewater isolates and 11 clinical isolates were screened for inclusion in the SNP analysis, in which only 15 SNPs differed between the two strains of ST11 Klebsiella pneumoniae of clinical and wastewater origin, which was highly homologous. In conclusion, the presence of multiple multi-drug resistant conditionally pathogenic bacteria in untreated hospital wastewater has the potential risk of spreading drug-resistant genes in the environment. The highly homologous Klebsiella pneumoniae isolated from hospital wastewater and clinics indicates the close association between hospital wastewater and clinical infections. Hospitals need to strengthen the monitoring of drug-resistant bacteria and drug-resistant genes in the wastewater environment, to prevent the widespread dissemination of drug-resistant bacteria and drug-resistant genes in hospital wastewater and to prevent nosocomial infections caused by drug-resistant bacteria in wastewater.

Objective:To investigate the effect of the number of positive preoperative serological tumor markers on the surgical approach and prognosis of patients with intrahepatic cholangiocarcinoma.Methods:This is a retrospective case-series study. Data from 548 patients with intrahepatic cholangiocarcinoma after radical resection from October 2010 to April 2019 were retrospectively collected in 10 hospitals of China. There were 277 males and 271 females with an age of (57.8±10.2)years(range:23 to 84 years). Four hundred and twenty-six patients(77.7%) had at least one positive preoperative serum tumor marker. The data collection included the results of 4 preoperative serological tumor markers,other preoperative indicators(5 prodromal symptoms, 6 medical history,8 preoperative serological indicators,5 preoperative imaging indicators,and 14 preoperative pathological examination indicators),baseline data (gender and age),surgical methods,and prognostic follow-up data. Four preoperative results of serologic tumor marker and surgical procedure were converted into categorical variables. The number of positive preoperative serum tumor markers was used as the treatment variable,the surgical method was used as the mediating variable,and the survival time was used as the outcome variable. Univariate and multivariate analysis were used to screen for other preoperative indicators which were independent factors that influenced the surgical procedure and the prognosis of patients as covariates to analyze the mediating effect.Results:Of the 548 patients included in the study, 176 patients (32.1%) underwent partial hepatectomy,151 patients(27.5%) underwent hemihepatectomy, and 221 patients(40.3%) underwent partial hepatectomy or hemihepatectomy combined with other treatments. The results of the univariate and multivariate analysis showed that the number of positive serum tumor markers,intrahepatic bile duct dilatation,portal vein invasion,pathological differentiation,pathological type,vascular invasion,T stage,N stage and maximum tumor diameter were independent factors influencing the surgical procedure(all P<0.05). Intrahepatic bile duct dilatation,pathological differentiation and T stage were independent prognostic factors for patients with intrahepatic cholangiocarcinoma(all P<0.05). Intrahepatic bile duct dilatation,differentiation and T stage were included as covariates in the mediation effect model. The results showed that the number of positive serum tumor markers before surgery had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.092, P=0.039),and had a positive predictive effect on the surgical method ( β=0.244, P<0.01). The number of positive serum tumor markers had a negative predictive effect on the survival time of patients with intrahepatic cholangiocarcinoma ( β=-0.151, P=0.002). Direct and indirect effects accounted for 71.3% and 28.7% of total effects,respectively. Conclusions:The higher the positive number of preoperative tumor markers,the worse the prognosis of patients with intrahepatic cholangiocarcinoma. The number of positive cells not only directly affects the prognosis of patients,but also indirectly affects the prognosis of patients by affecting the surgical method.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.