Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

Objective To explore the pathogenesis of Alzheimer's disease by examining the effects of dihydroartemisinin(DHA)on cognitive behavior,hippocampal,cerebral cortex and retinal cell morphology,β-amyloid(Aβ)and autophagy-related proteins in 5×FAD mice.Methods Twenty 5×FAD mice and 5 wild type(WT)mice were selected,all of which were female.The 5×FAD mice were randomly divided into model(M)group,donepezil(D)group,low-dose DHA(DHA-L)group,and high-dose DHA(DHA-H)group.The WT and M groups were not treated,and the D group was given donepezil 0.1 mg/kg per day.DHA-L group and DHA-H group were given 10 mg/kg and 20 mg/kg DHA per day,respectively.Group D,group DHA-L and group DHA-H were given intragastric administration once a day for 3 months.The changes of in cognitive behavior were measured by Morris experiment.HE staining was used to observe the arrangement and morphology of nerve cells in cerebral cortex,hippocampus and retina.The expressions of Aβ protein in cerebral cortex,hippocampus and retina were detected by immunohistochemistry.Western blotting detected the expression of autophagy related proteins(LC3-Ⅰ,LC3-Ⅱ,Beclin-1,P62,β-actin).Results The DHA-H group and the D group exhibited more frequent adoption of both linear and trending exploration routes.Compared to the model group,significant differences in the contents of Aβ in the hippocampal CA1,cerebral cortex S1,and retinal were observed(P＜0.0001)in the other four groups.The analysis also showed significant differences in autophagy-associated proteins between the DHA-L,DHA-H,and model groups(P＜0.01).Conclusion DHA improves cognitive function and increases the number of nerve cells in mice.It also reduces Aβ content in the cerebral cortex,hippocampus,and retina,along with improving autophagy-associated protein deposition in mice.

Objective To describe the clinical features of patients with primary sclerosing cholangitis(PSC)in China based on a nationwide multicenter patient cohort,and to investigate the risk factors for prognosis.Methods A retrospective cohort study was conducted among the patients with a confirmed diagnosis of PSC based on the electronic medical record system of seven grade A tertiary hospitals across the country,and related data were extracted.The Mann-Whitney U test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups.The Kaplan-Meier method was used to estimate liver transplant-free survival,and the log-rank test was used for comparison of survival rate between PSC patients with different features.The Cox regression model was used to identify independent risk factors for the prognosis of PSC patients and the interactions between key factors.Results A total of 107 patients were enrolled,among whom 55.6%(55/99)had large-duct PSC and 29.0%(31/107)had comorbidity with inflammatory bowel disease(IBD).The positivity rate of anti-neutrophil cytoplasmic antibody(ANCA)was 32.9%(24/73),and 50.0%(40/80)of the patients had an increase in IgG/IgM.The median symptom-to-diagnosis interval was 1 year(<1-4.0),and 38.3%(41/107)of the patients had progressed to decompensated cirrhosis at the time of diagnosis.The median liver transplant-free survival time was 114 months(95%confidence interval[CI]:62-166),with a 5-year survival rate of 65.7%.The multivariate analysis showed that an increase in total bile acid(TBA)(hazard ratio[HR]=1.006,95%CI:1.002-1.010,P=0.001)and a prolonged symptom-to-diagnosis interval(HR=1.252,95%CI:1.059-1.480,P=0.009)were independent risk factors for prognosis.The interaction analysis showed that compared with the female patients with TBA<50 μmol/L,both male and female patients with TBA≥50 μmol/L had a significant increase in the risk of liver transplantation or death(male:HR=16.563,95%CI:2.103-130.449,P<0.001;female:HR=17.009,95%CI:2.113-136.934,P<0.001),and compared with the patients with an age of<45 years and a TBA level of<50 μmol/L,the patients with an age of≥45 years and a TBA level of≥50 μmol/L had a significant increase in the risk of liver transplantation or death(HR=10.729,95%CI:1.325-86.859,P=0.026).Compared with the female patients with an symptom-to-diagnosis interval of≤2 years,the male patients with a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.825,95%CI:1.725-13.644,P=0.003),and compared with the patients with an age of<45 years and a symptom-to-diagnosis interval of≤2 years,the patients with an age of<45 years and a symptom-to-diagnosis interval of>2 years had an increased risk of liver transplantation or death(HR=4.983,95%CI:1.366-18.173,P=0.015).Conclusion Compared with the reports from Western countries,large-duct PSC is also the main type of PSC in China,but with a relatively low proportion,and there is also a relatively low proportion of patients with IBD or positive ANCA.An increase in TBA and a prolonged symptom-to-diagnosis interval are independent risk factors for prognosis,with significant interactions with age and sex.This suggests that early screening and intervention should be enhanced to improve prognosis.

The present analysis was based on the iteration of the 2023 WHO Essential Medicines Model List(23rd list)and Essential Medicines Model List for Children(9th list).In a methodological fashion,the adjustment procedure of the basic drug list and the materials required to submit the application were sorted out.Subsequently,a comprehensive synthesis of predominant features characterizing the 2023 edition of the EML and EMLc are summarized(offered).Notably,this edition boasts the highest count of medicines ever included featuring extensive inclusion of innovative drugs to fill the gap,select medicines for children carefully,and the emphasizing on clinical benefit evidence and public health affordability.It is suggested that China should update the NEML according to the national conditions and the experience of WHO as soon as possible,pay attention to the difference and connection between the list of essential medicines and the list of medical insurance,and play a meticulous role for establishing effective linkages between two lists.Such measures are envisaged to meet the basic drug needs,and ensure the accessibility and affordability of drugs,thereby optimizing the allocation of health resources.

CD200 and its receptor CD200R constitute an endogenous inhibitory signal. The binding of CD200 and CD200R can regulate the immune response to pathogenic stimuli, which has received much attention in recent years. It has been found that CD200-CD200R is involved in the regulation of many kinds of pathological inflammation, including autoimmune diseases, cardiac cerebrovascular disease, infection and tumor. This paper reviews the protein structure, distribution, expression, biological function of CD200-CD200R and the correlation with diseases, and analyses the current status and development ideas of CD200-CD200R as drug targets. It aims to provide theoretical support for new drug research and development based on this target.

BACKGROUND: Many studies have demonstrated the benefit of complete multivessel revascularization versus culprit-only intervention in patients of ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease. However, only a few single-center retrospective studies were performed on small Chinese cohorts. Our study aims to demonstrate the advantage of multivessel percutaneous intervention (PCI) strategy on 30-day in-hospital outcomes to patients with STEMI and multivessel disease in larger Chinese population. METHODS: From the Improving Care for Cardiovascular Disease in China-Acute Coronary Syndrome (CCC-ACS) project, 5935 patients with STEMI and multivessel disease undergoing PCI and hospitalized for fewer than 30 days were analyzed. After 5: 1 propensity score matching, 3577 patients with culprit-only PCI and 877 with in-hospital multivessel PCI were included. The primary outcome was major adverse cardiovascular and cerebrovascular event (MACCE), defined as a composite of myocardial infarction, all-cause death, stent thrombosis, heart failure, and stroke. RESULTS: Multivariable logistic regression analysis revealed that in-hospital multivessel PCI was associated with lower risk of 30-day MACCE (adjusted OR = 0.75, 95% CI: 0.57-0.98, P = 0.032) than culprit-only PCI and conferred no increased risk of all-cause death, myocardial infarction, stent thrombosis, stroke, or bleeding. Subgroup analysis showed that MACCE reduction was observed more often from patients with trans-femoral access (OR = 0.34, 95% CI: 0.15-0.74) than with trans-radial access (OR = 0.87, 95% CI: 0.66-1.16, P for interaction = 0.017). CONCLUSIONS The in-hospital multivessel PCI strategy was associated with a lower risk of 30-day MACCE than culprit-only PCI in patients with STEMI and multivessel coronary artery disease.

This study primarily concentrated on scientific problems of poor taste caused by unclear critical quality attributes of oral preparations manufactured by Chinese materia medica, successfully established an identification method for taste critical quality attribute and a taste improvement method combining electronic tongue with human senses, and determined the optimal taste formula, to improve patients' oral medication compliance. The study received ethical approval from the Review Committee of the Beijing University of Chinese Medicine. The results showed that the proportion of bitterness of Xiaoer Qingrening Granule was 61.8%, and its bitterness grade was 3.70, it was determined that bitterness is the critical quality attribute that caused the poor taste of Xiaoer Qingrening Granule. Additionally, the optimal taste formula per milliliter of Xiaoer Qingrening sugar-free intermediate was determined with allowable daily intake, solubility, and sweetness as the limiting conditions, which was 40 mg hydroxypropyl β-cyclodextrin, 180 mg trehalose, and 1.5 mg acesulfame potassium. Compared with the Xiaoer Qingrening Granule, the sensory evaluation score of the optimal taste formula was increased by 37.5 points. In conclusion, this study achieved the taste improvement of Xiaoer Qingrening Granule and formed a set of taste improvement strategies including the identification of taste critical quality attribute, the selection of the type and dosage of corrigent, and the optimization of taste formula, which provided a thought reference for the taste improvement of other oral preparations and a new perspective for quality control of intelligent manufacturing of traditional Chinese medicines.

OBJECTIVE To investigate the effect of gene CD47 on immune microenvironment of lung squamous cell carcinoma and predict its immune response. METHODS The differences in the expression of CD47 between lung squamous cell carcinoma tissues and normal tissues were compared through The Cancer Genome Atlas(TCGA) databases. CD47 involved immune-related pathways were analyzed by Gene Set Enrichment Analysis(GSEA). Tumor Immune Estimation Resource(TIMER) databases and TISIDB databases(http://cis.hku.hk/TISIDB/TISIDB) were employed to analyze the relationship between CD47 gene expression in lung squamous cell carcinoma and immune cells infiltration in the tumor microenvironment. And further explored the associations between CD47 and other immune-related molecules such as PD-1, PD-L1, CTLA-4, IDO-1. Using the pRRophetic and TIDE algorithms, this study predicted the correlation between the expression of CD47 gene and chemotherapy drug sensitivity as well as the response to immunotherapy. RESULTS Compared with normal tissues, CD47 was lower expressed in lung squamous cell carcinoma tissues. It was found that CD47 could activate immune-related pathways such as the inflammatory response, interferon alpha response, interferon gamma response and JAK-STAT pathway. In lung squamous cell carcinoma tissues, the expression level of CD47 was significantly positively correlated with the infiltration level of B-cells, CD8T-cells, CD4T-cells, macrophage, neutrophils and dendritic cells according to the two databases. At the same time, CD47 showed a positive correlation with other immune checkpoints such as PD-1, PD-L1, CTLA-4, IDO1. The result of chemotherapy sensitivity indicated that in lung squamous cell carcinoma tissues, IC50 values of high expression CD47 group were lower than that for chemotherapy drugs such as sunitinib, dasatinib, doxorubicin and gemcitabine. However, the response rate to immunotherapy was lower in the low expression group for the immunotherapy. CONCLUSION CD47 is low expressed in lung squamous tissue, it can activate immune related pathways, and has a high response rate to immunotherapy. It can be used as a novel molecular marker for lung squamous cell carcinoma.

Objective:This study aims to analyze the characteristics and basic principles of emergency surgery risks and anesthesia care of medical support at the landing site for China’s taikonauts of the Shenzhou-12, and to summarize China’s experience in medical support at the landing site for manned spaceflight, and ensure supports in special environments such as an emergency return of manned spaceflight.Methods:This study was carried out through literature research on relevant reports on the emergency surgery risks and aids of domestic and foreign astronauts at the landing sites, and summaries of the experience in medical support for taikonauts of spacecrafts from Shenzhou-5 to Shenzhou-11 at the landing sites. At the same time, according to the characteristics of Shenzhou-12 such as the long on-orbit time, the adjustment in the landing area, the optimization of the mission mode, and new search and rescue power, a series of organization, pre-arranged planning, equipment allocation, and effective anesthesia treatment plan were proposed and inspected in practice.Results:Based on the original anesthesia care plan of medical support, the first-aid carrier was adjusted and modified, the first-aid procedure was optimized, a new generation of supraglottic airway opening tool, video laryngoscope, portable ultrasound, and other devices were added, and the anesthesia care plan at the landing site for manned spaceflight was formulated to provide strong support for the medical care of taikonauts that had stayed in the outer space for a long time.Conclusions:Upon the targeted improvement and process optimization, the anesthesia care plan of medical support for taikonauts of Shenzhen-12 in the landing area fully meets the anesthesia requirement of medical support in special environments such as the emergency return of the taikonauts that have stayed in the outer space for a long time under the new orbital altitude.

Objective: To propose total posterior nasal neurectomy with transection of sphenopalatine neurovascular bundle from anatomy for the treatment of allergic rhinitis, and to explore its clinical application. Methods: Two fresh cadaveric heads (4 sides) were dissected through endoscopic transnasal middle meatus approach at Otorhinolaryngology Anatomy Laboratory of China-Japan Friendship Hospital. The structures of the craniofacial bone related to the surgical approach were observed. Twelve patients with allergic rhinitis who treated in Department of Otorhinolaryngology, China-Japan Friendship Hospital from Feb. 1 2019 to Jun. 10 2021 were selected. All the patients were treated by posterior nasal neurotomy with the technique of complete transection of sphenopalatine neurovascular bundle and followed up for 1 year after sugery. During the follow-up, 2 patients were lost. The other 10 patients included 4 males and 6 females, aging from 29 to 69 years. Visual Analogue Scale (VAS) and Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) were used to evaluate the effect of the surgery. SPSS 25.0 software was used for statistical analysis. Results: Important anatomic landmarks of transnasal middle meatus approach were obtained during anatomy, such as ethmoid crest, sphenopalatine foramen/notch, palatine orbital process and sphenopalatine process. The postoperative VAS scores of nose, eye, pharynx, ear and whole body and total VAS scores were significantly lower than those before operation, with statistically significant difference (nose 2.50±1.70 vs 6.47±2.17, eyes 1.15±0.89 vs 3.60±2.57, pharynx 1.30±1.36 vs 4.25±3.64, ear 1.10±1.03 vs 2.67±2.00, whole body 1.08±1.24 vs 3.60±1.17, total 7.13±4.31 vs 20.58±9.05, all P<0.05). The postoperative RQLQ scores of sleep, nose, eyes, practical problems, emotion, activity and the total RQLQ scores of patients were significantly lower than those before operation, with statistically significant difference (sleep 0.80±0.69 vs 2.93±1.33, nose 1.38±1.18 vs 3.93±1.50, eyes 0.58±0.66 vs 1.80±1.25, practical problems 1.10±1.22 vs 3.03±1.84, emotion 1.00±1.81 vs 2.58±2.00, activity 2.77±2.93 vs 6.00±1.85, total 8.99±8.92 vs 22.42±8.69, all P<0.05). There was no significant difference in preoperative and postoperative scores of non-nasal/ocular symptoms (1.37±1.60 vs 2.16±1.12, P=0.166). There was no other complication except 2 cases with short-term postoperative numbness. Conclusions: Total posterior nasal neurectomy with transection of sphenopalatine neurovascular bundle is a safe, effective and feasible method for the treatment of intractable allergic rhinitis, and its long-term efficacy needs further observation.
Denervation/methods* ; Female ; Humans ; Male ; Nose/surgery* ; Quality of Life ; Rhinitis, Allergic/surgery* ; Treatment Outcome