Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China / 中华放射学杂志

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Role of cerium oxide nanoparticles in doxorubicin-induced cardiotoxicity and its effect on P53 gene expression / 中国现代医生

@#Objective To study the effect of nano-ceria on doxorubicin-induced cardiotoxic injury and its effect on P53 gene expression,and to explore the mechanism of nano-ceria on doxorubicin-induced cardiotoxic injury.Methods H9C2 myocardial cells were cultured and randomly divided into five groups:control group,model group(1μmol/L adriamycin),nano-cerium oxide group(10μg/ml nano-cerium oxide),experimental group(1μmol/L adriamycin +10μg/ml nano-cerium oxide),and positive control group(1μmol/L adriamycin+10μmol/L dexperimine).The adriamycin induced cardiotoxicity model was established,and the viability of myocardial cells was measured by CCK-8 method.The contents of lactate dehydrogenase(LDH)and malondialdehyde(MDA)in myocardial cells were detected by biochemical method.The levels of reactive oxygen(ROS)and the apoptosis rate in myocardial cells were detected by flow cytometry.The expressions of Bax,Bcl-2 and P53 proteins in myocardial cells were detected by Western blot.Results Compared with the control group,the cell viability was decreased in the model group,the cell LDH and MDA contents were increased,the intracellular ROS level and apoptosis rate were increased,the expressions of Bax and P53 proteins were increased,and the expression of Bcl-2 protein was decreased,and the ratio of Bcl-2/Bax was decreased(all P<0.001).Compared with the model group,the experimental group showed increased cell viability,decreased cell LDH and MDA contents,decreased cell ROS content and apoptosis rate,decreased Bax and P53 protein expressions,and increased Bcl-2 protein expression,and the Bcl-2/Bax ratio was increased(all P<0.001).Conclusion Ceria nanoparticles can effectively prevent adriamycin-induced cardiotoxic injury,and its effect may be related to the down-regulation of P53 gene to inhibit cardiomyocyte apoptosis.

Refined protocol for newly onset identification in non-obese diabetic mice: an animal-friendly, cost-effective, and efficient alternative / 한국실험동물학회지

Background@#Therapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model. @*Results@#The observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37–38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring. @*Conclusions@#We demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment.

miR-185-5p alleviates the inflammatory response of acute gouty arthritis by inhibiting of IL-1β / 细胞与分子免疫学杂志

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.

Update and Interpretation of Elsevier Clinical Pathway for Gastric,Gastroesophageal Junction and Esophageal Cancer(Chinese Edition,2022) / 胃肠病学

The standardized treatment of malignant tumor has always been the direction of continuous improvement of major medical institutions.In recent years,the basic research,prevention,screening and diagnosis and treatment level of gastric,gastroesophageal junction and esophageal cancer have been greatly improved,resulting in a significant improvement in the 5 years'survival rate of patients,but there are still great differences in the diagnosis and treatment level among different regions.Chinese gastric cancer,gastroesophageal junction cancer and esophageal cancer differ greatly from European and American countries in etiology,pathological types,high incidence sites,etc.Therefore,the relevant guidelines of European and American countries cannot fully meet Chinese clinical practice.In 2021,Elsevier Publishing Group launched the Chinese edition of Elsevier clinical pathway for gastric,gastroesophageal junction and esophageal cancer,and the first update edition was made in 2022,which aims to promote the quality control of tumor diagnosis and treatment,standardize tumor diagnosis and treatment behaviors,promote the homogenization and standardization of tumor diagnosis and treatment,and ultimately improve the survival rate and quality of life of patients with malignant tumor.This pathway refers to the National Comprehensive Cancer Network clinical practice guidelines,the Chinese Society of Clinical Oncology guidelines,combines evidence-based medicine and clinical experience,and follows the scientific,universal,standardized and operable principles.It has been promoted and applied in clinical practice,and is constantly updated according to the latest research results.

Role of TIPE2 in sepsis-induced myocardial injury in mice: the relationship with AKT/GSK-3β/β-catenin signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of tumor necrosis factor-alpha-induced protein-8 like-2(TIPE2) in sepsis-induced myocardial injury and the relationship with serine-threonine kinase(AKT)/glycogen synthase kinase-3β(GSK-3β)/β-catenin signaling pathway in mice.Methods:Sixteen male wild-type C57BL/6N mice and 16 TIPE2-gene knockout C57BL/6N mice, aged 6-8 weeks, with a body mass index of 20-25 g, were divided into 4 groups using a random number table method: wild-type+ sham operation group(group WT-sham), wild-type+ cecal ligation and perforation(CLP) group(group WT-CLP), TIPE2-gene knockout sham operation group(group KO-sham) and TIPE2-gene knockout CLP group(group KO-CLP), with 8 mice in each group. The model of myocardial injury induced by sepsis was developed by CLP in anesthetized animals. Blood samples from the inferior vena cava were collected at 24 h after surgery for determination of the concentrations of cardiac troponin I(cTnI) in serum by enzyme-linked immunosorbent assay. Then the mice were sacrificed and myocardial tissues were collected for determination of the pathological changes(by hematoxylin and eosin staining), expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 mRNA(by quantitative polymerase chain reaction), and expression of TIPE2, phosphorylated AKT(p-AKT), phosphorylated GSK-3β(p-GSK-3β) and β-catenin(by Western blot).Results:Compared with the corresponding Sham groups, the serum cTnI concentration was significantly increased, the expression of TNF-α, IL-1β and IL-6 mRNA and expression of p-AKT, p-GSK-3β and β-catenin in myocardial tissues were up-regulated, the expression of TIPE2 was down-regulated( P<0.05), and the pathological changes of myocardium were found in corresponding CLP groups. Compared with group WT-CLP, the serum cTnI concentration was significantly increased, the expression of TNF-α, IL-1β and IL-6 mRNA and expression of p-AKT, p-GSK-3β and β-catenin in myocardial tissues were up-regulated, the expression of TIPE2 was down-regulated( P<0.05), and the pathological changes of myocardium were aggravated in group KO-CLP( P<0.05). Conclusions:TIPE2 reduces the myocardial injury probably through inhibiting the AKT/GSK-3β/β-catenin signaling pathway in septic mice.

Loss of ATM activity induces GADD45α-dependent apoptosis in cerebellar granular neurons / 中山大学学报(医学科学版)

objectiveTo explore the specific molecular mechanism of neuronal apoptosis induced by ATM inactivation. MethodsCGNs matured 7 days in vitro were cultured 8 h with 25 K， 5 K or 25 K medium containing ATM-specific inhibitors （Ku55933， 10 µmol/L； Ku60019， 15 µmol/L） for Hoechst stain and apoptosis analysis， or cultured for different lengths of time （2， 4， 8 h） to detect the protein expression levels of ATM， caspase-3 and cleaved caspase-3 by Western blotting. ATM and GADD45α specific siRNA was transfected into C6 cells and CGNs， and its interference efficiency was verified by q-PCR and Western blotting. CGNs matured for 5 days in vitro were transfected with ATM specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， Hoechst staining and apoptosis analysis were performed. CGNs matured for 7 days in vitro were treated with 25 K medium containing ATM specific inhibitors for 8 h， transcriptome sequencing， differential expression gene identification and pathway enrichment analysis were performed. CGNs matured for 5 days in vitro were co-transfected with GADD45α specific siRNA and pCMV-EGFP by calcium phosphate for 48 h， then treated with 5 K or 25 K medium containing 15 µmol/L Ku6 for 8 h. Hoechst staining and apoptosis analysis were performed. ResultsCompared with the 25 K， CGNs nuclear pyknosis rate， cleaved Caspase-3 and ATM protein expression level were increased in the 5 K and ATM-specific inhibitor groups. The mRNA and protein expression levels of ATM and GADD45α were effectively reduced after transfection of ATM and GADD45α specific siRNA in C6 cells and CGNs. Compared with control， CGNs transfected with ATM specific siRNA showed a higher nuclear pyknosis rate. Totally 835 genes were identified to be up-regulated and 848 genes to be down-regulated in the Ku55933 treatment group； 454 genes were identified to be up-regulated and 314 genes to be down-regulated in the Ku6 treatment group； 274 genes were co-up regulated in the Ku5 and Ku60019 treatment groups， while 179 genes were co-down-regulated in the Ku5 and Ku6 treatment groups and the expression of ATM downstream target GADD45α was upregulated. The enrichment results showed that TNF signaling pathway， NF-κB signaling pathway and Apoptosis signaling pathway were significantly enriched. Compared with control， mRNA and protein expression levels of GADD45α were increased in inhibitor treatment and 5 K， while knocking down GADD45α resulted in a decrease in nuclear pyknosis rate in the Ku60019 and 5 K treatment group. ConclusionLoss of ATM activity induces GADD45α-dependent cerebellar granular neuronal apoptosis.

Analysis of epidemic trends and status of schistosomiasis in Jiangxi Province from 2002 to 2021 / 上海预防医学

ObjectiveTo analyze the epidemic trends and current status in the prevalence of schistosomiasis in Jiangxi Province from 2002 to 2021， and to provide evidence for formulating and optimizing schistosomiasis control strategies in the province. MethodsEpidemiological data of schistosomiasis in Jiangxi Province from 2002 to 2021 were collected. The Joinpoint regression model was used to investigate the epidemic trends of schistosomiasis， and the annual average percent change （AAPC） was used to assess the changing trend of schistosomiasis infection in humans and bovines. SPSS 25.0 software was used to analyze the target achievement status， infection rate of schistosomiasis in humans and the areas with snails in 2021 to evaluate the differences among various districts and epidemic regions. ResultsBy 2021， 24 counties （61.50%） in the province had achieved the elimination goal， with hilly and marsh counties reaching 82.60% and 31.30%， respectively. The seropositive rate of schistosomiasis in human was 3.51% across the province. However， the seropositive rate in marshland areas （4.77%） was significantly higher than that in hilly areas （1.23 %） （χ2=3 827.51， P<0.001）. The total area with snails in the province was 84 938.32 hm2， including 82 196.86 hm2 in marshland areas and 2 741.46 hm2 in hilly areas. From 2002 to 2021， the infection rate of schistosomiasis in the humans and bovines exhibited a declining trend， with AAPC values of -48.70 and -39.70， respectively. The decline rate in the hilly areas was higher than that in marshland areas. However， the area with snail showed an upward trend （AAPC=0.50）， with a growth rate of 5.80% in hilly areas， which was greater than that in marshland areas （0.40%）. ConclusionFrom 2002 to 2021， the infection rate of schistosomiasis in humans and bovines in Jiangxi Province continued to decline， while the areas with snails increased. The prevention focus should still be on the marshland endemic areas， and attention should also be given to the risk of schistosomiasis in hilly endemic areas. Therefore， it is necessary to continue implementing a comprehensive prevention and control strategy that emphasizes controlling the sources of infection and adopts tailored measures based on local conditions and precise policies.

Application of video laryngoscope combined with bronchial blocker and double-lumen tube in the standardized training of anesthesia for tracheal intubation / 中华医学教育探索杂志

Objective:To explore the comparative study of video laryngoscopy combined with bronchial blocker and video laryngoscopy combined with double-lumen tube in the teaching of endotracheal intubation in thoracic surgery in the standardized residency training of anesthesia.Methods:The trainees of the standardized residency training were randomly divided into control group and experimental group for clinical teaching, with 25 ones in each group. The experimental group was treated with visual laryngoscopy combined with bronchial blocker, while the control group was treated with visual laryngoscopy combined with double-lumen tube group. The intubation time, intubation success rate, positioning time, hemodynamic changes, and complication incidence during intubation, as well as student assessment results were recorded. GraphPad Prism 6.0 was used for t test and Chi-square test. Results:The time of endotracheal intubation [(95.3±10.1) vs. (137.5±13.5)] and positioning time [(100.8±11.7) vs. (155.4±15.3)] in the experimental group were both shorter than those of the control group ( P< 0.001), the hemodynamic changes in patients with immediate intubation were smaller ( P<0.001), the success rate of intubation was higher (92% vs. 68%) ( P<0.001), the complication incidence was lower ( P<0.001) and the students' performance was higher ( P<0.001). Conclusion:In the anesthesia teaching of thoracic surgery, bronchial blocker can reduce the time of endotracheal intubation, lower the hemodynamic changes during intubation, cut down the incidence of complications, improve the success rate of endotracheal intubation and enhance the confidence of students.

Role of deubiquitinase OTUD1 in acute lung injury in septic mice: relationship with TAK1-MAPK signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of deubiquitinase OTUD1 in acute lung injury in septic mice and the relationship with transforming growth factor-beta activated kinase 1(TAK1)-mitogen-activated protein kinase (MAPK) signaling pathway.Methods:Twenty male wild-type (WT) and 20 OTUD1 gene knockout (KO) C57BL/6N mice, aged 6-8 weeks, weighing 20-25 g, were divided into 4 groups ( n=10 each) using a random number table method: wild-type+ sham operation group (WT-Sham group), wild-type+ sepsis group (WT-SEP group), OTUD1-KO+ sham operation group (KO-Sham group) and OTUD1-KO+ SEP group (KO-SEP group). The acute lung injury was induced by cecal ligation and perforation (CLP) in anesthetized septic mice. Mice were sacrificed at 24 h after operation, blood samples were collected from the abdominal aorta, and lung tissues were collected. Blood gas analysis was performed using the i-STAT blood gas analyzer, PaO 2 and FiO 2 were recorded, and the oxygenation index (OI) was calculated. The morphology of lung tissues was examined with a light microscope for evaluation of lung injury, and lung injury scores were calculated. The wet to dry lung weight (W/D) ratio was measured, and the activities of MPO were measured. The concentrations of TNF-α and IL-6 in plasma were detected by enzyme-linked immunosorbent assay, and the expression of OTUD1, phosphorylated TAK1 (p-TAK1), phosphorylated p38 (p-p38), phosphorylated c-Jun amino-terminal kinase (p-JNK) and phosphorylated extracellular signal-regulated kinase (p-ERK) was detected using Western blot. Results:Compared with WT-Sham group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in WT-SEP group ( P<0.05). Compared with WT-SEP group, the PaO 2 and OI were significantly decreased, the lung injury score, W/D ratio, MPO activity, and plasma TNF-α and IL-6 concentrations were increased, and the expression of OTUD1, p-TAK1, p-p38, p-JNK and p-ERK protein in lung tissues was up-regulated in KO-SEP group ( P<0.05). Conclusions:OTUD1 is involved in the endogenous protective mechanism against acute lung injury in septic mice, which may be related to the inhibition of TAK1-MAPK signaling pathway activation and decreased inflammatory responses.

Update and interpretation of Elsevier clinical pathway for gastric, gastroesophageal junction and esophageal cancer ( Chinese edition, 2022) / 中华消化杂志

The standardized treatment of malignant tumor has always been the direction of continuous improvement of major medical institutions. In recent years, the basic research, prevention, screening and diagnosis and treatment level of gastric, gastroesophageal junction and esophageal cancer have been greatly improved, resulting in a significant improvement in the 5 years′ survival rate of patients, but there are still great differences in the diagnosis and treatment level among different regions. Chinese gastric cancer, gastroesophageal junction cancer and esophageal cancer differ greatly from European and American countries in etiology, pathological types, high incidence sites, etc. Therefore, the relevant guidelines of European and American countries cannot fully meet Chinese clinical practice. In 2021, Elsevier Publishing Group launched the Chinese edition of Elsevier clinical pathway for gastric, gastroesophageal junction and esophageal cancer, and the first update edition was made in 2022, which aims to promote the quality control of tumor diagnosis and treatment, standardize tumor diagnosis and treatment behaviors, promote the homogenization and standardization of tumor diagnosis and treatment, and ultimately improve the survival rate and quality of life of patients with malignant tumor. This pathway refers to the National Comprehensive Cancer Network clinical practice guidelines, the Chinese Society of Clinical Oncology guidelines, combines evidence-based medicine and clinical experience, and follows the scientific, universal, standardized and operable principles. It has been promoted and applied in clinical practice, and is constantly updated according to the latest research results.

Making Progress through Exploration——Summary and Reflection on the Implementation of the Plan for the Protection and Development of Traditional Chinese Medicine(2015-2020) / 世界科学技术-中医药现代化

Chinese medicinal materials are the basis for the inheritance and development of traditional Chinese medicine,as well as strategic resources related to the national economy and people's livelihood.In 2015,12 departments,including the Ministry of Industry and Information Technology,and the State Administration of Traditional Chinese Medicine,jointly formulated the Plan for the Protection and Development of Traditional Chinese Medicine(2015-2020)(hereinafter referred to as the Plan),focusing on seven major construction tasks for the protection and development of traditional Chinese medicine.Through the summary and evaluation of the Plan,it can be seen that the overall development goals and 7 specific indicators have been achieved by 2020.It has been focused on solving the problems of the loss and depletion of some wild Chinese medicinal materials resources and the shortage of Chinese medicinal materials supply.Promoting to alleviate the problems,including the abuse of chemical fertilizers,pesticides,and growth regulators.The extensive production and management of Chinese medicinal materials,as well as the poor exchange of supply and demand information were effectively improved.On the whole,the development and protection of Chinese medicinal materials were promoted.Moreover,the dependence on wild Chinese medicinal materials was reduced through scientific development of Chinese medicinal materials production.And the sustainable development of the Chinese medicinal materials industry was coordinated with the protection of the ecological environment.However,there were still some problems and deficiencies,such as a lack of accurate information guidance,an incomplete price formation mechanism,and an incomplete whole-process traceability system of Chinese medicinal materials.It is suggested that during the 14th Five-Year Plan period,we should continuously strengthen the protection and sustainable development of traditional Chinese medicine resources,and build a new development pattern for traditional Chinese medicine industry based on the new development concept and requirement.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Associations of family functioning with sleep disturbance and depressive symptoms among primary and secondary school students / 中国学校卫生

Objective@#The study aims to explore the associations of family functioning with sleep disturbance and depressive symptoms among primary and secondary school students, to provide scientific reference for preventing depression in primary and middle school students.@*Methods@#A convenience sampling method was used to recruit 124 357 primary and secondary school students in Baoan District, Shenzhen. A self administered general information questionnaire, the Youth Self Rating Insomnia Scale, and the Patient Heath Questionnaire-9 were used to assess the students demographic characteristics, family functioning, sleep disturbance, and depressive symptoms.@*Results@#About 34.6% of students reported moderate family dysfunction, and 8.7% reported severe family dysfunction. The prevalence rates of sleep disturbance and depressive symptoms were 13.0% and 13.1% in elementary and secondary school students, respectively. The prevalence rates of sleep disturbance and depressive symptoms were statistically significantly higher in girls(14.6%, 16.8%) than boys(11.6%, 9.9%) ( χ 2=255.25, 1 269.50, P <0.01). Depressive symptoms were positively correlated with sleep disturbance ( r =0.61) and negatively correlated with family functioning ( r =-0.31)( P <0.01). Family functioning moderated the relationship between sleep disturbance and depressive symptoms, and the positive predictive effect of sleep disturbance on depressive symptoms decreases as the level of family functioning increases.@*Conclusion@#Family functioning buffers the effects of sleep disturbance on depressive symptoms among primary and secondary school students. Attention should be paid to sleep quality among primary and secondary school students, to improve their family functioning, and thus decrease and prevent the occurrence of depression in adolescents.

Optimization and screening of carrier for solid dispersion of olaparib based on the solubility parameter and differential scanning calorimetry / 药学学报

Solid dispersion, a dispersion system in which drug molecules are highly dispersed in carrier materials, has been commonly used to improve the solubility and dissolution rate of poorly soluble drugs. The miscibility between drug and carrier is crucial to improve the dissolution performance and stability of solid dispersion. Therefore, the selection of carrier types and the optimization of drug loading are very important. In the current study, the solubility parameter method and Flory-Huggins theory were used to predict the miscibility between olaparib (OLP) and different carriers (VA64, Soluplus, Plasdone S630 and Kollidon K29/32). Besides, the carrier material with good miscibility was experimentally screened by differential scanning calorimetry (DSC). The optimum of drug-carrier ratio was further performed based on the miscibility phase diagram of drug and carrier. Theoretical calculation and experimental evaluation showed that the miscibility of OLP and VA64 was the best, and the drug loading of 30% could meet the requirements of large drug loading and physical stability. Polarizing light microscope, X-ray powder diffraction, DSC and laser confocal Raman spectroscopy exhibited that OLP was amorphous form in the solid dispersion system. Powder dissolution test demonstrated that the solid dispersion showed significantly enhanced dissolution rate in comparison to crystalline OLP. In this study, theoretical calculation and experimental evaluation were used to screen the types of carriers and optimize the drug loading, which provides an efficient strategy for the selection of carrier and the amount used in solid dispersion.

Nifedipine promotes formation of autophagosomes and enhances expression of Beclinl in hepatoma cell line Huh-7 / 中国药理学通报

Aim To investigate the effect of nifedipine on the formation of autophagosomes in hepatoma cell line Huh-7 and its mechanism.Methods Different concentrations of nifedipine were used to interfere with the proliferation of Huh-7 cells in vitro.The effect of nifedipine on the proliferation of Huh-7 cells was detected by cell proliferation experiment and colony formation experiment.The expressions of Beclin1 and LC3B-Ⅱ were detected by Western blot.The effect of nifedipine on the formation of autophagosomes in Huh-7 cells was observed by laser scanning confocal microscopy.Results Nifedipine significantly inhibited the proliferation of Huh-7 cells in a time-and concentration-dependent manner.The IC50 of nifedipine on day 2 was 22.7 mg·L-1.Nifedipine at the concentration of 25 mg·L-1 significantly reduced the colony formation rate of Huh-7 cells compared with the control group, and the inhibition rate of colony formation was(95.46±0.45)%.Western blot analysis showed that nifedipine significantly up-regulated the protein expression levels of Beclin1 and LC3B-Ⅱ.The amount of autophagosomes in nifedipine group cells were more than that of control group, which was observed by laser scanning confocal microscopy.Conclusions Nifedipine significantly inhibits the proliferation of Huh-7 cells and promotes the formation of autophagosomes, which may be related to the up-regulation of Beclin1 protein expression by nifedipine.

Inhibitory activity of copper gluconate and disulfiram against papain-like protease of SARS-CoV-2 / 中国药理学通报

Aim To investigate the inhibitory effect of copper gluconate and disulfiran on the PLpro of SARS-CoV-2 and to explore the effect of combination of them on PLpro.Methods SARS-CoV-2 PLpro was purified by recombinant expression technology of he effects of copper gluconate and disulfiram on PLpro activity were studied by enzyme kinetic method.Results Copper gluconate and disulfiram had high inhibitory activity on SARS-CoV-2 PLpro,Ubiquitin-7-Amino-4-methylcoumarin(Ub-AMC)was used as the fluorescent substrate.The IC50 of copper gluconate was 33.02 nmol·L-1,showing competitive inhibition,and the IC50 of disulfiram was 480.4 nmol·L-1,showing non competitive inhibition,and the combination of the two inhibitors showed the advantage of synergistic inhibition.Conclusions Copper gluconate and disulfiram have a high inhibitory effect on SARS-CoV-2 PLpro protein,and the combination shows the advantage of synergistic inhibition.

Economic burden of patients with cervical cancer and precancerous lesions / 预防医学

Objective @#To investigate the economic burden of cervical cancer and precancerous lesions, so as to provide the evidence for improving the management of cervical cancer and formulating the policies for reducing the economic burden of cervical cancer and precancerous lesions. @*Methods@#The hospitalized patients with cervical cancer and precancerous lesions were recruited from four hospitals in Xinjiang Uygur Autonomous Region from September 2020 to June 2021. The direct medical expenditures, direct non-medical expenditures, duration of absence from work in patients and their family members as carers were collected using a questionnaire designed by the Cancer Hospital of the Chinese Academy of Medical Sciences, and the economic burdens of cervical cancer and precancerous lesions were estimated. The factors affecting the economic burden of cervical cancer were identified using a multivariable linear regression model.@*Results@#Totally 265 patients with cervical cancer and precancerous lesions were included, with an average age of ( 49.80±10.07 ) years. There were 170 patients with cervical cancer, including 64 cases with stage I, 79 cases with stage II, and 27 cases with stages III/Ⅳ, and 95 patients with precancerous lesions, including 33 cases with low-grade squamous intraepithelial lesion ( LSIL ) and 62 cases with high-grade squamous intraepithelial lesion ( HSIL ). The median economic burdens (interquartile range) were 11 481 ( 4 523 ), 17 850 ( 9 096 ), 112 883 ( 59 623 ), 150 875 ( 105 206 ) and 197 842 ( 61 844 ) Yuan per patient among cases with LSIL, HSIL, and stage I, II and III/Ⅳ cervical cancer, respectively, among which the direct medical expenditures accounted for 85.89% to 93.86%. The median economic burdens (interquartile range) were 708 ( 1 711 ), 11 678 (6 590), 2 557 ( 19 472 ), and 14 943 ( 27 773 ) Yuan per patient with precancerous lesions, and were 910 (1 530), 105 770 ( 91 019 ), 39 765 ( 30 490 ), and 146 445 ( 123 039 ) Yuan per patient with cervical cancer during the diagnostic phase, the clinical treatment phase, the follow-up phase, and in total, respectively. Multivariable linear regression analysis results showed that pathological stage ( β'=0.202, P=0.003 ) and duration of hospital stay ( β'=0.695, P<0.001 ) correlated with the economic burden among patients with cervical cancer. @*Conclusion@#There is a high economic burden among patients with cervical cancer and precancerous lesions. Advanced pathological stage and long duration of hospital stay may increase the economic burden among cervical cancer patients.

Correlation between gait parameters and balance in stroke hemiplegic patients / 中国康复理论与实践

@#Objective To investigate the relationship between gait spatiotemporal parameters and balance function in stroke hemiplegic patients. Methods From September, 2018 to March, 2020, 76 stroke hemiplegic patients (38 in Brunnstrom Ⅳ and V, respectively) were assessed balance function with Active Balancer EAB-100 and Star Excursion Balance Test (SEBT), and gait parameters of speed, cadence and asymmetry, named step length asymmetry ratio (SLA), swing time asymmetry ratio (SWTA), stance time asymmetry ratio (STA), maximum flexion angle ratio (MFA) of hip and knee. The correlation among gait parameters and balance function was analysed. Results The balance and gait parameters were better in those in Brunnstrom V than in Brunnstrom Ⅳ (|t| > 2.268, P < 0.05). The speed and cadence correlated with the most balance indexes (|r| > 0.335, P < 0.05). SLA correlated with SEBT in Brunnstrom Ⅳ patients (r = -0.467~-0.613, P < 0.01), while it correlated with medial-lateral (M-L) stability limits in Brunnstrom V patients (r = -0.356, P = 0.028). SWTA correlated with stability limit of Anterior-Posterior (A-P) (r = -0.335, P = 0.040) and M-L (r = 0.510, P = 0.001), and most of SEBT (r = -0.330~ -0.445, P < 0.05) in Brunnstrom Ⅳ patients. MFA of hip and knee correlated with balance indexes in Brunnstrom Ⅳ patients (|r| > 0.326, P < 0.05), while MFA of knee correlated with most balance indexes in Brunnstrom V patients (r > 0.329, P < 0.05), and MFA of hip correlated with A-P stability limit (r = 0.369, P = 0.023). Conclusion Both speed and cadence of steps can well respond to the balance function in stroke hemiplegic patients. For the asymmetry, it is related with balance in patients with poorer recovery.

Factor analysis on serum biomarkers in patients with stage Ⅰ silicosis / 中国职业医学

@#Objective ， To investigate the role of serum chemokines and oxidative and antioxidant biomarkers in occupational （ silicosis） Methods silicosis hereinafter referred to as . A total of 58 patients with stage Ⅰ silicosis were selected as the - （ ）， research subjects using convenient sampling method. The serum levels of nuclear factor erythroid 2 related factor 2 Nrf2 -（ - ） - （ - - ） - heme oxygenase 1 HO 1 and 8 isoprstaglandin F2α 8 iso PGF2α were determined by enzyme linked immunesorbent assay. （ ） （ - ） The serum levels of lipid peroxide LPO and total antioxidant capacity TAOC were determined by chemistry colorimetric method. - - （ - ）， Luminex flow fluorescence technology was used to detect the serum levels of interferon γ inducible protein10 IP10 macrophage （ ）- ， - - （ ） inflammatory protein MIP 1α MIP1β and macrophagederived chemokine MDC . The above indicators were analyzed by factor Results - analysis. The information extraction rate of the original indicators of the nine biomarkers was 58.5%96.5%. Four common ， ， （ ） ， factors were extracted including Nrf2 antioxidant signaling pathway helper T cell Th 1 dominant chemotaxis the total ， ， ， ， ， oxidation/antioxidant balance and Th2 dominant chemotaxis whose variance contribution rates were 32.2% 19.1% 16.4% ， ， Conclusion - and 11.8% respectively and the cumulative variance contribution rate was 79.5%. Both the oxidant antioxidant ， disturbance and the dominance chemotaxis are involved in the occurrence and development of silicosis and the Nrf2 antioxidant signaling pathway plays the most critical role.