The rationale for the design of control groups in tuina clinical trial is the foundation for rigorously validating the effectiveness and safety of this therapy. This article reviewed the current state of the design of tuina placebo in control groups of clinical trials， pointed out the necessity of setting up tuina placebo in clinical trials of tuina， analyzed the challenges in implementing blinding of tuina manipulation， and concluded that tuina placebo is still challenged by the placebo effect， the diversification of tuina manipulation but the lack of standardization， and the difficulty of implementing blinding due to the high level of public awareness of tuina. This article also summarized the design of placebo manipulation in three types of clinical trials， including spinal manipulation， acupressure， and paediatric tuina， and proposed four strategies for designing placebo tuina manipulation-controlling placebo effects， developing operational standards for placebo tuina manipulation， ensuring the rigor of blinding implementation， and applying new technologies to enhance the standardization and blinding capacity of placebo tuina methods. So the article is aimed at improving the methodological quality of tuina clinical trial designs， and promoting the standardization and scientificity of tuina clinical trial design.

Given the systematic, rigorous, and practical characteristics of medical disciplines, ensuring the teaching quality of online courses has become a significant focus. In traditional teaching models, teaching supervision is an important method to guarantee instructional quality, and introducing teaching supervision into online teaching activities is of great significance. This article systematically reviews and summarizes the domestic and international experience of conducting online medical courses. We explore the instructional supervision of online medical courses from the following perspectives: the meaning of supervision, the necessity of online supervision, online supervision methods and technical approaches, the feedback and application of supervision information, and the establishment of a standardized online supervision process.

Objective: To conduct a systematic review and meta-analysis of studies evaluating the oncological and fertility outcomes of early-stage endometrial cancer (EC) treated with the levonorgestrel-releasing intrauterine system (LIUS)-based regimens. Methods: The Meta-analyses Of Observational Studies in Epidemiology statement for meta-analyses was followed. Searches were conducted on MEDLINE, Embase, PubMed, Preprints, and the Cochrane Central Register of Controlled Trials from January 1990 to August 4, 2022. The Joanna Briggs Institute Critical Appraisal Checklist was used for quality assessment. The primary endpoint was the complete response (CR) rate and the secondary endpoints were relapse, pregnancy, and live birth rate. Results: A total of 25 studies (821 women) were included. The CR rate of LIUS-based regimens was 63.4% (95% confidence interval [CI]=52.3%–73.2%), with 29.6% (95% CI=23.3%–36.8%) of cases experiencing recurrence during follow-up. In sensitivity analyses, patients younger than 45 years of age with a body mass index <30 kg/m2 who were treated with LIUS-based regimens achieved a high CR rate of 84.6% (95% CI=80.3%–88.1%) over a median follow-up of more than 24 months. Overall pregnancy and live birth rates were 37.9% (95% CI=24.1%–53.9%) and 39.3% (95% CI=24.0%–57.0%), respectively. No statistical differences were apparent in CR or relapse rates among the LIUS+GnRH agonist, LIUS+oral progesterone, or hysteroscopic resection followed by LIUS subgroups. Conclusion LIUS-based therapies are viable for the conservative management of early-stage endometrioid EC on CR and fertility outcome.

Many people affected by fragile X syndrome (FXS) and autism spectrum disorders have sensory processing deficits, such as hypersensitivity to auditory, tactile, and visual stimuli. Like FXS in humans, loss of Fmr1 in rodents also cause sensory, behavioral, and cognitive deficits. However, the neural mechanisms underlying sensory impairment, especially vision impairment, remain unclear. It remains elusive whether the visual processing deficits originate from corrupted inputs, impaired perception in the primary sensory cortex, or altered integration in the higher cortex, and there is no effective treatment. In this study, we used a genetic knockout mouse model (Fmr1^KO), in vivo imaging, and behavioral measurements to show that the loss of Fmr1 impaired signal processing in the primary visual cortex (V1). Specifically, Fmr1^KO mice showed enhanced responses to low-intensity stimuli but normal responses to high-intensity stimuli. This abnormality was accompanied by enhancements in local network connectivity in V1 microcircuits and increased dendritic complexity of V1 neurons. These effects were ameliorated by the acute application of GABA_A receptor activators, which enhanced the activity of inhibitory neurons, or by reintroducing Fmr1 gene expression in knockout V1 neurons in both juvenile and young-adult mice. Overall, V1 plays an important role in the visual abnormalities of Fmr1^KO mice and it could be possible to rescue the sensory disturbances in developed FXS and autism patients.
Animals ; Disease Models, Animal ; Fragile X Mental Retardation Protein/metabolism* ; Fragile X Syndrome/metabolism* ; Humans ; Mice ; Mice, Knockout ; Neurons/metabolism*

ObjectiveTo analyze the feasibility， reliability and validity of the disability assessment for dementia scale for the elderly. MethodsA total of 290 dementia patients from 17 survey sites in 13 districts and counties of Chengdu were enrolled by convenient sampling method， and they were assessed using demographic data inventory， Mini-Mental State Examination （MMSE）， Neuropsychiatric Inventory （NPI）， Physical Self-Maintenance Scale （PSMS） and disability assessment for dementia scale for the elderly. Cronbach's α coefficient， Spearman-Brown coefficient， Guttman split-half coefficient and test-retest reliability were used to evaluate the internal consistency of above scales. Criterion-related validity of the scale was analyzed based on MMSE， NPI and PSMS. ResultsA total of 276 patients （95.17%） completed valid questionnaires. The intraclass correlation coefficient of the total score and each dimension were between 0.828~0.976， the Spearman-Brown coefficient were between 0.790~0.917， the Guttman split-half coefficient were between 0.812~0.857， and the Cronbach’s α coefficient were between 0.737~0.886. The cognitive function dimension score was positively correlated with the MMSE score （r=0.948， P<0.01）， the mental behavior symptom dimension score was positively correlated with the NPI score （r=0.893， P<0.01）， and the daily living ability dimension score was positively correlated with the PSMS score （r=0.997， P<0.01）. The dimensions scores were positively correlated with the total score of the scale （r=0.634~0.841， P<0.05）. ConclusionDisability of dementia assessment scale has good feasibility， reliability and validity， which is a reliable tool to assess senile dementia and disability.

Objective:To comprehensively analyze the prognostic prediction value of RNA binding protein, transcription factor gene expression and immune infiltration in hepatocellular carcinoma (HCC).Methods:Common gene sets associated with RNA-binding proteins and transcription factors were screened in TCGA ( n=365) , GSE54236 ( n=78) and GSE14520 ( n=221) datasets. Univariate Cox regression was used for primary screening. The survival regression model was constructed by LASSO-Cox. And a complex index [CIRT=(score-min)/max] was calculated. According to the median of CIRT, the HCC patients were divided into CIRT high group ( n=182) and CIRT low group ( n=182). The differences of prognosis, immune infiltration between the two groups were analyzed. Results:Of 37 prognostically relevant RNA binding protein and transcription factor genes were identified. The prognosis prediction model based on seven selected genes was determined by stepwise regression. Patients in the CIRT high group exhibited a lower percentage of macrophages in M1 ( P=0.032), macrophages in M2 ( P=0.009), resting mast cell ( P<0.001), activated NK cells ( P=0.007), and resting memory CD4 + T cells ( P<0.001), while patients in the CIRT low group showed a lower level of resting dendritic cells ( P=0.048), macrophages in M0 ( P<0.001), neutrophils ( P=0.049), follicular helper T cells ( P=0.004) and regulatory T cells ( P=0.001). GSEA analysis has shown that CIRT high groups were highly enriched in cell cycle, DNA repair pathways in TCGA and GSE14520. In the TCGA cohort, the CIRT low group had better overall survival than the CIRT high group. Analysis of 5-year follow-up data in the TCGA cohort showed that CIRT had a good predictive value for long-term survival of patients with liver cancer (area under receiver operating characteristic curve was 0.71). Conclusion:A novel prognostic index and classifier based on RNA-binding protein expression, transcription factors and immune expression profiles were developed and cross-cohort validated. CIRT could be used as an independent predictor.

Objective:To explore the predictive value of complement and coagulation indicators in sepsis related acute kidney injury (AKI).Methods:Clinical data of 217 patients with sepsis admitted to the Department of Internal Medicine and Intensive Care Unit of Affiliated Hospital of Jiangnan University from January 2018 to June 2019 were retrospectively analyzed. All patients were divided into sepsis with AKI group and without AKI group. Laboratory indicators of all patients were collected, including complement C 3, complement C 4, activated partial thrombin time (APTT), prothrombin time (PT), international normalized ratio (INR), D-dimer, procalcitonin(PCT), etc. logistic regression analysis was used to explore the risk factors of sepsis related AKI. Receiver operating characteristic curve (ROC) was used to evaluate the predictive value of independent risk factors. Results:Among 217 patients, 120 patients developed sepsis related AKI and 97 patients didn′t. PCT, lactic acid, PT, APTT, INR and D-dimer in AKI patients were significantly higher than those without AKI ( P<0.01). Complement C 3 and complement C 4 were significantly lower in AKI group ( P<0.01). Multivariate logistic regression analysis suggested that blood pressure<90/60 mmHg (1 mmHg=0.133 kPa)( OR=3.705, 95% CI 1.536-8.934, P=0.004), increased lactic acid ( OR=1.479, 95% CI 1.089-2.008, P=0.012), decreased complement C 3 ( OR=0.027, 95% CI 0.005-0.152, P<0.001) and prolonged APTT ( OR=1.090, 95% CI 1.047-1.137, P<0.001)were independent risk factors predicting AKI. The area under the ROC curve (AUC) of these multivariates were 0.741 (95% CI 0.675-0.807), 0.798 (95% CI 0.732-0.864), 0.712 (95% CI 0.643-0.781) and 0.716 (95% CI 0.648-0.783) respectively. The relevant sensitivity was 57.5%, 80.8%, 87.5%, 59.2%, and the specificity was 90.7%, 75.3%, 51.5%, 77.3%, respectively. The AUC of the combined four indicators was 0.880 (95 %CI 0.835-0.926) with the sensitivity 75.0% and the specificity 90.7%. Conclusion:The low level of complement C 3 and prolonged APTT predict sepsis related AKI, and the predictive value can be enhanced if hypotension and hyperlactacidemia are added.

OBJECTIVE： To prepare puerarin microemulsion with phase Ⅰ metabolic regulation （R-PR-ME） and to study pharmacokinetic characteristics of rats in vivo. METHODS： R-PR-ME and Puerarin microemulsion without metabolic regulation （NR-PR-ME） were prepared by Shah method. Pseudo-ternary phase diagram was used to optimize microemulsion formula using drug loading amount as index. The particle size and PDI of microemulsion were characterized by using a laser particle size analyzer. Rats were used as animal models， and HPLC method was used to determine the blood concentration of puerarin before and 5， 10， 15， 20， 30， 45， 60， 90， 120， 180， 240， 360， 480， 600 min after intragastric administration of R-PR-ME， NR-PR-ME and puerarin suspension （PR-SP） at puerarin dosage of 120 mg/kg. The pharmacokinetic parameters were calculated by using DAS 2.0 software. SPSS 19.0 software was used for statistical analysis. The relative bioavailability of R-PR-ME was calculated with NR-PR-ME as reference preparation. RESULTS： The formula of R-PR-ME included that oleoyl polyoxyl-6 glyserides （oil phase）-polysorbate 20 （emulsifier）-glycerides （co-emulsifier） mass ratio of 2 ∶ 4 ∶ 4； drug-loading amount of 67.50 mg/g， particle size was （22.59±0.53） nm （n＝3） and PDI was 0.182±0.017 （n＝3）. The formula of NR-PR-ME included that soybean oil （oil phase）-polysorbate 80 （emulsifier）- glycerol （co-emulsifier） mass ratio of 1 ∶ 4.5 ∶ 4.5， drug-loading amount of 61.32 mg/g， particle size of （15.45±1.06） nm（n＝3） and PDI of 0.156±0.012 （n＝3）. Pharmacokinetic parameters of R-PR-ME， NR-PR-ME and PR-SP included that AUC0-600 min were （134.187±37.152）， （65.145±18.762） and （49.623±12.143） μg·min/mL； cmax were （1.316±0.306）， （1.082±0.294） and （0.425±0.106） μg/mL； MRT were （155.068±33.204）， （100.264±27.683）， （60.524±14.086） min； t1/2β were （365.880±101.250）， （283.280±80.940）， （80.063±21.189） min （n＝6）， respectively. Compared with PR-SP， AUC0-600 min， cmax， MRT and t1/2β of R-PR-ME and NR-PR-ME were increased significantly （P＜0.05 or P＜0.01）. Compared with NR-PR-ME， AUC0-600 min， MRT and  t1/2β of R-PR-ME were more higher （P＜0.05）. The relative bioavailability of of R-PR-ME was 205.98％. CONCLUSIONS： R-PR-ME is prepared successfully with high drug-loading amount， and can significantly increase the bioavailability of puerarin in rats， compared with PR-SP and NR-PR-ME.

Objective To analyze the clinical and pathological features of chronic hepatitis B (CHB) patients with hepatic steatosis.Methods Clinical and pathological data of 841 patients with CHB who underwent liver biopsy in Zhejiang Provincial People’s Hospital during September 2015 to September 2018 were retrospectively reviewed.One hundred and thirty five gender and age-matched pairs of steatosis and non-steatosis patients entered the analysis.Multivariable Logistic regression and rank sum test were used to analyze the clinical features and risk factors of hepatic steatosis in CHB patients .Spearman correlation test was used to analyze the correlation between hepatic steatosis and HBV DNA , hepatic inflammation and fibrosis status.Results Logistic regression analysis showed that overweight ／obesity ( χ2 ＝3.947, OR ＝1.436, 95%CI 1.005-2.051, P＜0.05) and hyperlipidemia (χ2 ＝4.277,OR＝1.803,95%CI 1.031-3.151, P＜0.05) were the risk factors for hepatic steatosis in CHB patients.There was no correlation of hepatic steatosis with serum HBeAg and HBV DNA levels (Z＝-1.762,r＝-0.011, both P＞0.05). However, hepatic steatosis was negatively correlated with inflammatory grade and fibrosis grade of the liver (r＝-0.146 and -0.192, both P＜0.05).Conclusions Overweight／obesity and hyperlipidemia are associated with steatosis in CHB patients.Hepatic steatosis may not aggravate the degree of liver inflammation and fibrosis in CHB patients.

The annual congress of Japan Surgical Society is a famous academic event in the field of surgery,and the participants can learn from the latest research results of all the major surgical disciplines.The authors selected topics of the ll8th annual congress in 2018,including the latest research results and progresses of laparoscopic hepatectony,liver transplantation,extrahepatic bile duct carcinoma and pancreatic surgery.The purpose of this study is to provide new information and reference for optimizing the diagnosis and treatment of hepatobiliary and pancreatic diseases.