Rheumatoid arthritis belongs to arthralgia syndrome in the theory of traditional Chinese medicine， and cold-dampness obstruction syndrome and dampness-heat obstruction syndrome are core syndromes and main syndrome differentiation types of this disease. Fine therapeutic effects have been obtained in the long-term clinical practice of many famous traditional Chinese medicine practitioners following the syndrome differentiation and treatment based on the guiding principles of cold and heat. To adapt to the clinical diagnosis practice of combining disease differentiation and syndrome differentiation， and to better carry out basic research on integrated Chinese and Western medicine and preclinical study on new traditional Chinese medicines， Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-Dampness Obstruction Syndrome and Dampness-Heat Obstruction Syndrome （hereinafter referred to as the Guidelines） were compiled by our research group， in cooperation with the renowned experts in research fields including traditional Chinese medicine， clinical medicine， zoology and evidence-based medicine， which provide a meaningful reference for scientific research， teaching and clinical applications. The compilation process of the Guidelines was guided by the theory of disease and syndrome integration and the principles of "evidence takes the main place， consensus plays an auxiliary role， and experience serves as the reference". Based on the comprehensive evaluation of pathogenesis homology， behavioral phenotypic consistency， and drug treatment predictability compared between animal models and human diseases， by the nominal group method， "recommendations" were formed for recommendations supported by evidence， and "consensus recommendations" were formed for recommendations not supported by evidence. Guidelines were formed involving content such as animal types， arthritis modeling methods， external stimulation conditions， and modeling assessment indicators during the establishment of the animal models of rheumatoid arthritis with cold-dampness obstruction syndrome and dampness-heat obstruction syndrome. The Guidelines are applicable for the disease and syndrome research on rheumatoid arthritis， investigation of therapeutic mechanisms， and development of new traditional Chinese medicine. The Guidelines also provide a reference for the establishment of guidelines on other types of diseases and syndromes combined with animal models to further promote the modernization of traditional Chinese medicine research and its integration with international academic development.

The Guidelines for Establishing Animal Models of Rheumatoid Arthritis with Cold-dampness Obstruction Syndrome and Dampness-heat Obstruction Syndrome （hereinafter referred to as the Guidelines） （No. T/CACM1567-2024） was published by Chinese Association of Chinese Medicine on January 11， 2024. To assist researchers and medical workers in understanding and applying the Guidelines more accurately， and also to provide reference and assistance for the establishment of guidelines on other types of diseases and syndromes combined with animal models， this paper made a declaration of the workflow， technological links， development references， promotion of its application and after-effect evaluation of the Guidelines that has been made according to the requirements of "Draft Group Standard of the Standardization Office of the Chinese Association of Traditional Chinese Medicine".

Objective To compare the clinical effect of first-line chemotherapy containing oxaliplatin on left and right colon cancer.Methods A total of 120 patients with colon cancer admitted to Second Affiliated Hospital of Shanghai University from January 2020 to January 2024 were selected and divided into left colon cancer group(60 cases)and right colon cancer group(60 cases)according to tumor location.Both groups were treated with first-line chemotherapy containing oxaliplatin for 2 cycles.Disease control rate,serum tumor markers,serum inflammatory factors,cancer-causing symptom scores,quality of life and incidence of adverse reactions were compared between two groups.Results After treatment,disease control rate in left colon cancer group was significantly higher than that in right colon cancer group(x2=22.224,P＜0.00 1).The levels of serum carcinoembryonic antigen,carbohydrate antigen 125,carbohydrate antigen 153,C-reactive protein and interleukin-6 of left colon cancer group were lower than those of right colon cancer group(P＜0.05).The scores of cancer-related pain and fatigue of left colon cancer group were lower than those of right colon cancer group(P＜0.05).The quality of life in left colon cancer group was better than that in right colon cancer group(P＜0.05).Conclusion First-line chemotherapy containing oxaliplatin has better short-term efficacy in patients with left colon cancer,with better control of tumor progression,and can improre clinical symptoms and quality of life.

Objective To analyze the hepatitis B virus infection with extreme reduction of cholinesterase(CHE)not caused by liver synthesis dysfunction,and to explore its clinical significance.Methods The clinical data of 2 rare cases hospitalized in the 3rd people's hospital of Kunming in July 2021 and February 2022,including liver function,coagulation function,hepatitis B markers,hepatitis B virus volume,and whole exon sequencing,were collected and analyzed,and literature was reviewed.Results CHE was extremely reduced in 2 patients with HBV infection,liver synthesis function was good,and whole exon sequencing showed the presence of butyrylcholinesterase(BCHE)gene mutation.Conclusion The extremely low CHE in this case is not due to liver function disorder.Exon sequencing detected mutations in the BCHE gene in two patients.Screening for BCHE mutations may be necessary in patients with extremely low cholinesterase levels not due to liver dysfunction.

ObjectiveTo investigate the pollution level of deoxynivalenol （DON） in wheat flour and its products sold in Shanghai， and to assess the health risks of DON exposure for residents in Shanghai who ingested DON from wheat flour and its products. MethodsRisk monitoring data of DON in wheat flour and its products sold in Shanghai from 2017 to 2021 were combined with the consumption data of wheat flour and its products by Shanghai residents. A probabilistic assessment method was used to assess dietary exposure of DON in wheat flour and its products. ResultsThe overall detection rate of DON in wheat flour and its products was 77.3% （1 041/1 347）， with a mean concentration of 226.3 μg·kg^-1， P₅₀ of 130.0 μg·kg^-1 and a maximum value of 3 080.0 μg·kg^-1. The mean daily exposure and 95th percentile daily exposure （by body weight） of DON from wheat flour and its products in Shanghai residents were 0.279 μg·kg^-1 and 1.146 μg·kg， accounting for 27.9% and 114.6% of the daily tolerable intake of DON TDI， 1 μg·kg， respectively. The probability assessment results indicated that 6.1% of the whole population in Shanghai had DON exposure exceeding the TDI value. Among them， 12.8% of the population aged 6 years old and below， 16.4% of the population aged between 7 and 17 years old， 3.9% of the population aged between 18 and 59 years old and 3.2% of the population aged 60 years old and above exceeded the TDI value for daily DON exposure through wheat flour and its products. ConclusionCertain populations in Shanghai may face certain health risks from daily DON intake wheat flour and its products. Special attention should be paid to the health risk of daily DON exposure through wheat flour and its products for individuals age below 18 years old .

ObjectiveTo assess the health risk of dietary exposure to nonylphenol in infants aged 0-36 months through infant formula in Shanghai. MethodsA monitoring of nonylphenol pollution in infant formula was conducted in 2022. A total of 90 samples were obtained from maternal and infant stores， supermarkets， and online stores in Shanghai. Based on the daily consumption data of infant formula， a point assessment method was used to assess the dietary exposure to nonylphenol in infant formula. ResultsThe prevalence of nonylphenol in infant formula retailed in Shanghai was 95.6% （86/90）. The amount of nonylphenol varied from non-detected to 22.70 μg·kg^-1， with the mean value of 8.47 μg·kg^-1 and the P₅₀ value of 7.77 μg·kg^-1. The mean daily nonylphenol exposure （estimated by body weight） from infant formula in infants aged 0-6 months， 7-12 months and 13-36 months in Shanghai was 0.091， 0.068 and 0.054 μg·kg^-1， respectively； furthermore， the P₉₅ value of daily exposure （by body weight） was 0.228， 0.152 and 0.119 μg·kg^-1， respectively. These amounts were much lower than the tolerable daily intake （TDI） of nonylphenol （by body weight 5 μg·kg^-1）. ConclusionThe health risk of daliy nonylphenol intake from infant formula remains low among infants aged 0-36 months in Shanghai.

Objective: To assess the effectiveness of online and offline myopia prevention and control health education interventions using wearable behavior monitoring tools for non myopic elementary school students,so as to provide evidence based medical support for public health practices. Methods: From May to June in 2021, two schools were selected within the same county in Jiangsu Province. School 1 conducted online and offline parental health education ( n =111), while school 2 exclusively conducted offline health education activities, representing the traditional intervention group ( n =122). Students from both schools underwent monitoring through wearable behavior tracking tools, with feedback reports provided (eye distance, eye duration, ambient light, and outdoor exposure time). Both schools relied on activities to carry out health education interventions, and organized the distribution of promotional materials and display boards. The intervention group also established WeChat groups to conduct online "Healthy Parents Action" (answering and providing feedback on health knowledge related to myopia prevention and control, myopia prevention and control, science popularization, etc. raised by parents). Evaluation criteria included myopia rates, post dilation refractive error, and axial length, with a tracking period of two years (from 2021 to 2023). Additionally, the study collected refractive parameters from non myopic students who did not participate in wearable tool monitoring in the 12 classes across the two schools. Results: The baseline results indicated that there were no significant differences between the two groups in terms of refractive parameters and wearable tool monitoring results (including screen time, viewing distance, outdoor exposure time, and homework light exposure)( t/Z/χ 2=1.94,1.17,0.58,0.40,0.80,0.69,0.32, P >0.05). After a two-year follow up, in the first and second year, the myopia rate of the online Healthy Parents Action group (11.4%, 29.7%) were lower than that of the traditional group (26.2%, 50.9%), and the degree of refractive change in the intervention group [0.63(0.38,1.19)D] was lower than that of the traditional group [0.91(0.40,1.50)D], and all the differences were statistically significant( χ 2/ Z =4.93，10.37，2.29， P <0.05). However, there were no significant differences ( P >0.05) in axial length changes between the two groups over the twoyear intervention period. Nevertheless, in the second year, the axial length change in the traditional group [0.35(0.20,0.65)mm] was lower than that in the natural observation group [0.55(0.30,0.75)mm], and this difference was statistically significant ( Z =1.92, P <0.05). Conclusions Online and offline myopia prevention and control health education can effectively reduce myopia rates. The intervention mode combining wearable behavior monitoring tools with online health education may have better effects, but further large sample and multi center studies are needed to provide additional evidence and confirmation.

Objective:To explore the predictive value of HACOR score [heart rate (H), acidosis (A), consciousness (C), oxygenation (O), and respiratory rate (R)] on the clinical outcome of non-invasive positive pressure ventilation in patients with pulmonary encephalopathy due to chronic obstructive pulmonary disease (COPD).Methods:A prospective study was conducted. The patients with COPD combined with pulmonary encephalopathy who were admitted to Henan Provincial People's Hospital from January 1, 2017 to June 1, 2021 and initially received non-invasive positive pressure ventilation were enrolled. Besides non-invasive positive pressure ventilation, standard medical treatments were delivered to these patients according to guidelines. The need for endotracheal intubation was judged as failure of non-invasive ventilation treatment. Early failure was defined as the need for endotracheal intubation within 48 hours of treatment, and late failure was defined as the need for endotracheal intubation 48 hours and later. The HACOR score at different time points after non-invasive ventilation, the length of intensive care unit (ICU) stay, the total length of hospital stay, and the clinical outcome were recorded. The above indexes of patients with non-invasive ventilation were compared between successful and failed groups. The receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive effect of HACOR score on the failure of non-invasive positive pressure ventilation in the treatment of COPD with pulmonary encephalopathy.Results:A total of 630 patients were evaluated, and 51 patients were enrolled, including 42 males (82.35%) and 9 females (17.65%), with a median age of 70.0 (62.0, 78.0) years old. Among the 51 patients, 36 patients (70.59%) were successfully treated with non-invasive ventilation and discharged from the hospital eventually, and 15 patients (29.41%) failed and switched to invasive ventilation, of which 10 patients (19.61%) were defined early failure, 5 patients (9.80%) were late failure. The length of ICU and the total length of hospital stay of the non-invasive ventilation successful group were significantly longer than those of the non-invasive ventilation failure group [length of ICU stay (days): 13.0 (10.0, 16.0) vs. 5.0 (3.0, 8.0), total length of hospital stay (days): 23.0 (12.0, 28.0) vs. 12.0 (9.0, 15.0), both P < 0.01]. The HACOR score of patients at 1-2 hours in the non-invasive ventilation failure group was significantly higher than that in the successful group [10.47 (6.00, 16.00) vs. 6.00 (3.25, 8.00), P < 0.05]. However, there was no significant difference in HACOR score before non-invasive ventilation and at 3-6 hours between the two groups. The ROC curve showed that the area under the ROC curve (AUC) of 1-2 hour HACOR score after non-invasive ventilation for predicting non-invasive ventilation failure in COPD patients with pulmonary encephalopathy was 0.686, and the 95% confidence interval (95% CI) was 0.504-0.868. When the best cut-off value was 10.50, the sensitivity was 60.03%, the specificity was 86.10%, positive predictive value was 91.23%, and negative predictive value was 47.21%. Conclusions:Non-invasive positive pressure ventilation could prevent 70.59% of COPD patients with pulmonary encephalopathy from intubation. HACOR score was valuable to predict non-invasive positive pressure ventilation failure in pulmonary encephalopathy patients due to COPD.

ObjectiveTo investigate chlorate contamination level in infant formula sold in Shanghai， and to evaluate the dietary exposure risk to infants in Shanghai. MethodsWith the risk monitoring data of chlorate in infant formula sold in Shanghai in 2020， combined with the dietary consumption data of infants， the dietary exposure of chlorate in infant formula was assessed via the point assessment method. ResultsIn 2020， the overall detection rate of chlorate in 120 infant formula samples was 98.3% （118/120）， the mean content was 124.5 μg⋅kg^-1， the 50 percentile value was 64.6 μg⋅kg^-1， and the maximum value was 1 475.0 μg⋅kg^-1. The mean and 95 percentile value of daily chlorate intake from infant formula for infants aged 0‒36 months in Shanghai were 1.10 and 1.84 μg⋅kg^-1， accounting for 36.7% and 61.3% of the tolerable daily intake （TDI） of chlorate （3μg⋅kg^-1）， respectively. The mean， 50 percentile value and 95 percentile value of daily chlorate exposure of infants in different month-age groups （0‒6 months， 6‒12 months， 12‒36 months） through infant formula were lower than the TDI value. ConclusionThe health risk of daily chlorate intake from infant formula for infants and young children aged 0‒36 months in Shanghai is at an acceptable level.

Cabozantinib, mainly targeting cMet and vascular endothelial growth factor receptor 2, is the second-line treatment for patients with advanced hepatocellular carcinoma (HCC). However, the lower response rate and resistance limit its enduring clinical benefit. In this study, we found that cMet-low HCC cells showed primary resistance to cMet inhibitors, and the combination of cabozantinib and mammalian target of rapamycin (mTOR) inhibitor, rapamycin, exhibited a synergistic inhibitory effect on the in vitro cell proliferation and in vivo tumor growth of these cells. Mechanically, the combination of rapamycin with cabozantinib resulted in the remarkable inhibition of AKT, extracellular signal-regulated protein kinases, mTOR, and common downstream signal molecules of receptor tyrosine kinases; decreased cyclin D1 expression; and induced cell cycle arrest. Meanwhile, rapamycin enhanced the inhibitory effects of cabozantinib on the migration and tubule formation of human umbilical vascular endothelial cells and human growth factor-induced invasion of cMet inhibitor-resistant HCC cells under hypoxia condition. These effects were further validated in xenograft models. In conclusion, our findings uncover a potential combination therapy of cabozantinib and rapamycin to combat cabozantinib-resistant HCC.
Anilides/pharmacology* ; Animals ; Carcinoma, Hepatocellular/drug therapy* ; Cell Line, Tumor ; Cell Proliferation ; Endothelial Cells/metabolism* ; Humans ; Liver Neoplasms/drug therapy* ; Pyridines/pharmacology* ; Sirolimus/pharmacology* ; Xenograft Model Antitumor Assays