OBJECTIVE To evaluate the long-term cost-effectiveness of canagliflozin or semaglutide in patients with type 2 diabetes mellitus（T2DM）poorly controlled with metformin. METHODS Based on the perspective of China’s health system， a Markov model was used to calculate the long-term costs and utilities of canagliflozin or semaglutide combined with metformin for T2DM patients in China for 30 years based on the data from SUSTAIN 8 study. The incremental cost-effectiveness ratio（ICER） and incremental net monetary benefit （INMB） were calculated using one time the 2024 per capita gross domestic product（GDP） as the willingness-to-pay（WTP） threshold. One-way sensitivity analysis， probability sensitivity analysis and scenario analysis were conducted to confirm the stability of the conclusions. RESULTS Compared with canagliflozin + metformin， ICER of semaglutide combined with metformin was 260 485.67 yuan/quality-adjusted life year （QALY），which was higher than the WTP threshold set in this study （95 749 yuan/QALY），and the corresponding INMB was －61 576.24 yuan，indicating that the canagliflozin + metformin regimen was more cost-effective. The cost of diabetes without complications treatment in the semaglutide + metformin group had the greatest influence on INMB，but changes in parameters within the selected range did not drive decision reversal. With the increasing of WTP threshold，the economic acceptability of semaglutide + metformin regimen increased. Under the current WTP threshold，the annual cost of semaglutide should be reduced by 42.95% to make the semaglutide + metformin regimen more cost- effective. CONCLUSIONS From the perspective of China’s health system， canagliflozin + metformin is more cost-effective than semaglutide + metformin for T2DM patients yueru. with poor glycemic control with metformin alone.

ObjectiveTo analyze the epidemiological characteristics of long COVID and to investigate its main influencing factors by examining individuals infected with SARS-CoV-2 between March and June 2022 in two communities in Shanghai, to lay the foundation for further research on the mechanism and clinical treatment of long COVID, and to provide the basis for the development of inexpensive, convenient, and feasible prevention and intervention strategies. MethodsA cross-sectional study was conducted, enrolling 6 410 individuals infected with SARS-CoV-2. Data were collected through a questionnaire survey. The incidence and common symptoms of long COVID were analyzed, along with their associations with demographic characteristics, medical history, and behavioral factors. A logistic regression model was used to identify the major factors associated with the development of long COVID symptoms. ResultsThe overall incidence rate of long COVID among the study population was 13.9%. The most commonly reported symptoms included fatigue (65.1%), attention disorders (23.1%), and cough (16.9%). The analysis showed that having underlying chronic diseases (OR=2.580, 95%CI: 2.165‒3.074), a history of allergies (OR=1.418, 95%CI: 1.003‒1.971), current smoking (OR=1.461, 95%CI: 1.013‒2.079), ever smoking (OR=2.462, 95%CI: 1.687‒3.551), a greater number of symptoms during the acute phase [1 symptom (OR=1.778, 95%CI: 1.459‒2.162), 2 symptoms (OR=2.749, 95%CI: 2.209‒3.409), ≥3 symptoms (OR=7.792, 95%CI: 6.333‒9.593)] and aggravated symptoms during the acute phase (OR=1.082, 95%CI: 1.070‒1.094) were factors associated with a higher risk of developing long COVID symptoms. Additionally, individuals who had consumed alcohol in the past year (OR=1.914, 95%CI: 1.344‒2.684) were more prone to objective long COVID symptoms. Among individuals under 50 years of age, females (OR=1.427, 95%CI: 1.052‒1.943) were more likely to develop objective long COVID symptoms. ConclusionThis study has identified the diversity of long COVID symptoms, which involve multiple organs and systems, including fatigue, attention disorders, cough, and joint pain. It has also revealed associations between long COVID and various demographic factors (e.g., age, gender), personal medical history (e.g., underlying chronic diseases, history of allergies), acute-phase characteristics (e.g., number and severity of symptoms), and behavioral factors (e.g., smoking, alcohol consumption). These findings highlight the need for further research and ongoing surveillance of long COVID and may inform the development of more targeted health management strategies for specific populations.

OBJECTIVE To evaluate the safety， efficacy， and cost-effectiveness of sodium-glucose co-transporter 2 （SGLT-2） inhibitors for treating type 2 diabetes mellitus （T2DM）. METHODS Retrieved databases such as PubMed， Cochrane Library， Embase， CNKI， as well as relevant health technology assessment （HTA） official websites， HTA reports， systematic review/meta- analysis and pharmacoeconomic studies about SGLT-2 inhibitors （including 12 types such as canagliflozin， dapagliflozin， and empagliflozin） in the treatment of T2DM were collected from the inception to January 28， 2025. After literature screening data extraction and quality assessment， a descriptive analysis was conducted on the results of the included studies. RESULTS A total of 38 articles were included， comprising 30 systematic reviews/meta-analyses， 4 pharmacoeconomic studies， and 4 HTA reports. In terms of effectiveness， most research results showed that canagliflozin was effective in controlling blood glucose， reducing body weight， and lowering blood pressure compared to other SGLT-2 inhibitors， while empagliflozin could effectively reduce all-cause mortality. In terms of safety， compared with other SGLT-2 inhibitors， empagliflozin has a lower overall adverse event rate and cardiovascular death risk， canagliflozin presented a higher risk of hypoglycemia， and dapagliflozin had a higher risk of urinary tract infections. In terms of economics， empagliflozin possessed greater economic advantages over both dapagliflozin and canagliflozin， while canagliflozin offered more benefits than dapagliflozin. CONCLUSIONS The selection of SGLT-2 inhibitors for the treatment of T2DM should be individualized. Canagliflozin is recommended for patients with high cardiovascular risk. Empagliflozin boasts the best overall safety profile. Dapagliflozin should be used with caution in patients at high risk of urinary tract infections. Based on foreign economic evidence， empagliflozin has economic advantages. In the future， drug economic studies under the Chinese health system need to be conducted.

ObjectiveTo analyze the epidemiological characteristics and influencing factors of SARS-CoV-2 reinfection by conducting follow-up investigations among community residents who experienced their first SARS-CoV-2 infection between March and June 2022, so as to provide a scientific basis for predicting future epidemic trends and adjusting prevention and control strategies. MethodsA cohort study was conducted in Xuhui District, Shanghai. A total of 1 208 individuals with a documented primary SARS-CoV-2 infection between March and June 2022 were enrolled and followed-up longitudinally. Data were collected using structured questionnaire surveys to assess the reinfection rate, incidence density, and clinical manifestations of SARS-CoV-2 reinfection. A logistic regression model was used to analyze the influencing factors of SARS-CoV-2 reinfection. ResultsA total of 497 SARS-CoV-2 reinfection cases were observed among the 1 208 research subjects, with a reinfection rate of 41.14% and an incidence density of 0.63 cases per 1 000 person-days. The cumulative reinfection rates at 6, 9, 12, 15, and 18 months following the initial infection were 0.08%, 15.31%, 19.04%, 33.53%, and 38.25%, respectively. Compared with the primary infection, reinfection was more likely to be symptomatic, with a greater severity of fever, dry cough, sore throat, and runny nose. Being female, younger age, and symptom duration ≥7 days during the primary infection were identified as influencing factors for SARS-CoV-2 reinfection, while a higher socioeconomic status can reduce the risk of SARS-CoV-2 reinfection. ConclusionSARS-CoV-2 reinfection is relatively common and often symptomatic. Age, gender, income level, and the duration of symptoms during the primary infection are identified as infuencing factors for SARS-CoV-2 reinfection. Continuous monitoring of reinfection in the population is recommended, along with the development of effective strategies to mitigate the impact of reinfection.

[Objective]To investigate the association between screen content and the frequency of screen exposure at the age of one and a half years and hyperactive behavior in preschool,and to explore how the association is affected by the interaction between outdoor activities and screen behaviors,which could provide theoretical basis and feasible solutions for the prevention and intervention of behavioral problems in childhoood.[Methods]The survey was conducted from June 2022 to June 2023 in Huicheng District,Huizhou (China) stratified by whole cluster sampling methods. Parents and teachers of 5648 children in 61 kindergartens were sampled for questionnaire surveys. The Conners Teacher Rating Scale (TRS) was used to investigate hyperactive behavior. A self-administered questionnaire was used to investigate basic demographic information of children,screen content,frequency of screen exposure and outdoor activities at the age of one and a half years. Multivariate logistic regression was used to explore the association between video screen behavior and hyperactive behavior and its interaction with outdoor activities by controlling for covariates such as children's age,gender,and parental education.[Results]Result showed the overall prevalence of 3.2％ for hyperactive behavior,2.1％ for conduct problems,2.1％ for hyperactivity problems,1.3％ for inattention-passivity problems,and 0.9％ for hyperactivity index. After adjusting for confounding factors,multiple logistic regression analysis showed that screen exposure of "two to four times a week" at one and a half years old was associated with an increased detection rate of hyperactive behaviors in preschool children,with an estimated ORs (95％ CI) of 1.682 (1.141,2.480). Daily screen exposure was associated with increased detection rates of hyperactive behavior,conduct problems,hyperactivity issues,inattention-passivity problems,and hyperactivity index in pre-school age. The estimated ORs (95％ CI) were 2.136 (1.218,3.746),2.321 (1.185,4.546),2.300 (1.208,4.380),2.776 (1.267,6.085) and 3.640 (1.525,8.687),respectively. But the above associations were not found in children who were engaged in daily outdoor activities at the age of one and a half years (P value for interaction<0.001). No association was found between screen content and hyperactive behavior (P>0.05).[Conclusions]Frequency of screen exposure in early childhood is significantly associated with hyperactive behavior problems in preschool,and outdoor activities could weaken the correlation between high-frequency screen exposure and hyperactive behavior,suggesting that parents and schools should prioritize scientifically guiding children's video viewing behavior and outdoor activities,ensuring a well-arranged daily life,to lay a good foundation for the healthy development of children's behavior.

To explore the level of hsa_circ_0001588 in plasma of patients with gastric cancer and to analyze the relationship between the plasma level of hsa_circ_0001588 and clinical characteristic,toll like receptors 4(TLR4)and T lymphocyte subsets,this study enrolled 124 gastric cancer patients who were treated in our hospital from March 2021 to May 2022 as study group.Simultaneously,another 130 patients diagnosed with superficial gastritis by gastroscopy were selected as benign group,and 130 healthy individuals were set as control group.The plasma hsa_circ_0001588 level was measured by quantitative real-time polymerase chain reaction,the plasma level of TLR4 was detected by double antibody sandwich ELISA,and plasma CD3+,CD4+,CD8+,and CD4+/CD8+levels were tested by Wmini5146 flow cytometry.Then the diagnostic efficacy of plasma hsa_circ_0001588,TLR4 and T lymphocytes for gastric cancer was evaluated,and the correlation between the level of hsa_circ_0001588 in plasma and the level of TLR4 and T lymphocytes in gastric cancer patients was verified.Data showed that the levels of hsa_circ_0001588,TLR4 and CD8+in plasma of study group were higher than those of benign group and control group,while the levels of CD3+,CD4+and CD4+/CD8+were lower than those of benign group and control group(P＜0.05).Furthermore,a decrease was observed in plasma hsa_circ_0001588 level in gastric cancer patients after surgery compared to baseline data.Among gastric cancer patients of different clinicopathological characteristics,patients with high clinical stage,high degree of infiltration,poor differentiation and distant metastasis had high plasma hsa_circ_0001588 level(P＜0.05).Diagnostic analysis denoted that the separate test of plasma hsa_circ_0001588,TLR4 and T-lymphocytes all had good diagnostic efficacy for gastric cancer,while combined test showed the highest diagnostic efficacy.Comparison among gastric cancer patients revealed that high hsa_circ_0001588 expression group had lower expression of CD3+,CD4+and CD4+/CD8+,and higher expression of TLR4 and CD8+than those of low hsa_circ_0001588 expression group(P＜0.05),suggesting that plasma hsa_circ_0001588 level was negatively correlated with CD3+,CD4+and CD4+/CD8+expression,but positively correlated with TLR4 and CD8+.In conclusion,the level of hsa_circ_0001588 in plasma is elevated in patients with gastric cancer,and it has a negative correlation with CD3+,CD4+and CD4+/CD8+,but positive correlation with TLR4 and CD8+expression.

17q12 microdeletion syndrome is a rare genetic disease,commonly characterized by newly occurring mutations,which can cause abnormalities of the urinary and reproductive tract,diabetes mellitus,neurological and psychiatric disorders and mild deformities.This article reports a case of 17q12 microdeletion syndrome with CRYBB2 gene missense mutation,combined with menstrual abnormalities,multiple cysts in both kidneys,hypomagnesemia,hyperuricemia,small pancreatic morphology and low pancreatic enzyme levels.

Immune checkpoint inhibitor(ICI)associated diabetes mellitus(DM)a rare specific type of diabetes,usually developed after the treatment of programmed cell death protein 1(PD-1)inhibitor or programmed cell death ligand 1(PD-L1)inhibitor.We reported 4 cases of DM after ICI use.These patients had a subacute onset,6 to 17 months after the first use of the drug,with diabetic autoantibodies negative.Pancreas atrophy was observed in one of them.All of the patients received treatment of insulin.

Objective:To study the role and specific mechanisms of glucose-6-phosphate dehydrogenase (G6PD), a key enzyme for glycometabolism, mediated reduction stress in arsenic-induced malignant transformation of cells.Methods:Immortalized human skin keratinocyte-forming cells (HaCaT cells) were treated with sodium arsenite (NaAsO 2) at a concentration of 0.0 (control group) and 1.0 μmol/L (arsenic group), and malignant transformation indicators were tested using cell growth kinetics assay, cell scratch assay, and soft agar colony formation assay. At different stages of arsenic treatment (0, 1, 7, 14, 21, 28, 35 passages of cells), the effects of NaAsO 2 on glycometabolism in HaCaT cells were determined using corresponding reagent kits and Western blot, including glucose-6-phosphate (G6P), lactate, acetyl CoA, G6PD levels, as well as protein expression levels of hexokinase 2 (HK-2), 6-phosphofructose-2-kinase/fructose-2, 6-diphosphatase 3 (PFKFB3), pyruvate dehydrogenase kinase 1 (PDK1), 6-phosphoglucose dehydrogenase (PGD), and G6PD. Mitochondria were extracted, and the effects of NaAsO 2 on HaCaT cells and mitochondrial redox [reduced nicotinamide adenine dinucleotide phosphate (NADPH)/nicotinamide adenine dinucleotide phosphate (NADP +) ratio, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio] were determined using corresponding reagent kits. The effect of G6PD on reduction stress and NaAsO 2-induced malignant transformation of HaCaT cells was determined using small interfering RNA (siRNA) intervention method. Results:Compared 1.0 μmol/L NaAsO 2-cultured HaCaT cells up to 35 generations (T-HaCaT cells) with matching passage 0.0 μmol/L NaAsO 2-cultured HaCaT cells [(33.797 ± 0.280) h, 0.177 ± 0.015, 13.667 ± 2.625], the multiplication time [(24.042 ± 0.479) h] was shorter ( t = 30.45, P < 0.001), the cell migration rate (0.396 ± 0.039) was higher ( t = 9.08, P < 0.001), and the number of colonies formed in soft agar (73.667 ± 4.450) was higher ( t = 20.11, P < 0.001). Compared with matching passage control group cells and 0 generation of the same group, G6P level in the arsenic group was higher at passages 1, 7, 14, 21, 28 and 35 ( P < 0.05), lactate and G6PD levels were higher at passages 14, 21, 28 and 35 ( P < 0.05), acetyl CoA level was lower at passages 21, 28 and 35 ( P < 0.05), and protein expression levels of HK-2, PFKFB3, PDK1, PGD, and G6PD were higher at passages 7, 14, 21, 28 and 35 ( P < 0.05). The NADPH/NADP + ratio of cells was higher at passages 1, 14, 21, 28 and 35 ( P < 0.05), GSH/GSSG ratio was higher at passages 21, 28 and 35 ( P < 0.05). The ratio of mitochondrial NADPH/NADP + was higher at passages 1, 7, 21, 28 and 35 ( P < 0.05), the GSH/GSSG ratio was higher at passages 1, 7, 14, 21, 28 and 35 ( P < 0.05). G6PD expression was silenced by siRNA in T-HaCaT cells, compared with the T-HaCaT con siRNA-treated group, the T-HaCaT G6PD siRNA-treated group had lower NADPH/NADP + and GSH/GSSG ratios in both cells and mitochondria ( P < 0.05), longer cell multiplication time, lower cell migration rate, and fewer soft agar colonies ( P < 0.05). Conclusion:During the malignant transformation of HaCaT cells induced by NaAsO 2, G6PD and other enzymes related to glycometabolism are activated, leading to reprogramming of glycometabolism, resulting in an imbalance of cell redox homeostasis and enhanced reduction stress in cells and mitochondria, thereby promoting NaAsO 2 induced malignant transformation of HaCaT cells.

Objective:To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency.Methods:This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively.Results:The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 μmol/L) was found in all patients, and decreased to 20-70 μmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders.Conclusions:Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.