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.

Objective To understand the application effect of early screening scale and behavioral intervention effect in children with autism spectrum disorder (ASD). Methods A total of 348 children with suspected ASD were selected and evaluated using the Modified Checklist for Autism in Toddlers (M-CHAT) and Autism Behavior Checklist (ABC). The evaluation results were compared with those from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). Children enrolled were given Early start Denver model (ESDM) intervention. The evaluation results of Gesell Developmental Scale and Autism Treatment Evaluation Checklist (ATEC) scores were compared before and after intervention. Results The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating ASD in children aged 1-3 years were 89.53%, 90.70%, 89.92% and 0.78. The corresponding values of ABC were 78.49%, 81.40%, 79.46% and 0.56. The sensitivity, specificity, accuracy and Kappa value of M-CHAT for evaluating children aged >3-6 years were 87.30%, 77.78%, 84.44% and 0.64. The corresponding values of ABC were 85.71%, 77.78%, 83.33% and 0.62. The sensitivity and accuracy of M-CHAT were higher than ABC for evaluating ASD in children aged 1-3 years (P<0.05). There were no significant differences in sensitivity, specificity and accuracy between M-CHAT and ABC for evaluating ASD in children aged 3-6 years (P>0.05). After intervention, development quotients (DQ) of personal-social aspects, adaptability, language, gross motor, and fine motor of children with ASD were higher than those before intervention (P<0.05). ATEC scores for language, behavior, sensation, and social contact of children with ASD were lower than those before intervention (P<0.05). Conclusion M-CHAT and ABC both can be used for early screening of ASD in children, especially M-CHAT. Early behavioral intervention can effectively improve the condition and developmental level of children with ASD.

Salivary gland mucosa-associated lymphoid tissue lymphoma (SGML) is a subvariety of marginal zone B-cells that occurs outside of mucosal lymph nodes. The onset of SGML is closely related to immunity, chronic infections, and genetic factors, such as lymphoepithelial sialadenitis (LESA) and Sjogren’s syndrome (SS), as well as Helicobacter pylori, hepatitis C virus, Epstein-Barr virus, and human T-lymphocytic virus. The most common site of SGML is the parotid gland, followed by the submandibular gland, small salivary gland, and sublingual gland. SGML is more common in middle-aged and elderly women, and patients often have autoimmune diseases, such as Sjogren’s syndrome or rheumatoid arthritis. SGML can be diagnosed through clinical manifestations, imaging, and histopathology, but histopathological biopsy remains the main method for confirming SGML. Traditional treatment methods include anti-infective therapy and surgery combined with radiation or chemotherapy. In recent years, some new treatment methods, such as Bruton tyrosine kinase (BTK) inhibitors and programmed cell death protein-1 (PD-1) inhibitors, have been effective against recurrent or refractory SGML, but more clinical trial data are needed to support them. At present, the optimal treatment for SGML is not yet clear. Individualized treatment plans should be developed based on the location, staging, clinical characteristics, and overall health status of the patient. SGML progresses slowly and has a relatively good overall prognosis; however, the disease is recurrent, the treatment cycle is long, the recurrence rate is higher than that of other mucosa-associated lymphoid tissue lymphomas, and SGML may also cause other serious complications. Therefore, regular observation and follow-up are very important for its prognosis. This article reviews the etiology, diagnosis, treatment, and prognosis of SGML, with the aim of providing a reference for clinical diagnosis and treatment, and thus improve the survival rate of patients with SGML.

OBJECTIVE To evaluate the safety， efficacy and economics of dapagliflozin in the treatment of type 2 diabetes mellitus （T2DM） combined with cardiovascular disease （CVD）， and provide an evidence-based basis for clinical treatment decisions. METHODS PubMed， the Cochrane Library， Embase， Web of Science， CNKI， Wanfang data， VIP， SinoMed and official websites of domestic and foreign health technology assessment （HTA） organizations were systematically searched. HTA reports， systematic evaluations/meta-analyses， and pharmacoeconomic studies of dapagliflozin in the treatment of T2DM combined with CVD were searched. After data extraction and quality assessment， the results of the included studies were analyzed descriptively. RESULTS A total of 13 papers were included， of which 10 were systematic evaluations/meta-analyses and 3 were pharmacoeconomic studies. In terms of efficacy， dapagliflozin significantly reduced patients’ glycosylated hemoglobin， body weight， body mass index and blood pressure levels compared with placebo， without increasing the risk of all-cause mortality； in terms of safety， dapagliflozin did not increase the risk of overall adverse events， major adverse cardiovascular events， cardiovascular death， hospitalization for heart failure， myocardial infarction， stroke， bone fracture and renal hypoplasia； in terms of economics， the UK and Chinese studies found an economic advantage for dapagliflozin， the Thai study did not. CONCLUSIONS Dagliflozin has better efficacy and safety in the treatment of T2DM combined with CVD， and its economic findings are still controversial in different countries， with economic advantages in the context of current Chinese healthcare policies and drug prices.

Objective:To analyze the survival of pneumoconiosis patients in Guangzhou from 1958 to 2018, explore the factors affecting the survival of pneumoconiosis, and provide scientific basis for formulating the guidelines and policies for treatment and assistance of pneumoconiosis.Methods:From July 2019 to January 2020, 1194 cases of occupational pneumoconiosis patients diagnosed by institutions qualified for pneumoconiosis diagnosis in Guangzhou from June 1, 1958 to December 31, 2018 were studied. Excluding 258 patients who lacked survival data, 936 patients were included in the pneumoconiosis survival analysis. Life table method was used to estimate the survival rate, Kaplan-Meier method was used to draw the survival curve, log-rank test was used to compare the groups, and Cox proportional risk regression model was used to analyze the influencing factors of survival.Results:The 10, 20 and 30 years cumulative survival rates of pneumoconiosis patients in Guangzhou were 62.8%, 35.2% and 15.4%, respectively. The median survival time was 19.4 years. log-rank test showed that there were statistically significant differences in the survival curves of pneumoconiosis patients between group without tuberculosis and group with tuberculosis ( P<0.001), and there were statistically significant differences among different stages and categories of pneumoconiosis ( P<0.001). Age of exposure to dust ( HR=1.03, 95% CI: 1.01-1.05), age of diagnosis ( HR=1.02, 95% CI: 1.00-1.04), combined pulmonary tuberculosis ( HR=1.46, 95% CI: 1.18-1.81), stage of pneumoconiosis (stage Ⅲ vs. stage Ⅰ, HR=2.26, 95% CI: 1.47-3.48) and categories of pneumoconiosis (fibrogenic mineral dust pneumoconiosis and metallogenic pneumoconiosis, HR=2.45, 95% CI: 1.61-3.74; non-fibrogenic mineral pneumoconiosis and metallogenic pneumoconiosis, HR=2.67, 95% CI: 1.47-4.87; mixed pneumoconiosis and metallogenic pneumoconiosis, HR=2.25, 95% CI: 1.11-4.56) were the factors affecting the survival time of pneumoconiosis patients ( P<0.05) . Conclusion:Pulmonary tuberculosis may increase the risk of death in patients with pneumoconiosis. Mineral dust pneumoconiosis, mixed pneumoconiosis and stage Ⅲ pneumoconiosis may also have higher risk of death.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

We report a case of a male patient who developed persistent fever and central nervous system symptoms after eating raw snails for 10 days. The patient was diagnosed with Angiostrongyliasis depended on the clinical presentation, epidemiological history, and etiological results. The patient recovered after receiving albendazole anthelmintic and dexamethasone anti-inflammatory therapy. This article incorporates literature review to sort out the diagnosis and treatment of this patient, in order to provide feasible reference for clinicians.

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.

Objective:To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies.Methods:This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months.Results:Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work.Conclusions:Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

Objective:To analyze changes in energy metabolism and oxylipin metabolism in macrophages after stimulation by Mycobacterium marinum ( M. marinum) using targeted metabolomics, and to provide insights into the mechanisms underlying the immune defense by macrophages against M. marinum infections. Methods:Mouse bone marrow-derived macrophages were obtained from the bilateral femurs of mice, and cultured cells were divided into two groups: the active M. marinum group and the inactivated M. marinum group. Bacterial suspensions were prepared using M. marinum clinical isolates; the active M. marinum group was treated with live M. marinum suspensions for 12 hours, while the inactivated M. marinum group with inactivated M. marinum suspensions for 12 hours. Cell morphology was observed through microscopy, and cell length was measured. Cell lysates collected from both groups were subjected to liquid chromatography-tandem mass spectrometry analysis to detect energy and oxylipin metabolites. A t-test was utilized to compare the lengths of macrophages between the two groups, while principal component analysis and orthogonal partial least squares-discriminant analysis were conducted to identify differential metabolites. Results:Under the microscope, macrophages in the active M. marinum group formed more granuloma-like cell aggregates compared with those in the inactivated M. marinum group; the macrophages were significantly thinner and longer in the inactivated M. marinum group (439.52 ± 91.67 μm) than in the active M. marinum group (289.96 ± 70.11 μm, P < 0.001). Principal component analysis and orthogonal partial least squares-discriminant analysis of energy metabolism and oxylipin metabolism in macrophages demonstrated good separation between the two groups. As for the energy metabolism, a total of 12 differential metabolites were identified, with the amino acid metabolism showing the most significant changes. Specifically, there was a significant increase in the content of L-citrulline, while the content of L-leucine and serine decreased. As for the oxylipin metabolism, 20 differential metabolites were identified, with the arachidonic acid metabolism showing the most significant changes. Conclusions:Macrophages stimulated by live M. marinum exhibited altered amino acid metabolism and arachidonic acid metabolism compared with those stimulated by inactivated M. marinum, characterized by an increase in L-citrulline content, a decrease in L-leucine and serine levels, and alterations in arachidonic acid content.