Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

Psoriasis arthritis (PsA) is a chronic inflammatory musculoskeletal disease intricately linked to psoriasis (PsO), with a multifaceted etiology encompassing genetic, environmental, and immunological factors. Characterized by complex clinical manifestations, PsA often follows a protracted course with a propensity for relapses, potentially culminating in joint deformity and disability. The condition is further complicated by associated comorbidities such as inflammatory bowel disease, uveitis, cardiovascular disease, and metabolic syndrome, which significantly diminish patients′ quality of life. Early detection and screening of PsA are crucial for its management and prevention of adverse outcomes. However, in China, there is a notable deficiency in the recognition and early diagnosis of PsA, with missed or incorrect diagnoses being relatively common. The consensus comprises four overarching statements and sixteen detailed recommendations, with the overarching goal of enhancing the early diagnosis and treatment of PsA by clinical physicians, thereby improving patient outcomes.

OBJECTIVE: To explore the clinical features and genetic etiology of a child with Hoyeraal-Hreidarsson syndrome (HHS). METHODS: A child with HHS diagnosed at the Affiliated Hospital of Jining Medical University due to "developmental delay and anaemia" on April 27, 2024 was selected as the study subject. Clinical data of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members. Whole-exome sequencing was carried out, and candidate variant was verified by Sanger sequencing of his family members and bioinformatics analysis using CASAVA v1.8.2. The pathogenicity of the candidate variant was rated according to the Standards and Guidelines for the Interpretation of Sequence Variants released by the American College of Medical Genetics and Genomics (ACMG). Relevant literature on HHS cases reported in China was reviewed to analyze the clinical and genetic characteristics. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: 2024-10-C003). RESULTS: The child, a 7-month-old boy, had mainly manifested with growth retardation, developmental delay, microcephaly, cerebellar hypoplasia, immunodeficiency and bone marrow failure. Routine blood test indicated pancytopenia. The immunological workup showed reduction of B cells, NK cells and immunoglobulins. Cranial MRI demonstrated the volume of bilateral cerebellar hemispheres and brainstem and corpus callosum was small. Whole-exome sequencing revealed that he has harbored a hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene. Sanger sequencing showed that his mother and two sisters have carried the same variant. Based on the ACMG guidelines, the variant was predicted to be likely pathogenic (PM1+PM4+PS4_Supporting+PM2_Supporting). Four relevant literature were retrieved, which has involved 8 HHS cases. Together with the patient from this study, they have consisted of 8 males and 1 females. The most common symptoms of the 9 patients were blood system abnormalities and developmental delay. All patients had shown cerebellar dysplasia and anemia/erythrocytopenia. Among them, 3 cases have harbored TINF2 gene variants, and 6 cases had harbored DKC1 gene variants. The c.103_105del variant has not been reported in China previously. CONCLUSION The hemizygous c.103_105del (p.Glu35del) variant of the DKC1 gene probably underlay the disease in this child. Above finding has expanded the mutational and phenotypic spectra of the DKC1 gene, and has facilitated early diagnosis of HHS in this child.
Humans ; Infant ; Male ; Cell Cycle Proteins/genetics* ; Dyskeratosis Congenita/genetics* ; Exome Sequencing ; Fetal Growth Retardation/genetics* ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Mutation ; Nuclear Proteins/genetics* ; X-Linked Intellectual Disability/genetics*

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.

Objective:To analyze the access pathway,regulatory process and payment of digital therapies in various countries,so as to provide references and materials for the development of digital therapies in China.Methods:By using literature research method,text analy-sis method and comparative analysis method,it combed domestic and international policies related to digital therapy,described the policy support status of digital therapy in each country,and comparatively analyzed the differences in the definition,regulation and payment of digi-tal therapy products in each country.Results:The US,Germany,UK,Japan,South Korea,and other countries have introduced frame-works to define,categorize,and approve digital therapies,distinguishing them from other digital health products.China also includes digital therapies in its national planning,with Hainan leading in supportive policies.Regulatory processes slightly differ by country but generally in-volve determining risk levels and conducting comparative analysis.Currently,only the UK,Germany,Japan,etc.,offer health insurance reimbursement for digital therapies.Conclusion:Internationally,there are mature policy frameworks and experiences for digital therapies,and China can learn from the international experiences,while exploring the path of digital therapies with Chinese characteristics and continue to improve the policies of digital therapies and to meet the needs of patients.

Objective:To explore protective effect and possible mechanism of electroacupuncture at Zusanli combined with Yupingfengsan Jiawei on rats with acute lung injury.Methods:A total of 50 Wistar rats were randomly divided into control group,model group,Yupingfengsan Jiawei group(YPFSJW),electroacupuncture group(EA),acupuncture-medicine combination group(EA+YPFSJW),and acute lung injury model rats were constructed by intraperitoneal injection of lipopolysaccharide except control group.Lung tissue injury,oxidative damage and inflammatory factors were detected by wet/dry weight ratio,HE staining,TUNEL staining,myeloperoxidase(MPO),malondialdehyde(MDA),superoxide dismutase(SOD)and ELISA.qRT-PCR,immunohistochemical staining and Western blot were used to detect mRNA and related protein expressions.Results:Compared with control group,structure of lung tissue in model group was significantly damaged,alveolar wall was thickened,accompanied by pathological damage such as congestion and inflammatory cell infiltration,wet/dry ratio of lung tissue,apoptosis rate,inflammatory factors,oxidative damage level and mRNA expressions were significantly increased,and protein expressions of TLR4,MyD88,p-p65 and p-IκBα were significantly increased(P<0.05);compared with model group,Yupingfengsan Jiawei group,electroacupuncture group and acupuncture-medicine combination group had less inflammatory cell infiltration and congestion in lung tissue,wet/dry weight ratio of lung tissue,cell apopto-sis rate,inflammatory factors,oxidative damage levels and mRNA expressions were decreased,and TLR4,MyD88,p-p65,p-IκBαprotein expressions were decreased(P<0.05);compared with Yupingfengsan Jiawei group and electroacupuncture group,lung tissue alveolar structure of combined acupuncture and medicine group was relatively complete and clear,wet/dry weight ratio of lung tissue,cell apoptosis rate,inflammatory factors,oxidative damage levels and mRNA expressions were decreased,TLR4,MyD88,p-p65,p-IκBα protein expressions were decreased(P<0.05).Conclusion:Electroacupuncture combined with Yupingfengsan Jiawei can reduce acute lung injury in rats,whose mechanism may be related to regulation of protein levels related to NF-κB signaling pathway.

Objective:To analyze the access pathway,regulatory process and payment of digital therapies in various countries,so as to provide references and materials for the development of digital therapies in China.Methods:By using literature research method,text analy-sis method and comparative analysis method,it combed domestic and international policies related to digital therapy,described the policy support status of digital therapy in each country,and comparatively analyzed the differences in the definition,regulation and payment of digi-tal therapy products in each country.Results:The US,Germany,UK,Japan,South Korea,and other countries have introduced frame-works to define,categorize,and approve digital therapies,distinguishing them from other digital health products.China also includes digital therapies in its national planning,with Hainan leading in supportive policies.Regulatory processes slightly differ by country but generally in-volve determining risk levels and conducting comparative analysis.Currently,only the UK,Germany,Japan,etc.,offer health insurance reimbursement for digital therapies.Conclusion:Internationally,there are mature policy frameworks and experiences for digital therapies,and China can learn from the international experiences,while exploring the path of digital therapies with Chinese characteristics and continue to improve the policies of digital therapies and to meet the needs of patients.

Objective:To explore protective effect and possible mechanism of electroacupuncture at Zusanli combined with Yupingfengsan Jiawei on rats with acute lung injury.Methods:A total of 50 Wistar rats were randomly divided into control group,model group,Yupingfengsan Jiawei group(YPFSJW),electroacupuncture group(EA),acupuncture-medicine combination group(EA+YPFSJW),and acute lung injury model rats were constructed by intraperitoneal injection of lipopolysaccharide except control group.Lung tissue injury,oxidative damage and inflammatory factors were detected by wet/dry weight ratio,HE staining,TUNEL staining,myeloperoxidase(MPO),malondialdehyde(MDA),superoxide dismutase(SOD)and ELISA.qRT-PCR,immunohistochemical staining and Western blot were used to detect mRNA and related protein expressions.Results:Compared with control group,structure of lung tissue in model group was significantly damaged,alveolar wall was thickened,accompanied by pathological damage such as congestion and inflammatory cell infiltration,wet/dry ratio of lung tissue,apoptosis rate,inflammatory factors,oxidative damage level and mRNA expressions were significantly increased,and protein expressions of TLR4,MyD88,p-p65 and p-IκBα were significantly increased(P<0.05);compared with model group,Yupingfengsan Jiawei group,electroacupuncture group and acupuncture-medicine combination group had less inflammatory cell infiltration and congestion in lung tissue,wet/dry weight ratio of lung tissue,cell apopto-sis rate,inflammatory factors,oxidative damage levels and mRNA expressions were decreased,and TLR4,MyD88,p-p65,p-IκBαprotein expressions were decreased(P<0.05);compared with Yupingfengsan Jiawei group and electroacupuncture group,lung tissue alveolar structure of combined acupuncture and medicine group was relatively complete and clear,wet/dry weight ratio of lung tissue,cell apoptosis rate,inflammatory factors,oxidative damage levels and mRNA expressions were decreased,TLR4,MyD88,p-p65,p-IκBα protein expressions were decreased(P<0.05).Conclusion:Electroacupuncture combined with Yupingfengsan Jiawei can reduce acute lung injury in rats,whose mechanism may be related to regulation of protein levels related to NF-κB signaling pathway.

Psoriasis arthritis (PsA) is a chronic inflammatory musculoskeletal disease intricately linked to psoriasis (PsO), with a multifaceted etiology encompassing genetic, environmental, and immunological factors. Characterized by complex clinical manifestations, PsA often follows a protracted course with a propensity for relapses, potentially culminating in joint deformity and disability. The condition is further complicated by associated comorbidities such as inflammatory bowel disease, uveitis, cardiovascular disease, and metabolic syndrome, which significantly diminish patients′ quality of life. Early detection and screening of PsA are crucial for its management and prevention of adverse outcomes. However, in China, there is a notable deficiency in the recognition and early diagnosis of PsA, with missed or incorrect diagnoses being relatively common. The consensus comprises four overarching statements and sixteen detailed recommendations, with the overarching goal of enhancing the early diagnosis and treatment of PsA by clinical physicians, thereby improving patient outcomes.

Objective:To establish graded forecast models of pollen concentration in spring and summer-autumn in northern China, based on long-term data of pollen and allergic rhinitis (AR) medical visits in 8 cities of northern China.Methods:Pollen concentration and the characteristics of AR patients from 8 cities of northern China, including Beijing, Baotou, Hohhot, Xi′an, Xining, Cangzhou, Liaocheng and Zibo, were analyzed. Spearman′s correlation was used to examine the relationship between pollen concentration and daily AR patient visits. A pollen concentration grading was establish, and a pollen forecast model was created using the eXtreme gradient boosting (XGBoost) algorithm. The model incorporated meteorological factors and the 3-day moving average of pollen concentrations.Results:The spring pollen period started early and lasted long in Beijing and Xi ′an, while the summer-autumn pollen period started earlier and persisted longer in Xining, Baotou and Hohhot. During summer-autumn pollen period, and the spring period in most cities (except Baotou and Cangzhou), average daily patient visits were significantly higher than those in non-pollen periods. A strong correlation was observed between daily AR patient visits and the 3-day moving average of pollen concentrations in both the spring and summer-autumn periods across all cities. Based on the correlation, a pollen concentration grading standard of northern China was established. The accuracy evaluation of pollen concentration prediction model showed that the percentage of forecasts with either completely accurate or within one level difference exceeded 91% in spring and 95% in summer-autumn. The most important predictive variable in the model was the pollen level from previous day, followed by the temperature and humidity.Conclusion:The grading prediction model for pollen concentration provides guidance for AR patients in term of travel, early defense and treatment, as well as the determining medication schedules for clinical drug research and specific immunotherapy.