OBJECTIVES: To evaluate the clinical value of next-generation sequencing (NGS) in neonatal disease screening, particularly its advantages when combined with tandem mass spectrometry (MS/MS). METHODS: A prospective study was conducted involving blood samples from 1 999 neonates born at the Shenzhen Guangming District People's Hospital, between May and August 2021. All samples were initially screened using MS/MS and fluorescence immunoassay, followed by NGS to detect high-frequency variation sites in 135 related pathogenic genes. Suspected positive variants were validated using Sanger sequencing or multiplex ligation-dependent probe amplification in family studies. RESULTS: No confirmed positive cases were found in the MS/MS analysis of the 1 999 neonates. Genetic screening identified 58 positive cases (2.90%), 732 carriers of pathogenic genes (36.62%), and 1 209 negative cases (60.48%). One case of neonatal intrahepatic cholestasis was diagnosed (0.05%, 1/1 999). Fluorescence immunoassay identified 39 cases of glucose-6-phosphate dehydrogenase (G6PD) deficiency (1.95%, 39/1 999), while genetic screening identified 43 cases of G6PD deficiency (2.15%, 43/1 999). The fluorescence immunoassay also detected 6 cases of hyperthyrotropinemia (0.30%, 6/1 999), all of whom carried DUOX2 gene variants. The top ten pathogenic gene carrier rates were G6PD (12.8%), DUOX2 (8.7%), HBB (8.2%), ATP7B (6.6%), GJB2 (5.7%), SLC26A4 (5.6%), PAH (5.6%), ACADSB (4.6%), SLC25A13 (4.2%), and SLC22A5 (4.1%). CONCLUSIONS NGS can serve as an effective complement to MS/MS, significantly improving the detection rate of inherited metabolic disorders in neonates. When combined with family validation, it enables precise diagnosis, particularly demonstrating complementary advantages in screening for monogenic diseases such as G6PD deficiency.
Humans ; Infant, Newborn ; High-Throughput Nucleotide Sequencing/methods* ; Neonatal Screening/methods* ; Tandem Mass Spectrometry ; Prospective Studies ; Female ; Male ; Infant, Newborn, Diseases/diagnosis* ; Genetic Testing

OBJECTIVE: To explore the displacement and pressure distribution of American Chiropractic in a model of third lumbar syndrome based on finite element analysis. METHODS: On March 2021, CT and MRI images of a 23-year-old male patient with right third lumbar syndrome were selected. A 3D stl model was established using Mimics and CATIA, and the data was imported into Hypermesh, Abaqus & ANSYS. The elastic modulus and Poisson's ratio of the affected side material were adjusted to establish its finite element model. Based on the comparison of the operating positions and routines of the American Chiropractic and the lumbar spine oblique pull method, but with differences in the focus and direction of force, the experimental group simulated the American Chiropractic with the healthy side (left side) lying position of the model. The upper endplate of L₃ and the lower part below L₃ twisted accordingly with the body position, we applied a vertical forward thrust of 246 N to the plane formed by the L₄, L₅ spinous processes and L₄ upper articular processes;The control group simulates the oblique pull method of the lumbar spine, requiring the model to lie on the healthy side (left side), fix the upper endplate of L₄, and perform a horizontal rotation along the longitudinal axis of L₃ vertebral body. At this time, the contact force in the upward direction is also set to 246 N. Compare the displacement and stress differences between the L₁-L₅ intervertebral bodies, intervertebral discs, articular processes, and transverse process muscles in two intervention models. RESULTS: ① Under safe load conditions, a test force of 246 N was applied to the model, and the maximum vertebral displacement occurred on the right side of the L₃ vertebral body (1.197 mm) after manual intervention in the control group. The vertebral displacement between L₁-L₅ induced by manual intervention in the experimental group was smaller than that of the control group's manual intervention (P<0.05). ② The maximum vertebral body stress occurred on the right side of the L₃ vertebral body after manual intervention in the control group (98.425 MPa). The stress on each vertebral body formed by the experimental group's manual intervention was lower than that of the control group's manual intervention (P<0.05). ③The maximum intervertebral disc stress occurred on the right side of the L_2,3 intervertebral disc (6.282 MPa) after manual intervention in the control group. ④ The maximum joint process stress occurred on the right side of the L₄ upper joint process after manual intervention in the experimental group (1.587 MPa). The joint process stress on the left side below L₁ and the left side above and below L₂ induced by manual intervention in the experimental group was lower than that of the control group (P<0.05). ⑤The maximum stress on the intertransverse process muscle was observed at the right lateral L₃ process end (31.960 MPa) of L_3,4 in the control group after manual intervention. The stress on the L_2,3 and L_4,5 segments of the intertransverse process muscle induced by manual intervention in the experimental group was lower than that of the control group's manual intervention (P<0.05). CONCLUSION The mechanical feedback of the L₁-L₅ vertebral body, the lower left side of the articular process L₁, the upper and lower left side of the articular process L₂, and the L_2,3 and L_4,5 segments of the transverse process muscle in the model indicates that performing American Chiropractic for the treatment of third lumbar transverse process syndrome can accurately hit the target pain point and allow the patient's tissue to form a low stress and low tension state after manual operation, thereby reducing the possibility of tissue damage caused by hypertonia after intervertebral joint movement, making it relatively safe. The application of American Chiropractic will be a new supplement to the traditional treatment plan for third lumbar transverse process syndrome.
Humans ; Finite Element Analysis ; Male ; Lumbar Vertebrae/physiopathology* ; Biomechanical Phenomena ; Young Adult ; Manipulation, Chiropractic ; Adult ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P＜0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P＜0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P＜0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P＜0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

This report evaluates the preliminary outcomes of a "six-in-one" integrated cough and asthma center developed under a dual-contract physician model at the Changfeng Community Health Service Center in Putuo District, Shanghai. By combining the efforts of family doctors and medical specialists, the center integrated six core functions-clinical treatment, prevention, nursing, rehabilitation, pharmacy, and nutrition-into a seamless management system covering screening, diagnosis, therapy, and follow-up. Supported by specialist guidance and teaching clinics, the model significantly enhanced comprehensive respiratory disease management capabilities within the community setting. The initiative not only improved patient health outcomes but also strengthened multidisciplinary collaboration and resource efficiency, offering a replicable example for improving chronic disease management in primary care through integrated and coordinated service delivery.

Objective:To analyze the association between osteoporosis and the risk for Alzheimer's disease (AD).Methods:A total of 471 922 study subjects were selected from the UK Biobank database, including 12 818 osteoporosis cases and 459 104 controls. Cox proportional hazard regression model and competing risk model were used to evaluate the association between osteoporosis and AD after adjusting confounding factors. Furthermore, a Mendelian randomization (MR) study was conducted by using the data of two published genome-wide association studies, and 1 050 highly relevant single nucleotide polymorphisms were identified from the bone mineral density data as instrumental variables. The association between bone mineral density and the risk for AD was evaluated by using inverse variance weighted method, MR-Egger regression, and weighted median estimator method. Additionally, sensitivity analyses were performed.Results:After adjusting for confounders, no significant association between osteoporosis and an increased risk for AD was found in the cohort study (Cox proportional hazard regression model analysis: HR=1.10, 95% CI: 0.78-1.56, P=0.588). The MR analysis revealed no association between bone mineral density and the risk for AD (inverse-variance weighted: OR=1.03, 95% CI: 0.98-1.09, P=0.252), and the results remained robust in multiple sensitivity analyses. Conclusion:The study result does not support the association between osteoporosis and risk for AD.

Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

Objective:To analyze the association between osteoporosis and the risk for Alzheimer's disease (AD).Methods:A total of 471 922 study subjects were selected from the UK Biobank database, including 12 818 osteoporosis cases and 459 104 controls. Cox proportional hazard regression model and competing risk model were used to evaluate the association between osteoporosis and AD after adjusting confounding factors. Furthermore, a Mendelian randomization (MR) study was conducted by using the data of two published genome-wide association studies, and 1 050 highly relevant single nucleotide polymorphisms were identified from the bone mineral density data as instrumental variables. The association between bone mineral density and the risk for AD was evaluated by using inverse variance weighted method, MR-Egger regression, and weighted median estimator method. Additionally, sensitivity analyses were performed.Results:After adjusting for confounders, no significant association between osteoporosis and an increased risk for AD was found in the cohort study (Cox proportional hazard regression model analysis: HR=1.10, 95% CI: 0.78-1.56, P=0.588). The MR analysis revealed no association between bone mineral density and the risk for AD (inverse-variance weighted: OR=1.03, 95% CI: 0.98-1.09, P=0.252), and the results remained robust in multiple sensitivity analyses. Conclusion:The study result does not support the association between osteoporosis and risk for AD.

Aim To investigate the expression levels of cytoplasmic FMR1-interacting protein-1(CYFIP1)in colorectal cancer and assess the impact of CYFIP1 interaction on the proliferation and apoptosis of colorec-tal cancer cell HT29,along with its potential mecha-nisms.Methods Immunohistochemistry was em-ployed to assess CYFIP1 expression in 32 colorectal cancer tissues and adjacent tissues.Coexpressed genes were identified using the GEPIA2 website to predict potential correlations and binding sites.Following the construction of a siRNA-CYFIP1,alterations in cell proliferation,apoptosis,and levels of apoptosis-related proteins were evaluated through CCK-8 assay,Hoechst 33342/PI double staining assay,and Western blot a-nalysis,respectively.Results The immunohisto-chemical findings revealed a significantly elevated level of CYFIP1 expression in colorectal cancer tissues com-pared to paracancer tissues(P＜0.05).The expres-sion of CYFIP1 did not show any correlation with age and gender,but exhibited associations with TNM stage and lymph node metastasis(P＜0.05).A conserved TP53 binding site was predicted in the 3kbps DNA re-gion upstream of the CYFIP1 gene using GEPIA2,JASPAR databases,and rVista 2.0 promoter prediction software.Following transfection of HT29 cells with siRNA-CYFIP1,the clonogenesis and proliferation of cells significantly decreased(P＜0.05).Additional-ly,the levels of cleaved caspase-3 were elevated,while the expression levels of caspase-3 and Bcl-2 were reduced after transfection with siRNA-CYFIP1(P＜0.05),which might be related to the interaction be-tween CYFIP1 and TP53.Conclusions The upregu-lation of CYFIP1 in colorectal cancer is associated with TNM stage and lymph node metastasis.Upon silen-cing,CYFIP1 demonstrates the ability to suppress pro-liferation in HT29 cells and modulate the expression of apoptotic proteins.

Objective To explore the mechanism of Bufei Jiedu Granules in the treatment of methicillin-resistant Staphylococcus aureus(MRSA)chronic infection using network pharmacology;To verify it through animal experiments.Methods Active components and potential targets in Bufei Jiedu Granules were screened through the TCMSP database,and genes related to MRSA infection were retrieved through GeneCards,OMIM,DisGeNET,TTD,DrugBank and PharmGKB databases.The STRING database was employed to construct a protein-protein interaction network on common targets,and GO and KEGG pathway enrichment analysis were conducted to identify key signaling pathways for Bufei Jiedu Granules treatment of MRSA infection.The effects of Bufei Jiedu Granules on bacterial load and pathological changes in the lung,liver and kidney of MRSA chronic infection mice models were evaluated through WT and T/B immune cell deficient Rag2-/-mouse animal experiments.The mRNA expressions of inflammatory factors(IFN-γ,IL-10)and immune checkpoints(PD1,TIM3)were detected.Results Totally 54 active components related to Bufei Jiedu Granules were selected,and 50 potential targets related to MRSA infection were identified.118 signaling pathways significantly associated with MRSA infection were identified through GO and KEGG pathway enrichment analysis,in which the JAK-STAT signaling pathway,Th17 cell differentiation,and PD-L1 expression and PD-1 checkpoint pathway were closely related to cell activation and T cell differentiation.Animal experimental results indicated that Bufei Jiedu Granules could effectively reduce the bacterial load in organs and ameliorate the pathological damage in the chronic MRSA infection mouse model,increase the mRNA expression of IFN-γ in the lung tissue,and decrease the mRNA expressions of IL-10,PD1 and TIM3.Conclusion Bufei Jiedu Granules has the characteristics of multi-component and multi-target in the treatment of MRSA infection,and may be involved in adaptive immune activation to effectively treat chronic MRSA infection.

This report evaluates the preliminary outcomes of a "six-in-one" integrated cough and asthma center developed under a dual-contract physician model at the Changfeng Community Health Service Center in Putuo District, Shanghai. By combining the efforts of family doctors and medical specialists, the center integrated six core functions-clinical treatment, prevention, nursing, rehabilitation, pharmacy, and nutrition-into a seamless management system covering screening, diagnosis, therapy, and follow-up. Supported by specialist guidance and teaching clinics, the model significantly enhanced comprehensive respiratory disease management capabilities within the community setting. The initiative not only improved patient health outcomes but also strengthened multidisciplinary collaboration and resource efficiency, offering a replicable example for improving chronic disease management in primary care through integrated and coordinated service delivery.