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

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

Objective:To analyze the factors influencing recurrence after liver transplantation in patients with primary biliary cholangitis (PBC).Methods:Clinical data of 53 patients with PBC undergoing liver transplantation at the Department of General Surgery, Beijing Youan Hospital, Capital Medical University from August 2006 to January 2024 were retrospectively anaylyzed, including 11 males and 42 females, aged (55.1±7.9) years. Eight (15.1%) of the patients experienced recurrence within five years after liver transplantation. Univariate and multivariate logistic regression analyses were used to identify the factors influencing recurrence after transplantation. The receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of each variable for post-transplant recurrence.Results:Univariate logistic regression analysis showed that severe postoperative complications, positive anti-centromere antibodies, and postoperative CD4/CD45<0.4 were associated with recurrence after liver transplantation (all P<0.05). Further multivariate logistic regression analysis revealed that severe postoperative complications ( OR=23.183, 95% CI: 1.667-322.447, P=0.019), postoperative CD4/CD45<0.4 ( OR=9.272, 95% CI: 1.244-69.099, P=0.030), and positive anti-centromere antibodies ( OR=17.106, 95% CI: 1.381-211.878, P=0.027) were associated with a higher risk of recurrence after liver transplantation in patients with PBC. ROC curve analysis showed that the area under the curve for predicting recurrence after liver transplantation based on severe postoperative complications was 0.731 (95% CI: 0.539-0.922, P=0.039), with a sensitivity of 75.0% and a specificity of 71.1%. Conclusion:Severe postoperative complications, CD4/CD45 <0.4, and positive anti-centromere antibodies are risk factors for recurrence after liver transplantation in patients with PBC. Severe postoperative complications showed a good predictive efficacy for recurrence.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

ObjectiveTo evaluate the clinical efficacy of Maxing Loushi decoction in the treatment of acute exacerbation of chronic obstructive pulmonary disease （AECOPD） with phlegm turbidity obstructing lung syndrome， and to investigate its effects on inflammatory factors， immune function， and the programmed death-1（PD-1）/programmed death-ligand 1 （PD-L1） signaling pathway. MethodsA randomized controlled study was conducted， enrolling 90 hospitalized patients with AECOPD and phlegm turbidity obstructing lung syndrome in the Respiratory and Emergency Departments of Dongzhimen Hospital， Beijing University of Chinese Medicine， from April 2024 to December 2024. Patients were randomly assigned to a control group and an observation group using a random number table， with 45 patients in each group. The control group received conventional Western medical treatment， while the observation group received additional Maxing Loushi decoction for 14 days. Clinical efficacy， COPD Assessment Test （CAT） score， modified Medical Research Council Dyspnea Scale （mMRC）， 6-minute walk test （6MWT）， serum inflammatory factors， T lymphocyte subsets， and serum PD-1/PD-L1 levels were compared between the two groups before and after treatment. ResultsThe total clinical effective rate was 78.57% （33/42） in the control group and 95.35% （41/43） in the observation group， with the observation group showing significantly higher efficacy than that of the control group. The difference was statistically significant （χ² = 5.136， P<0.05）. After treatment， both groups showed significant reductions in CAT and mMRC scores （P<0.05， P<0.01） and significant increases in 6MWT compared to baseline （P<0.01）. The observation group demonstrated significantly greater improvements than the control group in this regard. Levels of inflammatory markers including C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）， monocyte chemoattractant protein-1（MCP-1）， and macrophage inflammatory protein-1α （MIP-1α） were significantly reduced in both groups （P<0.05， P<0.01）， with greater reductions in the observation group （P<0.05， P<0.01）. CD8⁺ levels were significantly reduced （P<0.01）， while CD3⁺， CD4⁺， and CD4⁺/CD8⁺ levels were significantly increased in both groups after treatment （P<0.05， P<0.01）， with more significant improvements observed in the observation group （P<0.05， P<0.01）. Serum PD-1 levels were reduced （P<0.05， P<0.01）， and PD-L1 levels were increased significantly in both groups after treatment （P<0.05， P<0.01）， with more pronounced changes in the observation group （P<0.05）. ConclusionMaxing Loushi decoction demonstrates definite therapeutic efficacy as an adjunctive treatment for patients with AECOPD and phlegm turbidity obstructing lung syndrome. It contributes to reducing serum inflammatory factors， improving immune function， and regulating the PD-1/PD-L1 signaling pathway.

Objective: To investigate the changing trends for associations of anxiety and depressive symptoms with smartphone addiction among middle school students, so as to provide a scientific basis for preventing smartphone addiction in middle school students. Methods: From 2022 to 2023, a method of combining convenient sampling with cluster sampling was used to select 8 923 middle school students from 27 junior high schools and 3 senior high schools in a district of Shenzhen City between September 2022 (baseline, T1) and September 2023 (follow up, T2). The Smartphone Addiction Scale-Short Version (SAS-SV), Patients Health Questionnaire-9 Item (PHQ-9), and Generalized Anxiety Disorder 7-item Scale (GAD-7) were administered to assess smartphone addiction, anxiety and depressive symptoms. Mixed effects models were used to analyze the association of anxiety and depressive symptoms with smartphone addiction among middle school students. Results: From September 2022 to September 2023, the reported prevalence of smartphone addiction increased from 24.22% to 25.25% ( χ 2=45.71); and smartphone addiction scores [ 24.00 (16.00, 32.00),25.00(16.00, 33.00)], anxiety symptom scores [2.00(0.00, 7.00),3.00(0.00, 7.00)] and depressive symptom scores[3.00(0.00, 8.00),5.00(0.00, 9.00)] all significantly increased ( Z =-17.43, -42.38, -41.57) (all P <0.05). There were statistically significant difference in the distribution of anxiety and depression symptom levels among middle school students in 2022 and 2023 ( χ 2=85.15, 106.85, both P <0.05). After adjusting for covariates such as age, gender and family background, mixed effects models revealed dose response associations of anxiety and depressive symptoms with smartphone addiction among middle school students:mild anxiety symptom( OR =3.22), moderate to severe anxiety symptom ( OR =5.36), mild depressive symptom ( OR =3.32) and moderate to severe depressive symptom ( OR =6.13) were significantly associated with higher risks of smartphone addiction (all P <0.05). Interaction effect analysis found that co existing anxiety and depressive symptoms synergistically increased addiction risk by 5.60 times ( OR =5.60) compared to the asymptomatic group, with 32% of the combined risk attributable to their interaction ( S=1.64, AP =0.32)(both P < 0.05 ). Conclusions Anxiety and depressive symptoms are significantly associated with smartphone addiction, exhibiting a synergistic effect. Attention should be paid to emotional issues and smartphone addiction among middle school students.

Objective To investigate the biomechanical differences in plantar pressure,postural stability,and plantar Visual Analogue Scale(VAS)scores between normal feet and unilateral/bilat-eral pes cavus,reveal their unique neuromechanical compensation mechanisms,and construct a sta-bility early warning model based on the minimum center of pressure(COP)trajectory classification.Methods A total of 70 patients with pes cavus from December 2023 to October 2024 were selected as study subjects,including 33 patients in the unilateral pes cavus group and 37 patients in the bilat-eral pes cavus group.During the same period,32 normal feet were included as normal foot group.A flat-panel plantar pressure testing system was used to collect dynamic plantar pressure data and COP trajectories from three groups at a self-selected walking speed.There were no statistically significant differences in baseline data such as age,gender,and body mass index among the three groups(P＞0.05).One-way analysis of variance and the Wilcoxon rank-sum test were used to compare the differences in maximum pressure,contact area,VAS scores,and the 95％confidence ellipse area of the COP among the three groups in 10 plantar regions.Results Patients with pes cavus exhibited lower peak pressure in the MF region compared to normal feet,while higher peak pressure in the M2,M3,and MH regions.Patients with bilateral pes cavus showed lower peak pressure in the T1 region compared to normal feet,and patients with unilateral pes cavus had lower peak pressure in the LH region compared to the normal group(P＜0.05).The plantar contact area in patients with pes cavus was reduced in the T1,M2,M3,M4,MF,and MH regions compared to normal feet(P＜0.05).The 95％confidence ellipse area of the COP was larger in both the bilateral and uni-lateral pes cavus groups compared to the normal foot group(P＜0.001).Unilateral pes cavus pres-ented a specific lateral COP drift(amplitude of 3 to 4 cm),which is a biomechanical manifestation of compensatory eversion of the unaffected foot.Patients with bilateral pes cavus exhibited a"bimod-al oscillation"trajectory(amplitude of 6 to 8 cm),suggesting possible vestibular-spinal regulatory dysfunction and the poorest postural stability.In the pes cavus group,there was a significant in-crease in pressure in the M2,M3,and MH regions,with peak pressures exceeding 190 kPa in pa-tients with bilateral pes cavus,which was highly correlated with plantar pain and could serve as a pain early warning threshold.Conclusion Unilateral and bilateral pes cavus exhibit significantly different neuromechanical compensation patterns.The classification based on the"lateral drift"and"bimodal oscillation"characteristics of the COP trajectory can serve as a stability early warning indi-cator for assessing fall risk.Decompression interventions targeting the key pressure regions of M2,M3,and MH(such as customized orthotic insoles)are the core strategies for alleviating pain and optimizing dynamic gait stability.

Cysteine protease inhibitor SN(Cystatin SN , CST1), a member of the type 2 cystatins superfamily, regulates tumor biological activities by modulating cysteine protease activity. CST1 is abnormally expressed in digestive system neoplasms, such as esophageal cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, and pancreatic cancer. CST1 influences tumor cell proliferation, migration, and epithelial-mesenchymal transition (EMT) through signaling pathways including Wnt, STAT3, and PI3K-AKT. Its expression levels significantly correlated with tumor stage, metastasis, and patient prognosis, suggesting its potiential as a novel biomarker for early diagnosis, therapeutic evaluation, and prognosis in digestive system neoplasms. This article systematically reviews the molecular characteristics of CST1, its mechanisms of action in digestive system neoplasms, clinical significance, and explores its potential as a therapeutic target.

Objective: : Baculovirus inhibitory of apoptosis repeat-containing 5 (BIRC5) is critically implicated in various types of tumors. However, the specific mechanisms by which it operates in glioma are yet to be fully understood. Methods: : The data sourced from The Cancer Genome Atlas and Gene Expression Omnibus were merged and analyzed using the R software to investigate the relationship between BIRC5 expression and prognosis and diagnosis outcomes. This exploration was conducted utilizing various biological information repositories. The correlation between BIRC5 and immunity was obtained based on TIMER and TISIDB databases. Results: : Gliomas displayed a markedly elevated level of BIRC5 expression compared to adjacent tissues. Patients with glioma who exhibit elevated levels of BIRC5 experience poorer prognoses and shorter survival times. Subgroup classification further revealed that heightened expression of BIRC5 led to diminished overall survival. Analysis of logistic regression and COX indicated that expression of BIRC5 serves as a risk factor in glioma development. Functional enrichment pathways showed that the 72 hub genes related to BIRC5 were mainly closely related to nuclear division, spindle, tubulin binding, and cell cycle in glioma patients. BBIRC5 methylation suggested that BIRC5 might influence the immune response regulation and the tumor microenvironment within gliomas. BIRC5 is associated with many chemicals. Additionally, studies conducted using cell experiments and pathological sections have consistently shown that BIRC5 expression is higher in tumor cells compared to normal cells and tissues. Conclusion : BIRC5 holds promise as a valuable tool in the diagnosis, prognosis, and management of gliomas.

Hepatocellular carcinoma (HCC) is currently the most common primary malignant tumor of liver. According to the statistic data, more than 300 000 patients die of HCC in China each year, accounting for approximately 50% of the total number of HCC deaths worldwide. Liver transplantation is one of the important methods for treating HCC. However, postoperative recurrence and metastasis of HCC affect the long-term survival of patients. The use of prognostic scoring models to assess the risk of recurrence after liver transplantation for HCC, regular follow-up and close monitoring of recipients, individualized, low-dose and combined immunosuppressive regimens and standardized antiviral therapy are all beneficial for reducing the risk of recurrence. Once recurrence and metastasis are confirmed, comprehensive treatment combining surgical resection, local treatment and systemic treatment is helpful in controlling disease progression and prolonging survival time. This article focuses on the new progress in the prevention and treatment of tumor recurrence and metastasis after liver transplantation for HCC, with the aim of providing reference and inspiration for future clinical practice and scientific research.