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 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.

BACKGROUND:At present,osteoarthritis has become a major disease affecting the quality of life of the elderly,and the therapeutic effect is poor,often focusing on preventing the disease process,and the pathogenesis of osteoarthritis is still not fully understood.Bioinformatics analysis was carried out to explore the main pathogenesis of osteoarthritis and related mechanisms of gene coding regulation. OBJECTIVE:To screen core differential genes with a major role in osteoarthritis by gene expression profiling. METHODS:Datasets were downloaded from the Gene Expression Omnibus(GEO):GSE114007,GSE117999,and GSE129147.Differential genes in the GSE114007 and GSE117999 data collections were screened using R software,performing differential genes to weighted gene co-expression network analysis.The module genes most relevant to osteoarthritis were selected to perform protein interaction analysis.Candidate core genes were selected using the cytocape software.The candidate core genes were subsequently subjected to least absolute shrinkage and selection operator regression and COX analysis to identify the core genes with a key role in osteoarthritis.The accuracy of the core genes was validated using an external dataset,GSE129147. RESULTS AND CONCLUSION:(1)A total of 477 differential genes were identified,265 differential genes associated with osteoarthritis were obtained by weighted gene co-expression network analysis,and 8 candidate core genes were identified.The least absolute shrinkage and selection operator regression analysis finally yielded a differential gene ASPM with core value that was externally validated.(2)It is concluded that abnormal gene ASPM expression screened by bioinformatics plays a key central role in osteoarthritis.

Objective To conduct preliminary evaluation of the reliability and safety of pancreatic duct-to-jejunum stent-bridging internal drainage as a supplementary approach to pancreaticojejunostomy in central pancreatectomy.Methods The clinical data of 28 patients who underwent robotic central pancreatectomy performed by our team between January 2021 and November 2024 were retrospectively collected,and and follow-up of postoperative endocrine and exocrine functions was performed.Based on the methods of digestive tract reconstruction adopted,the patients were divided into a conventional pancreaticojejunostomy group and a pancreatic duct-to-jejunum stent-bridging internal drainage group(PancreaticoJejunal-Stent bridge group).The operative time,digestive tract reconstruction time,and short-term complications were compared between the two groups.Results Among patients undergoing robotic central pancreatectomy,the digestive tract reconstruction time was shorter(t=5.168,P<0.001)in the PancreaticoJejunal-Stent bridge group([31.1±6.3]min)than that in the conventional pancreaticojejunostomy group([49.7±8.9]min)(t=5.168,P<0.001).The total operative time was(172.7±64.6)min in the PancreaticoJejunal-Stent bridge group and(200.1±52.7)min in the conventional pancreaticojejunostomy group,showing no statistically significant difference(t=1.215,P=0.235).In the PancreaticoJejunal-Stent bridge group,one patient developed a postoperative biochemical fistula,and 14 patients developed grade B pancreatic fistulas.Among the 14 patients with grade B pancreatic fistulas,1 case was complicated by fistula-related intra-abdominal infection,and 13 cases had drainage tube retention time of more than 21 days.In the conventional pancreaticojejunostomy group,2 patients developed postoperative biochemical fistulas,and 11 patients developed grade B pancreatic fistulas.Among the 11 patients with grade B pancreatic fistulas,1 case was complicated by fistula-related intra-abdominal infection,and 1 case was complicated by fistula-related intra-abdominal bleeding and infection.No postoperative gastroparesis,pancreatitis,or grade C pancreatic fistulas occurred in either group.There were no statistically significant differences between the two groups in overall postoperative complication rate(P=0.522),postoperative pancreatic fistula rate(P=0.583),intra-abdominal infection rate(P=0.583),or bleeding rate(P=0.464).Conclusion Pancreatic duct-to-jejunum stent-bridging internal drainage optimizes the anastomosis between the distal end of the pancreas and the jejunum during central pancreatectomy,shortens digestive tract reconstruction time,and reduces surgical complexity without increasing the risk of short-term severe postoperative complications.This approach is safe and feasible.

ObjectiveAt present, the most commonly used photosensitizers in photodynamic therapy are still chemical photosensitizers, such as porphyrin and methylene blue, in order to specifically target cellular tissues, and thus poison cells, chemical photosensitizers need to use antibody conjugation or a transgenically encoded tag with affinity for the modified photosensitizing ligand, e.g. FlAsH, ReAsh or Halo Tag. Gene-encoded photosensitizers can directly poison cells by targeting specific cell compartments or organelles. However, currently developed gene-encoded photosensitizers have low reactive oxygen species production and low cytotoxicity, so it is necessary to continue to develop and obtain photosensitizers with higher reactive oxygen species production for the treatment of microbial infections and tumors. MethodsIn this study, we developed a photosensitizer LovPSO2 based on the light-oxygen-voltage (LOV) structural domain of phototropin-1B-like from Oryza sativa japonica. LovPSO2 was expressed in E. coli BL21(DE3) and purified to obtain protein samples, the purified protein samples were added 3 µmol/L singlet oxygen probe of SOSG and 5 µmol/L superoxide anion probe of DHE after fixed to A₄₄₅=0.063±0.003, respectively, then measured every 2 min of singlet oxygen production for 10 min and every 1 min of superoxide anion production for 5 min under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1. ResultsThe results showed that LovPSO2 could produce a large amount of singlet oxygen under blue light irradiation at 445 nm, 70 µmol·m^-2·s^-1, and its singlet oxygen quantum yield was 0.61, but its superoxide anion yield was low, so in order to improve the superoxide anion yield of LovPSO2, a mutant with a relatively high superoxide anion yield was obtained by further development and design on its basis LovPRO2. The stability of proteins is crucial for research in drug development and drug delivery, among others. Temperature and light are the key factors affecting the production of reactive oxygen species (ROS) by photosensitive proteins and their stability, while the temperature in cell culture and mammals in vivo is about 37°C, and the temperature inside tumor cells is about 42-45°C. Therefore, we further analyzed the photostability of miniSOG, SOPP3, LovPSO2, and LovPRO2 and their thermostability at 37℃ and 45℃. The analysis of proteins thermostability showed that LovPSO2 and LovPRO2 had better thermostability at 37℃ and 45℃, respectively. Analysis of the photostability of the proteins showed that LovPRO2 had better photostability. In addition, to further determine the phototoxic effects of photosensitizers, LovPSO2 and LovPRO2 were expressed in E. coli BL21(DE3) and HeLa cells, respectively. The results showed that LovPSO2 and LovPRO2 had better phototoxicity to E. coli BL21(DE3) under blue light irradiation, and the cellular phototoxicity lethality was as high as 90% after 30 min of continuous light irradiation, but the phototoxicity was weaker in HeLa cells. The reason for this result may be that the intracellular environment exacerbated the photobleaching of FMN encapsulated by LovPSO2 and LovPRO2, respectively, which attenuated the damage of reactive oxygen species to animal cellular tissues, limiting its use as a mechanistic tool to study oxidative stress. ConclusionLovPSO2 and LovPRO2 can be used as antibacterial photosensitizers, which have broader application prospects in the food and medical fields.

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: The objective of this study was to investigate the clinical efficacy and safety of treating sepsis patients with Xuebijing injection (XBJI). METHODS: We conducted a retrospective analysis of 418 patients who experienced severe infections and were treated with XBJI from June 2018 to June 2021. Propensity score matching was used to match the patient cases. The study population included 209 pairs of cases (418 individuals), and the analysis included data from before and after a 14-day course of treatment with carbapenem alone, or carbapenem with XBJI. RESULTS: There were no significant differences in the 14-day mortality or length of hospital stay (P > 0.05) between the two groups. The combined treatment group had more patients with C-reactive protein that returned to normal levels (compared to baseline) than the non-combined treatment group (14.4% vs 8.1%; odds ratio [OR]: 0.528; 95% confidence interval [CI]: 0.282-0.991; P = 0.026). Similarly, the combined treatment group had higher procalcitonin attainment rate (55.0% vs 39.7%; OR: 0.513; 95% CI: 0.346-0.759; P = 0.001) than the non-combined treatment group. Further, more patients in the combined treatment group achieved normal creatinine levels than in the non-combined treatment group (64.1% vs 54.1%; OR: 0.659; 95% CI: 0.445-0.975; P = 0.037). CONCLUSION The combination of XBJI with carbapenem did not reduce the 14-day mortality rate of patients with severe infection, but it was able to reduce the level of inflammatory factors in patients with sepsis, and had a protective effect on liver and kidney function. Please cite this article as: Gong ZT, Yang HX, Zhu BB, Liu HH, Siri GL. Clinical efficacy of Xuebijing injection for the treatment of sepsis: A retrospective cohort study. J Integr Med. 2024; 22(6): 645-651.
Humans ; Drugs, Chinese Herbal/administration & dosage* ; Sepsis/mortality* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Aged ; Treatment Outcome ; Anti-Bacterial Agents/administration & dosage* ; C-Reactive Protein/analysis* ; Carbapenems/therapeutic use* ; Length of Stay ; Injections ; Adult ; Drug Therapy, Combination ; Procalcitonin/blood*

Objective To design a pressure reading system for splinting distal radius fractures to enable real-time monitoring of splint fixation pressure.Methods A pressure reading system for splinting distal radius fractures was developed with the components of a main contrl unit,a pressure and temperature acquisition unit and a power management unit.The main control unit had a STC15 series SCM as the main control chip,and the pressure and temperature acquisition unit was realized with a FSR400 thin film pressure sensor and a DS18B20 digital temperature measurement chip.The software of the system was developed with C language.The system developed was used to test the magnitude and distribution of the pressure on the splints by applying loads on the fixation straps at 90°,60° and 30° directions to the willow splint and 3D printing splint,respectively,with the total mass of the loads increased from 600 g to 1 200 g and each test repeated by 6 times.Results The system developed was capable of collecting the pressure values at real time and showed them on the display screen.The maximum pressure always occurred at the the connection between the fixation straps and the edge of the splints and the middle parts of the splints were subject to relatively low pressure in case of different loads,when the fixation straps were 90°,60° and 30° to the willow splint and 3D printing splint respectively.The maximum pressure on the willow splint was(239.17±4.49)g when the fixation strap was 90° to the splint and loaded with 1 200 g;the minimum pressure on the willow splint was(89.83±17.38)g when the fixation strap was 60° to the splint and loaded with 600 g.The maximum pressure on the 3D printing splint was(177.67±21.77)g when the fixation strap was 90° to the splint and loaded with 1 100 g;the minimum pressure was(66.50±3.02)g for the 3D printing splint when the fixation strap was 30° to the splint and loaded with 600 g.Conclusion The ssystem developed can read pressure values of the splint under different loads and angles,and the 3D printing splint behaves better than the willow splint in the evenness of pressure distribution.Theoretical references are provided for quantitative clinical treatment with splint fixation.[Chinese Medical Equipment Journal,2024,45(8):44-50]

Objective To study the effect of pain on the lumbar and hip joint moments in patients with lumbar disc herniation(LDH)while sitting and standing.Methods Dynamic data from 20 healthy controls and 20 patients with LDH were collected using an AMTI dynamometer.The differences in moments between the lumbar spine and hip joints in the sagittal and coronal planes for the two groups of subjects performing sitting-standing tasks were analyzed using statistical parameter mapping(SPM).Results Compared to the healthy control group,the LDH group showed a significant increase in the maximum lumbar flexion moment and the maximum hip adduction moment from standing to sitting(P＜0.05).SPM analysis showed that during the initial phase of standing(37％-42％),the hip abduction moment of the LDH group was significantly greater than that of the healthy control group(P=0.007).Conclusions Subjects with LDH have an unstable lumbar spine and pelvis during sitting and standing,especially at the stationary stage,which makes it difficult to achieve balance in their body.Therefore,increasing the hip abduction moment is necessary to maintain pelvic stability.During clinical evaluation and treatment,emphasis should be placed on the stable function of the spine and pelvis.

Objective To investigate the correlation of the distribution patterns of stem-branch circuit qi at birth and at conception of children with the predisposition to pediatric epilepsy.Methods A case-control study was conducted in 1 113 children with epilepsy(case group)and 2 346 non-epilepsy children(control group)who sought medical consultation in the Pediatric Outpatient Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine at the same period.Chi-square test and binary logistic regression were used to analyze the circuit qi endowment of children between the two groups at conception and at birth.Results(1)The analysis of the circuit qi distribution at birth showed that there was a statistically significant difference in the distribution of dominant qi between the case group and the control group at birth(P＜0.05).The initial qi(the first circuit qi in the theory of six climatic factors)accounted for the most(215 cases,19.30％)and the sixth qi accounted for the least(145 cases,13.0％).There was no significant difference in the distribution of suiyun(yearly evolutive phase),dominant circuit(regular yearly evolutive phase),guest circuit(alterable yearly evolutive phase),guest qi(alterable yearly circuit qi)and sitian(the first half of the alterable yearly circuit qi)at birth(P＞0.05).The results of binary logistic regression analysis showed that the risk of predisposition to epilepsy in the children was increased when the children were born in the Chinese lunar year of Ren(OR=1.444,95％CI:1.055-1.975),at the initial qi(OR=1.363,95％CI:1.057-1.757)and at the fifth qi(OR=1.378,95％CI:1.065-1.783).(2)The analysis on the distribution of circuit qi at conception showed that there was no significant difference in the distribution of suiyun and sitian-zaiquan semiannual circuit qi between the case group and the control group(P＞0.05).Binary logistic regression analysis showed that the risk of predisposition to epilepsy in the children was increased when pregnancy in the suiyun of taimu-taimu(OR=1.866,95％CI:1.142-3.048)and at sitian semiannual circuit qi of shaoyang minister fire and zaiquan semiannual circuit qi of jueyin wind-wood(OR=1.672,95％CI:1.004-2.786).Conclusion There is a certain correlation between circuit qi endowment and the prevalence of pediatric epilepsy.