Objective To observe the surgical outcomes and complications of transforaminal endoscopic lumbar discectomy(TELD)and interlaminar endoscopic lumbar discectomy(IELD)in the treatment of lumbar disc herniation(LDH)with prolapse type at the L4/5 segment using full-endoscopic spine surgery.Methods A retrospective analysis was conducted on the clinical data of 75 patients with L4/5 segmental prolapse type LDH who underwent spinal endoscopic surgery from November 2020 to November 2022.Among them,53 patients underwent TELD(TELD group)and 22 patients underwent IELD(IELD group).The surgical outcomes and postoperative therapeutic effect of the two groups were compared.Results Compared with the TELD group,the IELD group had significantly shorter operation time and fewer intraoperative fluoroscopy times,the differences were statistically significant(P<0.05);There were no statistically significant in the length of hospital stay and the incidence of complications between the two groups(P>0.05).All patients were followed up for 12 to 19 months after surgery.The visual analogue scale(VAS)score and Oswestry disability index(ODI)at the last follow-up in both groups were significantly lower than those before surgery,and the IELD group was significantly lower than the TELD group,the differences were statistically significant(P<0.05).Further analysis based on the location of the herniation and nerve roots revealed that,compared with preoperative values,the VAS scores and ODI at the last follow-up were significantly reduced in both groups of patients with shoulder-upper type herniation(10 cases in the TELD group and 6 cases in the IELD group),and the VAS score in the IELD group at the last follow-up was significantly lower than that in the TELD group,the differences were statistically significant(P<0.05).Similarly,both groups of patients with axillary type herniation(8 cases in the TELD group and 16 cases in the IELD group)exhibited significantly reduced VAS score and ODI at the last follow-up than those before operation,with significantly lower in the IELD group compared to the TELD group,the differences were statistically significant(P<0.05).Among the 35 patients with anterior-shoulder type herniation who underwent TELD,the VAS score and ODI at the last follow-up were also significantly lower than those before surgery,the difference was statistically significant(P<0.05).Further analysis based on the Lee classification of herniations revealed that,compared with preoperative values,the VAS score and ODI at the last follow-up were significantly reduced in both groups of patients with herniations in Lee zone Ⅲ(44 cases in the TELD group and 10 cases in the IELD group),and the ODI in the IELD group was significantly lower than that in the TELD group,the differences were statistically significant(P<0.05).Similarly,both groups of patients with LDH in Lee zone Ⅳ(9 cases in the TELD group and 12 cases in the IELD group)exhibited significantly reduced VAS score and ODI at the last follow-up,with significantly lower in the IELD group compared to the TELD group(P<0.05).Conclusion Both TELD and IELD can achieve satisfactory decompression effects in the treatment of LDH with prolapse type at the L4/5 segment.However,IELD offers a relatively shorter operative time,requires fewer X-ray fluoroscopies,and demonstrates superior decompression effects for shoulder-type,axillary-type,Lee Ⅲ and Lee Ⅳ.

Objective To explore the effect of young plasma intraperitoneal injection on the fertility and ovarian function of aging mice and analyze its potential molecular mechanism.Methods Fifty-four-week-old female C57BL/6 mice and 8-week-old male C57BL/6 mice were selected.Among them,the female mice were randomly divided into three groups:the young plasma group,the aging plasma group and the normal saline group.The young plasma group and the aging plasma group received intraperitoneal injection of plasma from young(25-29 years old)and elderly(45-49 years old)female donors,respectively.Each injection was 500 μL,administered every other day for 2 weeks.The saline group received an equal volume of saline.After the last injection,mating experiments were conducted to evaluate fertility.Ovarian histopathological changes were observed by HE staining.Oocytes and fertilized eggs were collected after superovulation and cultured in vitro to assess oocyte quality and embryo developmental potential.Transcriptomic analysis of ovarian tissue was performed,followed by KEGG and GO enrichment analysis.Results Compared with the normal saline group and the aging plasma group,the number of offspring increased in the young plasma group,which reflected higher extrusion rate of first polar body(PB1),decreased fragmentation rate of oocytes and increased conversion rate of two-cell embryos and increased formation rate of blastocysts.There were no significant differences in these indicators between the aging plasma group and the normal saline group.Transcriptomic sequencing revealed that the differentially expressed genes in ovarian tissue of the young plasma group were mainly involved in steroid biosynthesis and metabolic pathways.Among them,the expression level of steroid sulfatase protein was significantly upregulated.Conclusion Systemic infusion of young plasma enhances the reproductive potential of aging ovaries in elderly mice.The sulfated steroid metabolites in plasma may be key substances in restoring ovarian function and delaying the process of ovarian aging.

OBJECTIVES: To develop a heterogeneous graph prediction method based on the fusion of multi-layer semantics and topological information for addressing the challenges in drug-target interaction prediction, including insufficient modeling of high-order semantic dependencies, lack of adaptive fusion of semantic paths, and over-smoothing of node features. METHODS: A heterogeneous graph network with multiple types of entities such as drugs, proteins, side effects, and diseases was constructed, and graph embedding techniques were used to obtain low-dimensional feature representations. An adaptive metapath search module was introduced to automatically discover semantic path combinations for guiding the propagation of high-order semantic information. A semantic aggregation mechanism integrating multi-head attention was designed to automatically learn the importance of each semantic path based on contextual information and achieve differentiated aggregation and dynamic fusion among paths. A structure-aware gated graph convolutional module was then incorporated to regulate the feature propagation intensity for suppressing redundant information and redcuing over-smoothing. Finally, the potential interactions between drugs and targets were predicted through an inner product operation. RESULTS: Compared with existing drug-target interaction prediction methods, the proposed method achieved an average improvement of 3.4% and 2.4%, 3.0% and 3.8% in terms of the area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUPRC) on public datasets, respectively. CONCLUSIONS The drug-target interaction prediction method developed in this study can effectively extract complex high-order semantic and topological information from heterogeneous biological networks, thereby improving the accuracy and stability of drug-target interaction prediction. This method provides technical support and theoretical foundation for precise drug target discovery and targeted treatment of complex diseases.
Semantics ; Humans ; Drug Interactions ; Neural Networks, Computer ; Algorithms

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems faced by bus drivers and should receive special attention. Objective To explore the associations of weekly working hours and sleep quality with neck and lower back WMSDs among bus drivers, as well as assess the potential mediating role of sleep quality. Methods From June to December 2022, we recruited bus drivers from 5 subsidiaries of the Shenzhen Bus Group by convenient sampling method. Demographic characteristics, lifestyles, and work-related features of the bus drivers were collected through a questionnaire survey. The Pittsburgh Sleep Quality Index (PSQI) scale and the Musculoskeletal Disorders Survey Questionnaire were used to assess sleep quality and WMSDs respectively. Logistic regression models were applied to analyze the associations of weekly working hours and sleep quality with WMSDs in neck and lower back. Furthermore, mediation analysis was performed to investigate the role of sleep quality in the associations between weekly work hours and neck and lower back WMSDs. Results A total of 1792 valid questionnaires were collected, with a response rate of 95.07%. Among these, 89.3% of the bus drivers worked more than 40 h per week, and the positive rate of poor sleep quality was 28.2%. The overall positive rate of WMSDs within one year before the survey was 69.12%. Among different body regions, the leading positive rates were identified in neck and lower back regions, at 55.92% and 53.68%, respectively. The logistic regression model showed that compared to the bus drivers with weekly work hours ≤40 h, those weekly worked (40~48] h (OR=1.43, 95%CI: 1.02, 2.01; OR=1.65, 95%CI: 1.17, 2.34), (48~56] h (OR=2.69, 95%CI: 1.89, 3.83; OR=2.30, 95%CI: 1.62, 3.29) and ＞56 h (OR=2.63, 95%CI: 1.86, 3.74; OR=3.23, 95%CI: 2.27, 4.62) had significantly increased risk of WMSDs in neck and lower back. Additionally, when compared to those with good sleep quality, bus drivers with poor sleep quality had higher risks of both neck and lower back WMSDs (OR=4.08, 95%CI: 3.20, 5.23; OR=4.15, 95%CI: 3.26, 5.30, respectively). Further mediation analysis indicated that sleep quality partially mediated the associations between weekly working hours and both neck and lower back WMSDs, with 36.15% and 33.68% as the respective proportion of mediation. Conclusion The positive rate of WMSDs is high among bus drivers, and the most common WMSDs occur in neck and lower back. Long working hours and poor sleep quality are significantly associated with increased risks of neck and lower back WMSDs. Sleep quality may mediate the associations of weekly working hours with neck and lower back WMSDs.

Objective:To investigates the efficacy and safety of allogeneic hematopoietic stem cell transplantation(allo-HSCT)in treating older patients(≥60 years old)with hematologic malignancies.Methods:We conducted a retrospective study involving 67 patients aged 60 years and above, diagnosed with malignant hematological diseases, who received allo-HSCT at the Clinical Research Centrer for Haematologic Diseases of the First Affiliated Hospital of Soochow University between June 2015 and March 2023.We collected pre-transplant data, including the patients' age, gender, pre-transplantation disease risk stratification, disease status, and the haematopoietic cell transplantation comorbidity index(HCT-CI). We retrospectively analyzed clinical data regarding treatment-related toxicity, infections, acute and chronic graft-versus-host disease(a/cGVHD), as well as recurrent and non-recurrent deaths, to estimate the overall survival(OS)rate and event-free survival (EFS)rate.Results:Sixty-seven patients were included in the study, comprising 55 males(82.1%)and 12 females(17.9%), with a median age of 63(61, 65) years .The cohort consisted of 42 cases of acute myeloid leukaemia, 22 cases of myelodysplastic syndromes, and 3 cases of acute lymphoblastic leukaemia.The Kaplan-Meier analysis showed that the 1-year OS and EFS rates were 62.9% and 59.2%, respectively, while the 2-year OS and EFS rates were 55.3% and 51.8%, respectively.The cumulative incidence of 1-year non-relapse mortality and relapse was 25.4% and 21.2%, respectively.A total of 13 patients developed grade Ⅱ-Ⅳ aGVHD, with a 1-year cumulative incidence of 22.0%, and 7 patients developed cGVHD requiring treatment.When stratified by age group, the OS rate was higher in patients aged 60~64 years compared to those aged ≥65 years; however, this difference was not statistically significant(Log-rank χ2=0.99, P=0.317). In contrast, when stratified by disease load, the OS rate was significantly higher in the complete remission(CR)group than in the non-CR group, with a statistically significant difference(Log-rank χ2=15.04, P<0.001). When stratified by donor type, the OS rate was higher in the human leukocyte antigens (HLA) allogeneic group compared to the haploinsufficiency group; however, the difference was not statistically significant(Log-rank χ2=2.71, P=0.100). Twenty-seven patients died at an average of 125 days (range 3-1 054 days) after HSCT.The causes of death included leukemia recurrence in 9 cases (33.3%), infection in 8 cases (29.6%), GVHD in 5 cases (18.5%), poor implantation in 3 cases (11.1%), multi-organ failure in 1 case (3.7%), and cerebrovascular accident in 1 case (3.7%). The results of multifactorial analysis indicated that a pre-transplant tumor load greater than 5% was an independent risk factor for OS after transplantation ( HR=4.59, 95% CI: 2.01-10.42, P<0.001)as well as for disease recurrence ( OR=13.11, 95% CI: 1.96-87.87, P=0.008). Additionally, the occurrence of infection was identified as an independent risk factor for non-recurrent death after transplantation( OR=3.95, 95% CI: 1.13 to 13.71, P=0.031). Conclusions:For patients aged 60 years or older with hematologic malignancies, HSCT can serve as a viable treatment option, particularly for those with refractory recurrence and high cytogenetic risk, as it has the potential to significantly enhance prognosis and increase both EFS and OS rates.

Objective To observe the value of prenatal ultrasound evaluation on morphology of Sylvian fissure(SF)during the second and third trimesters for screening fetal abnormal cerebral cortical development.Methods Totally 876 fetuses in the second and third trimesters were retrospectively included.Prenatal ultrasound was performed to observe the morphology of fetal SF and whether there was complicated abnormalities of the development of cerebral cortical and other structures.Then prenatal ultrasound was regularly reexamined,and the pregnancy outcome,while the growth and development of newborns were followed up.Results Among 876 fetuses,normal SF morphology was observed in 861 fetuses(861/876,98.29％),while 11 fetuses(11/876,1.26％)had delayed SF development(normal SF morphology but inconsistent with gestational week)and 4 fetuses(4/876,0.46％)had abnormal SF morphology,all complicated with abnormal cerebral cortical development and/or intracranial and extracranial structural malformations,and reexamination of prenatal ultrasound showed that SF morphology was consistent with the gestational week in 4 fetuses,SF morphology still did not match the gestational week in 4 fetuses,and SF morphology was still abnormal in 2 fetuses.Among these 15 fetuses,6 were successfully born and grew well after followed up until 10-15 months,4 were induced labor,while the rest 4(3 with delayed SF development and 1 with abnormal SF morphology)complicated with other severe malformations and 1 with abnormal SF morphology were induced labor or lost to follow-up,hence not undergoing ultrasound re-examination.Conclusion Prenatal ultrasound evaluation on SF morphology during the second and third trimesters had important value for screening fetal abnormal cerebral cortical development.