Objective To explore the causal relationship between immune cells and heart failure (HF), and the mediating role of serum metabolites, in order to identify potential biomarkers and therapeutic targets. Methods We employed a two-sample Mendelian randomization (MR) analysis method based on genome-wide association study (GWAS) data, analyzing the direct and indirect effects of 731 types of immune cells and 1 400 metabolites on HF. We selected valid instrumental variables and conducted statistical analyses using R software. The primary analysis was performed using the inverse variance weighted method, supplemented by MR-Egger analysis and weighted median method. The stability of the results was assessed through tests such as Cochran’s Q test. Results Our research found a negative causal relationship between PD-L1 on CD14−CD16+ and HF. Sensitivity analysis supported this result. The reverse MR analysis did not find an effect of HF on PD-L1 on CD14−CD16+, indicating that PD-L1 on CD14−CD16+ might play a unidirectional role in reducing the risk of HF. Further mediation MR analysis showed that PD-L1 on CD14−CD16+ might influence the risk of HF onset by regulating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), with a mediation effect ratio of 6.7%. Conclusion PD-L1 on CD14−CD16+ may reduce the risk of HF by elevating the levels of sphingomyelin (d17:1/14:0, d16:1/15:0), which provides a new perspective for understanding the pathogenesis of HF.

The inflammatory microenvironment is closely associated with the initiation and progression of osteoarthritis （OA）， specifically manifesting as macrophage activation， dysregulation of inflammatory cytokines， and redox imbalance. Following an overview of the pathological characteristics of the OA inflammatory microenvironment， this paper reviews the research progress on the mechanism of traditional Chinese medicine （TCM） intervening in OA by modulating the inflammatory microenvironment. It has been found that TCM monomers/active ingredients （such as total alkaloids from Strychnos nux-vomica ， quercetin， triptolide， etc.）， herb pairs （e.g. Angelica pubescens - Gentiana macrophylla ， Carthami Flos-Lycopodii Herba）， and TCM formulas （such as Zhuanggu jianxi formula， Duhuo jisheng decoction and Rongjin niantong formula， etc.） can inhibit macrophage activation， reduce the release of proinflammatory cytokines and the generation of reactive oxygen species by inhibiting multiple signaling pathways， including nuclear factor-κB， Wnt/ β -catenin， and mitogen-activated protein kinase， thereby alleviating the articular inflammatory microenvironment， restoring local joint homeostasis， and slowing the progression of OA.

BACKGROUND: Urolithiasis is a widespread disease with a high prevalence worldwide. This study aims to evaluate the disease burden of urolithiasis and its trends from 1990 to 2021 globally, based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 database. METHODS: The numbers and age-standardized rates (ASRs) of incidence, disability-adjusted life years (DALYs), and mortality of urolithiasis were extracted from GBD 2021 to represent the disease burden. Joinpoint regression analyses were conducted to assess the temporal trends in the burden of urolithiasis. The male-to-female ASR ratio indices were used to evaluate sex disparities. Additionally, we explored the relationship between the ASR ratio and the sociodemographic index (SDI). RESULTS: The total numbers of incidence, DALY, and mortality of urolithiasis were 105,983,780 cases (95% uncertainty interval [UI] = 88,349,356-128,645,155 cases), 693,444 cases (95% UI = 567,765-850,490 cases), and 17,672 cases (95% UI = 13,932-21,241 cases), respectively, in 2021. There is an increasing trend in the number of these measures globally, whereas the ASRs have decreased over the past 30 years. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) were significantly higher in males than in females in 2021. The sex disparities in the age-standardized DALY rate (ASDR) and ASMR of urolithiasis were negatively correlated with the SDI. In 2021, the ASIR of urolithiasis was 964.70 (95% UI = 801.26-1175.09) per 100,000 people in China, which is much lower than the global average (1242.84 [95% UI = 1034.94-1506.99] per 100,000 people). Compared with the global average, a more pronounced decline in ASIR was observed in China from 1793.16 (1446.0-2235.14) in 1990 to 964.70 (801.26-1175.09) per 100,000 people in 2021. CONCLUSIONS Urolithiasis poses a significant healthcare burden worldwide. More robust global and national strategies are warranted to address the prevention and treatment, especially in low SDI countries and regions.
Humans ; Urolithiasis/mortality* ; Male ; Female ; Incidence ; Global Burden of Disease ; Disability-Adjusted Life Years ; Adult ; Middle Aged ; Risk Factors ; Sex Factors

Objective:To investigate optimal treatment strategy for pT3N0 laryngeal squamous cell carcinoma（SCC）. Methods:A retrospective study of 150 patients with pT3N0 laryngeal SCC treated in the First Affiliated Hospital of Chongqing Medical University was performed. The efficacies of partial laryngectomy and total laryngectomy, as well as surgery alone and postoperative radiotherapy were evaluated. The overall survival（OS）, disease specific survival（DSS） and disease-free survival（DFS） were analyzed with statistical package from SPSS. Results:Among the 108 patients with glottic laryngeal SCC, there were no significant differences in OS, DSS and DFS between the partial laryngectomy group and the total laryngectomy group（Log-rank=0.184, 0.010 and 0.051, P>0.05）. Similarly, there were no significant differences in OS, DSS and DFS between the surgery-alone group and postoperative radiotherapy group（Log-rank=0.214, 0.251 and 0.003, P>0.05）. Among the 38 patients with supraglottic laryngeal SCC, the OS in the total laryngectomy group was significantly higher than that in the partial laryngectomy group（Log-rank=7.338, P=0.007）. The DSS and DFS in the total laryngectomy group were higher than in the partial laryngectomy group, but the differences were not statistically significant（Log-rank=0.895 and 1.792; P>0.05）. The DFS in the postoperative radiotherapy group was significantly higher than in the surgery-alone group（Log-rank=7.172, P=0.007）, but there were no significant differences in OS and DSS between these two groups（Log-rank=0.010 and 0.876, P>0.05）. Conclusion:For pT3N0 glottic laryngeal cancer patients, the efficacy of partial laryngectomy is comparable to total laryngectomy, same as surgery alone and postoperative radiotherapy. For pT3N0 supraglottic laryngeal cancer patients, total laryngectomy could improve the overall survival, and postoperative radiotherapy could reduce the recurrence. Prospectively randomized study with large samples is still needed.
Humans ; Laryngeal Neoplasms/therapy* ; Laryngectomy/methods* ; Retrospective Studies ; Carcinoma, Squamous Cell/surgery* ; Male ; Female ; Middle Aged ; Disease-Free Survival ; Neoplasm Staging ; Aged ; Survival Rate ; Treatment Outcome

ObjectiveStudies have shown that nuciferine has anti-cerebral ischemia effect， but the specific mechanism of action has not been elaborated. Based on the transcriptome results， the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue， cell， pathological process， biological process and signaling pathway. MethodsThirty SD rats were randomly divided into the sham group， model group and nuciferine group（40 mg·kg^-1） according to weight. Except for the sham group， the model of middle cerebral artery occlusion（MCAO） was established by thread embolization method after 30 min of administration in the other two groups. Twenty-four hours after surgery， transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue， and gene ontology（GO） and kyoto encyclopedia of genes and genomes（KEGG） pathway enrichment analysis were performed for differentially expressed genes. The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue， cell， pathological process， biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform（TMNP）. ResultsTranscriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine. Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response， ion transport， cell proliferation and differentiation， and synaptic function. TMNP research found that at the tissue level， nuciferine could significantly improve the cerebral tissue injury caused by ischemia. At the cellular and pathological levels， nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells， mobilizing immune cells， regulating inflammation. And at the level of biological processes and signaling pathways， nuciferine mainly acted on the processes such as vascular remodeling， inflammation-related signaling pathways， and synaptic signaling. ConclusionCombined with the results of transcriptome sequencing， gene quantitative analysis and TMNP， the mechanism of nuciferine against cerebral ischemia may be related to processes such as intervening in stress response and inflammation， affecting vascular remodeling and regulating synaptic function. These results can provide a basis and reference for further study of the pharmacological mechanism of nuciferine against cerebral ischemia.

AIM: To observe the changes of corneal densitometry(CD)and higher-order aberrations after small incision lenticule extraction(SMILE), and to explore their correlations and influencing factors.METHODS: Prospective study. A total of 62 high-degree myopia and compound myopic astigmatism patients(62 eyes)who underwent SMILE in Urumqi Aier Eye Hospital from December 2022 to November 2023 were collected. The CD, root mean square of corneal higher-order aberrations(RMS HOA), spherical aberration, vertical coma, horizontal coma, and corneal epithelial thickness(CET)of the patients were measured before surgery, and at 1 d, 1 wk, 1, 3, and 6 mo after surgery, respectively.RESULTS:There were 4 patients lost to follow-up during the period, all due to failure to attend scheduled reexaminations. The number of complete and valid cases was 58 eyes. The CD in the central and paracentral regions of the anterior, middle, and total layer of the cornea increased significantly on the first day after surgery(all P<0.003). At 6 mo after surgery, there was a slight but statistically significant decrease in the CD of the central and paracentral regions of the anterior and the total anterior layer(all P<0.003). Compared with the preoperative baseline values, the RMS HOA, spherical aberration, and vertical coma significantly increased at 6 mo after surgery(all P<0.003), while the change in horizontal coma was not statistically significant. Compared with the preoperative baseline values, the CET in the central, paracentral, and peripheral regions of the cornea, as well as the total average CET in the 0-7 mm range of the cornea increased at 6 mo after surgery(all P<0.003). At 1 d after surgery, CD of the anterior layer and total layer in the central region of the cornea were positively correlated with the CET in the central region(rs=0.327, rs=0.250, all P<0.05). At 6 mo after the surgery, the CD of the middle layer and posterior layer in the central corneal region were negatively correlated with the preoperative spherical equivalent and the change of RMS HOA(all P<0.05).CONCLUSION:The anterior CD decreases at 6 mo after SMILE for high myopia correction, and there is a certain correlation between the changes in CD and some clinical parameters.

Objective:To investigate the effects of preoperative enteral nutrition on nutrition-related complications and gastrointestinal function in esophageal cancer patients by administering EN before surgery.Methods:A total of 215 patients who underwent thoracoscopic esophagectomy at Nanjing Hospital of Traditional Chinese Medicine between January 2018 and December 2020 were retrospectively analyzed in this study. Among them, 145 patients received enteral nutrition preconditioning, while 70 patients received traditional nutritional support. The nutritional risk was assessed according to the Nutritional Risk Screening 2002 (NRS2002), and the patients were categorized into non-nutritional risk group (NRS2002<3) and nutritional risk group (NRS2002≥3). Patients in the traditional nutritional support group with NRS2002<3 were provided with a regular diet three days prior to surgery, whereas those with NRS2002≥3 received intravenous fat emulsion amino acid glucose for nutritional support. In the enteral nutrition preconditioning group, patients with NRS2002<3 received 500 mL/d of enteral nutrition suspension orally in addition to their regular diet for 3 days preoperatively; those with NRS2002≥3 received received 1000 mL/d of enteral nutrition suspension orally or via gastric tube. Postoperative hospital stay, time to gas passage and defecation, hospital expenses, gastrointestinal dysfunction incidence including diarrhea, abdominal distension and constipation, postoperative routine blood indicators, anastomotic fistula occurrence as well as infectious complications such as pneumonia and wound infection were compared between groups. Measurement data with normal distribution was expressed as Mean±SD, independent sample t-test was used on comparison between groups. Counting data was expressed as case(%), χ2 test was used on comparison between groups, P<0.05 was considered as statistically significant. Results:The incidence of anastomotic leakage and infectious complications in the enteral nutrition pre-adaptation group was 4.83% (7/145) and 4.83% (7/145), respectively, showing no statistically significant differences compared to the traditional nutrition support group [2.86% (2/70) and 8.57% (6/70)] ( χ2=0.46 and 1.16, P=0.499 and 0.280, respectively). The incidences of gastrointestinal dysfunction and overall complications in the enteral nutrition pre-adaptation group were 5.52% (8/145) and 13.10% (19/145), respectively, which were significantly lower than those in the traditional nutrition support group [37.14% (26/70) and 45.71% (32/70)] ( χ2=35.47 and 27.75, both P<0.001). Postoperative outcomes in the enteral nutrition pre-adaptation group, including hospital stay (14.05±3.75 days), time to first flatus (25.75±5.03 hours), time to first defecation (49.25±5.98 hours), and hospitalization costs (85,200±13,500 CNY), were significantly better than those in the traditional nutrition support group [(16.46±4.79 days, 31.53±6.55 hours, 63.45±11.43 hours, and 93,500±20,100 CNY)] ( t=3.70, 6.52, 9.77, and 3.17, all P<0.001). No significant differences were observed in routine postoperative blood tests between the two groups (all P>0.05). Stratified analysis revealed that among patients with preoperative nutritional risk, the enteral nutrition pre-adaptation group demonstrated superior outcomes in hospitalization costs (82,300±11,000 CNY), time to first flatus (26.17±5.69 hours), time to first defecation (50.31±5.59 hours), overall complication rate (15.79%), and gastrointestinal dysfunction rate (7.89%) compared to the traditional nutrition support group [100,800±28,800 CNY, 31.42±6.29 hours, 60.80±9.89 hours, 54.55%, and 40.91%] ( t=2.89, P=0.008; t=3.32, P=0.002; t=4.57, P<0.001; χ2=9.97, P=0.002; χ2=9.49, P=0.002). Similarly, among patients without preoperative nutritional risk, the enteral nutrition pre-adaptation group showed better results in hospital stay (13.69±3.83 days), time to first flatus (25.60±4.80 hours), time to first defecation (48.87±6.10 hours), overall complication rate (12.15%), and gastrointestinal dysfunction rate (4.67%) compared to the traditional nutrition support group [16.60±4.36 days, 31.58±6.73 hours, 64.67±11.98 hours, 41.67%, and 35.42%] ( t=4.19, t=5.56, t=8.65, χ2=17.23, χ2=25.72, all P<0.001). Conclusion:Enteral nutrition pre-adaptation positively impacts post-esophagectomy nutrition-related complications and gastrointestinal dysfunction.nutrtional support before surgery can't be neglected.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To investigate the role of WW domain containing E3 ubiquitin protein ligase 1 (WWP1) in enamel development of mice.Methods:Single-cell RNA sequencing data of incisor tissues of postnatal day 7 (P7) mice and mandibular first molar tooth germs of P3.5 mice were used to analyze the expression of Wwp1 in dental epithelial cells. Immunohistochemistry was performed to observe the distribution and expression levels of WWP1 in the epithelium of mouse incisors and mandibular first molar tooth germs. Wwp1 knockout (Wwp1 KO) mice were generated and collected with their control littermates at P1, P7, three mice per group, as well as at P14, P28, 2 months (2M), and 3M, six mice per group. The enamel volumes of molars and incisors were analyzed using micro-CT. Scanning electron microscopy was employed to examine the enamel cross-sections of Wwp1 KO and control mice. Energy dispersive spectroscopy (EDS) was used to analyze the calcium and phosphorus content of the enamel rod of incisors. Immunofluorescence was performed to detect the expression of amelogenin (AMELX) in the ameloblasts of Wwp1 KO and control mice. Additionally, LS-8 ameloblast-like epithelial cells were cultured, and Wwp1 siRNA or overexpression plasmids were transfected to knock down or overexpress WWP1. The protein levels of AMELX were then assessed by Western blotting.Results:Single-cell sequencing result showed a high Wwp1 mRNA expression level in the epithelial cells of mouse incisors and mandibular molar tooth germs. Immunohistochemistry revealed the expression of WWP1 in presecretory, secretory, transitional, and mature ameloblasts. Wwp1 KO mice exhibited enamel developmental defects. The enamel volumes of molars and incisors in Wwp1 KO mice [(0.155±0.016), (0.300±0.017) μm 3] were reduced by 23.95% ( P<0.001) and 28.31% ( P<0.001) compared with the control group [(0.203±0.062), (0.418±0.023) μm 3] respectively. Scanning electron microscopy showed disorganized enamel structures in Wwp1 KO incisors and molars. EDS results showed the weight percent of calcium in the enamel rod of incisors decreased in Wwp1 KO mice [(20.74±0.91)%] compared with the control group [(30.30±3.83)%] ( P<0.001), and the calcium-to-phosphorus ratio decreased in Wwp1 KO mice (1.93±0.01) compared with the control group (2.02±0.01) ( P<0.001). Immunofluorescence showed weaker AMELX expression in ameloblasts of mandibular first molar tooth germs from P1 and P7 Wwp1 KO mice compared with the control group ( P<0.001, P<0.001). In LS-8 cells, Wwp1 knocked-down led to a decrease of AMELX protein expression, while WWP1 overexpression resulted in an increased AMELX protein level. Conclusions:WWP1 promotes ameloblast differentiation and enamel matrix mineralization, playing a critical role in enamel formation.

Objective:To observe the clinical efficacy of unilateral biportal endoscopy (UBE) assisted bilateral decompression in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side.Methods:A total of 20 patients with lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side treated with UBE from January 2022 to January 2024 in the Affiliated Hospital of Binzhou Medical University were retrospectively analyzed. There were 9 males and 11 females, aged 50.4±14.0 years (range, 23-72 years). The intervertebral disc herniation level included L 3-4 in 1 case, L 4-5 in 15 cases, and L 5S 1 in 4 cases. There were 10 cases on the left side and 10 cases on the right side. The duration of symptoms was 24.1±33.7 months (range, 1-120 months). Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to evaluate postoperative pain relief and functional recovery. The clinical efficacy was evaluated by modified MacNab criteria at 6 months after operation. Results:All patients successfully completed the operation. The operation time was 90.3±24.6 min (range, 55-134 mins). The VAS scores of patients at 3 days, 1 month, 3 months and 6 months after operation were 3.6±0.9, 2.2±0.7, 1.2±0.5 and 1.0±0.6, respectively, which were lower than those before operation (6.4±0.8), and the differences were statistically significant ( F=668.728, P<0.001). The ODI at 3 days, 1 month, 3 months and 6 months after operation were 34.2%±4.7%, 28.7%±2.8%, 24.3%±2.1% and 20.5%±2.0%, respectively, which were lower than 69.4%±5.2% before operation, and the differences were statistically significant ( F=515.578, P<0.001). The clinical efficacy was evaluated by modified MacNab criteria at 6 months after operation. Among 20 patients, 18 cases were excellent, 1 case was good, and 1 case was fair. All patients were followed up for 9.1±2.1 months (range, 6-14 months). One patient had a dural tear during the operation, but the range was small and there was no defect, and no further treatment was performed. Numbness of the lower limbs occurred 1 day after operation, and the symptoms disappeared after symptomatic treatment. There was no recurrence of lower limb symptoms, lumbar instability, intervertebral space infection or other complications at the last follow-up. Conclusion:Bilateral decompression with UBE is effective in the treatment of lumbar disc herniation with imaging herniation on one side and clinical symptoms on the contralateral side, which can improve the lumbar pain and function of patients.