Objective: This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery. Methods: This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression. Results: Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability. Conclusion Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.

This study aims to investigate the in vitro mechanisms underlying the beneficial effects of puerarin on hepatic insulin resistance(IR) based on the carbohydrate response element-binding protein(ChREBP)/peroxisome proliferator-activated receptor(PPAR)α/PPARγ axis involved in glucose and lipid metabolism. An IR-HepG2 cell model was established by treating cells with dexamethasone for 48 h, and the cells were then treated with 10, 20, and 40 μmol·L~(-1) puerarin for 24 h. Glucose levels and output in the extracellular fluid were measured by the glucose oxidase method, while cell viability was assessed by the cell counting kit-8(CCK-8) assay. The adenosine triphosphate(ATP) content and glycogen synthesis were evaluated through chemiluminescence and periodic acid-Schiff staining, respectively. Western blot was employed to quantify the protein levels of forkhead box protein O1(FoxO1), phosphorylated forkhead box protein O1 [p-FoxO1(Ser256)], glucagon, phosphofructokinase, liver type(PFKL), pyruvate kinase L-R(PKLR), pyruvate dehydrogenase complex 1(PDHA1), insulin receptor substrate 2(IRS2), phosphatidylinositol 3-kinase p85(PI3KR1), phosphorylated protein kinase B [p-Akt(Thr308)], glycogen synthase(GYS), glycogen phosphorylase, liver type(PYGL), adiponectin(ADPN), ChREBP, PPARα, and PPARγ. Additionally, the protein levels of acetyl-CoA carboxylase 1(ACC1), phosphorylated ATP citrate lyase [p-ACLY(Ser455)], sterol regulatory element binding protein 1c(SREBP-1c), peroxisome proliferator-activated receptor gamma coactivator 1α(PGC1α), carnitine palmitoyltransferase 1α(CPT1α), and glucagon receptor(GCGR) were also determined. Immunofluorescence was employed to visualize the expression and nuclear location of ChREBP/PPARα/PPARγ. Furthermore, quantitative PCR with the antagonists GW6471 and GW9662 was employed to assess Pparα, Pparγ, and Chrebp. The findings indicated that puerarin effectively reduced both the glucose level and glucose output in the extracellular fluid of IR-HepG2 cells without obvious effect on the cell viability, and it increased intracellular glycogen and ATP levels. Puerarin down-regulated the protein levels of FoxO1 and glucagon while up-regulating the protein levels of p-FoxO1(Ser256), PFKL, PKLR, PDHA1, IRS2, PI3KR1, p-Akt(Thr308), GYS, PYGL, ADPN, ACC1, SREBP-1c, p-ACLY(Ser455), PGC1α, CPT1α, and GCGR in IR-HepG2 cells. Furthermore, puerarin up-regulated both the mRNA and protein levels of ChREBP, PPARα, and PPARγ and promoted the translocation into the nucleus. GW6471 was observed to down-regulate the expression of Pparα while up-regulating the expression of Chrebp and Pparγ. GW9662 down-regulated the expression of Pparγ while up-regulating the expression of Pparα, with no significant effect on Chrebp. In summary, puerarin activated the hepatic ChREBP/PPARα/PPARγ axis, thereby coordinating the glucose and lipid metabolism, promoting the conversion of glucose to lipids to exert the blood glucose-lowering effect.
Isoflavones/pharmacology* ; Humans ; PPAR gamma/genetics* ; Hep G2 Cells ; Glucose/metabolism* ; Lipid Metabolism/drug effects* ; PPAR alpha/genetics* ; Liver/drug effects* ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/genetics* ; Insulin Resistance

This paper aims to investigate the hypoglycemic effect and mechanism of berberine in improving energy metabolism based on the multi-pathway regulation of brain and muscle aromatic hydrocarbon receptor nuclear translocal protein 1(BMAL1): cyclin kaput complex of day-night spontaneous output cyclin kaput(CLOCK). The dexamethasone-induced hepatic insulin resistance(IR) HepG2 cell model was used; 0.5, 1, 5, 10, 20 μmol·L~(-1) berberine were administered at 15, 18, 21, 24, 30, 36 h. The time-dose effect of glucose content in extracellular fluid was detected by glucose oxidase method. The optimal dosage and time of berberine were determined for the follow-up study. Glucose oxidase method and chemiluminescence method were respectively performed to detect hepatic glucose output and relative content of ATP in cells; Ca~(2+), reactive oxygen species(ROS), mitochondrial structure and membrane potential were detected by fluorescent probes. Moreover, ultraviolet colorimetry method was used to detect the liver type of pyruvate kinase(L-PK) and phosphoenol pyruvate carboxykinase(PEPCK). In addition, pyruvate dehydrogenase E1 subunit α1(PDHA1), phosphate fructocrine-liver type(PFKL), forkhead box protein O1(FoxO1), peroxisome proliferator-activated receptor gamma co-activator 1α(PGC1α), glucose-6-phosphatase(G6Pase), glucagon, phosphorylated nuclear factor-red blood cell 2-related factor 2(p-Nrf2)(Ser40), heme oxygenase 1(HO-1), NAD(P)H quinone oxidoreductase 1(NQO1), fibroblast growth factor 21(FGF21), uncoupled protein(UCP) 1 and UCP2 were detected by Western blot. BMAL1:CLOCK complex was detected by immunofluorescence double-staining method, combined with small molecule inhibitor CLK8. Western blot was used to detect PDHA1, PFKL, FoxO1, PGC1α, G6Pase, glucagon, Nrf2, HO-1, NQO1, FGF21, UCP1 and UCP2 in the CLK8 group. The results showed that berberine downregulated the glucose content in extracellular fluid in IR-HepG2 cells in a time-and dose-dependent manner. Moreover, berberine inhibited hepatic glucose output and reduced intracellular Ca~(2+) and ROS whereas elevated JC-1 membrane potential and improved mitochondrial structure to enhance ATP production. In addition, berberine upregulated the rate-limiting enzymes such as PFKL, L-PK and PDHA1 to promote glycolysis and aerobic oxidation but also downregulated PGC1α, FoxO1, G6Pase, PEPCK and glucagon to inhibit hepatic gluconeogenesis. Berberine not only upregulated p-Nrf2(Ser40), HO-1 and NQO1 to enhance antioxidant capacity but also upregulated FGF21, UCP1 and UCP2 to promote energy metabolism. Moreover, berberine increased BMAL1, CLOCK and nuclear BMAL1:CLOCK complex whereas CLK8 reduced the nuclear BMAL1:CLOCK complex. Finally, CLK8 decreased PDHA1, PFKL, Nrf2, HO-1, NQO1, FGF21, UCP1, UCP2 and increased FoxO1, PGC1α, G6Pase and glucagon compared with the 20 μmol·L~(-1) berberine group. BMAL1:CLOCK complex inhibited gluconeogenesis, promoted glycolysis and glucose aerobic oxidation pathways, improved the reduction status within mitochondria, protected mitochondrial structure and function, increased ATP energy storage and promoted energy consumption in IR-HepG2 cells. These results suggested that berberine mediated BMAL1:CLOCK complex to coordinate the regulation of hepatic IR cells to improve energy metabolism in vitro.
Humans ; Berberine/pharmacology* ; Gluconeogenesis/drug effects* ; Hep G2 Cells ; Glucose/metabolism* ; Liver/drug effects* ; Energy Metabolism/drug effects* ; Hypoglycemic Agents/pharmacology* ; ARNTL Transcription Factors/genetics* ; Glycolysis/drug effects* ; Oxidation-Reduction/drug effects*

PURPOSE: The rate of complications among patients undergoing surgery has increased due to infection with SARS-CoV-2 and other variants of concern. However, Omicron has shown decreased pathogenicity, raising questions about the risk of postoperative complications among patients who are infected with this variant. This study aimed to investigate complications and related factors among patients with recent Omicron infection prior to undergoing orthopedic surgery. METHODS: A historical control study was conducted. Data were collected from all patients who underwent surgery during 2 distinct periods: (1) between Dec 12, 2022 and Jan 31, 2023 (COVID-19 positive group), (2) between Dec 12, 2021 and Jan 31, 2022 (COVID-19 negative control group). The patients were at least 18 years old. Patients who received conservative treatment after admission or had high-risk diseases or special circumstances (use of anticoagulants before surgery) were excluded from the study. The study outcomes were the total complication rate and related factors. Binary logistic regression analysis was used to identify related factors, and odds ratio (OR) and 95% confidence interval (CI) were calculated to assess the impact of COVID-19 infection on complications. RESULTS: In the analysis, a total of 847 patients who underwent surgery were included, with 275 of these patients testing positive for COVID-19 and 572 testing negative. The COVID-19-positive group had a significantly higher rate of total complications (11.27%) than the control group (4.90%, p < 0.001). After adjusting for relevant factors, the OR was 3.08 (95% CI: 1.45-6.53). Patients who were diagnosed with COVID-19 at 3-4 weeks (OR = 0.20 (95% CI: 0.06-0.59), p = 0.005), 5-6 weeks (OR = 0.16 (95% CI: 0.04-0.59), p = 0.010), or ≥7 weeks (OR = 0.26 (95% CI: 0.06-1.02), p = 0.069) prior to surgery had a lower risk of complications than those who were diagnosed at 0-2 weeks prior to surgery. Seven factors (age, indications for surgery, time of operation, time of COVID-19 diagnosis prior to surgery, C-reactive protein levels, alanine transaminase levels, and aspartate aminotransferase levels) were found to be associated with complications; thus, these factors were used to create a nomogram. CONCLUSION Omicron continues to be a significant factor in the incidence of postoperative complications among patients undergoing orthopedic surgery. By identifying the factors associated with these complications, we can determine the optimal surgical timing, provide more accurate prognostic information, and offer appropriate consultation for orthopedic surgery patients who have been infected with Omicron.
Humans ; COVID-19/complications* ; Male ; Female ; Middle Aged ; Postoperative Complications/epidemiology* ; SARS-CoV-2 ; Orthopedic Procedures/adverse effects* ; Aged ; Nomograms ; Adult ; Retrospective Studies ; Risk Factors

OBJECTIVES: To evaluate the safety and efficacy of thiotepa (TT)-containing conditioning regimens for allogeneic hematopoietic stem cell transplantation (HSCT) in children with inborn errors of immunity (IEI). METHODS: Clinical data of 22 children with IEI who underwent HSCT were retrospectively reviewed. Survival after HSCT was estimated using the Kaplan-Meier method. RESULTS: Nine patients received a traditional conditioning regimen (fludarabine + busulfan + cyclophosphamide/etoposide) and underwent peripheral blood stem cell transplantation (PBSCT). Thirteen patients received a TT-containing modified conditioning regimen (TT + fludarabine + busulfan + cyclophosphamide), including seven PBSCT and six umbilical cord blood transplantation (UCBT) cases. Successful engraftment with complete donor chimerism was achieved in all patients. Acute graft-versus-host disease occurred in 12 patients (one with grade III and the remaining with grade I-II). Chronic graft-versus-host disease occurred in one patient. The incidence of EB viremia in UCBT patients was lower than that in PBSCT patients (P<0.05). Over a median follow-up of 36.0 months, one death occurred. The 3-year overall survival (OS) rate was 100% for the modified regimen and 88.9% ± 10.5% for the traditional regimen (P=0.229). When comparing transplantation types, the 3-year OS rates were 100% for UCBT and 93.8% ± 6.1% for PBSCT (P>0.05), and the 3-year event-free survival rates were 100% and 87.1% ± 8.6%, respectively (P>0.05). CONCLUSIONS TT-containing conditioning for allogeneic HSCT in children with IEI is safe and effective. Both UCBT and PBSCT may achieve high success rates.
Humans ; Retrospective Studies ; Transplantation Conditioning/methods* ; Thiotepa/therapeutic use* ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child, Preschool ; Infant ; Child ; Transplantation, Homologous ; Graft vs Host Disease ; Adolescent

Eightly-four novel thioheterocyclic nucleoside derivatives were designed, synthesized, and evaluated for antitumor activity in vitro and in vivo. Most of the compounds inhibited the growth of HCT116 and HeLa cancer cells in vitro, among them 33a and 36b exhibited potent activity against HCT116 cells (IC₅₀ = 0.27 and 0.49 μmol/L, respectively). Both compounds 33a and 36b inhibited cell metastasis, arrested the cell cycle in the G₂/M phase, and induced apoptosis in vitro. Mechanistic studies revealed that 33a and 36b increased ROS levels, led to DNA damage, ER stress, and mitochondrial dysfunction, and inhibited autophagy in HCT116 cells. Biological information analysis, RNA-sequencing, Gene Set Enrichment Analysis (GSEA), drug affinity responsive target stability (DARTS) assay, cellular thermal shift assay (CETSA), and SPR experiments identified that compounds 33a and 36b showed antitumor activity by suppressing the c-MYC pathway. c-MYC silencing assays indicated that c-MYC proteins participated in 33a-mediated anticancer activities in HCT116 cells. More importantly, compound 33a presented favorable pharmacokinetic properties in mice (T _1/2 = 6.8 h) and showed significant antitumor efficacy in vivo without obvious toxicity, showing promising potential for further clinical development.

Objective To clarify the effect of unilateral activation of the dopamine type I receptor medium-sized multi-spiny neurons(D1-MSN)in the dorsal striatum of mice on speed.Methods The transgenic animals were combined with optogenetic experiments to specifically activate the D1-MSN in the dorsal striatum of mice at different frequencies and to analyze the rotational behavior and speed of mice when stimulating the D1-MSN.Results Unilateral activation of D1-MSN induces contralateral rotational behavior in mice and either increases or decreases speed.The mechanisms by which different frequencies affect the speed of mice differently.As the frequency of stimulus increased,the contralateral rotational behavior of the mice increased.Unilateral stimulus of D1-MSN increased speed and induced contralateral rotational behavior,and the rotational behavior increased with increasing stimulus frequency.In the experiment where D1-MSN stimulus did not induce rotational behavior,it was found that 5 Hz stimulus still induced an increase in speed,but 15 Hz and 25 Hz stimulus did not induce an increase in speed.Further analysis of the pre-stimulus locomotor state of the mice showed that 5 Hz,15 Hz and 25 Hz stimulus increased speed when the average speed before stimulus was less than 5 cm/s.However,15 Hz stimulus decreased the speed when the average speed before stimulus was greater than 5 cm/s.Conclusion Unilateral activation of D1-MSN in the dorsal striatum modulates speed and induces contralateral rotational behavior in mice,and is related to the frequency of stimulus and the locomotor state of the mice before stimulus.

Objective To propose a lightweight deep learning network-based segmentation method for automatic segmenta-tion of the skeletal muscle at the third cervical spine(C3)level.Methods Firstly,121 patients with head and neck tumors admitted to the Department of Oncology of Zigong First People's Hospital from January 2019 to December 2022 were selected and randomly divided into a training set,a validation set and a test set in the ratio of 7∶1∶2.Secondly,a lightweight Mamba architecture was introduced into the UNet network and an attention gate(AG)mechanism was added to the skip connection path to construct a MB-UNet network model.Finally,the trained network models were evaluated for segmentation performance on the test set,the MB-UNet network model was compared with manual segmentation over the results of determination of skeletal muscle area(SMA),and with classical network models in terms of parameter scale and computation effort including UNet,Deeplab V3+,U2Net,VMUNet and UltraLight-VMUNet models.The time required by the MB-UNet network model for predicting SMA and that by the physician with the assistance of the model was summarized.Results When used for segmenting the skeletal muscle at C3 level the constructued MB-UNet network model gained advantages over the classical models,with a Dice similarity coefficient of 88.23%,an intersection over union(IoU)ratio of 78.94%,a sensitivity of 91.27%and a 95%Hausdorff distance of 7.13 mm;the SMA determined by manual segementation was basically close to that by the MB-UNet network model;the MB-UNet network model behaved generally better than the classical network models,with the computation effort being 1.88 GFLOPS and the parameter scale being 0.77M;it took the MB-UNet network model 1.93 s for the prediction on the test set,and only 2 min for the physician to obtain satisfactory results with the assistance of the MB-UNet network model,which was significantly shorter than that by munual segmentation(20 min).Conclusion The proposed method contributes to segmenting the skeletal muscle at C3 level precisely and rapidly and calculating SMA accurately,which helps clinicians to quickly diagnose sarcopenia in patients with head and neck tumors and improves the diagnostic efficiency.[Chinese Medical Equipment Journal,2025,46(8):11-17]

Background The adverse effects of long working hours, shift rotation, and job stress on the physical and mental health of occupational populations require urgent attention. Objective To investigate and compare the positive rates of WMSDs between different industries, analyze the exposure status of long working hours, shift rotation, and job stress among key occupational groups, and evaluate the impacts of these factors on WMSDs in the manufacturing and service industries. Methods The study subjects were derived from key occupational populations in Yunnan Province, recruited by the Chinese National Occupational Health Literacy Monitoring Survey in 2022. A cross-sectional design was used for this survey. The key occupational populations were recruited from the secondary industry (manufacturing industry, metal mining and beneficiation industry, and non-metal mining and beneficiation industry) by stratified random sampling and from the tertiary industry (medical and healthcare industry, education industry, environmental sanitation industry, transportation industry, and express/takeaway delivery industry) by proportional probability sampling, and 12014 front-line workers were finally included as survey participants. General information, work-related factors (shift rotation, weekly working hours, job stress, etc.) and WMSDs assessment results were obtained through a web-based self-reported questionnaire, and the associations of long working hours, shift rotation, and job stress with WMSDs were analyzed using χ² test and logistic regression. Results The average positive rate of WMSDs among the key occupational groups in Yunnan Province was 77.2%. The positive rate of WMSDs in the secondary industry group was 69.4%, while it was 81.6% in the tertiary industry group, with a statistically significant difference (P<0.001). Among the eight surveyed sectors, the education sector had the highest positive rate of WMSDs (94.2%). The single-site WMSDs mainly involved the neck, shoulders, and low back. In the secondary industry, WMSDs was reported in 1−2 body parts, while in the tertiary industry, WMSDs was mainly reported in multiple (≥5) body parts. Long working hours (OR: 1.119, 1.165, 1.163, respectively), shift rotation (OR: 1.094, 1.199, 1.230, respectively), and job stress (OR: 1.795, 1.854, 2.006, respectively) were risk factors for WMSDs in the neck, shoulder, or low back, and all three were also risk factors for multi-site WMSDs. Moreover, as the number of involved body parts increased, the effects of long working hours and job stress became more pronounced. For 1-2, 3-4, and 5 or more body parts compared to no pain reported, their OR values were 0.971 (95%CI: 0.871, 1.082), 1.133 (95%CI: 1.004, 1.279), and 1.285 (95%CI: 1.155, 1.429) for long working hours, respectively, and the OR values were 1.009 (95%CI: 0.878, 1.160), 1.360 (95%CI: 1.174, 1.575), and 2.797 (95%CI: 2.471, 3.166) for job stress, respectively. Conclusion The positive rate of WMSDs is higher in the tertiary industry than that in the secondary industry among the key occupational groups in Yunnan Province. Long working hours, rotating shift work, and job stress could significantly increase the risk of WMSDs.

Objective: This study investigates the potential of radiomics to predict postoperative progression of ossification of the posterior longitudinal ligament (OPLL) after posterior cervical spine surgery. Methods: This retrospective study included 473 patients diagnosed with OPLL at Peking University Third Hospital between October 2006 and September 2022. Patients underwent posterior spinal surgery and had at least 2 computed tomography (CT) examinations spaced at least 1 year apart. OPLL progression was defined as an annual growth rate exceeding 7.5%. Radiomic features were extracted from preoperative CT images of the OPLL lesions, followed by feature selection using correlation coefficient analysis and least absolute shrinkage and selection operator, and dimensionality reduction using principal component analysis. Univariable analysis identified significant clinical variables for constructing the clinical model. Logistic regression models, including the Rad-score model, clinical model, and combined model, were developed to predict OPLL progression. Results: Of the 473 patients, 191 (40.4%) experienced OPLL progression. On the testing set, the combined model, which incorporated the Rad-score and clinical variables (area under the receiver operating characteristic curve [AUC] = 0.751), outperformed both the radiomics-only model (AUC = 0.693) and the clinical model (AUC = 0.620). Calibration curves demonstrated good agreement between predicted probabilities and observed outcomes, and decision curve analysis confirmed the clinical utility of the combined model. SHAP (SHapley Additive exPlanations) analysis indicated that the Rad-score and age were key contributors to the model’s predictions, enhancing clinical interpretability. Conclusion Radiomics, combined with clinical variables, provides a valuable predictive tool for assessing the risk of postoperative progression in cervical OPLL, supporting more personalized treatment strategies. Prospective, multicenter validation is needed to confirm the utility of the model in broader clinical settings.