[Objective] To investigate the infection status and characteristics of HEV among voluntary blood donors in Ningbo, and to provide a basis for improving the blood screening strategy. [Methods] A total of 12 227 blood samples from voluntary blood donors in Ningbo from June 2022 to May 2023 were tested for HEV serology, enzymology, and nucleic acid testing. Furthermore, HEV gene sequencing was performed for genotyping analysis, and donors with reactive nucleic acid testing results were followed up to confirm their infection status. [Results] The reactivity rate of HEV Ag, anti-HEV IgM and anti-HEV IgG was 0.098%, 0.899% and 29.198%, respectively. There was no difference in the reactivity of anti-HEV IgM and anti-HEV IgG between genders, donation frequencies and donation types (P>0.05). The reactivity rate increased significantly with age (P<0.05). The rate of ALT disqualification (ALT>50U/L) was significantly higher than that in non-reactive samples (P<0.05). The HEV Ag reactivity rate (0.098%) was not correlated with gender, donation frequency, donation type or age. One HEV RNA positive case was found, with a positive rate of 0.008%(1/12 227). It was confirmed to be hepatitis E virus genotype 3 by sequencing analysis. Apart from HEV Ag reactivity, all other blood safety screening items were non-reactive, suggesting this case might be in the acute infection phase. The follow-up results showed that all indicators of the donor's previous blood donation were non-reactive. [Conclusion] Pre-donation ALT detection can reduce the risk of transfusion-transmitted HEV (TT-HEV) to a certain extent, and the effective way to prevent TT-HEV is to detect HEV RNA and serology of donor blood.

Objective To compare the effects of preserving and releasing the inferior pulmonary ligament (IPL) during thoracoscopic right upper lobe apical segment resection for non-small cell lung cancer patients, and to explore appropriate management methods for intraoperative IPL. Methods According to the prospective and open principle, the patients with non-small cell lung cancer who underwent thoracoscopic right upper lobe apical segment resection in the Cardiothoracic Surgery Department of Ningbo Second Hospital from January 2020 to November 2022 were selected and divided into two groups: a release group (receiving IPL release during thoracoscopic right upper lobe apical segment resection) and a retention group (receiving the same right upper lobe apical segment resection, but retaining IPL during operation). The clinical data of the two groups were compared. Results A total of 70 patients were included in this study, including 33 males and 37 females, aged 35-76 years. There were 35 patients in the release group with an average age of (57.02±9.25) years; 35 patients in the retention group with an average age of (56.81±9.94) years. The surgical time in the release group was statistically longer than that in the retention group (P=0.017). There was no statistical difference between the two groups in terms of intraoperative bleeding, duration of postoperative air leakage, time to achieve lung recruitment, drainage flow rate of the chest tube, retention time of the chest tube, incidence of postoperative complications, postoperative hospitalization days, or residual cavity rate one month after the surgery (P>0.05). Conclusion Compared to releasing IPL during thoracoscopic right upper lobe apical segment resection, preserving IPL can simplify surgical procedures, shorten surgical time and reduce trauma, and does not increase postoperative adverse effects. This further reflects the concept of minimally invasive surgery and can be applied to clinical practice.

Oral squamous cell carcinoma (OSCC) is the most common head and neck malignancy worldwide, accounting for more than 90% of all oral cancers, and is characterized by high invasiveness and poor long-term prognosis. Its etiology is multifactorial, involving tobacco use, alcohol consumption, and human papillomavirus (HPV) infection. Oral leukoplakia and erythroplakia are the main precancerous lesions lesions, with oral leukoplakia being the most common. Both OSCC and premalignant lesions are closely associated with aberrant activation of multiple signaling pathways. Post-translational modifications (such as ubiquitination and deubiquitination) play key roles in regulating these pathways by controlling protein stability and activity. Growing evidence indicates that dysregulated ubiquitination/deubiquitination can mediate OSCC initiation and progression via aberrant activation of signaling pathways. The ubiquitination/deubiquitination process mainly involves E3 ligases (E3s) that catalyze substrate ubiquitination, deubiquitinating enzymes (DUBs) that remove ubiquitin chains, and the 26S proteasome complex that degrades ubiquitinated substrates. Abnormal expression or mutation of E3s and DUBs can lead to altered stability of critical tumor-related proteins, thereby driving OSCC initiation and progression. Therefore, understanding the aberrantly activated signaling pathways in OSCC and the ubiquitination/deubiquitination mechanisms within these pathways will help elucidate the molecular mechanisms and improve OSCC treatment by targeting relevant components. Here, we summarize four aberrantly activated signaling pathways in OSCC―the PI3K/AKT/mTOR pathway, Wnt/β-catenin pathway, Hippo pathway, and canonical NF-κB pathway―and systematically review the regulatory mechanisms of ubiquitination/deubiquitination within these pathways, along with potential drug targets. PI3K/AKT/mTOR pathway is aberrantly activated in approximately 70% of OSCC cases. It is modulated by E3s (e.g., FBXW7 and NEDD4) and DUBs (e.g., USP7 and USP10): FBXW7 and USP10 inhibit signaling, while NEDD4 and USP7 potentiate it. Aberrant activation of the Wnt/β‑catenin pathway leads to β‑catenin nuclear translocation and induction of cell proliferation. This pathway is modulated by E3s (e.g., c-Cbl and RNF43) and DUBs (e.g., USP9X and USP20): c-Cbl and RNF43 inhibit signaling, while USP9X and USP20 potentiate it. Hippo pathway inactivation permits YAP/TAZ to enter the nucleus and promotes cancer cell metastasis. This pathway is modulated by E3s (e.g., CRL4^DCAF1 and SIAH2) and DUBs (e.g., USP1 and USP21): CRL4^DCAF1 and SIAH2 inhibit signaling, while USP1 and USP21 potentiate it. Persistent activation of the canonical NF-κB pathway is associated with an inflammatory microenvironment and chemotherapy resistance. This pathway is modulated by E3s (e.g., TRAF6 and LUBAC) and DUBs (e.g., A20 and CYLD): A20 and CYLD inhibit signaling, while TRAF6 and LUBAC potentiate it. Targeting these E3s and DUBs provides directions for OSCC drug research. Small-molecule inhibitors such as YCH2823 (a USP7 inhibitor), GSK2643943A (a USP20 inhibitor), and HOIPIN-8 (a LUBAC inhibitor) have shown promising antitumor activity in preclinical models; PROTAC molecules, by binding to surface sites of target proteins and recruiting E3s, achieve targeted ubiquitination and degradation of proteins insensitive to small-molecule inhibitors, for example, PU7-1-mediated USP7 degradation, offering new strategies to overcome traditional drug limitations. Currently, NX-1607 (a Cbl-b inhibitor) has entered phase I clinical trials, with preliminary results confirming its safety and antitumor activity. Future research on aberrant E3s and DUBs in OSCC and the development of highly specific inhibitors will be of great significance for OSCC precision therapy.

Objective To identify the independent predictors of programmed death-1 (PD-1) inhibitor-related endocrine adverse events and construct a clinically usable risk prediction model. Methods A total of 302 patients with solid tumors treated with PD-1 inhibitors were retrospectively enrolled. According to the presence or absence of endocrine immune-related adverse events (irAEs), the patients were divided into case group and control group. The clinical and laboratory indexes were compared between the two groups. Multivariable logistic regression was used to confirm independent predictors of endocrine irAEs. The nomogram was constructed, while the receiver operating characteristic (ROC) curve was used to test the prediction performance of the model. Results The overall incidence of endocrine irAEs was 21.9% (66/302), and the incidence of hypothyroidism was 19.5% (59/302). The age, PD-1 inhibitors, free thyroxine, thyroid peroxidase antibody (TPOAb), thyroglobulin, amylase, lymphocyte subset CD3 expression were statistically different between the two groups (P＜0.05). Multivariable logistic regression showed that higher expression of lymphocyte subset CD3 was a protective factor to prevent endocrine irAEs occurrence (P＝0.004), while age＜60 years, higher TPOAb and use of pembrolizumab were independent risk factors of endocrine irAEs (P＜0.05). The nomogram model thus constructed, and when the threshold probability of the model exceeded 0.1, its net benefit was higher. ROC curve showed that the AUC of the model to predict endocrine irAEs was 0.760. The prediction result of the model was highly consistent with the actual result. Conclusions The age, type of PD-1 inhibitor, baseline TPOAb level, and baseline CD3 expression can independently predict endocrine irAEs occurrence or not. The nomogram model based on this model has good predictive efficiency, which can provide reference for early identification of high-risk patients and immunotherapy management.

OBJECTIVE: To investigate the feasibility and effectiveness of the novel bone hook combined with finger-guided technique in the treatment of irreducible intertrochanteric femoral fractures in elderly. METHODS: Between January 2021 and August 2023, 23 elderly patients with irreducible intertrochanteric femoral fractures were treated with the novel bone hook combined with finger-guided technique. There were 10 males and 13 females; the age ranged from 68 to 93 years (mean, 76.2 years). The time from injury to operation ranged from 36 to 76 hours (mean, 51.2 hours). According to the classification standard proposed by TONG Dake et alin 2021, there were 10 cases of typeⅠA, 1 case of typeⅠB, 6 cases of type ⅡA, 4 cases of type ⅡB, and 2 cases of type ⅡC. The operation time, intraoperative blood loss, intraoperative fluoroscopy frequences, and quality of fracture reduction were recorded. The fracture healing time and occurrence of postoperative complications were observed during follow-up. At last follow-up, the Harris scoring system was used to evaluate the hip joint function. RESULTS: The operation time was 42-95 minutes (mean, 52.1 minutes). The intraoperative blood loss was 40-420 mL (mean, 126.5 mL). Intraoperative fluoroscopy was performed 14-34 times (mean, 20.7 times). According to the criteria proposed by Chang et al, the quality of fracture reduction was rated as good in 20 cases and acceptable in 3 cases. All patients were followed up 6-20 months (mean, 10.2 months). X-ray film showed that all fractures healed with the healing time of 3.0-5.5 months (mean, 4.0 months). At last follow-up, the Harris score of the hip joint ranged from 82 to 97 points (mean, 90.4 points). Among them, 14 cases were rated as excellent and 9 cases as good. No complication such as coxa vara, cutting of the cephalomedullary nail, nail withdrawal, or nail breakage occurred during follow-up. CONCLUSION The treatment of elderly patients with irreducible intertrochanteric femoral fractures by using the novel bone hook combined with finger-guided technique can achieve high-quality fracture reduction and fixation, and has a good effectiveness.
Humans ; Male ; Female ; Aged ; Aged, 80 and over ; Hip Fractures/diagnostic imaging* ; Fracture Fixation, Internal/instrumentation* ; Fracture Healing ; Treatment Outcome ; Operative Time ; Fracture Fixation, Intramedullary/instrumentation* ; Bone Nails ; Postoperative Complications/epidemiology* ; Feasibility Studies ; Fingers

PURPOSE: Percutaneous ilio-sacral screw (ISS) insertion using conventional C-arm fluoroscopy has been a widely employed technique for pelvic posterior ring fixation, particularly in developing regions. However, this approach presents technical challenges, leading to a high malposition rate. We introduced a new method for ISS insertion without additional equipment or software and suggested whether it could reduce the malposition rate and operating time. METHODS: This is a retrospective cohort study. The study included all patients who underwent percutaneous ISS fixation between January 2020 and December 2022. Patients treated with open reduction or other types of implants were excluded. The patients were divided into 2 groups based on the screw insertion method: Group A utilized the traditional dual-plane adjustment method, while Group B received the newly introduced method. In all cases, conventional C-arm fluoroscopy was the sole guidance during the surgical procedure. Malposition rate, radiation exposure, and operating time were compared between groups. Post-operative CT scans were used to assess screw accuracy using the Smith grading method. The Student's t-test or the Mann-Whitney U test was chosen for comparing the quantitative variables based on the normality test results. The Chi-squared test was utilized for comparing qualitative variables. RESULTS: A total of 72 patients with pelvic posterior ring disruption treated with percutaneous ISS under conventional fluoroscopy guidance were included in this study. Among them, 32 patients were in Group A and 40 patients were in Group B. In Group B, the average operation duration per screw was 33 min with 29 fluoroscopy applications, which was significantly lower than that in Group A (44 min, p < 0.001, 38 times, p < 0.001, respectively). Furthermore, the post-operative CT scan revealed that only 10.7% (6/56) of screws in Group B were inappropriately positioned according to the Smith criteria. CONCLUSION The novel method introduced in this study demonstrated a reduction in both malposition rates and operating time compared to the traditional dual-plane adjustment method. Precise pre-operative CT planning in conjunction with conventional fluoroscopy could establish this method as a widely applicable technique for percutaneous ISS fixation.
Humans ; Fluoroscopy/methods* ; Retrospective Studies ; Bone Screws ; Female ; Male ; Tomography, X-Ray Computed/methods* ; Sacrum/diagnostic imaging* ; Middle Aged ; Operative Time ; Adult ; Fracture Fixation, Internal/methods* ; Ilium/diagnostic imaging* ; Aged

PURPOSE: The secondary damage of spinal cord injury (SCI) starts from the collapse of the blood spinal cord barrier (BSCB) to chronic and devastating neurological deficits. Thereby, the retention of the integrity and permeability of BSCB is well-recognized as one of the major therapies to promote functional recovery after SCI. Previous studies have demonstrated that activation of hypoxia inducible factor-1α (HIF-1α) provides anti-apoptosis and neuroprotection in SCI. Endogenous HIF-1α, rapidly degraded by prolylhydroxylase, is insufficient for promoting functional recovery. Dimethyloxalylglycine (DMOG), a highly selective inhibitor of prolylhydroxylase, has been reported to have a positive effect on axon regeneration. However, the roles and underlying mechanisms of DMOG in BSCB restoration remain unclear. Herein, we aim to investigate pathological changes of BSCB restoration in rats with SCI treated by DOMG and evaluate the therapeutic effects of DMOG. METHODS: The work was performed from 2022 to 2023. In this study, Allen's impact model and human umbilical vein endothelial cells were employed to explore the mechanism of DMOG. In the phenotypic validation experiment, the rats were randomly divided into 3 groups: sham group, SCI group, and SCI + DMOG group (10 rats for each). Histological analysis via Nissl staining, Basso-Beattie-Bresnahan scale, and footprint analysis was used to evaluate the functional recovery after SCI. Western blotting, TUNEL assay, and immunofluorescence staining were employed to exhibit levels of tight junction and adhesion junction of BSCB, HIF-1α, cell apoptosis, and endoplasmic reticulum (ER) stress. The one-way ANOVA test was used for statistical analysis. The difference was considered statistically significant at p < 0.05. RESULTS: In this study, we observed the expression of HIF-1α reduced in the SCI model. DMOG treatment remarkably augmented HIF-1α level, alleviated endothelial cells apoptosis and disruption of BSCB, and enhanced functional recovery post-SCI. Besides, the administration of DMOG offset the activation of ER stress induced by SCI, but this phenomenon was blocked by tunicamycin (an ER stress activator). Finally, we disclosed that DMOG maintained the integrity and permeability of BSCB by inhibiting ER stress, and inhibition of HIF-1α erased the protection from DMOG. CONCLUSIONS Our findings illustrate that the administration of DMOG alleviates the devastation of BSCB and HIF-1α-induced inhibition of ER stress.
Spinal Cord Injuries/pathology* ; Animals ; Apoptosis/drug effects* ; Amino Acids, Dicarboxylic/therapeutic use* ; Recovery of Function/drug effects* ; Rats ; Rats, Sprague-Dawley ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Male ; Spinal Cord/blood supply*

BACKGROUND: Acupuncture therapy provides a complementary and alternative approach to treating major depressive disorder (MDD), but its efficacy and safety have still not been comprehensively assessed. Recently published systematic reviews remain confusing and inconclusive. OBJECTIVE: This systematic review evaluated the efficacy and safety of acupuncture therapy alone or combined with antidepressants for adult patients with mild and moderate MDD. SEARCH STRATEGY: Chinese Biomedical Literature Database, China National Knowledge Infrastructure Database, Wanfang Database, Chinese Science and Technology Journal Database, PubMed, Embase, and Cochrane Library were searched from their inceptions to March 2025. INCLUSION CRITERIA: Randomized controlled trials that compared acupuncture therapy with antidepressants, or acupuncture therapy plus antidepressants with acupuncture therapy or antidepressants for adult patients with mild and moderate MDD were included. DATA EXTRACTION AND ANALYSIS: Five reviewers independently extracted data from original literature using a standardized form, and the data were verified by two reviewers to ensure accuracy. Statistical meta-analyses, publication bias analyses, and subgroup analyses were performed by using Review Manager 5.3 software. The Grading of Recommendations Assessment, Development, and Evaluation approach was used to assess the certainty of the evidence. RESULTS: A total of 60 eligible studies including 4675 participants were included. Low-certainty evidence showed that compared with antidepressants, acupuncture therapy (standardized mean difference [SMD] = -0.57; 95% confidence interval [CI] = [-0.87, -0.27]; I² = 86%; P = 0.006) or acupuncture therapy plus antidepressants (SMD = -1.00; 95% CI = [-1.18, -0.81]; I² = 77%; P < 0.00001) may reduce the severity of depression at the end of treatment. Low-certainty evidence indicated that compared with acupuncture therapy alone, acupuncture therapy plus antidepressants slightly reduced the severity of depression at the end of treatment (SMD = -0.38; 95% CI = [-0.61, -0.14]; I² = 18%; P = 0.002). Similar results were also found for acupuncture's relief of insomnia. The reported adverse effects of acupuncture therapy were mild and transient. For most of the subgroup analyses, acupuncture type, scale type, and the course of treatment did not show a significant relative effect. CONCLUSION Acupuncture therapy may provide antidepressant effects and relieve insomnia with mild adverse effects for adult patients with mild and moderate MDD. But the certainty of evidence was very low. More high-quality, well designed, large-scale studies with long-term follow-up are needed in the future. Please cite this article as: Kuang HJ, Yang HS, Feng YX, Tang H, Fan Q, Xu YQ, Cui S, Musil R, Luxenburger H, Zhang YX, Zhao H, Zhang YQ. Efficacy and safety of acupuncture therapies for adult patients with mild and moderate major depressive disorder: A systematic review and meta-analysis. J Integr Med. 2025; 23(5):471-491.
Humans ; Acupuncture Therapy/methods* ; Depressive Disorder, Major/therapy* ; Adult ; Antidepressive Agents/therapeutic use* ; Treatment Outcome ; Randomized Controlled Trials as Topic

OBJECTIVE To study the difference of Huangqin decoction combined with Paeoniae Radix Alba(BS) and Paeoniae Radix Rubra(CS)'s effect on ulcerative colitis(UC) based on network pharmacological analysis and animal experiment. METHODS The active constituents of BS and CS were retrieved from TCMSP database and literature, and the potential target was predicted by Swiss Target Prediction. Ulcerative Colitis was used as key words to search disease targets in DisGenet, OMIM, and Genecard databases. The intersection target was obtained by Venny 2.1.0. Cytoscape 3.7.2 software was used to construct network of drug-consumption targets. The STRING platform was used for protein-protein interaction(PPI) network analysis, and Metascape database was applied for GO/WIKI analysis. A dextran sulfate sodium(DSS) induced UC mouse model was established to compare the anti-UC effects of Huangqing decoction combined with BS(HQT-BS) and CS(HQT-CS), respectively. RESULTS There were 7 active components of HQT-BS and 11 active components of HQT-CS in the treatment of ulcerative colitis, respectively, 5 of which were the same. There were 146 and 157 targets respectively, 106 of which were the same. The core targets of HQT-BS were SRC, HSP90AA1, and PIK3R1, while the core targets of HQT-CS were SRC, HSP90AA1, and STAT3. WIKI enrichment analysis showed that several signaling pathways were shared by both BS and CS, such as EGFR tyrosine kinase inhibitor resistance, Notch signaling pathway. EGF/EGFR signaling pathway was the specific pathway related to BS, while Nuclear receptors meta-pathway and Kit receptor signaling pathway were the specific pathways related to CS, respectively. Animal experiments showed that both HQT-BS and HQT-CS could significantly improve colon shortening and tissue pathological alternation induced by DSS. However, HQT-CS was more effective in reducing the expression of interleukin-6 and neurogenic locus notch homolog protein1. CONCLUSION Both HQT-BS and HQT-CS have anti-UC effect, and HQT-CS is the better one.

Photodynamic therapy is an emerging cancer therapy with clinical prospects, which plays a specific role in the tumor site and causes less harm to the human body. However, the toxicity of small molecules of hydrophobic photosensitizer, the tumor hypoxia microenvironment, and the biodegradability of nano-carrier systems affect its antitumor efficacy and metabolic clearance in vivo. In this paper, hexachloroplatinic acid was used as a novel oxidizing agent to initiate oxidative polymerization of pyrrole/amino pyrrole to achieve the amino functionalization; further reduced platinum acid anion in the nanostructures into platinum nanoclusters by sodium borohydride as a reducing agent to fabricate platinum nanocluster-doped polypyrrole nanoparticles (PtPPy); and finally, this functional nanoparticles delivering meso-tetra (4-carboxyphenyl) porphine (TCPP) were obtained by amide-bonded coupling of photosensitizers TCPP drug (PtPPy@T). The nanomedicine had a spherical structure, uniform morphology, a particle size of 91.93 ± 13.45 nm, and a zeta potential of -18.39 ± 1.4 mV. Experiments demonstrated that PtPPy@T could react with hydrogen peroxide overexpressed in the tumor to generate a large amount of oxygen, which could relieve the tumor hypoxia microenvironment, and at the same time, provided a sufficient substrate for the subsequent PDT; using 658 nm laser irradiation, the photodynamic effect of PtPPy@T was activated, which catalyzed the conversion of oxygen to singlet oxygen, thus triggering oxidative damage and inducing apoptosis in tumor cells; experimental studies showed that the PtPPy@T nanomedicine had a better tumor inhibitory effect in vivo and in vitro. All animal experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Radiological Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College (IRM/2-IACUC-2312-006).