Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

Compared to in vitro purified protein complexes, protein complexes in a working state within cells are often more complete, and their three-dimensional structures are in a fully physiological conformation. This is crucial for understanding the structural basis of important functions that protein complexes play in life activities and can also provide more precise target information for drug design. The direct in situ structural analysis of protein complexes within cells is known as in situ structural analysis of proteins, and cryo-electron tomography (cryo-ET) is the key technology for in situ structural analysis. However, cryo-ET has limitations such as low data acquisition throughput for tilt series, cumbersome data processing, and special sample requirements to achieve near-atomic resolution. These issues have become bottlenecks limiting the resolution and practical application of in situ structural analysis. In recent years, a method based on the analysis of non-tilted images has developed rapidly, allowing high-throughput, high-resolution structural analysis of protein complexes within cells. This review will discuss the principles of this method, compare its advantages and disadvantages with traditional tomography, and provide an outlook on in situ structural analysis of proteins. It is hoped that this review will assist structural biologists in better choosing suitable tools.

Objective To explore the disinfection effect of ozone combined with peracetic acid(PAA)on reducing the total number of aerobic bacteria in pure water from the terminal of centralized pure water supply system.Methods A two-stage controlled study was conducted,and microbial limit test was performed on the pure water from the ter-minal of centralized pure water supply system in a hospital.At the first stage,PAA disinfection method was adop-ted,and ozone enhanced disinfection(PAA combined with ozone disinfection)was adopted at the second stage.Dis-infection effects at different stages were compared.Results A total of 211 water specimens were collected for tes-ting,including 101 specimens from PAA disinfection group and 110 from ozone enhanced disinfection group.The bacterial colony qualification rate of terminal pure water from the ozone enhanced disinfection group was higher than PAA group(85.45％vs 74.26％,P=0.04).The median of aerobic bacterial colony number of the ozone enhanced disinfection group(2 CFU/mL)was significantly lower than that of the PAA disinfection group(20 CFU/mL).With time increase after disinfection,the number of aerobic bacteria colony in water specimens from the PAA disinfection group showed a significant upward trend(Day 1 vs Day 92:9 CFU/mL vs 1 062 CFU/mL),while the aerobic bac-teria fluctuation range in the pure water from the ozone enhanced disinfection group was relatively small(Day 1 vs Day 92:8 CFU/mL vs 58 CFU/mL).Conclusion The ozone combined with PAA disinfection method can signifi-cantly reduce the total number of aerobic bacteria in water from the terminal of centralized pure water supply sys-tem,with obvious maintaining effect.

Cardiac cephalalgia is a rare disease caused by underlying coronary artery disease that presents as headache with or without chest symptoms.Headache symptoms are often caused by referred pain,increased intracranial pressure and release of large amounts of pain-causing neurochemicals due to myocardial ischemia,and cortical hypoperfusion.Due to the low overall prevalence of the disease,the lack of chest pain typical of coronary heart disease,and the fact that it may be difficult to distinguish from headaches caused by neurological diseases,accurate diagnosis and treatment of the disease are often delayed.We report a case of acute coronary syndrome with headache only.Revascularization was achieved through percutaneous coronary intervention therapy,followed by standard secondary prevention pharmacotherapy.Follow-up six months postoperatively showed a significant improvement in exercise tolerance,with no further headache episodes.The purpose is to improve the understanding of patients with cardiac cephalalgia,with a view to early identification and timely intervention,and ultimately improve the symptoms and prognosis.

Objective: To explore the characteristics of pulmonary blood flow perfusion imaging of single photo emission computer tomography/computer tomography (SPECT/CT) in chronic pulmonary vascular Stenosis (CPVS) caused by different etiological factors. Methods: This is a retropective study. Present study screened 50 consecutive cases diagnosed with chronic pulmonary vascular stenosis from January 2019 to January 2020 in the department of cardiology of Gansu Provincial Hospital and underwent SPECT/CT pulmonary blood flow perfusion examination. Thirteen patients were excluded because of pulmonary vascular lesions with a disease course of less than 3 months and poor image quality. According to the etiology, patients were divided into fibrosing mediastinitis (FM) group, Takyasu's arteritis (PTA) group, and chronic thromboembolic pulmonary hypertension/chronic thromboembolic pulmonary disease (CTEPH/CTED) group. The severity of pulmonary blood flow perfusion was evaluated in accordance with the Begic scoring principle in the three groups. The overall Begic score, lung lobe scores among three groups were compared. CT signs of lung SPECT/CT, such as enlargement of hilar lymph node, atelectasis, bronchial stenosis, were also analyzed in three groups. Results: A total of 37 patients with chronic pulmonary vascular stenosis were finally enrolled (18 in the FM group, 5 in the PTA group, and 14 in the CTEPH/CTED group). The total Begic score of pulmonary perfusions was similar among the three groups (F=0.657,P>0.05). There was a statistically significant difference in the left upper lobe Begic score among the three groups (H=4.081, P<0.05). The left upper lobe Begic score was higher in the FM group than in the PTA group (3.44±2.50 vs. 1.60±0.55, P<0.05). As compared to other two groups, patients in FM group were featured with CT signs of higher percent of hilar enlargement (FM group vs. PTA group: 16/18 vs. 1/5, P=0.008; FM group vs. CTEPH/CTED group: 16/18 vs. 3/14, P=0.000 2), enlargement of the pulmonary hilum lymph nodes (FM group vs. PTA group: 14/18 vs. 1/5, P=0.033; FM group vs. CTEPH/CTED group: 14/18 vs. 2/14, P=0.001), and calcification of mediastinal soft tissue (FM group vs. PTA group: 11/18 to 0/5, P=0.037; FM group vs. CTEPH/CTED group: 11/18 vs. 1/14, P=0.003). The proportion of CT signs of bronchial stenosis (9/18 vs. 0/14, P=0.002) and atelectasis (9/18 vs. 1/14, P=0.002) was also higher in the FM group than in the CTEPH/CTED group. In case of abnormal pulmonary blood flow perfusion, the diagnostic accuracy of CT signs hilar enlargement, hilar lymph node enlargement, mediastinal soft tissue calcification, bronchial stenosis, and atelectasis for the diagnosis of FM were 81.1%, 83.8%, 78.4%, 75.7%, and 73.0%, respectively. Conclusion: There is no significant difference in the Begic score of SPECT/CT pulmonary blood flow perfusion imagines among the three groups of patients. Impaired pulmonary blood flow perfusion combined with typical CT signs is useful for identifying patients with FM.
Humans ; Constriction, Pathologic/diagnostic imaging* ; Perfusion ; Pulmonary Atelectasis ; Mediastinitis ; Calcinosis ; Lung/diagnostic imaging* ; Tomography, Emission-Computed, Single-Photon ; Tomography, X-Ray Computed

Humans ; Embolic Stroke ; Cardiomyopathies ; Stroke ; Atrial Fibrillation ; Risk Factors

Objective To evaluate the safety and efficacy of intravascular lithotripsy(IVL)in the treatment of coronary artery calcification lesions.Methods A total of 53 patients who underwent endovascular imaging guided treatment of coronary artery calcified lesions with either IVL or cutting balloon(CB)at the Affiliated Hospital of Jining Medical College from January 2023 to July 2023 were retrospectively analysed(IVL:n=18,CB:n=35)were retrospectively analysed to compare the technique,clinical success rate,major adverse cardiovascular events(MACE)and readmission for cardiovascular events in patients followed during hospitalisation and 1 month after the procedure.Results Clinical success rates were identical in the IVL and CB groups(100.0％vs.100.0％,P＞0.999),the minimum lumen area of lesions was similar in the VL and CB groups[(1.7±0.4)mm2 vs.(1.7±0.5 mm2),P=0.628].And there was a statistically significant difference in the overall mean lesion length between the IVL and CB groups[(28.4±9.6)mm vs.(20.9±8.6)mm,P=0.008].During the procedure,there were no complications such as aneurysm,thrombus,or emergency vessel closure.There was a statistically significant difference in the overall mean value of residual stenosis between the IVL and CB groups[(1.7±1.7)％vs.(6.9±2.0)％,P=0.049].There were no MACE in either group during hospitalisation or at the one-month follow-up(0 vs.0,P＞0.999),and 3 patients in the CB group were readmitted for angina pectoris(0 vs.8.6％,P=0.543),with no significant difference in readmission rates between the two groups.Conclusions The technique of intravascular lithotripsy is safe and effective in the treatment of coronary artery calcification lesions.

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.