Drug impurity control is essential for ensuring pharmaceutical quality.In this study,an unknown impurity at relative retention time(RRT)of 0.45 in Torasemide injection was systematically investigated using high performance liquid chromatography-ion trap time-of-flight mass spectrometry(LC-IT-TOF-MS/MS),forced degradation studies,and nuclear magnetic resonance(NMR)spectroscopy,aiming to elucidate its chemical structure,propose a formation mechanism,and establish a control strategy.By analysis of the ultraviolet absorption spectrum and high-resolution MS1 and MS2 data of the impurity,its possible structure was postulated.Subsequently,the target impurity was prepared via forced degradation experiment,and its structure was confirmed by NMR spectroscopy.A detailed analysis of its formation mechanism revealed that Torasemide first hydrolyzed in solution to form Torasemide sulfonamide,and then underwent condensation,dehydration,and cyclization reactions with trace amounts of formaldehyde in the excipient polyethylene glycol(PEG)400 to generate the impurity.It was experimentally proven that the target impurity was related to the residual oxygen content in Torasemide injection.Ultimately,by optimizing the prescription process,the target impurity level was controlled below the individual impurity limit of the final product(≤0.3%).This study provided valuable insights for enhancing the quality control of Torasemide injection.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of subsequent radiotherapy (RT) following first-line treatment with durvalumab plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). METHODS: A total of 122 patients with ES-SCLC from three hospitals during July 2019 to December 2021 were retrospectively analyzed. Inverse probability of treatment weighting (IPTW) analysis was performed to address potential confounding factors. The primary focus of our evaluation was to assess the impact of RT on progression-free survival (PFS) and overall survival (OS). RESULTS: After IPTW analysis, 49 patients received durvalumab plus platinum-etoposide (EP) chemotherapy followed by RT (Durva + EP + RT) and 72 patients received immunochemotherapy (Durva + EP). The median OS was 17.2 months vs . 12.3 months (hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.17-0.85, P = 0.020), and the median PFS was 8.9 months vs . 5.9 months (HR: 0.56, 95% CI: 0.32-0.97, P = 0.030) in Durva + EP + RT and Durva + EP groups, respectively. Thoracic radiation therapy (TRT) resulted in longer OS (17.2 months vs . 14.7 months) and PFS (9.1 months vs . 7.2 months) compared to RT directed to other metastatic sites. Among patients with oligo-metastasis, RT also showed significant benefits, with a median OS of 17.4 months vs . 13.7 months and median PFS of 9.8 months vs . 5.9 months compared to no RT. Continuous durvalumab treatment beyond progression (TBP) prolonged OS compared to patients without TBP, in both the Durva + EP + RT (NA vs . 15.8 months, HR: 0.48, 95% CI: 0.14-1.63, P = 0.238) and Durva + EP groups (12.3 months vs . 4.3 months, HR: 0.29, 95% CI: 0.10-0.81, P = 0.018). Grade 3 or 4 adverse events occurred in 13 (26.5%) and 13 (18.1%) patients, respectively, in the two groups; pneumonitis was mostly low-grade. CONCLUSION Addition of RT after first-line immunochemotherapy significantly improved survival outcomes with manageable toxicity in ES-SCLC.
Humans ; Small Cell Lung Carcinoma/therapy* ; Retrospective Studies ; Male ; Female ; Middle Aged ; Lung Neoplasms/therapy* ; Aged ; Antibodies, Monoclonal/therapeutic use* ; Adult ; Immunotherapy/methods* ; Aged, 80 and over

Neuroinflammatory responses play an important role in the pathogenesis of various diseases, particularly those affecting the central nervous system. Inhibition of neuroinflammation is a crucial therapeutic strategy for the management of central nervous system disorders. The intestinal microbial-gut-brain axis serves as a key regulatory pathway that modulates neuroinflammatory processes. Intestinal flora metabolites such as short-chain fatty acids, indoles and their derivatives, lipopolysaccharides, trimethylamine oxide, and secondary bile acids exert direct or indirect effects on neuroinflammation. Studies have shown that electroacupuncture (EA) modulates the composition of the intestinal microbiota and its metabolites, while also suppressing neuroinflammation by targeting the TLR4/NF- κ B, NLRP3/caspase-1, and microglial cell M2-type transformation pathways. This review discusses the mechanisms by which EA regulates neuroinflammation via intestinal microbiota and its metabolites, providing information and a foundation for further investigation of the precise therapeutic mechanisms of EA in neurological disorders.
Humans ; Gastrointestinal Microbiome ; Electroacupuncture ; Neuroinflammatory Diseases/metabolism* ; Animals

Objective To investigate the epidemiological characteristics of knee osteoarthritis(KOA)among military personnel in plateau regions and to explore its risk factors.Methods From July 2023 to July 2024,a multi-stage stratified cluster random sampling method was employed to survey the prevalence of KOA and related risk factors among military personnel in the northwest plateau regions of China,covering different altitudes(1500-4500 m)and geographical areas(Gansu,Qinghai,Tibet,and Xinjiang).All study subjects were divided into KOA and non-KOA groups based on the presence or absence of KOA.Variables including age,gender,body mass index(BMI),education level,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury were selected for univariate analyses between groups.Variables with P<0.05 in the univariate analyses were included in the binary multifactor logistic regression to identify risk factors for KOA.Results A total of 3000 questionnaires were distributed,and 2854 valid questionnaires were collected,with a response rate of 95.13%.The sample included 2584 males and 270 females,with 510 cases of KOA,resulting in a prevalence rate of 17.9%.Univariate analysis showed that there were statistically significant differences between KOA and non-KOA groups in terms of age,BMI,smoking status,military rank,military branch,service duration,regional altitude,annual average temperature,training duration,perceived training intensity,and history of knee injury(P<0.05).However,no significant differences were found in gender and education level(P>0.05).Binary multivariate logistic regression analysis revealed that older age(OR=1.382,P=0.017),higher BMI(P<0.01),smoking(OR=1.929,P<0.01),higher military rank(OR=1.485,P=0.007),being a member of the Armed Police(P<0.01),longer service duration(P<0.01),higher regional altitude(OR=1.459,P<0.01),lower annual average temperature(OR=1.188,P=0.001),longer training duration(P<0.01),higher perceived training intensity(OR=2.450,P<0.01),and history of knee injury(OR=2.768,P=0.002)were independent risk factors for KOA.Conclusions Older age,overweight/obesity,smoking,higher military rank,being a member of the Armed Police,longer service duration,higher altitude,cold climate,longer training duration,higher training intensity,and history of knee injury are independent risk factors for KOA among military personnel in the northwest plateau regions of China.

Objective:To investigate the clinical manifestations, serological and cerebrospinal fluid test results for syphilis, imaging features, and prognoses of cerebral syphilitic gumma.Methods:The clinical data of 1 patient with cerebral syphilitic gumma admitted to Department of Neurology, Second Affiliated Hospital of Soochow University in March 2023 were retrospectively analyzed. Papers about cerebral syphilitic gumma were searched from journals in Journal Citation Reports Q1 from 2000 to 2019, journals from 2020 to 2024 in PubMed, WOS, Embase, and Scopus databases, and journals from 2000 to 2024 in Wanfang Database, CNKI, and VIP database; the clinical data of 54 patients with cerebral syphilitic gumma reported in above databases and 1 patient in our hospital were collected for pooled analysis.Results:The main clinical manifestations of 55 cerebral syphilitic gumma patients included headache (32, 58.2%), lateral limb/facial weakness (25, 45.5%), nausea and vomiting (14, 25.5%), dizziness (11, 20.0%), sensory disturbances (10, 18.2%), blurred vision (7, 12.7%), seizure (5, 9.1%)), hearing loss (5, 9.1%), tinnitus (5, 9.1%), memory loss (3, 5.5%), aphasia (3, 5.5%), dysarthria (2, 3.6%), drop attack (2, 3.6%), weakness in opening eyes (2, 3.6%), unresponsiveness (1, 1.8%), Argyll-Robertson pupil (1, 1.8%), tabes dorsalis gait (1, 1.8%), and fever (1, 1.8%). In 51 patients who reported complete serologic test results, 45 patients (88.2%) were positive for non-specific antibodies to syphilis, and all patients were positive for specific antibodies to syphilis. In 34 patients underwent cerebrospinal fluid examination, 25 (73.5%) were positive for non-specific antibodies to syphilis, and 32 (94.1%) were positive for specific antibodies to syphilis. Isolated intracranial lesion (43, 78.2%) was mostly common in imaging test, and the frequently involved cranial sites were, orderly, the frontal lobe (14, 25.5%), parietal lobe (14, 25.5%), temporal lobe (5, 9.1%), frontotemporal lobe (3, 5.5%), frontoparietal lobe (2, 3.6%), parieto-occipital lobe (2, 3.6%), nucleus pulposus (1, 1.8%), clivus (1/55, 1.8%), and cerebral peduncle of the midbrain (1, 1.8%). Thirty patients (54.5%) were misdiagnosed as having other intracranial space-occupied diseases, orderly, glioma (11, 36.7%), metastatic tumors (5, 16.7%), meningiomas (4, 13.3%), other unexplained intracranial space-occupying (4, 13.3%), brain abscess (3, 10.0%), cavernous hemangioma (1, 3.3%), intracranial lymphoma (1, 3.3%), auditory nerve and pituitary tumors (1, 3.3%). Of the 42 patients who reported prognosis after anti-syphilitic treatments, 41 had varying degrees of improvement, and one died of brain herniation.Conclusion:Because of atypical clinical manifestations and lack of clear diagnostic criteria, cerebral syphilitic gumma is often misdiagnosed as intracranial tumors; cerebral syphilitic gumma should be considered in patients with positive non-specific antibodies to syphilis/specific antibodies to syphilis in serum and cerebrospinal fluid having neurological symptoms and intracranial space-occupied foci; timely diagnosed and treated patients can prognosed well.

Objective:To investigate and assess hemolytic transfusion reaction in patient with complex and combined anti-Fya and anti-Jkb which so as to provide a safety blood transfusion strategy.Methods:ABO/Rh blood grouping,antibody screening and identification,and Coombs'tests were performed by the routine serological methods include manual tube and automatic blood group analyzer with matching micro-column gel cards from Diagnostic Grifols and Jiangsu LIBO.The hospital information system and laboratory information system were used to collect dada on patients' blood routine tests,liver and kidney function,coagulation,cardiac function,and other clinical indicators before and after blood transfusion were analyzed and compared in conjunction with the patients'clinical manifestations.Results:The patient's blood group was A/CcDEe.Before two transfusion,the anti-body screening were positive which identification were anti-Fya and anti-Fya combined with anti-Jkb respectively,while the Coomb's test were positive with anti-C3 and anti-IgG combined with anti-C3 respectively.No agglutination and hemolysis was observed in saline medium cross-matching test before two transfusion of Fya-red blood cell.But before re-transfusion agglutinated reaction was observed in cross-matching test by DG Gel Coombs,which strength was 2+on whether major or minor side.The patient developed soy sauce urine/hemoglobinuria and fever after transfused Fya-red blood cell again.Primary laboratory indicators were observed to be elevated,include C-reactive protein from 3.06 mg/L to 29.97 mg/L,total bilirubin from 21.4 μmol/L to 276.3 μmol/L,direct bilirubin from 8.4 μmol/L to 135.6 μmol/L,lactate dehydrogenase from 166 U/L to 1453 U/L.Urinary free hemoglobin test was 4+.The main laboratory indicators reflecting the heart,liver,kidney and circulatory coagulation function also have vary increased and gradually returned to normal after a week. Conclusion:Jkb-incompatible transfusion of the Kidd blood group system can lead to acute hemolytic transfusion reaction,but in emergency implementing incompatible transfusion due to IgG antibodies outside of the primary blood group (such as ABO/RhD)can ensure the implementation of emergency operation.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

Objective:To investigate the risk factors of depression in patients with lacunar cerebral infarction 3 months after discharge, and build a risk prediction model.Methods:The clinical data of 237 patients with lacunar cerebral infarction diagnosed and treated in the Second Affiliated Hospital of Wannan Medical College from January 1, 2021 to January 1, 2022 were retrospectively analyzed. Demographic data, laboratory indicators and risk factors of cardiovascular disease were collected when the patients were admitted to hospital. The patient health questionnaire-9 (PHQ-9) score was used to assess the risk of post-stroke depression (PSD) 3 months after discharge. Univariate and multivariate logistic regression analyses were used to identify independent risk factors of depression. A predictive model was constructed based on the above risk factors. The predictive efficacy was evaluated by receiver operating characteristic (ROC) curve, and the clinical applicability of the predictive model was measured by calibration curve and decision curve.Results:Fifty-four patients with lacunar infarction (22.80%) showed symptoms of depression at 3 months after discharge. Multivariate logistic regression showed that women ( OR=2.952, 95% CI: 1.403-6.213, P=0.004), cystatin C ( OR=2.964, 95% CI: 1.222-7.191, P=0.016), apolipoprotein B ( OR=4.836, 95% CI: 1.533-15.258, P=0.007) were the independent risk factors for PSD in patients with lacunar infarction. Activity of daily living (ADL) score ( OR=0.939, 95% CI: 0.915-0.964, P<0.001) was a protective factor for PSD in patients with lacunar infarction. The area under the curve (AUC) of the prediction model was 0.779 (95% CI: 0.703-0.855, P<0.001), which was better than other predictors. Hosmer-Lemeshow H test showed that the model was well calibrated ( P=0.588). In addition, the prediction model of decision curve analysis had a good clinical applicability. Conclusions:The predictive model based on gender, laboratory indicators and daily life ability score can evaluate the risk of PSD in patients with lacunar infarction 3 months after discharge. It is good predictive efficacy and clinical applicability which worth clinical promotion and application.