OBJECTIVE: To comprehensively evaluate the effect of icariin in alleviating reproductive function damage (RFD) in male mice via in vitro and in vivo experiments. METHODS: We isolated Leydig cells from 60 KM male mice in vitro, and examined the toxic effect of icariin on the Leydig cells using Cell Counting Kit-8 (CCK-8). We equally randomized the mice into six groups: normal control, RFD model control (made by intraperitoneal injection of busulfan at 10 mg/kg combined with cyclophosphamide (CP) at 120 mg/kg), positive control, and low-, medium- and high-dose icariin. After modeling, we treated the mice in the positive control group with Wuziyanzong Pills and those in the low-, medium- and high-dose icariin groups by intragastrical administration of icariin at 20, 40 and 80 mg/kg-1, respectively, for 30 successive days. Then we obtained the weight and visceral coefficients of the reproductive organs, calculated the sperm count, observed the pathological changes in the testis tissue by HE staining, measured the serum testosterone (T) level by ELISA, determined the indexes of testicular oxidative stress and nitric oxide (NO) signaling pathway by colorimetric assay, and detected the expression levels of the pro-apoptotic genes Fas and Bax by qRT-PCR. RESULTS: CCK-8 assay confirmed that icariin had no toxic effect on the isolated Leydig cells of the mice, and could effectively reduce busulfan- and CP-induced cytotoxicity and promote the secretion of serum T. Icariin at 80 mg/kg significantly increased the visceral coefficient of the testis and promoted spermatogenesis (P<0.05), but had little effect on the visceral coefficient of the epididymis in the RFD model mice. Testicular histomorphometric observation revealed significantly improved testis structure, intact boundary membrane of seminiferous tubules and increased numbers of various types of spermatogenic cells of the model mice after treated with icariin. Compared with the mice in the model control group, those treated with high-dose icariin showed a significantly reduced content of malondialdehyde (MDA) (by 35.3%, P<0.01), elevated total antioxidant capacity (TAOC) and superoxide dismutase (T-SOD) activity (P<0.05), and decreased NO content and nitric oxide synthase (NOS) activity in the testis tissue (P<0.01). In addition, icariin exhibited an evident inhibitory effect on the expressions of the pro-apoptotic genes Bax and Fas. CONCLUSION Icariin can ameliorate oxidative stress-induced damage to the testicular function and protect spermatogenesis of male mice by elevating TAOC, decreasing NOS activity, inhibiting the NO level in the testis, and suppressing busulfan- and CP-induced apoptosis of testicular cells.
Animals ; Male ; Cyclophosphamide/adverse effects* ; Mice ; Busulfan/adverse effects* ; Flavonoids/pharmacology* ; Leydig Cells/drug effects* ; Oxidative Stress/drug effects* ; Testis/drug effects* ; Apoptosis/drug effects* ; Testosterone/blood*

OBJECTIVE To predict the in vivo bioequivalence of lenvatinib mesilate capsules and reference preparation by using the parallel artificial membrane permeability analysis. METHODS Based on the biopharmaceutics classification system classification of lenvatinib mesilate and the parallel artificial membrane permeation model, the in vitro dissolution permeation rate test model of lenvatinib mesilate capsules was established, through real-time monitoring of the dissolution and penetration of lenvartinib mesylate capsules and reference preparations in fasting gastric juice, intestinal fluid and postprandial intestinal fluid, the flux and total penetration of drugs through the membrane were calculated. RESULTS In fasting state and fed state, the 90% confidence interval of geometric mean ratio of two key quality parameters (permeation flux and permeation amount) of the preparation A all were in the range of 80.00%−125.00%, the preparation B did not fall into this interval. CONCLUSION This research method can predict the bioequivalence of renvartinib mesylate capsule and reference preparation, and has a certain correlation in vivo and in vitro.

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 distribution patterns of traditional Chinese medicine(TCM)constitution in 959 patients with endometriosis(EMs).Methods From January 2019 to November 2019,959 EMs patients were selected from Guang'anmen Hospital of China Academy of Chinese Medical Sciences,Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University,Beijing Hospital,Dongfang Hospital of Beijing University of Chinese Medicine,Beijing Friendship Hospital Affiliated to Capital Medical University,and Fuxing Hospital Affiliated to Capital Medical University.The general clinical information of the patients was recorded and then the TCM constitution was identified.After that,the correlation of TCM constitution distribution with concurrent constitution and the relationship of TCM constitution distribution with age and the complication of dysmenorrhea were analyzed.Results(1)The constitution types of EMs patients listed in descending order of the proportion were yang deficiency constitution(65.1％,624/959),qi stagnation constitution(58.4％,560/959),qi deficiency constitution(52.8％,506/959),blood stasis constitution(44.2％,424/959),phlegm-damp constitution(42.5％,408/959),damp-heat constitution(41.9％,402/959),yin deficiency constitution(39.6％,380/959),balanced constitution(26.8％,257/959),and inherited special constitution(16.6％,159/959).Among the patients,there were fewer patients with single constitution,accounting for 20.2％(194/959),and most of them had concurrent constitution types,accounting for 79.8％(765/959).(2)The association rule mining based on Apriori algorithm obtained 33 related rules.The concurrent constitution types of qi deficiency-yang deficiency,blood stasis-yang deficiency,and blood stasis-qi stagnation were the association rules with high confidence.(3)Compared with patients aged 35 years and below,the patients over 35 years old were predominated by high proportion of blood stasis constitution(P＜0.05).Compared with patients without dysmenorrhea,the patients with dysmenorrhea had the increased proportion of biased constitutions and the decreased proportion of balanced constitution(P＜0.05 or P＜0.01).Conclusion Yang deficiency constitution,qi stagnation constitution,qi deficiency constitution and blood stasis constitution are the high-risk constitution types of EMs patients.The concurrent constitution types are commonly seen in EMs patients,which are more common than single biased constitution.Management of EMs patients with the methods of warming yang,relieving stagnation,benefiting qi and activating blood will be helpful for correcting the biased constitutions in time and preventing disease progression,which will achieve the preventive treatment efficacy through TCM constitution correction.

Objective To explore the efficacy and influencing factors of polyethylene glycol interferon α-2b(Peg-IFNα-2b)combined nucleoside analogues(NAs)in the treatment of hepatitis B virus e-antigen(HBeAg)-negative chronic hepatitis B(CHB)patients who had received NAs treatment,and evaluate the correlation of mononucleotide polymorphisms of interleukin-28B and programmed death receptor-1(PD-1)with interferon treatment response.Methods HBeAg-negative CHB patients who visited Xiangya Hospital of Central South University from January 2020 to December 2022 were analyzed retrospectively.Patients with Peg-IFNα-2b and NAs treatment were as the study group,while those with NAs therapy alone as the control group.Clinical efficacy of two groups of patients at the 12nd,24th,and 48th weeks of treatment,as well as the persistent response and recurrence at the 72nd week were analyzed.PD-1 and IL-28B single nucleotide polymorphisms were adopted to evaluate the value of HBeAg-nega-tive CHB patients in response to interferon treatment.Results At the 48th week of treatment,the response rate of HBeAg-negative CHB patients in the study group was higher than that in the control group(52.05％[38/73]vs 1.64％[1/61],P＜0.05).Among HBeAg-negative CHB patients in the study group,response rates at 48th week of treatment in patients with baseline HBsAg＜100 IU/mL and HBsAg＜1 000 IU/mL were higher than those with HBsAg≥1 000 IU/mL,respectively(both P＜0.05).Univariate and multivariate analyses showed that in HBeAg-negative CHB patients in the study group,the baseline HBsAg levels(OR=1.004,95％CI:1.001-1.006)and HBsAg decline magnitude at the 24th week of treatment(OR=0.111,95％CI:0.034-0.362)were influencing factors for the response of interferon treatment combined with NAs(both P＜0.05).The results of single nucleo-tide polymorphism analysis showed that in HBeAg-negative CHB patients in the study group,the proportion of PD-1 rs10204525 C/T heterozygous mutation in the response population was higher(66.67％vs 16.67％,P＜0.05),while that of IL-28B mutation was not significantly different(P＞0.05).Conclusion Combined treatment with Peg-IFNa-2b can achieve higher HBsAg clearance rate and serological conversion rate in HBeAg-negative CHB patients who had received NAs treatment.HBsAg decline magnitude at the 24th week of treatment can better pre-dict the response at the 48th week of treatment.Patients with low baseline HBsAg level and those carrying PD-1 rs10204525C/T heterozygous mutation gene present better therapeutic effect after receiving Peg-IFNa-2b.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: To investigate the association between the response to repeated negative HIV testing and the risk sexual behaviors in men who have sex with men (MSM) in Chengdu. Methods: A total of 610 MSM were recruited by convenience sampling method through Chengdu Tongle Health Consultation Service Centre from March to May 2022. Data were collected from the MSM through questionnaire survey, including the demographic characteristics, sexual behaviors in the past 6 months, the response to rerpeated negative HIV testing. Univariate and multivariate logistic regression models were conducted to analyze the association between the response to repeated negative HIV testing and risk sexual behavior. Results: A total of 579 (94.9%) participants participated in the questionnaire survey and 354 (61.1%) subjects were included in the study.For the negative HIV testing, some MSM believed that they had taken effective protection measures (17.03±2.20), some believed that they were lucky (7.50±1.87) and some believed that they were at low risk (8.87±3.62). Multivariate logistic regression model showed that protected sexual behavior was negatively associated with group sex (aOR=0.80, 95%CI: 0.67-0.95), lucky was positively associated with casual sex (aOR=1.20, 95%CI: 1.06-1.35), inconsistent condom use (aOR=1.21, 95%CI: 1.06-1.37), group sex (aOR=1.26, 95%CI: 1.00-1.60), and multiple sexual partners (aOR=1.24, 95%CI: 1.09-1.42) and low risk perception was positively associated with multiple sexual partners only (aOR=1.08, 95%CI: 1.01-1.15). Conclusions: There were high levels of recognition of protected sexual behavior and lucky dimensions in response to repeated negative HIV testing and well risk perception in MSM in Chengdu. In HIV testing and counseling services, intervention and risk warning should be strengthened in MSM who believed that they are lucky to improve their awareness of safe sex and reduce the negative effects of fluke mind.
Male ; Humans ; Homosexuality, Male ; HIV Infections/prevention & control* ; Sexual and Gender Minorities ; Sexual Behavior ; HIV Testing ; Logistic Models

Comprehensive characterization of metabolites and metabolic profiles in plasma has considerable sig-nificance in determining the efficacy and safety of traditional Chinese medicine(TCM)in vivo.However,this process is usually hindered by the insufficient characteristic fragments of metabolites,ubiquitous matrix interference,and complicated screening and identification procedures for metabolites.In this study,an effective strategy was established to systematically characterize the metabolites,deduce the metabolic pathways,and describe the metabolic profiles of bufadienolides isolated from Venenum Bufonis in vivo.The strategy was divided into five steps.First,the blank and test plasma samples were injected into an ultra-high performance liquid chromatography/linear trap quadrupole-orbitrap-mass spectrometry(MS)system in the full scan mode continuously five times to screen for valid matrix compounds and metabolites.Second,an extension-mass defect filter model was established to obtain the targeted precursor ions of the list of bufadienolide metabolites,which reduced approximately 39％of the interfering ions.Third,an acquisition model was developed and used to trigger more tandem MS(MS/MS)fragments of precursor ions based on the targeted ion list.The acquisition mode enhanced the acquisition capability by approximately four times than that of the regular data-dependent acquisition mode.Fourth,the acquired data were imported into Compound Discoverer software for identification of metabolites with metabolic network prediction.The main in vivo metabolic pathways of bufadienolides were elucidated.A total of 147 metabolites were characterized,and the main biotransformation reactions of bufadienolides were hydroxylation,dihydroxylation,and isomerization.Finally,the main prototype bufadienolides in plasma at different time points were determined using LC-MS/MS,and the metabolic profiles were clearly identified.This strategy could be widely used to elucidate the metabolic profiles of TCM preparations or Chinese patent medicines in vivo and provide critical data for rational drug use.

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Objective:By analyzing the clinical and pathologic manifestations of systemic mastocytosis (SM) to improve the recognition of the disease.Methods:Clinical manifestations, diagnosis and treatment of a middle-aged male patient with SM was reported with multidisciplinary discussions.Results:A middle-aged man with bone pain, thyroid nodules and lymphadenectasis came to our clinic. Thyroid cancer with lymph node and bone metastasis was suspected by imaging examination. The pathological results showed cell proliferation with transparent cytoplasm and irregular nuclear in the trabecular bone. Toluidine blue staining showed the proliferated cells were mast cells(+). Immunohistochemistry showed proliferating mast cells stained with CD117 and CD2. SM with extensive bone marrow involvement was diagnosed and treated with thalidomide and calcitriol.Conclusion:Knowing the characteristics of SM is helpful for accurate diagnosis and treatment.