Objective To investigate the ameliorative effect of Evodiamine on primary dysmenorrhea in rats and its possible mechanism.Methods Female SD rats were randomly divided into normal group,model group,evodiamine low dose group,evodiamine medium dose group,evodiamine high dose group and positive control group,with 10 rats in each group.The primary dysmenorrhea model was established in all the other groups except the normal group.The rats in evodiamine low,medium and high dose groups were intragaically given 10,20 and 40 mg·kg-1 evodipine,respectively.Rats in positive control group were given 2.1 g·kg-1 Tongjingbao granules every day,and rats in normal group and model group were given the same amount of 0.9％NaCl.The times and latency of twisting were recorded in each group.The expression level of serum related factors and the content of Ca2+in uterine tissue were detected by enzyme-linked immunosorbent assay(ELISA).Serum malondialdehyde(MDA)and superoxide dismutase(SOD)levels were detected by thiobarbituric acid method and xanthine oxidase method.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of uterus in each group.The expression of uterine tissue protein was detected by Western blot.Results The prostaglandin F2α(PGF2α)/prostaglandin E2(PGE2)values of normal group,model group,evodiamine low dose group,evodiamine medium dose group,evodiamine high dose group and positive control group were 0.73±0.07,2.35±0.44,1.84±0.18,1.40±0.17,1.04±0.12,and 0.97±0.14;Ca2+content were(1.00±0.17),(2.57±0.33),(2.01±0.24),(1.68±0.11),(1.38±0.16)and(1.78±0.10)nmol·gprot-1;MDA levels were(3.11±0.19),(5.07±0.19),(4.54±0.18),(4.01±0.13),(3.37±0.25)and(4.25±0.37)nmol·mL-1;prostaglandin E receptor 2(EP2)protein levels were 0.25±0.03,0.75±0.09,0.62±0.06,0.53±0.06,0.32±0.03,0.72±0.07,respectively;the Nod-like receptor protein 3(NLPP3)protein levels were 0.35±0.04,0.87±0.07,0.71±0.03,0.58±0.04,0.42±0.03 and 0.82±0.05;the protein levels of cysteine aspartic acid specific protease-1(caspase-1)were 0.40±0.06,0.90±0.07,0.73±0.07,0.59±0.06,0.45±0.03 and 0.86±0.07,respectively.The above indicators,comparison between model group and normal group,comparison between evodiamine low,medium,high dose groups and model group,comparison between different dosage groups of evodiamine,the differences were all statistically significant(all P＜0.05).Conclusion Evodiamine may improve primary dysmenorrhea in rats by inhibiting EP2/NLRP3/caspase-1 pathway.

Objective This study aimed to evaluate whether the onset of the plateau phase of slow hepatitis B surface antigen decline in patients with chronic hepatitis B treated with intermittent interferon therapy is related to the frequency of dendritic cell subsets and expression of the costimulatory molecules CD40,CD80,CD83,and CD86. Method This was a cross-sectional study in which patients were divided into a natural history group(namely NH group),a long-term oral nucleoside analogs treatment group(namely NA group),and a plateau-arriving group(namely P group).The percentage of plasmacytoid dendritic cell and myeloid dendritic cell subsets in peripheral blood lymphocytes and monocytes and the mean fluorescence intensity of their surface costimulatory molecules were detected using a flow cytometer. Results In total,143 patients were enrolled(NH group,n = 49;NA group,n = 47;P group,n = 47).The results demonstrated that CD141/CD1c double negative myeloid dendritic cell(DNmDC)/lymphocytes and monocytes(%)in P group(0.041[0.024,0.069])was significantly lower than that in NH group(0.270[0.135,0.407])and NA group(0.273[0.150,0.443]),and CD86 mean fluorescence intensity of DNmDCs in P group(1832.0[1484.0,2793.0])was significantly lower than that in NH group(4316.0[2958.0,5169.0])and NA group(3299.0[2534.0,4371.0]),Adjusted P all<0.001. Conclusion Reduced DNmDCs and impaired maturation may be associated with the onset of the plateau phase during intermittent interferon therapy in patients with chronic hepatitis B.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

Objective:To retrospectively analyze the viral levels and associated factors in patients with hepatitis B virus (HBV)-related primary liver cancer (PHC) in real-world settings and further explore the correlation between low viral load (LVL) and/or low-level viremia (LLV) and PHC.Methods:Five hundred twenty-four cases with HBV-related PHC with complete pathologically confirmed data from 2013 to 2020 were included. Percentages (%) were used to express their viral load, antiviral (oral) status, patient compliance, presence or absence of cirrhosis, family history of liver cancer, and others. LVL definition: After excluding detection errors by PCR method, serum HBV DNA <50-2 000 IU/ml, and those who had received antiviral drug treatment were called LLV. Antiviral treatment (AVT) rate definition: As of the confirmed diagnosis of PHC, those who had been regularly treated using oral antiviral drugs for six months or more (≥6 months).Results:General situation: The ratio of male to female enrolled patients was 15.90:1 (493/31). Patients aged >40 years accounted for 91.98% (482 cases). Hepatitis B surface antigen (HBsAg) positivity condition: The ratio of HBsAg-positive to HBsAg-negative/anti-HBc-positive (HBsAg-/anti-HBc+) PHC patients was 5.89:1 (448/76). Among the 76 HBsAg-/anti-HBc+patients, the ratio of HBsAg-/anti-HBs+/anti-HBc+ to HBsAg-/anti-HBs-/anti-HBc+ patients was 0.95:1 (37/39). Hepatitis B e antigen (HBeA) positivity condition: The ratio of HBeAg-negative to HBeAg-positive cases was 3.23:1 (400/124). HBV DNA level condition: The medical history records of 75.00% of patients (393/524) had traceable HBV DNA test reports. Out of 393 patients, 45.04% (177/393) accounted for undetectable HBV DNA, 13.49% (53/393) accounted for LVL, 41.48% (163/393) accounted for HBV DNA exceeding the upper limit of LVL, and 4.07% (16/393) accounted for LLV. Among HBsAg-positive and HBsAg-/anti-HBc+ patients, the HBV DNA positivity rates were 59.12% (214/362) and 6.45% (2/31), respectively. Antiviral treatment condition: Among the 448 HBsAg-positive PHC patients, the total AVT rate was 18.08% (81/448), of which seven patients did not have their HBV DNA results traced back. Among them, the AVT rate of 148 patients with HBV DNA lower than the lowest detection value was 41.22% (61/148); the AVT rate of 53 patients with LVL was 18.87% (10/53); and the AVT rate of 163 patients with HBV DNA≥LVL upper limit was 1.84% (3/163). Liver cirrhosis and family history condition: 348 patients (66.41%) had liver cirrhosis. 67 patients (12.79%) had a distinct family history of HBV-related liver cirrhosis and liver cancer. Alpha-fetoprotein (AFP) condition: 514 patients underwent AFP testing, with 30.93% of the patients had normal AFP levels, and 69.07% had AFP levels exceeding the upper limit of normal values (355/514). Among them, 10 μg/L400 μg/L accounted for 34.44% (177/514) and 34.63% (178/514), respectively. Tissue typing condition: 99.05% (519/524) were hepatocellular carcinoma, and well-differentiated and moderately differentiated cases accounted for only 8.59%.Conclusions:In the real world, comprehensive, timely screening, standardized, and effective antiviral treatment have not yet been achieved for patients with chronic hepatitis B, resulting in the persistence of HBsAg and/or HBV DNA positivity (especially LVL and/or LLV). Although LVL does not account for a high proportion among all HBV-related PHC populations, the vast majority of LVL populations have not received any antiviral treatment. In addition, some PHC populations with HBV DNA>2 000 IU/ml have not received standard antiviral treatment before the onset of the disease, which should be paid attention to. At the same time, HBsAg-/anti-HBc+ populations may have latent HBV infection and may even progress to PHC. Notably, PHC may still occur after HBeAg seronegative conversion.

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.

Concurrent chemoradiotherapy (CCRT) refers to the simultaneous treatment of chemotherapy and radiotherapy, and the effect of radiotherapy is enhanced with low-dose chemotherapy, which can reduce tumor recurrence and metastasis and improve clinical prognosis of patients. At present, the main factors for the increase of radiosensitivity of concurrent chemotherapy is that concurrent chemotherapy prevents the repair of tumor cells, and chemotherapy and radiotherapy act on different cell cycles and have synergistic effects. However, even for patients with locally advanced cervical cancer (LACC) who have undergone CCRT, the 5-year survival rate is only 60%, which is still not ideal. In order to improve the efficacy, researchers have conducted a series of exploratory studies, which consist of the combination of targeted drugs and immunodrugs, and neoadjuvant regimens before CCRT, etc. Although targeted or immunologic drugs are effective treatment of LACC, in view of the lack of large-scale evidence-based medical evidence, multi-center prospective and randomized phase III clinical trials and high-level articles are needed to improve the level of evidence-based medicine. This consensus summarizes several key evidence-based medical studies published recently, especially the clinical research progress in targeted and immunological therapies, providing reference for domestic peers.

Objective:To provide references for the application of finite element model in the study of cervical vertebra by statistically analysing the frequency, numerical value, properties, and boundary setting of the finite element model and the corresponding material features as well as boundary settings in the literature.Methods:The literature on cervical vertebra-related finite element models was collected from CNKI, Wanfang, VIP, PubMed, Web of Science, and Embase databases from January 2013 to December 2023. The quality assessment was followed by manual screening. The data sources, application classification, material properties (Young’s modulus and Poisson’s ratio), and boundary conditions of cervical vertebra, cervical intervertebral, and cervical ligaments were statistically analyzed.Results:A total of 102 papers were included. The finite element models of the cervical vertebra were derived from medical image reconstruction modeling techniques, predominantly CT plain scan and magnetic resonance imaging. Among the 102 cervical vertebra models, the C3-C7 (lower cervical segment) model appeared with the highest frequency (19). The Young’s modulus of the cortical bone, cancellous bone, and posterior structure of cervical vertebrae were set at about 12 000 or 10 000, 440, and 3 600 MPa, respectively, and the Poisson’s ratios were mainly set at about 0.29 or 0.30, 0.29, and 0.29. The Young’s modulus of the cervical intervertebral disc endplate, nucleus pulposus, and annulus fibrosus were concentrated around 500 or 2 000, 1, and 100 MPa, respectively, and the Poisson’s ratios were set at about 0.40, 0.50, and 0.40, respectively. The Young’s modulus of the anterior longitudinal ligament, posterior longitudinal ligament, transverse ligament, ligamentum flavum, interspinous ligament, capsular ligament, and articular cartilage of the cervical spine were set around 30, 20, 20, 6-10, 4-8, 10 or 20, 10 MPa, and the Poisson’s ratios were set at aoubt 0.30, 0.30, 0.30, 0.30, 0.30, 0.40, and 0.30, respectively. The Young’s modulus of the upper cervical interdental ligament, lamina, cruciate ligament, nuchal ligament, and pterygoid ligament were set at about 10, 10, 10 or 20, 20, and 5 MPa, respectively, and the Poisson’s ratios were set at about 0.30. Head weight settings were more common at 50, 74, and 100 N.Conclusions:The finite element model of the cervical vertebra has great value in the study of cervical spondylosis, but further optimization is still needed in the assignment of material properties, mesh division, and model verification to improve the accuracy and clinical applicability of the model.

Objective To investigate the application value of ultrafast pulse wave velocity (ufPWV) technique in the assessment of carotid artery elasticity decline in the patients with simple hypertriglyceridemia (TG).Methods The patients visiting the cardiology outpatient department of Jiangsu Provincial Hospital of Traditional Chinese Medicine/Affiliated Hospital of Nanjing University of Chinese Medicine from January 2020 to March 2022 were selected,the serum lipid satisfied:TG≥1.7 mmol/L,moreover total cholesterol (TC)<5.2 mmol/L,low density lipoprotein cholesterol (LDL-C)<3.4 mmol/L and high density lipoprotein cholesterol (HDL-C)>1.0 mmol/L,they were included into the simple high TG group (n=63).Sixty-eight healthy subjects undergoing physical examination in this hospital were selected as the normal blood lipid group and their blood lipid indicators TG,TC,LDL-C and HDL-C all were within the normal range.The clinical data of all subjects were collected.The ufPWV technique was used to detect the common carotid artery pulse wave velocity of beginning systole (PWV-BS),pulse wave velocity of ending systolic (PWV-ES) and carotid intima-media thickness (cIMT).Results The body mass index (BMI),systolic blood pressure,diastolic blood pres-sure,TG,fasting blood glucose (FBG),cIMT and PWV-ES value had statistical differences between the sim-ple high TG group and normal blood lipid group (P<0.05);PWV-BS,PWV-ES and cIMT were positively correlated with age,and the PWV-ES correlation was the highest (r=0.607,P<0.001),followed by cIMT (r=0.590,P<0.001),and PWV-BS (r=0.325,P<0.001) was the lowest;the Logistic regression analysis showed that PWV-ES could serve as a predictive factor of carotid artery elasticity decline in the population with simple TG,moreover which was independent of the factors such as age,gender,BMI,systolic blood pres-sure,diastolic blood pressure and FBG (OR=1.449,P<0.005).Conclusion The ufPWV technique could e-valuate the decline phenomenon of carotid artery elasticity in the population with simple high TG,and the ele-vated PWV-ES is an independent risk factor for carotid artery elasticity decline in this population.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Glioblastoma(GBM)is a lethal cancer with limited therapeutic options.Dendritic cell(DC)-based cancer vaccines provide a promising approach for GBM treatment.Clinical studies suggest that other immu-notherapeutic agents may be combined with DC vaccines to further enhance antitumor activity.Here,we report a GBM case with combination immunotherapy consisting of DC vaccines,anti-programmed death-1(anti-PD-1)and poly I:C as well as the chemotherapeutic agent cyclophosphamide that was integrated with standard chemoradiation therapy,and the patient remained disease-free for 69 months.The patient received DC vaccines loaded with multiple forms of tumor antigens,including mRNA-tumor associated antigens(TAA),mRNA-neoantigens,and hypochlorous acid(HOCl)-oxidized tumor lysates.Furthermore,mRNA-TAAAs were modified with a novel TriVac technology that fuses TAAs with a destabilization domain and inserts TAAs into full-length lysosomal associated membrane protein-1 to enhance major histo-compatibility complex(MHC)class Ⅰ and Ⅱ antigen presentation.The treatment consisted of 42 DC cancer vaccine infusions,26 anti-PD-1 antibody nivolumab administrations and 126 poly I:C injections for DC infusions.The patient also received 28 doses of cyclophosphamide for depletion of regulatory T cells.No immunotherapy-related adverse events were observed during the treatment.Robust antitumor CD4+and CD8+T-cell responses were detected.The patient remains free of disease progression.This is the first case report on the combination of the above three agents to treat glioblastoma patients.Our results suggest that integrated combination immunotherapy is safe and feasible for long-term treatment in this patient.A large-scale trial to validate these findings is warranted.