Objective: To investigate the status of drug resistance before anti-retroviral therapy among newly dignosed HIV/AIDS patients aged ≥50 years in Yangzhou City, Jiangsu Province, so as to provide the evidence for improving the anti-retroviral therapy effect of AIDS. Methods: HIV/AIDS patients aged ≥50 years who were newly dignosed in Yangzhou City from 2021 to 2024 and did not receive anti-retroviral therapy were selected. Basic information were collected through the Chinese Disease Prevention and Control Information System. Blood samples were collected to determine CD4+T lymphocyte (CD4 cell) counts and HIV-1 viral load. Following nucleic acid extraction, the pol gene region was amplified using reverse transcription and nested PCR, and subsequently subjected to Sanger sequencing. The resulting sequences were uploaded to the Stanford University HIV Drug Resistance Database to analyze drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and nucleoside reverse transcriptase inhibitors (NRTIs). Results: Totally 404 blood samples from HIV/AIDS patients were collected, with successful sequencing of the pol gene region in 341 cases. Among them, 253 (74.19%) were males and 88 (25.81%) were females, with a mean age of (62.48±7.60) years. A total of 152 cases (44.57%) had CD4 cell counts below 200 cells/μL, and 296 cases (86.80%) had HIV-1 viral loads exceeding 5 000 copies/mL. A total of 87 cases exhibited drug resistance-associated mutations, corresponding to a mutation rate of 25.51%. The predominant mutation site was V179, with a mutation rate of 17.01%. A total of 29 cases exhibited resistance to at least one drug, resulting in a resistance rate of 8.50%. The resistance rates to NNRTIs, PIs, and NRTIs were 5.57%, 2.93%, and 1.17%, respectively. The HIV/AIDS patients exhibited varying degrees of resistance to 13 anti-retroviral drugs, with low- or intermediate-level drug resistance being predominant. High-level drug resistance cases were observed against NNRTIs such as nevirapine and efavirenz. Conclusions The drug resistance rate before anti-retroviral therapy among newly dignosed HIV/AIDS patients aged ≥50 years in Yangzhou City was at a moderate level. The predominant resistance mutation was observed at V179 site, with NNRTIs resistance being most prevalent, primarily demonstrating low- or intermediate-level drug resistance.

Natural products are important sources for the discovery of anti-tumor drugs. Evodiamine is the main alkaloid component of the traditional Chinese herb Wu-Chu-Yu, and it has weak antitumor activity. In recent years, a number of highly active antitumor candidates have been discovered with a significant progress. This article reviews the research progress of evodiamine-based antitumor drug design strategies, in order to provide reference for the development of new drugs with natural products as leads.

Objective To analyze the clinical characteristics of high energy metabolism in lung cancer patients and its correlation with body composition,nutritional status,and quality of life,and to develop a corresponding risk prediction model.Methods Retrospectively analyzed 132 primary lung cancer patients admitted to the First Hospital of Shanxi Medical University from January 2022 to May 2023,and categorized into high(n=94)and low energy metabolism group(n=38)based on their metabolic status.Differences in clinical data,body composition,Patient Generated Subjective Global Assessment(PG-SGA)scores,and European Organization for Research and treatment of Cancer(EORTC)Quality of Life Questionnaire-Core 30(QLQ-C30)scores were compared between the two groups.Logistic regression was used to identify the risk factors for high energy metabolism in lung cancer patients,and a risk prediction model was established accordingly;the Hosmer-Lemeshow test was used to assess the model fit,and the ROC curve was used to test the predictive efficacy of the model.Results Of the 132 patients with primary lung cancer,94(71.2%)exhibited high energy metabolism.Compared with low energy metabolism group,patients in high-energy metabolism group had a smoking index of 400 or higher,advanced disease staging of stage Ⅲ or Ⅳ,and higher levels of IL-6 level,low adiposity index,low skeletal muscle index,and malnutrition(P<0.05),and lower levels of total protein,albumin,hemoglobin level,and prognostic nutritional index(PNI)(P<0.05).There was no significant difference in age,gender,height,weight,BMI and disease type between the two groups(P>0.05).Logistic regression analysis showed that smoking index≥400,advanced disease stage,IL-6≥3.775 ng/L,and PNI<46.43 were independent risk factors for high energy metabolism in lung cancer patients.The AUC of the ROC curve for the established prediction model of high energy metabolism in lung cancer patients was 0.834(95%CI 0.763-0.904).Conclusion The high energy metabolic risk prediction model of lung cancer patients established in this study has good fit and prediction efficiency.

Objective:To investigate the timing and features of fine-needle aspiration biopsy (FNAB) guided by ultrasound for Bethesda Ⅲ thyroid nodules and to further optimize the puncture scheme.Methods:A retrospective analysis was conducted on data from patients who underwent rFNAB for Bethesda Ⅲ thyroid nodules at the China-japan Union Hospital of Jilin University Thyroid Surgery Department from Dec. 2020 to Dec. 2022. The study included 71 cases (73 nodules), consisting of 57 females and 14 males, with an average age of (45.7±10.4) years. Patients were grouped based on rFNAB results: Bethesda Ⅱ as the benign group ( n=21), Bethesda Ⅴ/Ⅵ as the malignant group ( n=39), and the remaining cases categorized as the indeterminate group ( n=13). Data on rFNAB results, puncture interval time, postoperative pathology, ultrasound features, and FNAB characteristics were recorded. Descriptive statistics were used for categorical data, presented as percentages and numbers, while continuous data were presented as mean ± standard deviation ( ± s). The χ2 test or Fisher's exact test was applied for analysis. Results:In this study, rFNAB was performed on 73 Bethesda Ⅲ thyroid nodules. The results showed that 60 nodules (82.2%) received a definite diagnosis, while 13 nodules (17.8%) were indeterminate. There was a statistically significant difference in the calcification classification between the malignant group and the benign group as well as the indeterminate group ( P<0.05). Among the malignant group, 29 patients underwent surgical treatment, with only 2 cases (8.0%) showing intermediate recurrence risk when surgery was performed more than three months after the initial FNAB. Upon reevaluation of the 31 initial FNAB samples from the malignant group, 9 samples (29.0%) exhibited mild cytological atypia, and 22 samples (71.0%) had poor quality specimens, mainly comprising fibrous and calcified components. Conclusions:For nodules initially classified as Bethesda Ⅲ, if suspicious ultrasound features persist or emerge, especially if microcalcifications are present, rFNAB should be performed after a follow-up period exceeding three months. However, during the puncture, multiple points should be targeted at the non-calcified areas of the nodule to enhance the accuracy and reliability of rFNAB.

Objective To explore the efficacy of early hyperbaric oxygen therapy(HBOT)combined with median nerve electrical stimulation(MNES)in the treatment of severe traumatic brain injury(sTBI)and its impact on hemodynamics,coma degree,and neurological function of patients.Methods A total of 78 patients with sTBI admitted to the General Hospital of Western Theater Command from March 2020 to October 2021 were selected as the research subjects.The patients were randomly divided into the control group and the observation group,with 39 patients in each group.The patients in both groups underwent basic treatments such as water,electrolyte and acid-base balance,nutritional support,anti-infection,and decompressive craniectomy.On this basis,patients in the control group received early HBOT,while patients in the observation group received both HBOT and MNES.Their clinical efficacy was compared between the two groups.Before and after treatment,dual-channel transcranial Doppler ultrasound was performed to detect hemodynamic indicators such as peak systolic blood flow velocity(Vs),mean blood flow velocity(Vm),and pulsatility index(PI)in the middle cerebral artery of patients in the two groups.The Glasgow Coma Scale(GCS)score was used to evaluate the degree of coma of patients in the two groups,the National Institutes of Health Stroke Scale(NIHSS)score was used to assess the neurological deficits of patients in the two groups,and the enzyme-linked immunosorbent assay was used to measure the levels of central nervous system specific protein(S100-β),glial fibrillary acidic protein(GFAP),and myelin basic protein(MBP).Complications during treatment of patients in the two groups were recorded,and their incidence was compared.Results The total effective rate of patients in the control and observation groups was 79.49％(31/39)and 92.31％(36/39),respectively.The total effective rate in the observation group was significantly higher than that in the control group(x2=8.971,P＜0.05).There was no significant difference in Vm,Vs,and PI between the two groups before treatment(P＞0.05).After treatment,the Vm and Vs in both groups were significantly higher than those before treatment,while the PI was significantly lower than that before treatment(P＜0.05);and the Vm and Vs in the observation group were signifi-cantly higher than that those in the control group,while the PI was significantly lower than that in the control group(P＜0.05).There was no significant difference in GCS and NIHSS scores between the two groups before treatment(P＞0.05).After treatment,the GCS score in both groups was significantly higher than that before treatment,while the NIHSS score was significantly lower than that before treatment(P＜0.05);and the GCS score in the observation group was significantly higher than that in the control group,while the NIHSS score was significantly lower than that in the control group(P＜0.05).There was no significant difference in S100-β,GFAP,and MBP levels between the two groups before treatment(P＞0.05).After treatment,the S100-β,GFAP,and MBP levels in both groups were significantly lower than those before treatment(P＜0.05),and the S100-β,GFAP,and MBP levels in the observation group were significantly lower than those in the control group(P＜0.05).During treatment,the incidence of complications in the control and observation groups was 23.08％(9/39)and 20.51％(8/39),respectively,showing no significant difference(x2=2.328,P＞0.05).Conclusion Early HBOT combined with MNES shows good efficacy in treating sTBI,which can effectively improve the patients'hemodynamic level,alleviate the severity of coma,enhance neurological function,and promote early recovery of consciousness,without increased risk of complications.

Objective To investigate the effect of the HtrA serine peptidase 3(HTRA3)gene on choroidal neovascu-larization(CNV)and M2 macrophage polarization.Methods Fasting venous blood was collected from 30 patients with wet age-related macular degeneration(wAMD group)and 30 healthy subjects(normal group).The serum HTRA3 messen-ger ribonucleic acid(mRNA)level was detected by quantitative reverse transcription polymerase chain reaction(qRT-PCR).RF/6A cells were randomly divided into the control group,NC-sh group and HTRA3-sh group.Lentiviral vectors of NC-shRNA and HTRA3-shRNA were transfected into RF/6A cells in the NC-sh group and HTRA3-sh group by Lipo-fectamine2000.HTRA3 transfection was detected by qRT-PCR and Western blot.Then,the RF/6A cells were randomly di-vided into the N group,H group,H+NC-sh group and H+HTRA3-sh group.After cell transfection,RF/6A cells in the N group were cultured in a RPMI 1640 complete medium at a normoxia state,and cells in other groups were cultured in a RP-MI 1640 medium with 200 mmol·L-1 CoCl2 at a hypoxia state.Tubule formation was measured by Matrigel.The C57BL/6J mice were divided into the control group,CNV group,CNV+NC-sh group and CNV+HTRA3-sh group,with 12 mice in each group.Mice in the control group were unmodeled mice,and mice in the other groups were laser-induced CNV model mice.NC-shRNA and HTRA3-shRNA lentiviral vectors with a titer of 1 × 1011 TU·mL-1 were administered to mice in the CNV+NC-sh group and CNV+HTRA3-sh group via intravitreal injection.Mice in the control group and CNV group were in-jected with phosphate buffered saline.After 7 days of treatment,the mice were examined by fundus fluorescein angiogra-phy,and the eyeballs received hematoxylin & eosin staining.The mRNA levels of HTRA3,chitinase-like protein 3(Ym-1),arginase 1(Arg-1),inducible nitric oxide synthase(iNOS),cyclooxygenase-2(COX-2)and vascular endothelial growth factor(VEGF)in RF/6A cells or choroidal tissues were detected by qRT-PCR.The protein expression levels of HTRA3,VEGF and nuclear factor kappa B(NF-κB)p65 in RF/6A cells or choroidal tissues were detected by Western blot.Re-sults Compared with the normal group,serum HTRA3 mRNA level of patients in the wAMD group increased(t=11.804,P＜0.001).Compared with the control group and NC-sh group,the expressions of HTRA3 mRNA and protein in RF/6A cells in the HTRA3-sh group decreased(all P＜0.05).Compared with the N group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF in RF/6A cells in the H group increased(all P＜0.05).Compared with the H+NC-sh group,the number of closed lumen and the mRNA and protein expressions of HTRA3 and VEGF decreased in RF/6A cells in the H+HTRA3-sh group(all P＜0.05).Compared with the control group,the mRNA and protein expression levels of HTRA3 increased,the relative fluorescence intensity of CNV increased,the mRNA levels of Ym-1 and Arg-1 in-creased,the iNOS and COX-2 mRNA levels decreased,and the NF-κB p65 protein expression level increased in mice of the CNV group(all P＜0.05).Compared with the CNV+NC-sh group,the mRNA and protein expression levels of HTRA3 de-creased,the relative fluorescence intensity of CNV decreased,the mRNA levels of Ym-1 and Arg-1 decreased,the mRNA levels of iNOS and COX-2 increased,and the NF-κB p65 protein expression level decreased in mice of the CNV+HTRA3-sh group(all P＜0.05).Conclusion Down-regulation of HTRA3 can inhibit the formation of CNV and the polarization of M2 macrophages.HTRA3 may be an important potential target for the prevention and treatment of wAMD.

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 evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

Objective:To evaluate the efficacy of acute T-cell lymphoblastic leukemia(T-ALL)in children and explore the prognostic risk factors.Methods:The clinical data of 127 newly diagnosed children with T-ALL admitted to five hospitals in Fujian province from April 2011 to December 2020 were retrospectively analyzed,and compared with children with newly diagnosed acute precursor B-cell lymphoblastic leukemia(B-ALL)in the same period.Kaplan-Meier analysis was used to evaluate the overall survival(OS)and event-free survival(EFS),and COX proportional hazard regression model was used to evaluate the prognostic factors.Among 116 children with T-ALL who received standard treatment,78 cases received the Chinese Childhood Leukemia Collaborative Group(CCLG)-ALL 2008 protocol(CCLG-ALL 2008 group),and 38 cases received the China Childhood Cancer Collaborative Group(CCCG)-ALL 2015 protocol(CCCG-ALL 2015 group).The efficacy and serious adverse event(SAE)incidence of the two groups were compared.Results:Proportion of male,age ≥ 10 years old,white blood cell count(WBC)≥ 50 × 109/L,central nervous system leukemia,minimal residual disease(MRD)≥ 1％during induction therapy,and MRD ≥ 0.01％at the end of induction in T-ALL children were significantly higher than those in B-ALL children(P＜0.05).The expected 10-year EFS and OS of T-ALL were 59.7％and 66.0％,respectively,which were significantly lower than those of B-ALL(P＜0.001).COX analysis showed that WBC ≥ 100 x 109/L at initial diagnosis and failure to achieve complete remission(CR)after induction were independent risk factors for poor prognosis.Compared with CCLG-ALL 2008 group,CCCG-ALL 2015 group had lower incidence of infection-related SAE(15.8％vs 34.6％,P=0.042),but higher EFS and OS(73.9％vs 57.2％,PEFS=0.090;86.5％vs 62.3％,PoS=0.023).Conclusions:The prognosis of children with T-ALL is worse than children with B-ALL.WBC ≥ 100 × 109/L at initial diagnosis and non-CR after induction(especially mediastinal mass has not disappeared)are the risk factors for poor prognosis.CCCG-ALL 2015 regimen may reduce infection-related SAE and improve efficacy.

Objective:To investigate the efficacy and safety of Venetoclax combined with CACAG regimen in treatment of patients with refractory/relapse acute myeloid leukemia(R/R AML).Methods:The study was a singlecenter prospective clinical trial.The enrolled patients met the criteria for R/R AML.Treatment included Azacidine(75mg/m2,d1-7),Ara-C(75-100 mg/m2,q12h,d1-5),Aclacinomycin(20 mg d1,d3,d5),Chidamide(30 mg d1,d4),Venetoclax(100 mg d1,200 mg d2,400 mg d3-d14,in combination with Triazole Drug,reduced to 100 mg/d),and granulocyte colony-stimulating factor(300 μg/d until neutrophil recovery).The primary endpoint of observation was overall response rate after 1 course of treatment.Results:A total of 19 patients were enrolled from January 2022 to April 2023.After 1 course of treatmen,the overall response rate was 81.3％(13/16),the CR rate was 68.8％(11/16),and the PR was 12.5％(2/16).Among the 11 patients who got CR/CRi,8 cases achieved CRm(minimal residual disease negative CR)and 3 cases did not.As of March 27,2023,the median follow-up time was 111(19-406)days.The six-month overall survival and progression-free survival rates were both 55.7％,the 1-year overall survival and progression-free survival rates were 46.4％and 47.7％,respectively.In addition,compared with the non-CRm group,CRm patients had a better PFS(377 days vsi11 days,P=0.046).Treatment-related adverse events were mainly 3-4 degrees of bone marrow suppression,complicated by various degrees of infection(n=12),hypokalemia(n=12)and hypocalcemia(n=10)and elevated liver enzymes(n=8),of which 3/4 degrees accounted for 47.4％(9/19).Conclusion:The Venetoclax combined with CACAG regimen is an effective salvage therapy for patients with R/R AML,with high remission rate and safety profile.