Objective　To investigate the distribution characteristics of genetic subtypes among newly reported human immunodeficiency virus type 1 (HIV-1) cases in Tongzhou District, Beijing, from 2021 to 2022, and to analyze the molecular epidemiological characteristics and drug resistance patterns of HIV-1 in the area. Methods　Newly reported HIV-1 cases in Tongzhou District, Beijing, from 2021 to 2022, were taken as the study population. Nested PCR was used to amplify the HIV-1 pol region gene, and the gene sequences were obtained through first-generation sequencing. A phylogenetic tree was constructed to analyze the HIV-1 genetic subtypes and drug resistance. Results　There were 308 new HIV-1 cases reported in Tongzhou District, Beijing from 2021 to 2022. A total of 230 HIV-1 pol region gene sequences were obtained, with a case coverage rate of 74.68%. Seven HIV-1 genotypes were identified, with CRF07_BC (42.17%) and CRF01_AE (36.09%) being the main prevalent strains. Furthermore, new epidemic types such as CRF55_01B, CRF01_AE, and BC recombinants were detected. There were statistically significant differences (χ2=17.845, P<0.05; χ2=7.731, P<0.05) in the genotype composition ratio among newly reported HIV-1 cases across different age groups and detection routes, while no significant differences (P>0.05) were observed concerning gender, transmission route, marital status, and others. A total of 64 cases (27.83%) showed drug-resistant mutations, with 27 mutation sites identified in total. There were significant differences (χ2=53.674, P<0.05) in the mutation rates among different HIV-1 genotypes, with the highest mutation rate (100.0%) observed in CRF55_01B. Drug resistance to PIs, NRTIs, and NNRTIs was observed in 18 cases (7.83%), with resistance rates of 3.04%, 0.87%, and 4.35%, respectively. High-level drug resistance was observed in eight cases, including one case of NRTI resistance (mutation site M184V) and the remainder exhibiting NNRTI resistance, involving sites such as M184V, K103N, Y188L, and Y188C. Conclusions　The genotype of HIV-1 in Tongzhou District is diverse, with CRF07_BC and CRF01_AE as the predominant strains. The total drug resistance rate reached a moderate level. We should strengthen the analysis of HIV-1 genotypes and drug resistance monitoring, focusing unique recombinants and resistance-related gene mutations.

Stresses induced by the deficiency or excess of trace mineral elements, such as manganese (Mn), represent a common limiting factor for the production of crops like Brassica napus. To identify key genes involved in Mn allocation in B. napus and elucidate the underlying mechanisms, a member of the metal tolerance protein (MTP) family obtained in the previous screening of cDNA library of B. napus under Mn stress was selected as the research subject. Based on the sequence information and phylogenetic analysis, it was named as BnMTP10. It belongs to the Mn-cation diffusion facilitator (CDF) subfamily. Expression of BnMTP10 in yeast significantly improved the tolerance of transformants to excessive Mn and iron (Fe) and reduced the accumulation of Mn and Fe. However, the yeast transformants exhibited no significant changes in tolerance to excess cadmium, boron, aluminum, zinc, or copper. The qRT-PCR results demonstrated that the flowers of B. napus had the highest expression of BnMTP10, followed by roots and leaves. Subcellular localization studies revealed that BnMTP10 was localized in the endoplasmic reticulum (ER). Compared with wild-type plants, transgenic Arabidopsis overexpressing BnMTP10 exhibited enhanced tolerance to excessive Mn stress but showed no significant difference under Fe stress. Correspondingly, under excessive Mn stress, the Mn content in the roots of transgenic Arabidopsis increased significantly. However, under excessive Fe stress, the Fe content in transgenic Arabidopsis did not alter significantly. According to the results, we hypothesize that BnMTP10 may alleviate excessive Mn stress in plants by mediating Mn transport to the ER. This study facilitated our understanding of efficient mineral nutrients, and provided theoretical foundations and gene resources for breeding B. napus.
Brassica napus/genetics* ; Manganese/metabolism* ; Plants, Genetically Modified/genetics* ; Plant Proteins/physiology* ; Arabidopsis/metabolism* ; Gene Expression Regulation, Plant ; Phylogeny ; Cation Transport Proteins/metabolism* ; Stress, Physiological

There are millions of patients with taxane-induced peripheral neuropathy （TIPN）， and there is no effective treatment or prevention measure in clinical practice. The occurrence of TIPN may be related to the dosage form of paclitaxel drugs， genetic and molecular markers， drug dosage and chemotherapy cycle， patient factors， etc. At present， drugs for treating TIPN mainly include those that inhibit axonal degeneration （such as dosazosin， tamsulosin）， prevent mitochondrial dysfunction （such as glutathione trisulfides， antioxidants α -lipoic acid）， improve calcium imbalance in the internal environment （Shaoyao gancao decoction， N-type voltage-gated calcium channel inhibitor IPPQ）， and inhibit neuroinflammation （such as chemokine inhibitors and selective interleukin-8 receptor inhibitors DF2726A）. Further exploration of drug treatment strategies targeting different induction mechanisms is expected to become a new direction for precise clinical prevention and personalized treatment of TIPN.

OBJECTIVE To provide reference for strengthening the standardized management of off-label drug use in cancer hospitals. METHODS The evaluation system for off-label drug use was established to standardize the application， approval， and filing process for off-label drug use in our hospital. The changes in off-label drug application quantity， proportion， disease category and drug category in our hospital were compared before （October 1st， 2021-September 30th， 2022） and after （October 1st， 2022- September 30th， 2023） the establishment of the evaluation system； drug items supported by high-level evidence screened by pharmacy department were analyzed statistically. RESULTS The number of off-label drug use applications in our hospital had gradually increased， from 306 pieces in the fourth quarter of 2021 to 3 828 pieces in the third quarter of 2023. In the year before the construction of the evaluation system， there were a total of 4 482 applications for off-label drug use， and in the year after the construction of the evaluation system， there were 11 840 applications for off-label drug use. After the construction of the evaluation system， the proportion of unregistered off-label drug use significantly decreased， compared to the same period last year （P＜0.05）. Among them， there were no unregistered applications for off-label drug use for digestive system tumors， head and neck tumors， and radioactive drugs； lymphoma， breast tumors，urogenital system tumors， cytotoxic drugs and new anti-tumor drugs all had a decrease of over 70% in unregistered off-label drug applications. Twenty-seven off-label drug use items related to 19 drugs supported by high-level evidence were screened by the pharmacy department of our hospital， among which 25 items were drug use beyond indication. CONCLUSIONS The establishment of off-label drug use evaluation system in cancer hospital is helpful to the rational use and refined management of clinical anti-tumor drugs.

AIM:To explore the fundus vascular characteristics of healthy individuals based on deep learning techniques, with a view to discovering the range of normal values of the fundus arteries and veins, as well as the relationship between physiological factors, such as gender, age, body mass index(BMI), blood pressure, and fundus vasculature characteristics.METHODS:Fundus images of healthy people were taken from a professional fundus camera, and the subject's blood pressure and laboratory test was collected. Additionally, the fundus arteries and veins were segmented by the improved U-Net model, and the color, morphology and Haralick texture features of the vessels were extracted from computer vision technology.RESULTS:A total of 4 487 cases fundus images were taken and 326 cases with healthy and clear fundus images were screened, including 200 males and 126 females. There were differences in the morphology, color, and textural characteristics of the left and right eyes, as well as of the fundus arterioles and veins, with a mean vessel width(width)of 1.146 in the arteries and 1.430 in the veins, and an arteriovenous ratio about 4:5. Fundus artery and vein characteristics in healthy individuals of different ages(21-30, 31-40, 41-50): compared with the healthy population aged 21-30 and 31-40 years, arterial and venous inverse difference moment(idm), f12 and venous angular second moment(asm)values increased, and arterial and venous contrast(con), entropy(ent), difference entropy(den), and venous sum entropy(sen)values decreased in 41-50 years. Compared with the 21-30 years age group, arterial f12 values increased and venous con values decreased in 31-40 years(all P<0.05). Fundus vascular characteristics of healthy individuals of different sexes: compared with male, fundus arterial and venous sum average(sav), sum variance(sva)values, arterial curved values, and venous b mean, bsd, variance(var), sen, ent values increased in female, while venous area value of female decreased(all P<0.05). There were no statistically significant differences in fundus arteriosus and venous features in healthy subjects with different levels of BMI(all P>0.05). Fundus characteristics of healthy people with different degrees of blood pressure: there were statistically significant differences in fundus arteriosus area, width, and venous con, idm, dva, and den values between the normal blood pressure and high blood pressure groups(all P<0.05).CONCLUSION: The characteristics of the left and right eyes as well as the fundus arteries and veins differ in healthy individuals and correlate with physiological factors such as gender, age and blood pressure, which have the value of a potential microcirculation marker.

Objective:To analyze the clinical characteristics of novel coronavirus (COVID-19) infection in liver transplant recipients.Methods:Clinical data of 130 liver transplant recipients with COVID-19 infection followed in Hebei Medical University Third Hospital from November 2022 to January 2023 were retrospectively collected, including 103 males and 27 females, aged (53.6±11.4) years. The severity of COVID-19 infection, its clinical symptoms, and negative conversion time for each recipient were analyzed and compared.Results:For the disease severity, 121 (93.1%) were mild, 5 (3.8%) were moderate, 3 (2.3%) were severe, and 1 (0.8%) was critically severe. The most common symptoms in the 126 patients with mild to moderate COVID-19 infection were successively fever, fatigue, cough and myalgia, with a negative conversion time of (10.1±4.5) (3.0-29.0)d. In those who underwent transplantation less than 12 months ( n=28), those who were taking mycophenolate mofetil ( n=53) and those who were taking methylprednisolone ( n=10), the negative conversion time was (11.6±5.1) d, (11.4±5.4) d, and (13.4±6.4) d, respectively, longer compared to those who underwent transplantation more than 12 months (9.7±4.2 d, n=98), and who were not taking mycophenolate mofetil (9.2±3.4 d, n=73) or methylprednisolone (9.8±4.2 d, n=116, all P<0.05). The negative conversion times were longer in recipients with symptoms (eg. fatigue and cough) than those in asymptomatic recipients (11.0±5.1 d vs. 9.0±3.3 d, t=2.64, P=0.009, and 11.4±5.2 d vs. 9.0±3.4 d, t=2.92, P=0.004). Conclusion:The COVID-19 infection in liver transplant recipients was mainly mild and moderate. The most common symptoms are fever, fatigue, cough and myalgia. The short time (less than 12 months) after liver transplantation, oral mycophenolate mofetil and methylprednisolone, with symptoms (fatigue and cough) could be associated with a prolonged negative conversion time.

Microneedle percutaneous immunization is achieved by puncturing the stratum corneum of the skin with microneedles so that the vaccine is efficiently recognized by antigen-presenting cells to induce a specific immune response. Due to the advantages of efficient induction of immune response, low pain and easy storage, transdermal immunization by microneedles has been widely used for immunization of various vaccines in recent years. This review summarizes the materials of microneedles, application for transcutaneous immunization, as well as the challenges that need to be addressed.
Administration, Cutaneous ; Drug Delivery Systems ; Needles ; Vaccination ; Vaccines

OBJECTIVE：To systematicall y review the pharmacoeconomics of anticoagulants for the prevention and therapy of venous thromboembolism （VTE）in cancer patients. METHODS ：Retrieved from PubMed ，Embase，Cochrane library ，CNKI， Wanfang database ，VIP，SinoMed，The NHS Economic Evaluation Database ，The Healthy Technology Assessment Database and EconLit，supplemented by manual retrieval ，the economic evaluation studies on the prevention and therapy of VTE in cancer patients with different anticoagulants were collected. The retrieval time was from the inception to Nov. 12th，2020. After screening and extracting ，the Consolidated Health Economic Evaluation Reporting Standards （CHEERS）was used to evaluate the quality of the included literatures. The basic characteristics of the included literatures were summarized by descriptive methods ，and the economic results were summarized according to medication purpose and different intervention grouping. RESULTS ：A total of 15 literatures were included. Three literatures were of excellent quality ；ten were of good quality ；and the other two were of moderate quality. Included studies were widely conducted in countries of different economic levels ，including China （1 piece），the United States（7 pieces），Canada（3 pieces），France（2 pieces），the Netherlands （1 piece），Brazil（1 piece）and Austria （1 piece）. For preventing VTE in cancer patients ，the economic evaluation results of warfarin and low-molecular-weight heparin （LMWH）needed to be updated. Novel oral anticoagulants （NOACs）for the prevention of VTE were less cost-effective among cancer patients with medium- and high-risk venous thrombosis in China than in the United States ，but the economic advantage increased among the high-risk patients. Compared to enoxaparin ，aspirin was absolutely dominant to preventing VTE in patients with myeloma. For the treatment of VTE in cancer patients ，LMWH was not cost-effective ，compared to warfarin in the United States ；but it was cost-effective in Canada and some countries of Northern Europe. Compared with LMWH ，NOACs could save total cost ，but the incremental utility in the United States and Brazil were opposite. Sensitivity analysis showed that economic results were sensitive to drug prices ，the baseline rate of thrombosis risk ，and the risk of adverse events （thrombosis recurrence ，major bleeding and death ） of different interventions ，the first two of which could reverse the conclusions. CONCLUSIONS ：For the prevention of VTE in cancer patients ，compared with no intervention or placebo ，the economic advantages of NOACs were different in different countries or for patients with different thrombosis risk ；the economics of warfarin and LMWH were not yet clear. Aspirin had obvious economic advantages compared with enoxaparin. For the treatment of VTE in cancer patients ，LMWH had different economic advantages compared with warfarin in different countries ；NOACs could save costs compared with LMWH. Economic strategies are greatly affected by the risk of diseases ，medical systems ，drug price ，patient preferences and values ，economic levels ，cost-utility threshold standards in different countries. Therefore ，the final economic strategies need to be based on the contexts of different countries.

Objective:To investigate the expression of human epidermal growth factor receptor 2 (HER2) in pancreatic ductal adenocarcinoma(PDAC) and its relationship with the prognosis of patients with PDAC.Methods:From January 2001 to December 2012, 109 paraffin embedded PDAC tissue samples and 27 normal pancreatic tissue samples were collected from the Department of Pathology, Huadong Hospital Affiliated to Fudan University. The expression of HER2 protein in pancreatic tissue was detected by immunohistochemical Envision two-step method. HER2 expression was evaluated according to Hercept test, and its relationship with clinicopathological features and survival time was analyzed.Results:The expression of HER2 protein was negative (-) in 29.4% of PDAC tissues, weakly positive (+ ) in 35.8%, positive (+ + ) in 25.7% and strongly positive (+ + + ) in 9.2%, respectively, and the overexpression rate (+ + , + + + ) was 34.9%; the negative (-) and weakly positive (+ ) expression of HER2 protein in normal pancreatic tissues accounted for 88.9% and 11.1% respectively. There was no expression with positive (+ + ) or strongly positive (+ + + ), therefore, the overexpression rate was 0. The overexpression rate of HER2 protein in PDAC and normal pancreatic tissues was significantly different ( P=0.000). The expression of HER2 protein was significantly correlated with age, and the expression of HER2 protein in patients with PDAC over 65 years old was significantly higher than that in patients with PDAC under 65 years old ( P=0.043), but not with gender, tumor location, tumor grade, T stage, N stage and nerve invasion (all P>0.05). Univariate Cox proportional hazards analysis showed that HER2 expression was associated with postoperative survival time of patients with PDAC ( P=0.032). Multivariate Cox proportional hazards analysis showed that HER2 expression was an independent prognostic factor for survival of patients with PDAC ( P=0.040). The median survival period of patients with HER2 expression + + + was significantly longer than that of patients with HER2 expression -~+ + (128.4 months vs 21.5 months), and the difference was statistically significant ( P=0.038). Conclusions:The overexpression of HER2 in PDAC tissue was related to the age of patients. The survival time of patients with HER2 strongly positive PDAC was significantly longer. HER2 can be considered as an index to evaluate the biological behavior and prognosis of PDAC.

Objective:To investigate the causes of immune failure in the population with high vaccination rate of measles and rubella vaccine in Beijing by detecting the IgG antibody affinity in suspected cases of measles and rubella.Methods:Serum samples of 276 suspected cases of measles and rubella were tested for IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA). The affinity of IgG antibody was detected, and the relative affinity index was calculated.Results:Among the 276 suspected cases, 104 were measles and 108 were rubella. Six measles cases had vaccination history and were caused by primary immunization failure ( n=3) and secondary immunization failure ( n=3). Twelve rubella cases had vaccination history and were due to primary immunization failure ( n=4) and secondary immunization failure ( n=8). Specific high-affinity antibodies were detected in nine measles cases and seven rubella cases without vaccination history, which indicated that these cases were reinfected. In the cases without measles or rubella, other pathogenic infections including mixed infections were detected, which were mainly caused by EB virus. Conclusions:Both primary and secondary immunization failure occurred in the population with immunization history. Reinfection was found in the patients who had not received vaccination against measles or rubella. Other pathogenic infections were existed among the cases without measles or rubella. Thus, misdiagnosis was responsible for the increased proportion of measles and rubella patients with immunization history in suspected cases in recent years. Full-course vaccination was conducive to produce high-affinity antibodies against measles and rubella. A supplementary vaccination campaign should be launched to consolidate the immune barrier against measles and rubella in key population or high-risk population, aiming to block the circulation of measles virus and achieve the goal of eliminating measles.