Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective The objective of this study is to examine the expression level of the S100A7A protein in both gastric cancer tissues and cells,as well as to evaluate its impact on the malignant phenotype of gastric cancer(GC)cells.Methods Immunohistochemical assay was used to detect the expression characteristics of S100A7A in 21 gastric cancer tissues and their corresponding paracancerous tissues,as well as to investigate its correlation with gastric cancer clinicopathological factors.Gastric cancer cells were genetically modified to overex-press S100A7A through plasmid transfection.Subsequently,the impact of S100A7A on the proliferation,migra-tion,and invasion capacities of gastric cancer cells was assessed using cell proliferation assays(EdU assay and plate cloning assay)as well as cell migration and invasion assays(Transwell assay and scratch assay).Results The expression of S100A7A protein was higher in GC tissues than in paracancerous tissues;Overexpression of S100A7A may increase gastric cancer cell proliferation,migration,and invasion.Conclusion S100A7A is a possible oncogene in GC and is predicted to serve as a new diagnostic and therapeutic target for the disease.

Currently,human health due to corona virus disease 2019(COVID-19)pandemic has been seriously threatened.The coronavirus severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike(S)protein plays a crucial role in virus transmission and several S-based therapeutic approaches have been approved for the treatment of COVID-19.However,the efficacy is compromised by the SARS-CoV-2 evolvement and mutation.Here we report the SARS-CoV-2 S protein receptor-binding domain(RBD)inhibitor licorice-saponin A3(A3)could widely inhibit RBD of SARS-CoV-2 variants,including Beta,Delta,and Omicron BA.1,XBB and BQ1.1.Furthermore,A3 could potently inhibit SARS-CoV-2 Omicron virus in Vero E6 cells,with EC50 of 1.016 pM.The mechanism was related to binding with Y453 of RBD deter-mined by hydrogen-deuterium exchange mass spectrometry(HDX-MS)analysis combined with quan-tum mechanics/molecular mechanics(QM/MM)simulations.Interestingly,phosphoproteomics analysis and multi fluorescent immunohistochemistry(mIHC)respectively indicated that A3 also inhibits host inflammation by directly modulating the JNK and p38 mitogen-activated protein kinase(MAPK)path-ways and rebalancing the corresponding immune dysregulation.This work supports A3 as a promising broad-spectrum small molecule drug candidate for COVID-19.

This article reports the diagnosis and treatment of a case of acromegaly in a pregnant patient who took bromocriptine during pregnancy and delivered successfully. A retrospective summary of the clinical data and treatment outcomes before and after two pregnancies of the patient is provided. The patient took bromocriptine during the second pregnancy, and her condition remained stable. A baby girl was delivered by caesarean section at full term. The article suggests that pregnancy in acromegaly patients, after the stabilization of the condition, can lead to favorable outcomes. The use of dopamine receptor agonists during pregnancy does not increase adverse events during the perinatal period.

Objective:To understand the epidemiological characteristics and post-exposure prophylaxis (PEP) situation of rabies exposure population in the animal injury outpatient department of Lishui Central Hospital, so as to provide reference for rabies prevention and control in this region.Methods:The epidemiological data of 6 471 rabies-exposed persons in Lishui Central Hospital from 2021 to 2023 were retrospectively analyzed, including the gender and age of exposed persons, the month and location of injury, the species of injured animals, the exposure grade, rabies vaccination, rabies passive immunization agents, etc.Results:From 2021 to 2023, a total of 6 471 cases of rabies exposure were treated in the animal injury outpatient department of Lishui Central Hospital. From 2021 to 2023, 1 133 cases, 2 135 cases and 3 203 cases were treated respectively. April to November was the peak period of exposure. The population of 21 to 30 years had the highest rate of treatment, reaching 27.79% (1 798/6 471), and was a high-risk group of exposure. The age composition ratio of rabies exposure in the three years was statistically significantly different ( χ2=43.82, P<0.001); the male to female ratio was 1∶1.14 ( χ2=1.63, P=0.442); 3 317 cases (51.26%, 3 317/6 471) were injured by cats, and 2 614 cases (42.16%, 2 614/6 471) were injured by dogs, cats and dogs were the main injured animals ( χ2=18.63, P=0.098). The upper limbs (4 131/6 471, 63.84%) and lower limbs (1 848/6 471, 28.56%) were the most exposed sites, and there was a statistically significant difference in the exposure composition ratio of each site in three years ( χ2=105.79, P<0.001). Grade II exposure accounted for 31.79% (2 057/6 471), grade III exposure accounted for 62.31% (4 032/6 471). Among grade III exposure individuals, those who used passive immune preparations accounted for 55.13% (2 232/4 032). Conclusions:The number of rabies-exposed patients in the animal injury outpatient department of Lishui Central Hospital has been increasing year by year, and the population of patients injured by cats and dogs is particularly prominent. The utilization rate of passive immune preparations for grade III exposure patients still needs to be further improved.

Objective To investigate the needs and feedback from clinical medical students on the diversified teaching mode adopted by the Department of Endocrinology in Peking Union Medical College Hospital.Methods Questionnaires were distributed to the medicine students who were in clinical rotation in Peking Union Medical Col-lege,and the teaching status and teaching effect was investigated.Results A total of 95 valid questionnaires were received.The attending physicians and the teaching resident physicians performed well in the daily teaching activi-ties.The medical students believed that outpatient training was necessary in addition to ward rotations.After the ro-tation in the endocrinology department,the self-evaluated score of mastery of endocrinology knowledge had been significantly improved,especially in those who rotated in outpatient clinic,suggesting that outpatient teaching was of great significance.In addition,the establishment of a self-learning platform including clinical cases and videos in endocrinology could be used as an important supplementary means for clinical teaching.Conclusions Outpatient training improves learning outcomes of medical students,so must be kept and further strengthened in the future.Building a database of typical clinical cases and teaching videos can improve the training quality.

Objective To investigate the clinical prognosis value of serum microRNA(miR)-138-5p and miR-212-5p levels in prostate cancer.Methods A total of 95 cases of prostate cancer patients admitted to the First Hospital of Handan from July 2020 to June 2021 were collected.Based on follow-up records for two years after surgery,these patients were separated into a poor prognosis group(n=52)and a good prognosis group(n=43),and 48 healthy volunteers who underwent a physical examination at the hospital were collected as the healthy control group.In addition,quantitative real-time fluorescence-PCR(qRT-PCR)was applied to detect the relative expression levels of miR-138-5p and miR-212-5p in the serum of study subjects,and the clinical data of the patients were collected and analyzed.Multivariate COX regression was applied to analyze factors that affected the prognosis of prostate cancer patients.The predictive value of serum miR-138-5p and miR-212-5p for the prognosis of prostate patients was tested,and receiver operating characteristic(ROC)curves were plotted.Pearson method was applied to analyze the correlation between the expression of serum miR-138-5p and miR-212-5p and the Gleason score.Results Compared to the healthy control group,the serum levels of miR-138-5p(0.88±0.10,0.83±0.09 vs 1.01±0.10),and miR-212-5p(0.75±0.09,0.71±0.08 vs 1.02±0.11)were lower in the good prostate cancer prognosis group and poor prostate cancer prognosis group,and the differences were significant(t=14.021,22.275;9.825,18.063,all P＜0.05).The prognosis of prostate cancer patients was related to TNM staging,bone metastasis,tissue differentiation degree,preoperative PSA level,and Gleason score(x2=4.417～7.187,t=14.235,all P＜0.05).Serum miR-138-5p[HR(95％CI):0.871(0.785～0.966)],and miR-212-5p[HR(95％CI):0.822(0.725～0.932)]were protective factors for poor prognosis(all P＜0.05).While Gleason score[HR(95％CI):1.253(1.026～1.530)],TNM stage[HR(95％CI):1.224(1.024～1.463)],bone metastasis[HR(95％CI):1.398(1.036～1.887)],tissue differentiation degree[HR(95％CI):1.520(1.146～2.016)]and PSA level[HR(95％CI):1.426(1.094～1.858)]were all risk factors for poor prognosis(all P＜0.05).The AUC(95％CI)of serum miR-138-5p and miR-212-5p were 0.883(95％CI:0.801～0.940)and 0.863(95％CI:0.777～0.925),respectively.Serum miR-138-5p and miR-212-5p were negatively correlated with the Gleason score(r=-0.610,-0.420,all P＜0.05).Conclusion Serum miR-138-5p and miR-212-5p levels are elevated in patients with poor prostate cancer prognosis and may have a certain auxiliary predictive value for prostate cancer patient prognosis.

Objective To analyze the confirmation results of initial screening positive for human immunodeficiency virus (HIV) antibodies and to investigate the rationality of the gray zone for the signal-to-cutoff (S/CO) ratio values obtained by chemiluminescence assay. Methods A total of 184 specimens with positive HIV antibody screening results were collected. Confirmation was conducted using the Western blot (WB) method and viral nucleic acid testing, and the confirmation outcomes and band distribution were observed. The receiver operating characteristic (ROC) curve was employed to predict the optimal cutoff value, and the rationality of S/CO values in establishing a gray zone for HIV antibody was analyzed. Results Among the 184 HIV antibody screening positive samples, 153(83.15%) were initially screened by chemiluminescence, and 31 (16.85%) were screened by colloidal gold method. Male cases (57.07%) and those aged 40 years or older (75.00%) had higher proportion of initial screening positivity than females and other age groups. Supplemental WB testing revealed that 101 (54.89%) cases were confirmed as HIV-1 antibody positive, 56(30.43%) were negative, and 27(14.67%) were indeterminate. Of the 27 indeterminate cases, one was confirmed positive by NAT (initial S/CO value by chemiluminescence5.60), while the remaining 26 were negative. The positive agreement rates between chemiluminescence, colloidal gold and supplemental WB testing were 65.36% and 3.23%, respectively, with statistically significant difference (χ²=40.191, P < 0.05). Among 27 cases with indeterminate HIV-1 antibody results, upon further nucleic acid testing for viral load, one case exhibited WB banding pattern of P24+gp160, and the nucleic acid load confirmed this case as positive. In the distribution of band patterns among indeterminate samples, P24 had the highest occurrence (74.07%), followed by P66 (11.11%), gp160 (7.41%) as well as P17 and gp41 (both 3.70%). The ROC curve predicted the optimal S/CO cutoff value to be 5.15, with an area under the curve (AUC) of 0.904, sensitivity and specificity of 83.30% and 76.40%, respectively, and 95%CI of 0.861 to 0.948. There was a good correlation between the WB band patterns and confirmation results for initial screening positive cases (P < 0.05), with the highest correlation found for the P24 band (r=0.910). Conclusion There is a certain rate of false positives among HIV antibody initial screening positive cases, and effective screening can be achieved through WB testing. Additionally, based on the current testing platform, the gray zone for HIV antibody S/CO values in the chemiluminescence assay is set at 1.00 to 5.15, which exhibits high sensitivity.

Objective:To explore the material basis and mechanism of Linggui Zhugan Decoction in treating hypertension and obesity by means of network pharmacology and molecular docking technique.Methods:The TCMSP was retrieved and the main active components and action targets of Linggui Zhugan Decoction were screened. The GeneCards, OMIM, TTD, DisGeNET and DrugBank databases were used to screen disease-related targets of hypertension and obesity. The Cytoscape 3.9.0 was used to draw Chinese materia medica-composition-intersection target-disease network diagram. The STRING 11.5 database was used to draw PPI network. The cytoNCA plug-in was used to screen core active components and targets. The bioenrichment analysis of GO and KEGG was carried out in the R4.1.2, and the Chinese materia medica-intersection target-path diagram was drawn, and the core active components and core targets were docked in PyMOL and AutoDockTools 1.5.7.Results:A total of 102 potentially active components and 62 intersection targets were obtained, and 8 active components and 7 core targets were screened. Enrichment analysis showed that the key targets were mainly enriched through the signaling pathways of fluid shear stress and atherosclerosis, lipid and atherosclerosis, and AGE-RAGE, which were involved in biological processes such as the response to nutritional levels and the regulation of small molecule metabolism. Molecular docking showed that there were 37 groups with addinity < -7 kcal/mol.Conclusion:The main active components of Linggui Zhugan Decoction are quercetin, kaempferol and naringenin, which may play a role in fluid shear stress and atherosclerosis pathway, lipid and atherosclerosis pathway and AGE-RAGE signal pathway through AKT1, EGFR, IL1B and other targets.

Objective:To investigate the risk factor of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and the application value of its risk scoring model.Methods:The retrospective cross-sectional study was conducted. The clinicopathological data of 149 patients with HCC who were admitted to two medical centers, including 97 cases in the Jiangnan University Medical Center and 52 cases in the Affiliated Xingtai People′s Hospital of Hebei Medical University, from January 2017 to April 2020 were collected. There were 116 males and 33 females, aged (58±12)years. There were 74 cases with VETC and 75 cases without VETC. Observation indica-tors: (1) clinical characteristics of patients with and without VETC; (2) imaging features of patients with and without VETC; (3) multivariable analysis of HCC patients with VETC; (4) construction of VETC related risk scoring model and its performance evaluation; (5) postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolutes, and comparison between groups was conducted using the chi-square test and continuous correction chi-square test. Variables of clinical and imaging characteristics with statistically signifi-cant were included in the multivariate analysis. Multivariate analysis was conducted using the Logistic regression model of backward stepwise selection. VETC related risk scoring model was constructed based on the results of Logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the sensitivity, specificity, accuracy and their 95% confidence interval ( CI) were calculated. The maximizing Youden index was the optimal cutoff value for VETC prediction. The Hosmer Lemeshow goodness of fit test was used to assess the consistency between VETC risk scoring model predicted VTEC status and the true VETC status. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with and without VETC. Cases with postoperative albumin <36 g/L were 57 in patients with VETC, versus 68 in patients without VETC, respectively, showing a significant difference between them ( χ2=5.13, P<0.05). (2) Imaging features of patients with and without VETC. Cases with lesion imaging presence as nonperipheral washout, cases with lesion imaging presence as mosaic architecture, cases with lesion imaging presence as intratumoral hemorrhage, cases with lesion imaging presence as corona enhancement, cases with lesion imaging presence as non-smooth tumor margin, cases with lesion imaging presence as peritumoral enhancement in arterial phase, cases with lesion imaging presence as intratumoral arteries, cases with lesion imaging presence as peritumoral hypointensity in hepatobiliary phase, cases with lesion imaging enhancement type as uniform low enhancement, uniform high enhance-ment, heterogeneous enhancement with septations and heterogeneous enhancement with irregular ring-like structures, cases with intratumoral necrosis or ischemic, cases with tumor diameter >5 cm were 73, 35, 33, 15, 39, 28, 42, 27, 4, 5, 27, 38, 45, 46 in patients with VETC, versus 64, 16, 13, 3, 19, 15, 9, 13, 9, 35, 5, 26, 10, 10 in patients without VETC, respectively, showing significant differences in the above indicators between them ( χ2=8.92, 11.15, 12.97, 9.28, 11.74, 5.77, 33.14, 6.96, 41.79, 36.05, 37.86, P<0.05). (3) Multivariable analysis of patients with VETC. Results of multivariable analysis showed that lesion imaging enhancement as heterogeneous enhancement with septations, lesion imaging enhancement as heterogeneous enhancement with irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm were independent risk factors influen-cing patients with VETC ( odds ratio=4.18, 7.62, 4.23, 4.08, 95% CI as 1.60?11.60, 2.00?31.70, 1.71?10.90, 1.60?10.80), P<0.05). (4) Construction of VETC related risk scoring model and its performance evaluation. The VETC related risk scoring model was constructed as (heterogeneous enhancement with septations, presence: 1.0, absence: 0)+(heterogeneous enhancement with irregular ring-like structures, presence: 1.5, absence: 0)+(intratumoral necrosis or ischemia, presence: 1.0, absence: 0)+(main tumor diameter >5 cm, presence: 1.0, absence: 0). The AUC, sensitivity, specificity, and accuracy of VETC related risk scoring model were 0.86 (95% CI as 0.80?0.92), 79.7% (95% CI as 69.2%?87.3%), 80.0% (95% CI as 69.6%?87.5%) and 79.9% (95% CI as 72.7%?85.5%), respectively. Results of Hosmer-Lemeshow goodness of fit test showed a good consistency between VETC risk scoring model predicted VETC status and true VETC status ( P>0.05). (5) Postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. All 149 patients were followed up for 29(range, 26?35)months. The time to tumor recurrence and 2-year cumulative tumor recurrence rate of 149 patients were 29(range, 24?33)months and 43.0%, respectively. The 2-year tumor cumulative recurrence rate of patients with and without VETC predicted by risk scoring model was 47.8% and 37.9%, respectively, showing a significant difference between ( χ2=3.90, P<0.05). The 2-year cumulative tumor recurrence rate of patients with and without VETC confirmed by postoperative histopathological examination was 47.4% and 38.1%, respectively, showing a significant difference between ( χ2=4.20, P<0.05). Conclusions:Lesion imaging enhancement as heterogeneous enhancement with septations or irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm are independent risk factors influen-cing HCC patients with VETC. The proposed risk scoring model based on those three risk factors achieves an optimal preoperative diagnostic performance.