OBJECTIVE To explore the effects of piperacillin/tazobactam combined with acetylcysteine solution on severe pneumonia after cerebral infarction,and to analyze its impact on cardiopulmonary and neurological function.METHODS A total of 86 patients with severe pneumonia after cerebral infarction admitted to Yulin Xingyuan Hos-pital from Jan.2022 to Jun.2024 were selected and divided into a control group and a study group using the ran-dom number table method(single blind),with 43 cases in each group.The control group was treated with intrave-nous drip of piperacillin/tazobactam,while the study group received additional inhalation of acetylcysteine solution based on the control group's treatment.The levels of inflammatory factors[C-reactive protein(CRP),interleukin-6(IL-6)and procalcitonin(PCT)],lung function indicators[forced vital capacity(FVC),peak expiratory flow rate(PEF),forced expiratory volume in one second(FEV1)and mean maximal expiratory flow rate(MMEF)],cardiac function indicators[left ventricular ejection fraction(LVEF),cardiac output(CO),cardiac index(CI)and stroke volume(SV)],NIH Stroke Scale(NIHSS)score,clinical efficacy,and the occurrence of adverse reactions were compared before and after treatment.RESULTS Compared with the control group,the study group had low levels of CRP,IL-6,PCT and NIHSS scores after treatment(P<0.05),and high levels of FVC,PEF,FEV1,MMEF,LVEF,CO,CI,and SV after treatment(P<0.05).The overall response rate in the study group was 95.35%,higher than 81.40%in the control group(χ2=4.074,P=0.044).There was no statistically significant difference in the incidence of adverse reactions between the control group and the study group during treatments(χ2=0.179,P=0.672).CONCLUSION Piperacillin/tazobactam combined with inhaled acetylcysteine solution for the treatment of severe pneumonia after cerebral infarction can improve clinical efficacy,reduce levels of inflamma-tory factors,and enhance cardiopulmonary and neurological functions in patients,which has a high safety profile.

Objective To explore the prevention effectiveness of a mode,conducting targeted corrective training based on motor dysfunction detected by military joint function screening,on military training injuries in new recruits during recruit basic training in order to cope with the high incidence of military training injuries among them.Method A military personnel joint function screening was conducted on the new recruits in a training base of Joint Logistics Support Force.Based on the results of screening,the new recruits with a single action score of 1 and a total score of<10 were subjected and served as corrective training participants.Through cluster sampling,the new recruits were randomly divided into an experimental group(n=223)and a control group(n=223).The control group were trained according to the regular training plan,while the experimental group completed their designated training tasks and a 2-month corrective training for motor dysfunction at the same time.The entire corrective training process was carried out by our key personnel who had received relevant training.Medical records of the medical security department of the experimental unit were collected and evaluated for the injury situation.The score of joint function screening was analyzed using independent sample t test.The incidence of training injuries was analyzed using Chi-square test or Fisher's exact test.Result After corrective training,the score of joint function was higher in the experimental group than the score before training(15.12±2.13 vs 10.58±2.83),and the score was also higher than that of the control group(15.12±2.13 vs 14.19±1.97,P<0.05).During the recruit basic training period,the incidence of training injuries was notably lower in the experimental group than the control group(12.5％vs 34.5％,Chi-square=5.469,P=0.001).Only for those who were injured during the training,11 people(39.2％)in the experimental group scored less than 10,which was obviously lower than the 49 people(63.6％)in the control group(Chi-square=4.972,P=0.026).Conclusion Our mode,corrective training based on the results of military personnel joint function screening,can effectively reduce the incidence of military training injuries in new recruits during recruit basic training,and exerts a good preventive effect against military training injuries.

Objective To identify recruit movement dysfunction based on military joint function screening and assessment,implement targeted corrective training,explore the impact of this assessment-correction system on knowledge-attitude-belief-practice(KABP)related factors,and scientifically evaluate its efficacy in preventing recruit military training injuries within the knowledge-attitude-belief-practice theoretical framework.Methods A cluster randomized controlled trial was conducted at a recruit training base of the Joint Logistics Support Force from March to May 2025,enrolling 446 recruits.Participants were randomly assigned to an experimental group(n=223)or control group(n=223)using a random number table.The control group followed the routine training program,while the experimental group additionally received a 2-month targeted corrective training for movement dysfunction alongside the established training tasks.Knowledge-attitude-belief-practice questionnaires were administered to both groups at the initial,intermediate,and advanced stages of the corrective training.Univariate logistic regression was used to preliminarily screen KABP-related factors,and a multivariate logistic regression model was further constructed to analyze the role of KABP factors in the corrective training.Results The experimental group had a cumulative training injury incidence of 40 cases(17.9%),which was significantly lower than that of the control group(83 cases,37.2%;χ2=20.757,P<0.001).The experimental group showed varying degrees of improvement in knowledge,attitude and belief,and practice dimensions(P<0.05),while the control group exhibited no significant changes in the three KABP dimensions across the three surveys.Logistic regression analysis revealed:In the first round,total practice score was significantly negatively associated with training injury incidence rate(OR=0.863,95%CI:0.822～0.906,P<0.001),whereas knowledge and attitude-belief dimensions showed no significant association;In the second round,both total knowledge score(OR=0.925,95%CI:0.903～0.946,P<0.001)and total practice score(OR=0.906,95%CI:0.874～0.940,P<0.001)significantly reduced the risk of military training injuries,with attitude-belief dimension still showing no significant effect;In the third round,all three KABP dimensions were significantly negatively associated with military training injury incidence rate(knowledge:OR=0.905,95%CI:0.884～0.926,P<0.001;attitude and belief:OR=0.942,95%CI:0.899～0.988,P=0.013;behavior:OR=0.882,95%CI:0.841～0.924,P<0.001).Conclusion Joint function screening and corrective training can significantly reduce the incidence of recruit training injuries,primarily by optimizing knowledge mastery and movement behavior;belief cultivation,however,requires long-term practical accumulation.

OBJECTIVE To explore the effects of piperacillin/tazobactam combined with acetylcysteine solution on severe pneumonia after cerebral infarction,and to analyze its impact on cardiopulmonary and neurological function.METHODS A total of 86 patients with severe pneumonia after cerebral infarction admitted to Yulin Xingyuan Hos-pital from Jan.2022 to Jun.2024 were selected and divided into a control group and a study group using the ran-dom number table method(single blind),with 43 cases in each group.The control group was treated with intrave-nous drip of piperacillin/tazobactam,while the study group received additional inhalation of acetylcysteine solution based on the control group's treatment.The levels of inflammatory factors[C-reactive protein(CRP),interleukin-6(IL-6)and procalcitonin(PCT)],lung function indicators[forced vital capacity(FVC),peak expiratory flow rate(PEF),forced expiratory volume in one second(FEV1)and mean maximal expiratory flow rate(MMEF)],cardiac function indicators[left ventricular ejection fraction(LVEF),cardiac output(CO),cardiac index(CI)and stroke volume(SV)],NIH Stroke Scale(NIHSS)score,clinical efficacy,and the occurrence of adverse reactions were compared before and after treatment.RESULTS Compared with the control group,the study group had low levels of CRP,IL-6,PCT and NIHSS scores after treatment(P<0.05),and high levels of FVC,PEF,FEV1,MMEF,LVEF,CO,CI,and SV after treatment(P<0.05).The overall response rate in the study group was 95.35%,higher than 81.40%in the control group(χ2=4.074,P=0.044).There was no statistically significant difference in the incidence of adverse reactions between the control group and the study group during treatments(χ2=0.179,P=0.672).CONCLUSION Piperacillin/tazobactam combined with inhaled acetylcysteine solution for the treatment of severe pneumonia after cerebral infarction can improve clinical efficacy,reduce levels of inflamma-tory factors,and enhance cardiopulmonary and neurological functions in patients,which has a high safety profile.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

ObjectiveTo explore the effects of modified Gualou Zhishitang combined with piperacillin sodium and tazobactam sodium on the immune function and serum levels of inflammatory cytokines in the patients with stroke-associated pneumonia （SAP， syndrome of phlegm-heat accumulation in lung）. MethodEighty SAP patients with the syndrome of phlegm-heat accumulation in lung were randomized into a control group （40 cases） and a study group （40 cases）. The SAP patients in the control group were treated with piperacillin sodium and tazobtam sodium， while those in the study group were treated with modified Gualou Zhishitang on the basis of the treatment in the control group for 2 consecutive weeks. The clinical therapeutic effects， immune function indexes， inflammation indexes， and lung function of SAP patients in the two groups before and after treatment were determined and compared. ResultAfter treatment， the scores of lesion， pulmonary rales， cough， fever， phlegm color， and constipation in both groups decreased （P<0.05）. After treatment， the ratio of forced expiratory volume in the first second to forced expiratory volume （FEV₁/FVC） and forced expiratory volume in the first second as percentage of predicted value（FEV₁%） in both groups improved （P<0.05）， and the study group outperformed the control group （P<0.05）. The treatment decreased the neutrophil to lymphocyte ratio （NLR） in the two groups （P<0.05）， and the study group had lower NLR than the control group after treatment （P<0.05）. The serum levels of procalcitonin （PCT） and hypersensitive C-reactive protein （hs-CRP） in both groups declined after treatment （P<0.05）， and the declines were more significant in the study group than in the control group （P<0.05）. After treatment， the study group was better than the control group （P<0.05）. The treatment in both groups elevated the levels of CD3⁺， CD4⁺， and CD4⁺/CD8⁺ in the peripheral blood and lowered the level of CD8⁺ （P<0.05）， and the changes were more significant in the study group than in the control group （P<0.05）. The total response rate of the study group was 95.00% （38/40）， which was higher than that （80.00%， 32/40） of the control group （χ²=4.114，P<0.05）. There was no significant difference in the incidence of adverse reactions between the two groups. ConclusionModified Gualhou Zhishitang combined with piperacillin sodium and tazobactam sodium demonstrates a significant therapeutic effect on the SAP patients with the syndrome of phlegm-heat accumulation in lung. This therapy can mitigate the clinical symptoms， improve the lung function， lower the serum levels of inflammatory cytokines， and improve the immune capacity， with high safety.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.

Background Procymidone (PCM) exposure can cause damage to reproductive organs of male mice, but whether its mechanism is related to the retinoic acid (RA) signaling pathway is unclear. Objective To explore the possible mechanism of PCM-induced testes damage in adolescent mice. Methods Three-week-old ICR mice (n=64) were randomly divided into a control group and three dose groups (low, medium, and high), with 16 mice in each group. PCM was administered orally at 0, 50, 100, and 200 mg·kg⁻¹·d⁻¹ for 21 consecutive days. Serum and bilateral testes in each mouse were collected to detect content of testosterone in serum and to observe histological changes in testis section after the mice were sacrificed one week after cessation of drug administration. Real-time fluorescence quantitative PCR and Western blotting were used to detect the mRNA expression abundances of genes related to the RA signaling pathway and apoptosis genes Casp9 and Casp12, and the protein expression levels of CYP26A1, ALDH2, and CASP9 respectively. Results Compared with the control group, there was no significant change in the overall appearance and testicular appearance of mice in each dose group after the PCM exposure. According to pathological section observation, the testicular seminiferous tubules of mice in the low-dose group showed slight atrophy and reduced sperm production; the testes of mice in the medium- and the high-dose groups showed obvious pathological damage (e.g. dilated lumen of seminiferous tubules, damaged spermatogenic epithelium, decreased number of spermatogonia, and partial absence of sertoli cells); as the concentration of PCM increased, the degree of spermatogenic epithelial damage in mice gradually increased and the number of spermatozoa in the seminiferous tubules decreased. There were no significant differences in the distance between the anus and the genitals, testicular mass, testicular volume, and testicular organ coefficient among the four groups of mice (P>0.05). The body weights of the mice in the low-, medium-, and high-dose groups were (34.91±1.89), (34.88±1.75), and (32.94±1.37) g respectively, and that in the high-dose group was lower than that in the control group, (35.93±1.99) g, (P<0.05); the serum testosterone concentrations were (313.77±5.32), (305.31±3.47), and (304.80±5.28) pg·mL⁻¹ respectively, which were lower than that in the control group, (319.05±1.92) pg·mL⁻¹ (P<0.05); as the dose of PCM increased, the body weight and serum testosterone concentration showed decreasing trends. The mRNA expression levels of Stra6 and Rbp1 in the high-dose group were higher than those in the control group (P<0.05); the mRNA expression levels of Aldh2, Aldh1a1, Aldh1a3, Rarα, Rar\begin{document}$\beta $\end{document}, Rxrα and Rxr\begin{document}$\beta $\end{document} in the medium-and the high-dose groups were higher than those in the control group (P<0.05); the mRNA expression levels of Cyp26a1 and Cyp26b1 in the medium- and high-dose groups were lower than those in the control group(P<0.05); the mRNA expression levels of apoptosis genes Casp9 and Casp12 in the medium-and the high-dose groups were higher than those in the control group (P<0.05). The protein expression level of CYP26A1 in each exposure group was lower than that in the control group (P<0.05), and the expression level decreased with increasing concentration of PCM; the expression level of ALDH2 protein in the medium- and the high-dose groups and the protein expression level of CASP9 in each exposure group were higher than those in the control group (P<0.05), and the levels increased with increasing concentration of PCM. Conclusion PCM can damage the testis tissues of adolescent mice, where RA signaling pathway, Casp9 and Casp12 genes, and CASP9 protein are activated.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

The function of drugs is based on the interaction between drug molecules and their targets.Qualitative analysis and quantitative detection of drug-target interactions run through the whole process from drug discovery to clinical practice.After decades of development, the study methods on the interaction between drug molecules and target proteins have been transformed from traditional biochemical experiments to a diversity of efficient and accurate technology systems supported by advanced molecular biology and biophysics theory.In this review, representative methods and techniques were introduced from aspects of target discovery and validation, affinity determination, interaction sites and structural analysis, which might provide some references for drug discovery and mechanism exploration.