ObjectiveTo evaluate the clinical efficacy and safety of Jingmaiyan granules （composed of Lonicerae Japonicae Flos， Sedi Herba， Paeoniae Radix Rubra， Moutan Cortex， Rhei Radix et Rhizoma Praeparata， and Glycyrrhizae Radix et Rhizoma） combined with external application of Jinhuang Ointment in treating acute-stage blood heat stasis type superficial thrombophlebitis （ST） of lower extremities， and to explore their effects on hemorheology and serum inflammatory factors. MethodsA randomized， double-blind， placebo-controlled clinical trial was conducted. A total of 124 patients with lower extremity ST were randomized into two groups（62 cases in each group）. The control group received external application of Jinhuang ointment and oral placebo treatment， while the observation group received external application of Jinhuang ointment and oral Jingmaiyan granules. Both groups were treated for 2 weeks. The clinical symptom scores， therapeutic efficacy of traditional Chinese medicine （TCM） syndrome， pain visual analog scale （VAS） scores， hemorheological indices ［including whole blood high-shear， medium-shear， and low-shear viscosity， as well as plasma viscosity （PV）］， and inflammatory factors ［C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）］ were compared before and after treatment. ResultsAfter 2 weeks of treatment， the total effective rate in the observation group （98.3%， 60/62） was significantly higher than that in the control group （83.8%， 52/62）， with a statistically significant difference （Z=3.512 1， P<0.05）. Compared with pre-treatment scores， the scores for skin color， skin temperature， swelling， pain， and cord or nodules were significantly reduced in both groups （P<0.05）， with more pronounced improvement in the observation group （P<0.05）. Additionally， compared with pre-treatment levels， the whole blood viscosity （low-， medium-， and high-shear） significantly improved in both groups after treatment （P<0.05）， with more marked improvement in the observation group （P<0.05）. Furthermore， the plasma viscosity， CRP， IL-6， and TNF-α levels were significantly reduced in both groups after treatment （P<0.05）， with more pronounced improvement observed in the observation group （P<0.05）. ConclusionThe combination of external application of Jinhuang ointment and oral Jingmaiyan granules effectively improves clinical symptoms， hemorheological abnormalities， and inflammatory responses in patients with acute stage blood heat stasis type ST of lower extremities. The treatment is safe and holds clinical promotion value.

Zoledronic acid (ZA), a nitrogen-containing bisphosphonate with established clinical utility in osteoporosis management, exhibits emerging antitumor potential in estrogen receptor-positive breast cancer. However, the molecular mechanisms underlying its nonapoptotic anticancer effects remain poorly characterized. This study revealed that ZA induced ferroptosis in ER+ breast cancer cells through dual suppression of cystine-glutamate antiporter SLC7A11 and glutathione peroxidase 4 (GPX4), key repressors of ferroptosis. Pharmacological inhibition of ferroptosis using Ferrostatin-1 significantly attenuated ZA-induced cytotoxicity, while combinatorial treatment with the GPX4 inhibitor RSL3 synergistically enhanced lipid peroxidation and cell death. Mechanistically, ZA activated the Hippo-YAP signaling pathway, promoting YAP phosphorylation, proteasomal degradation, and cytoplasmic retention, thereby silencing SLC7A11 and GPX4. We established a novel metabolic vulnerability in hormone-responsive malignancies.These findings position ZA as a bifunctional ferroptosis inducer in ER+ breast cancer, offering a promising strategy to overcome endocrine resistance.

Objective To evaluate the efficacy and safety of 450nm semiconductor blue laser vaporization prostatectomy in high-risk benign prostatic hyperplasia (BPH) patients without discontinuing anticoagulant drugs, so as to provide a safe and effectiveminimally invasive treatment option for such patients. Methods A total of 40 high-risk BPH patients who underwent 450nm semiconductor blue laser vaporization prostatectomy in our hospital during Sep. 2023 and Dec. 2024 were selected as the research subjects. The patients were divided into two groups: the oral medication group took oral anticoagulants during the perioperative period, while the discontinuation group discontinued anticoagulants, with 20 cases in either group. The perioperative indicators and changes including international prostate symptom score (IPSS), quality of life score (QoL), maximum urinary flow rate (Qmax) and post-void residual (PVR) were compared between the two groups.Results There were no statistically significant differences between the oral medication group and discontinuation group in operation time [(28.83±15.52)min vs. (26.43±14.02)min], postoperative catheter indwelling time [(3.04±0.89) d vs. (3.23±1.01) d], bladder irrigation time [(27.36±7.54) h vs. (25.46±7.10) h], and decrease in hemoglobin [(8.08±1.82)g/L vs. (7.56±1.68)g/L] (all P＞0.05). Three month after surgery, Qmax in both groups was higher, while IPSS, QoL and PVR were significantly lower (P＜0.05), but there were no statistically significant differences between the two groups (P＞0.05). No serious complications such as urinary incontinence or massive hemorrhage occurred.Conclusion 450nm semiconductor blue laser vaporization prostatectomy for high-risk BPH patients is characterized by high vaporization efficiency and good hemostatic effects. It can significantly improve the clinical symptoms with high safety, especially for high-risk patients who cannot discontinue anticoagulants.

Objective To explore the risk prediction value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid enhanced magnetic resonance imaging(Gd-EOB-MRI)liver imaging reporting and data system version 2018(LI-RADS v2018)with contrast-enhanced ultrasound(CEUS)LI-RADS version 2017(LI-RADS v2017)in high-risk patients with hepatocellular carcinoma(HCC).Methods The clinical and imaging data of 122 high-risk patients for HCC(with a total of 134 liver lesions)who underwent both Gd-EOB-MRI and CEUS examination at the same time and obtained pathological results within one month were retrospectively col-lected.The nodules were classified according to the CT/MRI LI-RADS v2018 and CEUS LI-RADS v2017 criteria,and the LI-RADS classification results of the two imaging methods were subjected to Cohen's Kappa test.Using pathological results as the gold stand-ard,the diagnostic efficacy of LI-RADS v2018 and LI-RADS v2017 with LR-5 as the standard for HCC was calculated separately.Results The overall consistency between the Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classification standards was good(Kappa=0.691,P＜0.001).Using LR-5 as the standard for diagnosing HCC,the sensitivity of Gd-EOB-MRI and CEUS was 84.7％and 81.2％,the specificity was 79.6％and 73.5％,the positive predictive value was 87.8％and 84.1％,the negative predictive value was 75.0％and 69.2％,and the accuracy was 82.8％and 78.4％,respectively.There was no statistically significant difference in the diagnostic efficacy of the diagnosis of HCC by LR-5 between the two imaging methods(P＞0.05).Conclusion The Gd-EOB-MRI LI-RADS v2018 and CEUS LI-RADS v2017 classifica-tion standards show good overall agreement.The diagnostic efficacy of Gd-EOB-MRI for HCC using LR-5 classification is better than that of CEUS.

Objective To evaluate the early efficacy and safety of the regimens containing delamanid and linezolid in the treatment of rifampicin resistant tuberculosis(RR-TB).Methods A total of 47 patients diagnosed with RR-TB at Public Health Clinical Center of Chengdu from August 2020 to December 2021 were enrolled,including 22 cases(46.8％)of multidrug-resistant tuberculosis(MDR-TB),8 cases(17.0％)of RR-TB,and 17 cases(36.2％)of pre-extensively drug-resistant tuberculosis(pre-XDR-TB).All patients were treated with a regimen based on delamanid and linezolid.The efficacy and safety were evaluated at 24 weeks of treatment.Results Among the 47 patients,46(97.9％)completed 24 weeks of treatment and 1(2.1％)was lost to follow-up.At 24 weeks,the sputum culture conversion rate was 100％in the 43 patients with positive baseline sputum culture.The median conversion time was 2(2,8)weeks.Imaging examination showed absorption in 46 patients(97.9％).Overall,40 patients(85.1％)experienced varying degrees of adverse events(AEs)within 24 weeks.Eleven patients(23.4％)experienced AEs possibly related to delamanid,mainly including QTcF interval prolongation(12.8％),gastrointestinal reactions(8.5％),dizziness(2.1％),headache(2.1％),and allergy(2.1％).Six patients permanently discontinued delamanid due to AEs including gastrointestinal reactions(6.4％),prolonged QTcF interval(2.1％),severe dizziness(2.1％),and drug allergy(2.1％).Patients with low baseline CD4+T lymphocyte counts(OR=0.991,95％CI:0.984-0.999)were more likely to experience delamanid-related AEs.Thirty patients(63.8％)experienced AEs possibly related to linezolid,including myelosuppression(55.3％),peripheral neuropathy(6.4％),optic neuritis occurred(2.1％),and allergy(2.1％).Three patients(6.4％)discontinued linezolid permanently due to severe anemia,peripheral neuropathy,and allergy.Conclusions The treatment regimens containing delamanid and linezolid for RR-TB showed a high sputum culture conversion rate and good tolerance at 24 weeks.Attention should be paid to gastrointestinal reactions and cellular immunity during treatment.

Objective To understand the molecular epidemiological characteristics and hypervirulence evolution trend of ST11 carbapenem-resistant Klebsiella pneumoniae(CRKP)isolated from medical institutions in Shanghai,and provide scientific basis for formulating the prevention and control measures of drug-resistant organisms.Methods A total of 201 strains of CRKP isolated from 12 medical institutions in Shanghai from 2021 to 2022 were collected.Antimicrobial susceptibility testing and whole genome sequencing were performed.The concatenated data was used for multilocus sequencing typing(MLST),serum typing(wzi typing),as well as analysis of resistance and viru-lence genes.Results All 201 CRKP strains were multidrug-resistant organisms(MDROs).These strains were al-most completely resistant to carbapenems,cephalosporins,and quinolones.Drug resistance gene analysis showed that 93.03％of CRKP strains carried KPC gene.201 CRKP strains were divided into 6 ST types and 10 capsule wzi types,with ST11-KL64(n=104)being the dominant type,followed by ST15-KL19(n=54).52.24％(n=105)of CRKP carried rpmA/rpmA2+iucA+iutA+iroN genes.Conclusion CRKP isolated from medical institutions in Shanghai is mainly ST11-KL64 type with severe multidrug resistance,and more than half of the strains are hyper-virulent carbapenem-resistant Klebsiella pneumoniae(hv-CRKP).It is necessary to continuously strengthen the monitoring of the molecular characteristics of CRKP,so as to prevent outbreaks of healthcare-associated infection.

Objective To evaluate the early efficacy and safety of the regimens containing delamanid and linezolid in the treatment of rifampicin resistant tuberculosis(RR-TB).Methods A total of 47 patients diagnosed with RR-TB at Public Health Clinical Center of Chengdu from August 2020 to December 2021 were enrolled,including 22 cases(46.8％)of multidrug-resistant tuberculosis(MDR-TB),8 cases(17.0％)of RR-TB,and 17 cases(36.2％)of pre-extensively drug-resistant tuberculosis(pre-XDR-TB).All patients were treated with a regimen based on delamanid and linezolid.The efficacy and safety were evaluated at 24 weeks of treatment.Results Among the 47 patients,46(97.9％)completed 24 weeks of treatment and 1(2.1％)was lost to follow-up.At 24 weeks,the sputum culture conversion rate was 100％in the 43 patients with positive baseline sputum culture.The median conversion time was 2(2,8)weeks.Imaging examination showed absorption in 46 patients(97.9％).Overall,40 patients(85.1％)experienced varying degrees of adverse events(AEs)within 24 weeks.Eleven patients(23.4％)experienced AEs possibly related to delamanid,mainly including QTcF interval prolongation(12.8％),gastrointestinal reactions(8.5％),dizziness(2.1％),headache(2.1％),and allergy(2.1％).Six patients permanently discontinued delamanid due to AEs including gastrointestinal reactions(6.4％),prolonged QTcF interval(2.1％),severe dizziness(2.1％),and drug allergy(2.1％).Patients with low baseline CD4+T lymphocyte counts(OR=0.991,95％CI:0.984-0.999)were more likely to experience delamanid-related AEs.Thirty patients(63.8％)experienced AEs possibly related to linezolid,including myelosuppression(55.3％),peripheral neuropathy(6.4％),optic neuritis occurred(2.1％),and allergy(2.1％).Three patients(6.4％)discontinued linezolid permanently due to severe anemia,peripheral neuropathy,and allergy.Conclusions The treatment regimens containing delamanid and linezolid for RR-TB showed a high sputum culture conversion rate and good tolerance at 24 weeks.Attention should be paid to gastrointestinal reactions and cellular immunity during treatment.

Objective To investigate the clinical application of ceftazidime/avibactam(CAZ/AVI)in lung trans-plant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli(CRGNB),and ana-lyze the factors affecting the prognosis.Methods Lung transplant recipients who had CRGNB pulmonary infection and were treated with CAZ/AVI were included in the analysis.Based on 14-day clinical response,14-day microbial response,and 30-day survival status,the recipients were divided into a clinical response group and a clinical failure group,a microbial response group and a microbial failure group,as well as a survival group and a death group,re-spectively.Univariate analysis was conducted on various data from the two groups.Factors affecting therapeutic ef-ficacy and survival were included in a binary logistic regression model.Independent risk factors for CAZ/AVI anti-infective efficacy and all-cause mortality outcomes were analyzed.Results A total of 43 recipients were included.After 14-day anti-infective treatment,32 recipients(74.42％)achieved clinical response,and 30 recipients(69.77％)achieved microbial response.34 recipients(79.07％)survived 30 days after CAZ/AVI treatment.The Charlson comorbidity index(CCI),proportion of renal dysfunction,and incidence of shock in recipients in the clini-cal response group were all lower than those in the clinical failure group(P＜0.05),while the serum albumin(ALB)level was higher(P＜0.05).The incidence of shock in recipients in the microbial response group was lower than that in the microbial failure group(P＜0.05).CCI,proportion of renal dysfunction,and incidence of shock in recipients in the survival group were all lower than those in the death group(all P＜0.05),while ALB level was higher during treatment period(P＜0.05).Multivariate analysis of 14-day clinical response and 30-day survival showed that higher CCI was an independent risk factor affecting 14-day clinical response of recipients(OR=2.22,95％CI:1.07-4.63),while lower ALB levels(OR=0.72,95％CI:0.54-0.98)and higher CCI(OR=5.27,95％CI:1.18-23.58)were independent risk factors for 30-day all-cause mortality in recipients with pulmonary in-fection after lung transplant.Conclusion CAZ/AVI may be an effective drug for treating pulmonary infection caused by CRGNB in lung transplant recipients.Higher CCI is an independent risk factor for 14-day clinical failure in recipients after CAZ/AVI treatment.Lower ALB level and higher CCI are independent risk factors for increased 30-day mortality in recipients.

Objective:To explore the protective effect and mechanism of Rougan Tongluo Decoction on ischemic stroke induced motor disorder rats based on NOD-like receptor thermal protein domain associated protein 3(NLRP3)/Gasdermin D(GSDMD)/Cysteinyl aspartate specific proteinase 1(Caspase-1)pathway.Methods:Establishing a rat model of ischemic stroke with motor disorders using the modified suture method.The rats were randomly divided into model control group,Rougan Tongluo Decoction low,medium and high dose groups and butylphthalide soft capsule group,with 10 rats in each group,Another 10 rats were selected as sham surgery group.After 28 days of administration,the neurological function of rats in each group was evaluated by the Zea-Longa scoring method;The forelimb grasping force of rats in each group was detected by grip tester;The coordination ability of rats was evaluated by rat-mouse rotarod instrument;The expression of NLRP3,GSDMD,Caspase-1 protein and Interleukin-1β(IL-1β)was detected by immunohistochemistry.Results:The NLRP3,Caspase-1,GSDMD protein and IL-1β expression Zea-Longa score in the cerebral cortex of the model control group were significantly higher than those in sham surgery group,the forelimb grasping force was lower than that in sham surgery group,and the latency period for turning the baton was shorter than that in sham surgery group(P＜0.05).The Zeba-Longa score,NLRP3,Caspase-1,GSDMD protein and IL-1 β expression in the cerebral cortex the butylphthalide soft capsule group,low dose,medium dose,high dose Rougan Tongluo decoction group were lower than those in model control group,the forelimb grasping force was higher than that in model control group,and the latency period for turning the baton was longer than that in model control group(P＜0.05).Conclusion:Rougan Tongluo Decoction may alleviate inflammatory response by regulating the NLRP3/Caspase-1/GSDMD signaling pathway to improve neurological function and motor ability in ischemic stroke induced motor disorder rats.

Objective:To perform RHD gene detection on a blood sample with serological weak D phenotype.Methods:A specimen received by the People's Hospital of Zhijin County was serologically identified by the microcolumn gel method and saline method.RHD gene detection was conducted by the PCR-SSP method,and the full sequence determination of the 10 exons amplified was performed.The sequencing results were compared with the ISBT database to determine the genotype.Bioinformatics tool was used to predict the functional damage of mutant proteins,and Alphafold-3 was used for tertiary structural modeling of wild-type and mutant RhD proteins,and the structures of the two proteins were compared and analyzed to explore the reasons why mutations lead to weak serological manifestations.Results:The patient's genotype was identified as RHD*DV.5/RHD*01N.01 heterozygote,with the complete deletion of RHD genes on one chromosome,unable to express the D antigen.On the other chromosome,a G＞A mutation occurred at the 697th base of the 5th exon,resulting in a partial D phenotype.This mutation causes internal hydrogen bond changes at the 233 position of RhD protein,resulting in a change in the conformation of the protein,affecting binding to the corresponding antibody.Conclusion:The patient is a heterozygous mutant individual with RHD*DV.5/RHD*01N.01,exhibiting a partial D phenotype serologically.This variation is extremely rare and has been scarcely reported globally.