OBJECTIVE: To observe the efficacy and safety of 21-day venetoclax (VEN) plus azacitidine (AZA) (21-day VA) in newly diagnosed unfit acute myeloid leukemia (AML) patients in the real-world. METHODS: The clinical data of patients with unfit-AML who received 21-day VA regimen from December 2020 to July 2024 in our center and completed at least 1 cycle of therapeutic effect assessment was retrospectively collected to analyze the safety, efficacy and its influencing factors. RESULTS: A total of 59 patients were enrolled in our study, with a median age of 67(48-87) years old. After 1 cycle of therapy, the composite complete remission (cCR) rate was 74.5%, 54.2% of cases were negative for minimal residual disease (MRD). Among them, the MRD negative rate of patients with NPM1 mutation was significantly higher than that of patients without NPM1 mutation ( P =0.032). The median follow-up of patients was 19(2-38) months, the best cCR and MRD negative rates were 78% and 64.4%, respectively, the median overall survival (OS) time was 12 months, and the median progression free survival (PFS) time was 5 months. Multivariate Cox regression analysis showed less than 4 cycles of VA chemotherapy were independent risk factor for PFS and OS ( P < 0.05). After achieving remission, anemia and thrombocytopenia improved with the increase of the number of chemotherapy cycle. CONCLUSION In real-world, 21-day VA regimen still shows significant efficacy in the treatment of newly diagnosed unfit-AML, without adversely affecting remission rate and MRD negative rate of the first cycle.
Humans ; Leukemia, Myeloid, Acute/drug therapy* ; Aged ; Middle Aged ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use* ; Sulfonamides/therapeutic use* ; Azacitidine/therapeutic use* ; Aged, 80 and over ; Male ; Female ; Retrospective Studies ; Nucleophosmin ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Remission Induction ; Mutation ; Treatment Outcome

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Objective To understand the impact of bed-making manipulation on the air surrounding bed units in hemodialysis room,evaluate the effectiveness of routine terminal disinfection,and provide scientific basis for optimi-zing infection control measures.Methods Air specimens(pre-bed-making group)and environmental object surface specimens(pre-terminal disinfection group)around bed units were collected when hemodialysis was about to be fi-nished.Air specimens after bed-making(bed-making group)and environmental object surface specimens after ter-minal disinfection(terminal disinfection group)were also collected.Bacterial colonies were counted and identified.Results A total of 714 air specimens were collected from 238 bed units of 45 hemodialysis units before and during bed-making.The average bacterial colony count during bed-making was higher than that before bed-making([2.72±3.43]CFU/plate vs[0.69±1.50]CFU/plate,P＜0.05).The qualified rate of microbial colony count before bed-making was higher than that during bed-making(96.64％vs 64.71％,P＜0.05).A total of 450 environmental ob-ject surface specimens from 90 bed units of 45 hemodialysis units were collected before and after terminal disinfec-tion.The average bacterial colony count before terminal disinfection was higher than that after terminal disinfection([8.18±20.6]CFU/cm2 vs[1.49±3.44]CFU/cm2.P＜0.05).The qualified rate of microbial colony count after terminal disinfection was higher than that before terminal disinfection(98.22％vs 92.44％,P＜0.05).The micro-organisms in the air and environment were mainly coagulase negative Staphylococcus.Conclusion Bed-making has a certain impact on the air microorganisms around the bed units,and terminal disinfection can reduce the bacterial co-lony count of the environment.It is necessary to pay attention to the cleaning and disinfection of the environment for medical treatment,and carry out bed-making manipulation under clear condition to minimize the risk of infection.

Aim To evaluate the ameliorative effects of different ratios of Renshen-Huangjing(RH) on SPS-induced PTSD-like behaviors in mice,and to investi-gate the action mechanism using bioinformatics analysis and experimental studies.Methods The aqueous ex-tract was extracted in four ratios of RH in a total weight of 60 g,i.e.1∶0(RH1),2∶1(RH2),1∶2(RH3),and 0∶1(RH4).The extraction rates of Rg1,Rb1,and polysaccharides from different ratios of RH were then detected using UPLC-UV method.The SPS model was established,and RH1,RH2,RH3 and RH4(400 mg·kg-1)were administered by intragas-tric gavage for 14 day,followed by behavioral tests to e-valuate the PTSD-like behaviors.The serum CORT,IL-1β and IL-10 were determined by ELISA.The possible targets of action were analyzed using bioinformatics.The expression levels of Calpain-1,PSD95,BDNF and GluN2B in the hippocampus were detected by Western blot.Results The SPS model induced PTSD-like be-haviors in mice.Serum levels of CORT and IL-1β in-creased and level of IL-10 decreased in SPS model.After treatment with different ratios of RHs,RH2 showed the best therapeutic effect,which was manifes-ted in the suppression of PTSD-like behaviors,the re-duction of CORT and IL-1β levels,and the promotion of IL-10 levels;160 overlapping targets might explain the therapeutic effects of RH on PTSD,and these tar-gets were enriched in inhibiting synaptic damage,exer-ting antioxidant properties and suppressing neuroin-flammation,respectively.RH2 prevented the SPS-in-duced decrease in the expression of Calpain-1,PSD95,BDNF and the elevation of GluN2B.Molecular docking showed strong binding of Rg1 and Rb1 to Calpain-1,PSD95,and BDNF,respectively.Conclusions The a-queous extract of RH in a 2∶1 ratio can more effec-tively prevent SPS-induced PTSD-like behaviors,and its effect may be related to targets such as Calpain-1,PSD95,BDNF and GluN2B.

Aim To systematically investigate the ac-tive components,targets,and regulatory pathways of Po-lygonum capitatum in intervening atherosclerosis(AS)through network pharmacology,molecular docking and animal experiments.Methods Active components of Polygonum capitatum and AS-related targets were screened and identified through database searches.Protein-protein interaction(PPI)network analysis was performed using the STRING database,followed by GO and KEGG enrichment analyses via the David plat-form.Molecular docking validation was conducted with AutoDock.An AS model was established in Syrian golden hamsters fed a high-fat diet.Predicted pathways and targets were validated using qPCR,ELISA,and histopathological assessment of aortic and hepatic tis-sues via HE staining.Results Network pharmacology identified 27 potential active components of Polygonum capitatum(primarily flavonoids such as quercetin and luteolin)and 110 drug-disease intersection targets,in-cluding core targets MMP-9,ALB,and AKT1.GO and KEGG analyses enriched 593 and 125 pathways,re-spectively,with the NF-κB inflammatory pathway,TNF signaling pathway and lipid metabolism/atherosclerosis pathways highlighted as key mechanisms.Animal ex-periments demonstrated that Polygonum capitatum im-proved serum lipid profiles(reduced TC,TG,LDL-C)in AS hamsters,suppressed the MMP-9/NF-κB signa-ling pathway(downregulated MMP-9,p65 phosphoryla-tion,TNF-α,and IL-6),and inhibited VSMC synthetic phenotypic transformation(upregulated α-SMA and myocardin)by downregulating MCPIP1.Additionally,Polygonum capitatum ameliorated aortic lesions and he-patic lipid deposition in AS hamsters.Conclusions Polygonum capitatum alleviates AS by synergistically regulating the MMP-9/NF-κB/MCPIP1 axis through flavonoid components,suppressing vascular inflammato-ry cascades and maintaining VSMC contractile pheno-types.This reflects Polygonum capitatum's multi-com-ponent,multi-pathway,and multi-target characteristics in combating AS.

OBJECTIVE: To assess the effectiveness of bone acupuncture in improving pain and function in degenerative lumbar spinal stenosis (DLSS) and compare it with Jiaji acupuncture. METHODS: From January to December 2023, 80 DLSS patients were treated with acupuncture and divided into bone acupuncture and Jiaji acupuncture groups. Among them, 40 patients in the bone acupuncture group included 15 males and 25 females, with a mean age of (60.60±6.98) years old;anthor 40 patients in the Jiaji acupuncture group included 16 males and 24 females, with a mean age of (61.48±9.55) years old. The Roland Morris disability questionnaire(RMDQ), walking distance, visual analogue scale(VAS), and the MOS item short from health survey(SF-36) of two groups at baseline, 2 weeks, 4 weeks, and 12 weeks post-treatment were compared. RESULTS: Eighty patients were followed up for 3 to 5 months with an average of (3.62±0.59) months. There was no significant differences in general data and the scores before treatment between two groups(P>0.05). The RMDQ scores in both groups decreased significantly at 2, 4 and 12 weeks after treatment compared with before treatment(P<0.05), at each time point after treatment, the decrease was more significant in the bone acupuncture group than in the Jiaji acupuncture group(P<0.05). The VAS of waist and leg in both groups was significantly lower at 2, 4 and 12 weeks after treatment that before treatment(P<0.05). At all time points after treatment, the waist VAS in the bone acupuncture group was reduced more significant than in the Jiaji acupuncture group(P<0.05);there was no significant difference in leg VAS at 2 and 12 weeks after treatment between two groups(P>0.05), the improvement was more significant in the bone acupuncture group in the 4 weeks after treatment than in the Jiaji acupuncture group. The SF-36 scores in both groups were significantly higher at 2, 4, and 12 weeks after treatment than before treatment(P<0.05);the SF-36 score raised more significant in the bone acupuncture group than in the Jiaji acupunture group(P<0.05). No significant difference in the walking distance between two groups at 2 weeks after treatment(P>0.05);the walking distance in the bone acupuncture group was significantly higher than that in the Jiaji acupuncture group at 4 and 12 weeks after treatment(P<0.05). CONCLUSION Bone-penetrating acupuncture moderately improves functional impairment, pain, and quality of life in patients with DLSS, showing better efficacy than Jiaji acupuncture.
Humans ; Female ; Male ; Middle Aged ; Acupuncture Therapy/methods* ; Spinal Stenosis/physiopathology* ; Aged ; Lumbar Vertebrae/physiopathology* ; Pain Management

Objective To understand the impact of bed-making manipulation on the air surrounding bed units in hemodialysis room,evaluate the effectiveness of routine terminal disinfection,and provide scientific basis for optimi-zing infection control measures.Methods Air specimens(pre-bed-making group)and environmental object surface specimens(pre-terminal disinfection group)around bed units were collected when hemodialysis was about to be fi-nished.Air specimens after bed-making(bed-making group)and environmental object surface specimens after ter-minal disinfection(terminal disinfection group)were also collected.Bacterial colonies were counted and identified.Results A total of 714 air specimens were collected from 238 bed units of 45 hemodialysis units before and during bed-making.The average bacterial colony count during bed-making was higher than that before bed-making([2.72±3.43]CFU/plate vs[0.69±1.50]CFU/plate,P＜0.05).The qualified rate of microbial colony count before bed-making was higher than that during bed-making(96.64％vs 64.71％,P＜0.05).A total of 450 environmental ob-ject surface specimens from 90 bed units of 45 hemodialysis units were collected before and after terminal disinfec-tion.The average bacterial colony count before terminal disinfection was higher than that after terminal disinfection([8.18±20.6]CFU/cm2 vs[1.49±3.44]CFU/cm2.P＜0.05).The qualified rate of microbial colony count after terminal disinfection was higher than that before terminal disinfection(98.22％vs 92.44％,P＜0.05).The micro-organisms in the air and environment were mainly coagulase negative Staphylococcus.Conclusion Bed-making has a certain impact on the air microorganisms around the bed units,and terminal disinfection can reduce the bacterial co-lony count of the environment.It is necessary to pay attention to the cleaning and disinfection of the environment for medical treatment,and carry out bed-making manipulation under clear condition to minimize the risk of infection.

Objective To establish the HPLC analysis method for ketoconazole related substances,and to provide technical support for the improvement of the quality standard and the purity of ketoconazole.Methods Gradient elution conditions were optimized based on the chromatographic parameters outlined in the 2024"British Pharmacopoeia"for ketoconazole cream.A C18 column(4.6 mm×150 mm,3 μm)was used to facilitate the elution process using a gradient of acetonitrile and acetate buffer,and detection performed at a wavelength of 230 nm.Results The known impurities and potentially genotoxic impurities in the material drugs of ketoconazole can be more effectively separated using the established methods,which are both robust and highly sensitive.The content of the two potentially geno toxic impurities,six known impurities and unknown impurities in the 21 batches of ketoconazole sourced from five raw material pharmaceutical companies is below the specified limit requirements.Conclusion This method contributes to improving the quality of ketoconazole ingredients,ensuring the safety of ketoconazole preparations,and better supporting the regulatory supervision.

[Objective] To establish a method for detecting the potency of recombinant human coagulation factor Ⅶa for injection. [Methods] By adding the sample and factor Ⅶ deficient plasma to the sample cup and activating the reaction with prothrombin time assay reagent (PT reagent), the coagulation time of the sample was determined by the change in magnetic bead swing amplitude in the sample cup. The logarithm of coagulation time was inversely proportional to the logarithm of human factor Ⅶa potency. [Results] Under the experimental conditions, the specificity of the methodology was evaluated through spiked recovery, and the recovery rates ranged from 90.0% to 110.0%. Within the range from 0.125 to 1.000 IU/mL, there was a good linear response between the potency and coagulation time of the standard and sample, with correlation coefficients r>0.99. As for the accuracy and repeatability, the recovery rates of various concentrations detected in the stock solution were 101.0%, 100.0% and 112.0%, respectively, with RSD values of 2.6%, 4.0% and 0.0%, respectively. The recovery rates of various concentrations in finished product testing were 104.0%, 94.7% and 112.0%, respectively, with RSD values of 1.9%, 2.4% and 0.0%, respectively. As for the intermediate precision, the RSD were 4.5% and 3.7%, respectively. After treated with sample diluent, the sample was tested at room temperature for 6 hours and still exhibited relatively stable biological activity. [Conclusion] This detection method is accurate, stable, easy to operate and highly automated, and is suitable for detecting the potency of recombinant human coagulation factor Ⅶa for Injection.

OBJECTIVE To investigate the quality and management of cleaning and disinfection of soft endoscopes in Wuxi hospitals,to analyze the existing problems and put forward suggestions for improvement,and to provide references for endoscope-related infection in hospitals.METHODS From Sep.to Nov.2024,the cleaning and disin-fection status and managements of soft endoscopes were investigated.Endoscopes were sampling for adenosine triphosphate(ATP)biofluorescence and bacteriological testing;final rinsing water,hands of disinfection person-nels,disinfectants and environmental surfaces were collected for bacteriological testing.RESULTS Totally 68.18％of hospitals performed daily leaks test before cleaning,and 81.82％used o-Phthalaldehyde;81.25％of hospitals used peracetic acid in endoscopy sterilization,with only 1 hospital using glutaraldehyde.Totally 86.36％of hospi-tals monitored the concentration of disinfectants before daily works.There were statistically significant differ-ences in full-time,education levels,age and working experience of personnels among different levels of hospitals(P＜0.05).The pass rate of the 60 endoscope ATP specimens was 88.33％,and there were statistically signifi-cant differences in the pass rate of gastroscopic ATP testing among different levels of hospitals(P=0.032).The qualification status differed significantly in the types of endoscopes and the time length of enzyme washing(P＜0.05).All 60 endoscopic bacteriological samples were qualified,while 141 environmental bacteriological samples were with a pass rate of 94.33％.Unqualified samples were mainly for disinfection personnel's hands,rinse tank faucets,final rinse water.Rolestonella piercei and Staphylococcus wolffii were detected in one failed final rinse wa-ter by mass spectrometry.CONCLUSIONS The overall equipment and staffing of the surveyed endoscope centers(rooms)basically meet operational needs and generally follow endoscope cleaning and disinfection guidelines.However,there are still deficiencies in cleaning and disinfection management,equipment maintenance,disinfect-ant concentration monitoring and personnel training.Further efforts are needed to strengthen the disinfection quali-ty monitoring of endoscope and related factors.