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 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 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 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.

[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 comprehensively evaluate the medical service capacity of 50 first batch county medical sub-centers in Guizhou Province,it provides the basis and references for further research on the construction of county medical sub-centers in Guizhou province and improvement of the medical service capacity of township health centers(community health service centers)in Guizhou Province.Methods:Through TOPSIS method,RSR method and the fuzzy combination method,the medical service capacity of the primary medical institutions in the county medical sub-center was evaluated.Results:Among the first batch of 50 county-level secondary medical centers,the top three in terms of medical service capabilities were G18,G6,and G36,while the last three were G27,G15,and G22.Conclusion:There were significant differences in the medical and health service capacity among the 50 sub-centers.It is suggested to continue to increase the support for sub-centers,formulate relevant policies according to local conditions and time conditions,and improve the medical service capacity of sub-centers.

AIM:To explore the potential mecha-nism of arecoline in promoting oral submucous fi-brosis based on key factors of phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)pathway.METHODS:SD rats were randomly divided into arecoline low-dose group,arecoline medium-dose group,and are-coline high-dose group(5,10,and 15 mg/mL).The oral buccal mucosa was injected with the corre-sponding concentration of arecoline(ANE)solution to induce the establishment of oral submucous fi-brosis(OSF)models,with 8 rats in each group.An-other 8 unmodeled rats were selected as the blank group,and the changes in mouth opening of the rats were detected after 8 weeks of grouping and intervention.HE and Masson staining were used to observe the pathological changes of oral buccal mucosa,measure the length of epithelial staple process and calculate collagen volume fraction.Western blot and qRT-PCR were used to detect the expression of collagen-Ⅰ(COL-Ⅰ),E-cadherin,fibro-nectin(FN)and PI3K/Akt/mTOR signaling pathway-related proteins and mRNA in rat oral buccal muco-sa.The levels of tumor necrosis factor(TNF)-α,in-terleukin(IL)-1β and transforming growth factor(TGF)-β1 in rat serum were detected by ELISA.Hu-man immortalized keratinocytes(HaCaT cell line)were cultured in vitro,and the effects of different concentrations of arecoline,PI3K activator,and PI3K inhibitor on the survival rate of HaCaT cells were investigated by CCK-8 method.According to the results of CCK-8,the concentration of arecoline 75 μg/mL,the concentration of PI3K activator 10μmol/L,and the concentration of PI3K inhibitor 2μmol/L were selected as the subsequent experi-mental concentrations.The cells were set as blank group,arecoline group,PI3K activator group,PI3K inhibitor group,and arecoline+PI3K inhibitor group.The mRNA expression levels of COL-Ⅰ,E-cad-herin,FN,PI3K,Akt,and mTOR in each group of cells were detected by qRT-PCR.The levels of TNF-α,IL-1β and TGF-β1 in each group of cells were de-tected by ELISA.RESULTS:Compared with the blank group,the arecoline low-dose group,the are-coline medium-dose group,and the arecoline high-dose group significantly reduced the mouth open-ing,significantly shortened the length of the epi-thelial staple process,significantly increased the collagen volume fraction,inflammatory cell infiltra-tion,and severe pathological damage.The protein expression levels of COL-Ⅰ,FN,p-PI3K,p-Akt,and p-mTOR were up-regulated,and the protein expres-sion levels of E-cadherin were down-regulated.The mRNA expressions of COL-Ⅰ,FN,PI3K,Akt,and mTOR were significantly increased.The mRNA ex-pression of E-cadherin was significantly reduced,and the levels of TNF-α,IL-1β,and TGF-β1 were sig-nificantly increased(all P＜0.05 or P＜0.01).Com-pared with the blank group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the arecoline group and the PI3K activator group were up-regulated,and the mRNA expression lev-els of E-cadherin were down-regulated.Compared with the blank group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the PI3K inhibitor group were down-regulated,and the mRNA expression levels of E-cadherin were up-regulated.Compared with the PI3K inhibitor group,the mRNA expression levels of COL-Ⅰ,FN,PI3K,Akt,and mTOR in the cells of the arecoline+PI3K inhibi-tor group were up-regulated,the mRNA expression levels of E-cadherin were down-regulated,and the levels of TNF-α,IL-1β,and TGF-β1 were significant-ly increased(all P＜0.05 or P＜0.01).CONCLUSION:Arecoline can significantly promote oral submucous fibrosis,which may play a pro-fibrotic role by up-regulating the PI3K/Akt/mTOR signaling pathway.

Objective To explore the relationship between the head injury criterion(HIC)values in anterior-posterior(AP)collisions and lateral-medial(LM)collisions.Methods A total of 102 male SD rats were randomly divided into a control group of 0 m(6 rats),4 AP groups(12 rats/group)and 4 LM groups(12 rats/group).After adaptive training,the classical Marmarou model was used to execute the brain AP and LM collisions under a series of different height impacts,and the HIC values were calculated.The experimental group data of the walk-pole test and grip strength test were collected at 24 hours before and after injury,and the data of the proportion of hemorrhage in the corpus callosum and pyramidal tracts were collected at 24 hours after injury.Results As the collision heights increased in both AP and LM groups,there were positive correlations with changes in WP test time and peak GS,and corresponding increases in the proportion of hemorrhage in the cc and py.According to the mathematical relationships between the comprehensive injury degrees and HIC values,it was found that at the same injury degree,LM-HIC value was less than AP-HIC value.A mathematical relationship between AP-HIC and LM-HIC was fitted based on the comprehensive injury degrees.At the same HIC,LM group experienced more severe injuries,and AP group was more tolerant to head collision.Conclusion The injury severity in LM group is greater than that of AP group at the same HIC.Preliminary results show there is a linear mathematical relationship between AP-HIC and LM-HIC.These results can be expected to expand the application scope of HIC and achieve an accurate assessment of the LM collision severity.

Objective:To investigate how age and nail-tract volumetric bone mineral density (vBMD) are associated with postoperative mechanical performance of proximal femoral nail anti-rotation (PFNA-Ⅱ) fixation for geriatric intertrochanteric fractures using a finite-element analysis.Methods:Fifteen elderly patients with intertrochanteric fracture of the femur were selected for this study. They were 11 females and 4 males and divided into 5 groups based on their ages ( n=3): 55-year-old, 65-year-old, 75-year-old, 85-year-old, and 95-year-old groups. After three-dimensional models of the proximal femur were constructed using the preoperative CT data of their healthy contralateral hip, 31-A1.2 fractures of the AO/OTA type were created and PFNA-Ⅱ fixations simulated. Two loading schemes were created: graded quasi-static axial loads (700 N, 1,400 N, 2,100 N, and 2,800 N) were applied to compute equivalent plastic strain volumes in the femoral head region; displacement-controlled loading was applied to failure to derive load-displacement curves for stiffness and the maximum failure load. Nail-tract vBMD and regional hip vBMDs were measured by quantitative CT. Pearson correlation analysis was conducted to investigate the associations of age and nail-tract vBMD with the aforementioned mechanical indicators. Results:Under the same load, compared with the 55-year-old, 65-year-old, and 75-year-old groups, the plastic strain unit volumes of the fracture models in the 85-year-old and 95-year-old groups increased significantly. Under a load of 700 N, no plastic strain was observed in the fracture models in the 55-year-old, 65-year-old, and 75-year-old groups, while an average plastic strain of approximately 50 mm 3 was observed in the fracture models in the 85-year-old group. Under a load of 2,800 N, the high strain areas in the fracture models in the 85-year-old and 95-year-old groups were mainly concentrated at the tip of the head nail and the junction between the head nail and the main nail. Load-displacement curves showed a marked reduction in the failure load in patients aged ≥85 years. Under loads of 1,400 N, 2,100 N, and 2,800 N, there was a strong association between the nail-tract vBMD and the volume of the plastic strain unit ( r=-0.82, -0.88, -0.89, respectively), which was stronger than those for total-hip vBMD. Conclusions:Finite-element analysis indicates that age and nail-tract vBMD are closely related to local plastic strain and overall stiffness of the proximal femur after PFNA-Ⅱ fixation for the geriatric intertrochanteric fractures. Patients aged ≥85 years old are more prone to plastic yielding, which compromises fixation stability.

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.