Objective: To optimize the technology and process for recovering immune cells from discarded leukocyte filter through reverse flushing, and to investigate the effects of different reverse flushing solutions and physical conditions (temperature, soaking, and ultrasound) on the cell recovery rate. Additionally, to evaluate the feasibility and quality of isolating and culturing NK cells from the recovered cells. Methods: Normal saline, PBS, and PBS-EDTA were used as reverse flushing solutions to backwash the filter, and the white blood cell recovery rates were compared. The reverse flushing efficiency was optimized by adjusting the temperature of the reverse flushing solution, filter soaking treatment and ultrasonic treatment. The Ficoll separation method was employed to isolate peripheral blood mononuclear cells (PBMCs) from the elution solution and conduct in vitro expansion and culture. Lymphocyte subsets were identified and quantified using flow cytometry. Results: The physiological saline served as the backflush fluid was the most stable. The reverse temperature had a significant impact on the recovery rate of white blood cell subgroups. The recovery rates of lymphocytes and monocytes at 37℃ were significantly higher than those at 4℃ [(35.56±5.55)% vs (22.88±0.31)%, (32.42±4.82)% vs (8.00±1.6)%, t=5.581 and 5.758, respectively, both P<0.001)], and at 25℃ [(35.56±5.55)% vs (22.42±6.13)%, t=5.904, P<0.001; (32.4±4.82)% vs (21.11±1.23)%, t=2.629, P=0.030)]. The recovery rates of white blood cell subgroups after 37℃ immersion were higher than those after direct reverse flow at 37℃, but the difference was not statistically significant (P>0.05). The recovery rate of cells after ultrasonic immersion at 25℃ was further increased compared to that after immersion at 25℃, but the difference was not statistically significant (P>0.05). The purity of the NK cells obtained through sorting reached (94.2±4.5)%, and the viability was (94.8±0.9)%. After 15 days of culture, the cell count was expanded approximately 450 times, yielding more than 10 /mL highly active NK cells. Conclusion: By optimizing the backflushing process, immune cells can be efficiently recovered from discarded filters. The 37℃ backflow liquid has the best backflow effect; soaking and ultrasonic treatment can be used as auxiliary methods to improve recovery rates. The NK cells from this source have high purity, good activity, and strong expansion ability, and can be used as a reliable cell source for immunotherapy research, and in line with the circular economy concept of resource reuse.

Objective:To observe the clinical effect of urokinase along the pipeline under offline status to dissolve dialyzer microthrombus in patients undergoing continuous renal replacement therapy (CRRT).Methods:A prospective research method was adopted. A total of 248 CRRT patients with dialyzer microthrombus in Sinopharm-Gezhouba Central Hospital from January 2017 to December 2021 were selected. The patients were divided into experimental group (continued CRRT treatment after urokinase along the pipeline under offline status to dissolve dialyzer microthrombus) and control group (continued CRRT treatment after dialyzer replacement) by random number table method with 124 cases in each group. The baseline data were recorded, including gender, age, primary disease, hemoglobin, platelet count, hematocrit, plasma albumin, D-dimer, fibrinogen, anticoagulant method and symptoms associated with dialyzer microthrombus. The blood indexes were detected before and after treatment of microthrombus, and the symptom scores were performed. The blood indexes included creatinine, urea nitrogen, β 2 microglobulin (β 2-MG), international normalized ratio (INR), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α); and the symptom scores included acute physiology and chronic health status score Ⅱ (APACHE Ⅱ) and (APACHE Ⅱ) and sequential organ failure score. The initial transmembrane pressure, transmembrane pressure before disembarkation, CRRT treatment extension time and coagulation classification were recorded. In experimental group, the blood coagulation function indexes before and after treatment were detected, including prothrombin time (PT), activated partial prothrombin time (APTT), thrombin time (TT) and fibrinogen (Fib). The adverse reactions were recorded, including black stools, arrhythmias and wound bleeding. Results:There were no statistical differences in baseline data, initial transmembrane pressure, transmembrane pressure before disembarkation, CRRT treatment extension time and coagulation classification between two groups ( P>0.05). There were no statistical differences in creatinine, urea nitrogen, β 2-MG, INR, hs-CRP, IL-6, TNF-α, APACHE Ⅱ and SOFA before treatment between two groups ( P>0.05); after treatment, the indexes in both groups were significantly lower than before treatment, and the indexes in experimental group were significantly lower than those in control group: (179.1 ± 41.2) μmol/L vs. (187.1 ± 53.9) μmol/L, (7.3 ± 2.8) mmol/L vs. (9.3 ± 2.5) mmol/L, (2.5 ± 0.6) mg/L vs. (4.2 ± 0.7) mg/L, 1.0 ± 0.3 vs. 1.8 ± 0.5, (8.7 ± 1.1) mg/L vs. (10.6 ± 2.4) mg/L, (21.5 ± 12.7) ng/L vs. (29.5 ± 10.3) ng/L, (20.2 ± 6.1) ng/L vs. (26.6 ± 7.2) ng/L, (12.1 ± 6.9) scores vs. (17.2 ± 5.2) scores and (5.9 ± 1.8) scores vs. (6.8 ± 1.9) scores, and there were statistical differences ( P<0.05). In experimental group, there were no statistical differences in PT, APTT, TT and Fib between before treatment and after treatment ( P>0.05). The incidence of adverse reactions in experimental group was significantly lower than that in control group: 4.03%(5/124) vs. 12.90%(16/124), and there was statistical difference ( χ2 = 6.30, P<0.05). Conclusions:The urokinase along the pipeline under offline status to dissolve dialyzer microthrombus in patients undergoing CRRT is safer, cheaper and more efficient. It can improve the biocompatibility of tissue with dialyzer and pipe, prolong the use time of the dialyzer, and complete renal replacement therapy.

Objective:To evaluate the efficacy and safety of tripterygium glycosides (TG) in the adjuvant treatment for patients with lupus nephritis(LN).Methods:A retrospective propensity-matched study was conducted using data collected from LN inpatients who addmitted to nanjing Drum Hospital between January 2010 and June 2022. Patients were divided into TG-treated and non-TG-treated groups according to whether or not they were treated with TG or not in a 1∶2 ratio. Univariate and multivariate analyses corrected for confounders were performed using binary logistic regression models, and odds ratios ( OR) and corresponding 95% confidence intervals ( CI) were calculated. Results:A total of 177 patients with active LN were included, 59 in TG-treated group and 118 in non-TG-treated group, and the baseline data and other medications used in the trial were roughly comparable in both groups. In the TG treatment group, complete remission (CR) and partial remission (PR) patients accounted for 37.3% (22 cases) and 55.9% (33 cases), respectively. Concomitant treatment with TG was contributed to the achievement of CR [an adjusted OR(95% CI) 2.95 (1.27, 6.87), P=0.012]. The doses of TG ≥40 mg/d and treatment for 12 to 42 weeks were associated with improved CR [ OR(95% CI)=2.94(1.16,7.45), P=0.023; adjusted OR(95% CI)=3.42(1.21,9.63), P=0.020 respectively]. In addition, the combination of TG and hydroxychloroquine improved patients′ CR rates compared with monotherapy, no additive interactions between TG and immunosuppressive drugs were found. Concomitant treatment with TG did not cause additional safety concerns. Conclusion:Adjuvant therapy with TG can effectively and safely improve LN remission.

Tumor's occurrence and development are closely related to metabolic abnormalities. Central Carbon Metabolism (CCM) is the core network of biological metabolism, and its abnormal activation drives tumor cell proliferation, invasion, and immune escape. Hedyotidis Herba is a classic anti-tumor conventional Chinese materia medica. Its active components interfere with the core links of CCM (glycolysis, tricarboxylic acid cycle and pentose phosphate pathway) by targeting key signaling pathways such as PI3K/Akt, AMPK, P53, Wnt/β-catenin, MAPK, Nrf2 and TGF-β, so as to inhibit the energy metabolism of tumor cells, regulate the acidification state of microenvironment, block the production of metabolic precursors, and curb tumor cell metastasis and immune escape.

Objective To analyze the correlations of autoimmune diseases(AIDs)with the risk of developing pancreatic endocrine and exocrine diseases.Methods A total of 451,497 participants from the UK Biobank were recruited,with the primary outcomes being pancreatic endocrine and exo-crine diseases.International Classification of Diseases 9/10(ICD9/10)codes were used to define each AIDs,the pancreatic endocrine and exocrine diseases.Multivariable Cox proportional hazards models were employed to assess the relationships between AIDs and pancreatic endocrine and exocrine diseases,with adjustments for age,gender,ethnicity,Townsend deprivation index,smoking,alcohol consumption,body mass index,waist circumference,hip circumference,hypertension,dyslipidemia,and gallstones.Results A total of 415,497 participants were included,among which 37,482 de-veloped pancreas-related diseases during follow-up.Among patients with AIDs,the proportions of those with pancreatic exocrine and endocrine diseases were significantly increased(P＜0.05).Rheumatoid arthritis[HR(95％CI):1.438(1.161 to 1.781)],ankylosing spondylitis[HR(95％CI):1.675(1.009 to 2.780)],ulcerative colitis[HR(95％CI):1.335(1.037 to 1.719)],and Crohn's disease[HR(95％CI):1.530(1.154 to 2.028)]were all associated with an increased risk of de-veloping pancreatic exocrine diseases(all P＜0.05);additionally,rheumatoid arthritis[HR(95％CI):1.119(1.004 to 1.248)],ulcerative colitis[HR(95％CI):1.324(1.175 to 1.491)],sys-temic sclerosis[HR(95％CI):2.08(1.355 to 3.191)],and Crohn's disease[HR(95％CI):1.394(1.197 to 1.624)]were also associated with an increased risk of developing pancreatic en-docrine diseases(all P＜0.05).Conclusion Overall AIDs and some specific AIDs are associated with an increased risk of developing pancreatic endocrine and exocrine diseases,and early preven-tion of pancreatic diseases in patients with AIDs should be emphasized in clinical practice.

Objective To analyze the short-term prognosis value of middle ear risk index(MERI)in predicting the poor hearing recovery 6 months after transcanal endoscopic ear surgery(TEES)for children with cholesteatoma-type middle ear infection and the related factors affecting poor hearing recovery after TEES surgery.Methods A total of 70 children with cholesteatoma-type middle ear infection who underwent TEES were selected as the research subjects,and their outcomes were followed up for 6 months postoperatively.Pure tone audiometry was performed to collect the air-bone-gap(ABG)values of children,and they were divided into two groups according to ABG values:the group with good prognosis(ABG≤20 dBHL,n=49)and the group with poor prognosis(ABG>20 dBHL,n=21).The general information and the postoperative outcomes of MERI,ABG and quality of life improvement(Otitis Media-6,OM-6 score)of the two groups were compared.The independent risk factors for poor hearing recovery of TEES for children with cholesteatoma-type middle ear infection were analyzed by multivariate Logistic regression analysis.Receiver operating characteristic(ROC)curve was developed to study the predictive value of MERI in patients with cholestatomatous otitis media with TEES.Results Compared with the good prognosis group,the disease course of children in the poor prognosis group was longer,the scores of MERI,ABG and OM-6 before and after surgery were higher,the proportion of high-risk was higher(P＜0.05).The multivariate Logistic regression analysis showed that longer course of illness,higher MERI,higher preoperative ABG values and higher preoperative OM-6 scores were independent risk factors for poor hearing recovery of TEES for children with cholesteatoma-type middle ear infection.The ROC curve showed that the AUC(95%CI)of MERI predicting poor hearing recovery at 6 months post-TEES in cholesteatoma otitis media children was 0.828(95%CI:0.718-0.907),sensitivity was 81.0%and specificity was 75.5%.Conclusion MERI can be used as an effective tool to predict the short-term hearing recovery of children with cholestatoma otitis media undergoing tympanoplasty.The longer the course of disease,the higher the MERI.The higher the preoperative ABG,the higher the preoperative OM-6 score.The higher the risk of poor hearing recovery after TEES operation in children with cholestatoma otitis media,which needs clinical attention.

Objective To investigate the characteristics and correlation between peak oxygen uptake(VO?peak)and heart rate recov-ery(HRR)during cardiopulmonary exercise test(CPET)in patients with coronary borderline lesions.Methods From January,2022 to January,2024,183 patients with coronary borderline lesions in Beijing Bo'ai Hospital were divided into low cardiorespiratory fitness(LCF)group(n=61),moderate cardiorespiratory fitness(MCF)group(n=62)and high cardiorespiratory fitness(HCF)group(n=60)based on VO?peak.Their characteristics and CPET parameters including VO?peak,exercise-phase heart rate(HR1,HR2,HR3),and post-exercise heart rate recovery(HRR1,HRR2,HRR3)were analyzed.Results After adjusting for age and body mass index,analysis of covariance showed that the peak heart rate,HR1,HR2 and HR3 were the lowest in LCF group(F>5.388,P<0.01).Repeated-measures analysis of variance showed that the inter-and intra-group effects were significant in HRR(F>14.561,P<0.001).Partial correlation analy-sis showed that VO?peak positively correlated with HRR1(r=0.404,P<0.001),HRR2(r=0.379,P<0.001)and HRR3(r=0.425,P<0.001).Conclusion In patients with coronary artery borderline lesions,VO?peak demonstrated a significant inverse correlation with HRR,the lower the VO?peak,the more delays of HRR.

Objective To analyze the disease burden of chronic kidney diseases (CKD) attributed to high body mass index (BMI) in China from 1992 to 2021 and predict the disease burden for the next decade, and to provide evidence for the prevention and treatment of CKD. Methods Using the Global Burden of Disease (GBD) database and the Joinpoint model, the average annual percentage rate change (AAPC) of the mortality rate and disability-adjusted life year (DALY) rate was calculated to describe and analyze the CKD disease burden attributed to high BMI in China from 1992 to 2021. The ARIMA model was employed to predict and analyze the change trend of the CKD disease burden. Results From 1992 to 2021, the mortality rate and DALY rate attributed to high BMI-induced chronic kidney disease showed an upward trend. Compared to 1992, the attributed number of deaths increased by 324.38%, and DALYs increased by 268.56%; the mortality rate increased by 64.00%, and the DALY rate grew by 51.62%. From 1992 to 2021, the mortality rate and DALY rate for males were lower than those for females, but the growth rate for males exceeded that of females. From 1992 to 2021, the mortality rate and DALY rate of chronic kidney disease attributed to high BMI in China increased with age. The average annual change rate of chronic kidney disease attributed to high BMI in China from 1992 to 2021 (mortality rate: 1.40 per 100,000 (95% CI: 1.04–1.76), DALY rate: 1.43 per 100 000 (95% CI: 1.17–1.70)) was higher than thHuaiyin Normal University, Huai'anher social demographic index (SDI) regions. The ARIMA model predicted that the age-standardized mortality rate increased from 2.91 per 100 000 in 2022 to 3.05 per 100 000 in 2026, and the age-standardized DALY rate increased from 69.65 per 100 000 in 2022 to 73.58 per 100 000 in 2026. Conclusion Chronic kidney disease attributed to high BMI in China is on the rise, and it will continue to grow in the future. The focus of CKD prevention and control should be on males and the elderly, while active measures should be taken to reduce the occurrence and progression of chronic kidney disease.

Objective:To investigate the application effect of a novel zipper device in wound healing after incision and drainage of cuta-neous abscesses in children,and to explore its optimal intervention timing.Methods:A total of 50 children who attended the outpatient service of Department of Pediatric surgery from September 2023 to September 2024 were enrolled and divided into two groups accord-ing to the parity of the date of visit.The 26 children with the odd date of visit were enrolled as experimental group,and the 24 children with the even date of visit were enrolled as control group.The same anti-infective dressings were used for wound dressing in both groups after incision and drainage,and when there was a significant reduction in wound exudate and the fresh granulation tissue emerged at wound base,the zipper device was used for the children in the experimental group,and dressing change was performed for the children in the control group until the wound was completely healed.The two groups were compared in terms of wound healing time,healing rate,and the total costs of dressing change,and the multiple linear regression model and the restricted cubic spline(RCS)model were used to analyze the association between the in-tervention time of the zipper device and wound healing time.Re-sults:Compared with the control group,the experimental group had a significantly shorter wound healing time,a significantly higher wound healing rate,and significantly lower total costs of dressing change(P<0.001).The multiple linear regression model showed that the infection size of skin abscess and the intervention time of the zipper device were strongly associated with wound healing time(P<0.05).After adjustment for infection size,the RCS model analysis showed a significant linear dose-response relationship between intervention time and wound healing time(Pnonlinear=0.406),and wound healing time shortened with the reduction in intervention time(P<0.001).Conclusion:The application of the novel zipper device can help with the healing of cutaneous abscesses in children,and it is recommended to apply the device as early as possible after control of wound infection,in order to promote early wound healing.

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction