Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Objective To explore the effect of step frequency-controlled walking exercise on vascular endothelial injury in postmenopausal patients with essential hypertension.Methods According to the screening criteria,postmenopausal women aged 55～60 years with essential hypertension and age-matched healthy women with normal blood pressure were recruited.The hypertensive patients were fur-ther divided into an exercise training group(ET)(n=23)that received step frequency-based walking intervention,and a positive control group(PC)(n=23)without exercise intervention.The normotensive healthy subjects were assigned to a negative control group(NC)(n=23).The exercise training lasted 45 to 60 minutes every other day,at least three times a week,for 12 weeks.Before and after the in-tervention,the following parameters were measured:morphological indices[body fat percentage and waist-to-hip ratio(WHR)],blood pressure indicators[systolic blood pressure(SBP)and diastolic blood pressure(SDP)],lipid metabolism markers consisting of the total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-c),and high-density lipoprotein cholesterol,and vascular en-dothelial injury parameters such as endothelial microparticles(EMPs),high-sensitivity C-reactive pro-tein(hs-CRP),and superoxide dismutase(SOD).Results After the intervention,the ET group exhibit-ed significant improvements compared to baseline(P<0.05).Specifically,reductions were observed in body fat percentage,WHR,SBP,TC,TG,LDL-c,EMPs,and hs-CRP(P<0.05).Meanwhile,HDL-c and SOD levels increased significantly(P<0.05).Most of the above indicators demonstrated sig-nificant improvements in the ET group compared to the PC group after the intervention(P<0.05).Con-clusion A 12-week step frequency-controlled walking exercise at moderate intensity improves body com-position,SBP,lipid metabolism,and vascular endothelial function in postmenopausal patients with hy-pertension,suggesting its potentialto reduce cardiovascular risk in this population.

Objective To explore the effect of step frequency-controlled walking exercise on vascular endothelial injury in postmenopausal patients with essential hypertension.Methods According to the screening criteria,postmenopausal women aged 55～60 years with essential hypertension and age-matched healthy women with normal blood pressure were recruited.The hypertensive patients were fur-ther divided into an exercise training group(ET)(n=23)that received step frequency-based walking intervention,and a positive control group(PC)(n=23)without exercise intervention.The normotensive healthy subjects were assigned to a negative control group(NC)(n=23).The exercise training lasted 45 to 60 minutes every other day,at least three times a week,for 12 weeks.Before and after the in-tervention,the following parameters were measured:morphological indices[body fat percentage and waist-to-hip ratio(WHR)],blood pressure indicators[systolic blood pressure(SBP)and diastolic blood pressure(SDP)],lipid metabolism markers consisting of the total cholesterol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-c),and high-density lipoprotein cholesterol,and vascular en-dothelial injury parameters such as endothelial microparticles(EMPs),high-sensitivity C-reactive pro-tein(hs-CRP),and superoxide dismutase(SOD).Results After the intervention,the ET group exhibit-ed significant improvements compared to baseline(P<0.05).Specifically,reductions were observed in body fat percentage,WHR,SBP,TC,TG,LDL-c,EMPs,and hs-CRP(P<0.05).Meanwhile,HDL-c and SOD levels increased significantly(P<0.05).Most of the above indicators demonstrated sig-nificant improvements in the ET group compared to the PC group after the intervention(P<0.05).Con-clusion A 12-week step frequency-controlled walking exercise at moderate intensity improves body com-position,SBP,lipid metabolism,and vascular endothelial function in postmenopausal patients with hy-pertension,suggesting its potentialto reduce cardiovascular risk in this population.

Objective To search and integrate relevant evidence of Traditional Chinese Medicine rehabilitation care during recovery of stroke patients with limb dysfunction,and to provide the evidence for clinical practice.Methods We systematically search domestic and foreign guideline websites,professional association websites,and databases such as Cochrane Library,PubMed,Embase,CNKI,CBM for evidence on Chinese medicine rehabilitation care for limb dysfunction following stroke.The search included guidelines,clinical decisions,evidence summaries,systematic reviews,expert consensuses,and randomized controlled trials,with the search timeframe spanning from the inception of the respective databases to May 2023.The literature was evaluated and rated for quality by 2 researchers independently.Results A total of 17 articles,including 7 guidelines,4 systematic reviews,1 evidence summary and 5 randomized controlled trials were included to summarize 28 pieces of evidence on Traditional Chinese Medicine rehabilitation care for stroke patients with limb dysfunction.The evidence can be categorized into 4 areas,including evaluation,Traditional Chinese Medicine nursing technology,health education and precautions.Conclusion Traditional Chinese Medicine nursing technology for stroke patients with limb dysfunction have various forms and rich contents.Appropriate Traditional Chinese Medicine nursing techniques should be selected according to the actual situation and the willingness of patients to promote the rehabilitation of their limb functions.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective:To observe the effect and underlying mechanism of down-regulation of VEGFA on the radiosensitivity of esophageal cancer ECA-109 cells.Methods:Esophageal cancer cells were divided into four groups: sh-VEGFA group, vector control group, X-ray plussh-VEGFA group and X-ray plus vector group. The expressions of VEGFA gene and protein were detected by qPCR and Western blot, respectively. Cell proliferation and survival was measured by CCK8 assay and cloning formation, respectively. Cell apoptosis was detected by flow cytometry, and γ-H2AX foci were detected by immune-fluorescence assay.Results:Compared with the vector group, the expression of VEGFA gene was decreased in sh-VEGFA group ( t=11.98, P<0.05), and the expression of VEGFA protein was also reduced( t=12.38, P<0.05). After VEGFA being down-regulated, the cell proliferation( A450)was obviously inhibited( t=2.78, 7.25, 21.93, 13.21, P<0.05), and the cell clone formation of the sh-VEGFA group was significantly decreased so that D0, Dqand SF2 of sh-VEGFA group were decreased( t=5.83, 8.56, 7.68, P<0.05), and SERD0and SERDqwere increased. Compared with the vector group, the apoptosis rate in the sh-VEGFA group and the X-ray group was significantly increased and further increased in the sh-VEGFA plus X-ray group( t=17.63, 22.48, 33.87, P<0.05), and the number of γ-H2AX foci in both sh-VEGFA and vector groups were significantly increased within 2 h after X-ray irradiation. At 24 h after irradiation, the number of γ-H2AX foci returned to normal level in the vector group but remained at a higher level in the sh-VEGFA group ( t=7.00, P<0.05). Conclusions:Down-regulation of VEGFA inhibits the proliferation and colony formation, promotes apoptosis and hence increases the radiosensitivity of esophageal carcinoma cells via a pathway related to DNA damage repair.

Objective:To observe and analyze the risk factors related to vitreous re-hemorrhage (PVH) after anti-VEGF drugs combined with vitrectomy (PPV) in patients with proliferative diabetic retinopathy (PDR).Methods:Retrospective analysis study. From April 2017 to July 2018, 100 eyes of 87 PDR patients who were diagnosed in Jiaxing Eye Hospital and received anti-VEGF drugs combined with 25G PPV were included in the study. Among them, there were 44 eyes in 38 males and 56 eyes in 49 females. The age ranged from 26 to 83 years, with an average age of 57.72±8.82 years. All patients were type 2 diabetes, with an average duration of diabetes 10.84±6.03 years. All affected eyes were assisted by the same doctor with a non-contact wide-angle lens under the standard three-channel 25G PPV of the flat part of the ciliary body. Five to 7 days before the operation, intravitreal injection of ranibizumab or conbercept 0.05 ml (10 mg/ml) was performed. The incidence of PVH was observed. The age of PVH patients, duration of diabetes, vision before operation, average fasting blood glucose and average postprandial blood glucose before operation, systolic blood pressure and diastolic blood pressure before surgery, laser treatment before surgery, lens removal during operation, intraocular filling during operation, retinal laser points during operation, and fundus lesions during operation (hyperplasia film, Retinal hemorrhage, vascular occlusion, proliferative retinal traction, retinal hiatus, retinal detachment, exudation, neovascularization) were analyzed to find out the cause of PVH. Spearman bivariate correlation analysis and binary logistic regression analysis were performed on the data.Results:Of the 100 eyes of 87 patients, PVH occurred in 17 eyes (17%). There were statistically significant differences in the number of eyes with vascular occlusion and proliferative traction during surgery in patients with and without PVH ( χ2=5.741, 8.103; P<0.05). There was no significant difference in age ( t=-1.364), duration of diabetes ( t=0.538), preoperative vision ( t=1.897), preoperative fasting blood glucose level ( t=1.938), preoperative postprandial blood glucose level ( t=1.508), preoperative systolic blood pressure ( t=-0.571), preoperative diastolic blood pressure ( t=0.275), whether received laser treatment ( χ2=2.678), the number of laser points during operation ( t=0.565), whether received lens removal during operation ( χ2=0.331), whether found new blood vessels during operation ( χ2=2.741) and whether received intraocular filling during operation ( χ2=0.060) between the patients with and without PVH ( P>0.05). Spearman's bivariate correlation analysis showed that patients with low vision, poor control of fasting blood glucose levels, vascular occlusion and proliferative retinal traction during the operation were related risk factors for PVH ( rs=0.208, 0.229, 0.240, 0.285; P<0.05). Binary logistic regression analysis showed that fundus vascular occlusion and hyperplastic retinal traction may be independent risk factors for PVH during surgery ( OR=5.175, 13.915; P<0.05). Conclusion:Fundus vascular occlusion and retinal traction caused by fibrovascular membrane hyperplasia in PPV may be independent risk factors for PVH in patients with PDR after anti-VEGF drugs combined with PPV.

Objective To establish spastic cerebral palsy model of macaque by partial resection of motor cortex and explore its evaluation method.Methods Four individuals of 3-month-old macaques were divided into healthy control group and operation model group according to random number table.Partial resection of the motor cortex was carried out in operation model group,in which precentral gyrus cortex from above the right lateral cerebral fissure to the inter-hemicerebral fissure,together with the posterior-superior frontal gyrus (about 0.3 to 0.5 cm in front of the anterior median sulcus) cortex were removed with the depth of about 0.5 to 0.6 cm.After the operation,the continuous camera shooting was used to record whether left limb motor dysfunction and abnormal posture existed or not.Muscle tension was assessed by manual examination of muscle tone with reference to the modified Ashworth scale.The quantitative indexes of the two groups were detected by using the gross motor and fine motor assessment scale.9.4T magnetic resonance imaging (MRI) was used to detect the brain imaging changes.Results After operation,the macaque in the operation model group immediately showed left hemiparesis,left upper limb abnormal lifting,left lower limb paralysis,left limb claudication,and eating mainly relied on the right side of the body.After 6 weeks of operation,left limb activity of the operation model group was significantly lower than that of the healthy control group,and the gross motor scores and fine motor scores were significantly lower than those of the healthy control group(Friedman test:χ2=33.939,P<0.05;χ2=37.526,P<0.05).The macaque in the operation model group showed some symptoms that abnormal posture mainly tilted to the left for the rest,sitting in a corner of the monkey cage,left arm was put on the cage to maintain postural balance,and movement was left slightly inclined,which had simulated the typical clinical manifestations of human spastic hemiplegic cerebral palsy.Muscle tension was checked by hand,and the left limb paralysis and muscle tension decreased after operation in the model group,and the left muscle tension increased gradually after 5 weeks,and gradually increased to score 4 points and the score remained 3 after 10 weeks.Brain MRI of 3 weeks postoperatively suggested scar tissue formation after right motor cortex resection,which supported the pathological changes of the hemiplegic cerebral palsy models.Conclusions Through the partial resection of the motor cortex,the model of spastic cerebral palsy was established successfully.The results of behavioral evaluation and MRI showed that the model was consis-tent with spastic hemiplegia.

Objective To evaluate the effect of conventional or goal-directed fluid management on hemodynamics in patients undergoing orthopaedic arthroscopic shoulder surgery in beach chair po-sition.Methods Thirty healthy adult patients,male 1 7 cases,female 13 cases,aged 18-65 years, weight 49-68 kg,ASA Ⅰor Ⅱ,undergoing elective arthroscopic shoulder surgery,were enrolled.Pa-tients were randomly assigned to the group R(Routine group,n = 1 5 )and the group S(SVV/CI/MAP-directed,n =1 5).All patients received 10 ml/kg of hydroxyethyl starch rapidly in group R;while in group S,if SVV > 13%,patients would receive 3 ml/kg of hydroxyethyl starch in 5 min, then the changes of each index were observed;if SVV <13% and CI< 2.5 L·min-1 ·m-2 ,given dopamine 0.5~1 μg·kg-1 ·min-1 ,until CI>2.5 L·min-1 ·m-2 .At 5 min after anesthesia induc-tion,patients were placed in a 60° upright position.The hemodynamic changes were monitored by FloTrac/Vigileo system.Heart rate (HR),mean artery pressure(MAP),cardiac index(CI),stroke volume variation(SVV),stroke volume index (SVI),were recorded on pre-induction (T1 ),post-induc-tion (T2 ),immediately after in beach chair position (T3 ),5 min after in beach chair position(T4 ),30 min after in beach chair position(T5 ),and at the end of surgery(T6 ).The duration of surgery,crys-talloid requirements,colloid requirements,urinary output,the dose of vasoactive drugs and the inci-dence of hypotension were recorded.Results Compared with T1 ,MAP,CI and SVI at T3-T5 point (after in BCP to the end of the surgery)were higher in both group(P <0.05 ).Compared with T2 , SVV in group R at T3-T5 were significantly increased (P <0.05),while SVV in group S only at T3 was slightly increased (P <0.05).Compared with group R,MAP,CI and SVI at T3-T5 were signif-icantly higher respectively,while SVV were higher at T3-T5 in group R (P <0.05).Compared with group R,the colloid requirements and total requirements in group S were significantly increased(P <0.05).Compared with group R,the doses of dopamine and ephedrine,the urinary output,the inci-dence of hypotension in group S were significantly reduced(P <0.05).Conclusion SVV/CI/MAP-di-rected fluid management is safer,more effective and renders much more stable hemodynamic than the routine fluid management.

To explore the application of protein fingerprint technique and differential diagnosis in bacteriological negative pulmonary tuberculosis and pneumonia ,60 patients with bacteriological negative pulmonary tuberculosis ,60 patients with pneumonia ,and 60 healthy volunteers were selected from known clinical cases .Surface strengthening laser desorption ioniza-tion time of flight mass spectrometry (SELDI ToF Ms) and protein chip technology were applied to detect serum proteins ,and analyze their protein peaks by Ciphergen protein chip 3 .1 .1 software .Comparison of the serum protein fingerprinting data from the pool of 180 patients and healthy volunteers showed significant difference in 5 protein peaks (1 028 .49 ,4 796 .56 ,7 564 .77 , 8 048 .02 ,and 11 526 .75 m/z) identified between pulmonary tuberculosis and pneumonia (P<0 .01) .The total effective rate of the 5 protein peaks as a diagnosis model for differential diagnosis of bacteriological negative pulmonary tuberculosis and pneumonia was 84 .2% (101/120) ,the specificity was 82 .5% (52/63) ,the sensitivity was 85 .9% (49/57) ,the positive pre-dictive value was 86 .7% (52/60) ,and the negative predictive value was 81 .7% (49/60) .The total effective rate of the diagno-sis model for differential diagnosis of bacteriological negative pulmonary tuberculosis ,pneumonia and healthy volunteers was 89 .4% (161/180) .The specificity was 100% (60/60) ,the sensitivity was 84 .2% (101/120) ,the positive predictive value was 100% (101/101) ,and the negative predictive value was 75 .9% (60/79) .Protein fingerprinting technology is advanta-geous of being a simple method ,quick detection ,and requires less amount of sample .It is an effective means to screening the tuberculosis specific markers .We found the good diagnosis model through the detection of serum protein by protein fingerprint-ing technology .