BACKGROUND: Regulatory dendritic cell (DCreg) subset exhibits a unique capacity for inducing immune tolerance among the variety subsets of dendritic cells (DCs) within gut-associated lymphoid tissues (GALTs). Fms-like tyrosine kinase 3 ligand (FLT3L) is involved in the differentiation of DCregs and the subsequent expansion of regulatory T-cells (Tregs) mediated by DCregs, though the precise mechanism remains poorly understood. This study aimed to explore the expansion mechanism of Treg induced by DCreg and the role of FLT3L in this process. METHODS: DCregs were distinguished from other DC subsets isolated from GALTs of BALB/c mice through a mixed lymphocyte reaction assay. The functions and mechanisms by which FLT3L promoted Treg expansion via DCregs were investigated in vitro through co-culture experiments involving DCregs and either CD4 + CD25 - T-cells or CD4 + CD25 + T-cells. Additionally, an in vivo experiment was conducted using a dextran sulfate sodium (DSS)-induced colitis model in mice. RESULTS: CD103 + CD11b + DC exhibited DCreg-like functionality and was identified as DCreg for subsequent investigation. Analysis of Foxp3 + Treg percentages within a co-culture system of CD4 + CD25 - T-cells and DCregs, with or without FLT3L, demonstrated the involvement of the FLT3/FLT3L axis in driving the differentiation of precursor T-cells into Foxp3 + Tregs induced by DCregs. Cell migration and co-culture assays revealed that the FLT3/FLT3L axis enhanced DCreg migration toward Tregs via the Rho pathway. Additionally, it was observed that DCregs could promote Treg proliferation through the Notch pathway, as inhibition of Notch signaling by DAPT (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) suppressed Treg expansion within the co-culture system of DCregs and CD4 + T-cells or CD4 + CD25 + T-cells. Furthermore, the FLT3/FLT3L axis influenced JAG1 expression in DCregs, indirectly modulating Treg expansion. In vivo experiments further established that FLT3L promoted DCreg expansion and restored Treg balance in DSS-induced colitis models, thereby ameliorating colitis symptoms in mice. CONCLUSION The FLT3/FLT3L axis is integral to the maintenance of DCreg function in Treg expansion.
Animals ; T-Lymphocytes, Regulatory/immunology* ; Dendritic Cells/immunology* ; Mice ; Mice, Inbred BALB C ; Membrane Proteins/metabolism* ; Receptors, Notch/metabolism* ; Lymphoid Tissue/metabolism* ; Signal Transduction/physiology* ; Coculture Techniques ; Flow Cytometry

Objective To observe the effects of Xin-Gui Gel Plaster(Cinnamomi Cortex,Asari Radix et Rhizoma,Euodiae Fructus,Chuanxiong Rhizoma,Borneolum Syntheticum)on peripheral neuropathy in diabetic rats.Methods A single intraperitoneal injection of 1%streptozotonic(STZ,35 mg·kg-1)was used to replicate a type 2 diabetes mellitus(T2DM)rat model followed by the induction of diabetic peripheral neuropathy(DPN)in combination with a long-term(8 consecutive weeks)high-fat and high-sugar diet.SD rats were randomly divided into normal group,model group,Mecobalamin group and Xin-Gui Gel Plaster group,with 6 rats in each group.The rats in the Xin-Gui Gel Plaster group were given Xin-Gui Gel Plaster at acupoints once a day for 8 weeks;the rats in the Mecobalamin group were given Mecobalamin solution by gavage(0.045 mg·kg-1),and the rats in the normal group and the model group were given physiological saline by gavage.Body mass and fasting blood glucose(FBG)were measured at weeks 2,4,6 and 8;the latency of thermal withdrawal latency(TWL)was measured at weeks 4 and 8;nerve conduction velocities,including motor nerve conduction velocity(MNCV)and sensory nerve conduction velocity(SNCV),were measured at week 8;and serum total cholesterol(TC),triglyceride(TG),fasting blood glucose(FBG)were measured using a fully automated biochemical analyzer.Fasting insulin(FINS)levels were detected by ELISA,and the index of insulin resistance(HOMA-IR)was calculated;and pathological changes in the sciatic nerve tissues of rats were observed by HE staining.Results Compared with the normal group,rats in the model group had significantly lower body mass and FINS levels(P＜0.01),significantly higher levels of FBG,TC,TG and HOMA-IR(P＜0.05,P＜0.01);TWL,MNCV and SNCV were significantly decreased(P＜0.01),and sciatic nerve fibres were disorganized and loosely aligned,with demyelination,axon atrophy and vacuole-like phenomenon.Compared with the model group,there was no significant change in body mass and levels of FBG,TC and TG in the Xin-Gui Gel Plaster group(P＞0.05),FINS level was significantly increased(P＜0.05),and HOMA-IR levels was significantly decreased(P＜0.05);TWL,MNCV and SNCV in the Mecobalamin group and Xin-Gui Gel Plaster group were significantly increased(P＜0.05,P＜0.01),sciatic nerve lesions were improved to different degrees,nerve fibre arrangement was more regular,myelin deficiency and axonal atrophy were significantly improved.Conclusion Xin-Gui Gel Plaster can improve insulin resistance,relieve thermal stimulation sensitivity,improve sciatic nerve conduction velocity to a certain extent in DPN rats,and have a protective effect on peripheral nerves in diabetic rats,but the hypoglycemic and hypolipidemic effects are not obvious.

17q12 microdeletion syndrome is a rare genetic disease,commonly characterized by newly occurring mutations,which can cause abnormalities of the urinary and reproductive tract,diabetes mellitus,neurological and psychiatric disorders and mild deformities.This article reports a case of 17q12 microdeletion syndrome with CRYBB2 gene missense mutation,combined with menstrual abnormalities,multiple cysts in both kidneys,hypomagnesemia,hyperuricemia,small pancreatic morphology and low pancreatic enzyme levels.

Immune checkpoint inhibitor(ICI)associated diabetes mellitus(DM)a rare specific type of diabetes,usually developed after the treatment of programmed cell death protein 1(PD-1)inhibitor or programmed cell death ligand 1(PD-L1)inhibitor.We reported 4 cases of DM after ICI use.These patients had a subacute onset,6 to 17 months after the first use of the drug,with diabetic autoantibodies negative.Pancreas atrophy was observed in one of them.All of the patients received treatment of insulin.

Objective:To compare the changes in pelvic floor electrophysiology and imaging in female patients with myofascial pelvic pain (MFPP), and to explore the characteristics and significance of these changes.Methods:A total of 49 MFPP patients who were admitted to the of Dalian Women′s and Children′s Medical Center (Group) from January 2019 to October 2021 were randomly selected as the research group, and 41 healthy women during the same period were selected as the control group. Both groups filled in the center′s medical history and general condition survey form. French PHENIX series pelvic floor muscle potential detection instrument was used to detect the resting vaginal muscle potential and maximum muscle potential of the two groups. The static tension, dynamic tension and pelvic floor muscle contraction force of the two groups were measured by French PHENIX series electronic tensioning apparatus with 5° and 10° opening respectively. Two dimensional transperineal ultrasound and three dimensional transvaginal ultrasound produced by B-K Company in Denmark were used to measure the length between the lower margin of the bladder neck from the symphysis pubis and the bladder neck and the bladder bottom (BND, BSD), the diameter of the genital tract hiatus and the angle of the anus and rectum. The area, anterior-posterior diameter, transverse diameter and different damage degrees of levator ani levator were measured.Results:The resting muscle potential of the study group was higher than that of the control group: 2 μV vs. 1 μV ( P<0.05); the maximum vaginal myopotential was higher than that of the control group: 7 μV vs. 6 μV ( P<0.05). The static tension, dynamic tension and contractile force: 204 g/m 2 vs. 175 g/m 2, 450 g/m 2 vs. 410 g/m 2 and 237 g/m 2 vs. 51 g/m 2 of pelvic floor muscle in the study group were higher than those in the control group when the tensioner was opened for 5° ( P<0.05). In resting state, BND, BSD and reproductive tract hiatus diameter in the study group were smaller than those in the control group: 14.0 mm vs. 16.7 mm, 15.3 mm vs. 19.7 mm, 46.7 mm vs. 49.5 mm ( P<0.05). The anal angle was greater than that of the control group: 129° vs. 112° ( P<0.05). The anal right angle in the study group was greater than that in the control group: 113° vs. 109° ( P<0.05). In the resting state, the area of levator ANI hiatus: 10.1 cm 2 vs. 11.6 cm 2, anterior and posterior diameters: 44.2 mm vs. 47.4 mm, transverse diameters and the defect scores of levator ani in the study group were all smaller than those in the control group ( P<0.05). Conclusions:MFPP presents with persistent pelvic floor muscle spasm and loss of coordination. MFPP can be treated by spasmolysis of pelvic floor muscle and fascia, which provides reference value for clinical treatment.

ObjectiveTo investigate the characteristics of serum perfluoroalkyl substances （PFASs） exposure and potential influencing factors among community residents in Songjiang District， Shanghai. MethodsIn August 2021， residents who underwent routine health checkups in a community in Songjiang District， Shanghai were recruited as study subjects. The inclusion criteria were adult residents who had lived in the area for more than 3 years， had no occupational exposure history， no underlying diseases， were not pregnant， and were able to complete the questionnaire independently and sign the informed consent form. A questionnaire survey was conducted and venous blood samples were collected. The concentrations of 15 PFASs in serum were determined using ultra-high performance liquid chromatography-tandem quadrupole mass spectrometry （UPLC-MS/MS）. Ordered multi-class logistic regression， interquartile range （IQR）， and odds ratio （OR） were used to explore the influencing factors and risk magnitude of serum PFASs concentrations. ResultsOf the 15 PFASs， 14 were detected， and the detection rates of 7 PFASs were higher than 50%. The highest detected concentrations among the PFASs were PFOS （perfluorooctane sulfonate）， PFOA （perfluorooctanoic acid）， and PFHxS （perfluorohexane sulfonate）， with median concentrations of 48.61 μg∙L^-1， 37.29 μg∙L^-1， and 36.51 μg∙L^-1， respectively. The strongest correlation was between PFDA and PFUnDA （r=0.93， P<0.05）， followed by PFOS and PFDA （r=0.86， P<0.05）. Age， frequency of plastic product use， time spent indoors per day， personal annual income， tea consumption， and daily water intake were potential factors for exposure to PFASs. Among them， age was positively correlated with PFASs； tea consumption was positively correlated with PFNA and PFOA； PFHpA was negatively correlated with the frequency of plastic product use and personal annual income； and PFOS was negatively correlated with the time spent indoors per day. ConclusionThe exposure to serum PFASs among community residents in Songjiang District was relatively serious， and the main components were traditional PFOA， PFOS， and PFHx. Different sociodemographic characteristics had varying degrees of influence on the concentrations of PFASs in serum. The impact of PFASs exposure on the health of community residents deserves further investigation.

Objective:To investigate the psychological stress and related factors of community medical staff in Shanghai during infectious public health emergencies.Methods:Random cluster sampling, questionnaires combining general demographic information, self-rating anxiety scale(SAS), self-rating depression scale(SDS)and yale-brown obsessive compulsive scale(YB)were administrated to investigate the psychological stress of medical staff from 20 community healthcare centers in 10 Shanghai districts.Results:A total of 696 valid questionnaires were collected. 17.36% of the staff had SAS scores exceeding the boundary value. Nurses, staff with per capita monthly family income<5 000 yuan, or with below-average family relations presented higher SAS scores. 28.19% of the staff had SDS scores exceeding the boundary value. Staff with 5-10 years seniority, nurses, with per capita monthly family income<5 000 yuan, and with poor family relations presented higher SDS scores. 6.68% of the staff had YB score≥16. Nurses presented a higher YB score.Conclusions:Some community healthcare center staff experienced psychological stress during public health emergencies.Factors associated with psychological stress, such as 5-10 years′ seniority, nurses, per capita monthly family income<5 000 yuan, below-average or poor family relations, deserve more attention in order to prevent from or alleviate harmful psychological stress.

Objective To investigate the clinical value of C-reactive protein (CRP) combined with prothrombin time (PT) and partially activated thromboplastin time (APTY) in the diagnosis of neonatal late-onset sepsis.Methods From January 2013 to January 2018,100 neonates with sepsis admitted to our department of neonatology in Lishui Maternal and Child Health-Care Center were collected.According to the results of blood culture,neonates with positive blood culture were classified as sepsis group A (53 cases),and neonates with negative blood culture were classified as sepsis group B (47 cases).Another 50 normal newborns born at the same period were included in the control group.The CRP,PT and APTT values of the three groups were detected and compared.The receiver-operating characteristic curves (ROC) were plotted to obtain the area under ROC curve (AUC) and the sensitivity,specificity,positive predictive value and negative predictive value.Another ROC curve was plotted to obtain the area under ROC curve (AUC) and the sensitivity,specificity,positive predictive value,and negative predictive value for a new variable,CPR + PT + APTT,which was established using a binomial logistic regression method.Results The results of CPR,PT and APTT in the control group,sepsis group A and sepsis group B all increased in turn (F=10.616,6.155,5.243,P =0.000,0.000,0.000).CPR + PT + APTT had the largest AUC (0.94),the highest sensitivity (93.42％),the highest specificity (91.66％),the highest positive predictive value (92.60％),and the highest negative predictive value (78.55％) in the four indicators.Conclusion When blood culture fails to diagnose late-onset neonatal sepsis,combined detection of CPR + PT + APTT can provide some clues for its early diagnosis,which is worthy of clinical attention.

Objective To explore the value of three-dimensional ultrasonic technique in precise pelvic floor reparation. Methods One hundred and twenty-six patients with Ⅱ - Ⅳ degree pelvic organ prolapse were selected. The patients were divided into traditional group (57 cases, transvaginal hysterectomy and vaginal wall reparation) and study group (69 cases, transvaginal hysterectomy and vaginal wall reparation combined with indication of transvaginal three-dimensional ultrasound). The changes of perioperative indexes and postoperative recurrence rate were compared between 2 groups. Results There were no statistical differences in surgery time, intraoperative blood loss, retention catheterization time postoperative exhaust and defecation time duration in hospital and postoperative complication between 2 groups (P＞0.05). The subjective and objective cure rate 3 months after operation in both groups was 100.0% ; there were no statistical differences 6 months after operation between 2 groups (P＞0.05). The objective cure rates 12 and 24 months after operation in study group were significantly higher than those in traditional group: 20.0% (11/55) vs. 7.5% (5/67) and 27.3% (15/55) vs. 11.9% (8/67), and there were statistical differences (P＜0.05). Conclusions The recurrence rate of precise traditional pelvic floor reparation with the guidance of transvaginal three-dimensional ultrasound is significantly lower than that of traditional pelvic floor reparation.

Objective To explore the therapeutic effect and clinical significance of pelvic floor rehabilitation technique in female with myofascial chronic pelvic pain (MCPP) by detecting the pressure pain thresholds (PPTs). Methods One hundred healthy female (control group) and 324 female MCPP patients (observation group) from January 2009 to December 2016 were selected. Automatic body surface and vaginal pressure pain detector was applied to detect two groups′PPTs of the 34 spots. The difference of PPTs at each spot was analyzed in two groups. In addition, 51 patients with moderate and severe MCPP were selected to record the changes of PPTs and pain scores before and after the treatment of pelvic floor rehabilitation technique. Results The average PPTs of the abdomen, vulva, pelvic floor and vaginal front and back fornix, bilateral adnexa uteri and sacrouterine ligament in the observation group were significantly lower than those in the control group (P<0.01 or<0.05). The average PPTs of the abdomen, vulva, pelvic floor muscles and vaginal front and back fornix, bilateral adnexa uteri and sacrouterine ligament of 51 MCPP patients after treatment were significantly higher than those before treatment (P<0.01). After treatment, PPTs and pain scores of the pelvic floor muscles, bilateral adnexa uteri, bilateral sacrouterine ligament, bilateral sacral spine ligament and vaginal front and back fornix were negatively correlated (r =- 0.78 to- 0.19, P = 0.01 to 0.04); there was a negative correlation between the PPTs and pain scores of the left and right latissimus dorsi (r=-0.28, P=0.04;r=-0.32, P=0.02). The complete remission rate with the pelvic floor rehabilitation technique in 51 patients with MCPP was 9.8％(5/51), the significant remission rate was 90.2％(46/51), and the total remission rate was 100.0％ (51/51). Conclusions Compared with the normal healthy ones, female with MCPP has lower PPTs in the abdomen, perineum, vagina and pelvic floor. The effect of pelvic floor rehabilitation technique on MCPP is well, which can increase patients′PPTs to reduce pain scores. It is a worthwhile method to treat these diseases.