Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia(ALSP)is a clinically rare autosomal dominant genetic disease,and its specific pathogenesis is not yet clear.The colony-stimulating factor 1 receptor(CSF1R)is a transmembrane tyrosine kinase receptor on the cell surface and mutations in the gene encoding it have been identified as potential pathogenic factors for ALSP.However,the specific mechanisms by which CSF1R gene mutations lead to the onset of ALSP are still unclear.After reviewing the mutation sites and pathogenic mechanisms of CSF1R in the pathogenesis of ALSP,CSF1R mutations have been shown to cause microglial dysfunction through mechanisms such as dominant-negative effects,loss of function,haploinsufficiency,and gain of function,thereby leading to the onset of ALSP.A deeper understanding of the causes of ALSP will help in exploring potential treatment methods.

Objective To investigate the effect of leflunomide(LEF)on the expression of associated autophagy genes in synoviocytes of rheumatoid arthritis(RA)by regulating HIF-1α signal pathway.Methods Three genera-tions of RA synovial cells were divided into blank control group,LEF group and Tripterygium wilfordii polyglyco-sides group.The blank control group was added with the same volume of DMEM culture medium.The drug group was treated with LEF(concentration 0.2 mg/ml)and Tripterygium wilfordii polyglycosides(concentration 0.03 mg/ml),the proliferation and apoptosis of synovial cells were detected by flow cytometry,the expression of IL-1 β,TNF-α,ANGPTL-4 and VEGF was detected by ELISA,the expression of HIF-1α mRNA was detected by qRT-PCR,and the expression of HIF-1 α,Beclin-1 and BNIP3 protein was detected by Western blot.Results Com-pared with Tripterygium wilfordii polyglycosides group,the expression of IL-1 α,TNF-α,ANGPTL-4 and VEGF in synovial supernatant of LEF group decreased;compared with the blank control group,the expression of HIF-1αmRNA in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious;compared with the blank control group,the protein expressions of HIF-1α,Bec-lin-1 and BNIP3 in synovial cells of LEF group and Tripterygium wilfordii polyglycosides group decreased,and the effect of LEF group was the most obvious.Conclusion LEF can inhibit the expression of inflammatory factors in RA synovial cells,inhibit HIF-1α signaling pathway,inhibit the expression of autophagy-related genes Beclin-1 and BNIP3,and improve the pathological state of synovitis.

Objective:To investigate the pathological spectrum and variation of adult renal biopsies in People's Hospital of Xinjiang Uygur Autonomous Region from 1986 to 2020.Methods:The pathological data of 5 652 adult renal biopsies from August 1986 to December 2020 were retrospectively collected, and characteristics of pathological spectrum were analyzed. Regarding every 5 years as a research stage, the whole period was divided into 7 stages to analyze the pathological features and variation of renal biopsies. The first stage (P1) started from August 1986 to December 1990. The second stage (P2) started from January 1991 to December 1995. The third stage (P3) started from January 1996 to December 2000. The fourth stage (P4) started from January 2001 to December 2005. The fifth stage (P5) started from January 2006 to December 2010. The sixth stage (P6) started from January 2011 to December 2015. The seventh stage (P7) started from January 2016 to December 2020.Results:The age was (36.47±14.86) years old (18-83 years old) in 5 652 renal biopsies. There were 2 961 males (52.39%). There were 5 636 cases of autologous kidney biopsy and 16 cases of transplanted kidney biopsy. The descending order of incidence classified by disease types were primary glomerular disease (PGD, 4 470 cases, 79.31%), secondary glomerular disease (SGD, 994 cases, 17.64%), tubular-interstitial disease (160 cases, 2.84%), and hereditary nephropathy (12 cases, 0.21%). IgA nephropathy (IgAN, 1 573 cases, 35.19%) was the most frequent pathologic type of PGD, followed by membranous nephropathy (MN, 1 028 cases, 23.00%), mesangial proliferative glomerulonephritis (MsPGN, 878 cases, 19.64%), minimal change disease (MCD, 427 cases, 9.55%), and focal segmental glomerulosclerosis (345 cases, 7.72%). Lupus nephritis (LN, 251 cases, 25.25%) was the most common type of SGD, followed by hypertension nephropathy (193 cases, 19.42%), diabetic kidney disease (168 cases, 16.90%), purpura nephritis (138 cases, 13.88%), and ischemic nephropathy (90 cases, 9.05%). IgAN was the most common type of primary glomerulonephritis and mainly occurred in the age group of 18-59 years old. PGD was the most common glomerular disease in Han nationality (78.33%), Uygur nationality (81.72%) and other ethnic (77.15%) groups. Using Bonferroni correction method, the incidence of PGD in Uygur nationality was higher than that in Han nationality ( P<0.017). From P1 to P7, the detection rates of MN and MCD were increased in common renal pathological types, meanwhile, the ratio of MsPGN was decreased (all P<0.05). From P5 to P7, the detection rates of MN in Han nationality and Uygur nationality increased in the common pathological types of PGD, meanwhile, the ratio of MsPGN decreased (all P<0.05). LN was the most common SGD. The incidence of LN in females was higher than that in males ( P<0.001). Using Bonferroni correction method, the incidence of SGD in Uygur nationality was lower than that in Han nationality ( P<0.017). There was no significant variation in the common pathological type of SGD in Han and Uygur nationalities. Chronic rejection was the main pathological type of transplanted kidney biopsies. Conclusions:PGD is the main type of kidney disease spectrum in People's Hospital of Xinjiang Uygur Autonomous Region. IgAN is the most common PGD and mainly occurrs in the age group of 18-59 years old. As time goes by, the proportion of MN and MCD is increased, meanwhile the proportion of MsPGN is decreased significantly. LN is the most common SGD.

The pathophysiology of visceral pain in patients with irritable bowel syndrome remains largely unknown. Our previous study showed that neonatal maternal deprivation (NMD) does not induce visceral hypersensitivity at the age of 6 weeks in rats. The aim of this study was to determine whether NMD followed by adult stress at the age of 6 weeks induces visceral pain in rats and to investigate the roles of adrenergic signaling in visceral pain. Here we showed that NMD rats exhibited visceral hypersensitivity 6 h and 24 h after the termination of adult multiple stressors (AMSs). The plasma level of norepinephrine was significantly increased in NMD rats after AMSs. Whole-cell patch-clamp recording showed that the excitability of dorsal root ganglion (DRG) neurons from NMD rats with AMSs was remarkably increased. The expression of β adrenergic receptors at the protein and mRNA levels was markedly higher in NMD rats with AMSs than in rats with NMD alone. Inhibition of β adrenergic receptors with propranolol or butoxamine enhanced the colorectal distention threshold and application of butoxamine also reversed the enhanced hypersensitivity of DRG neurons. Overall, our data demonstrate that AMS induces visceral hypersensitivity in NMD rats, in part due to enhanced NE-β adrenergic signaling in DRGs.
Adrenergic Agents ; pharmacology ; Animals ; Ganglia, Spinal ; drug effects ; Hyperalgesia ; drug therapy ; physiopathology ; Hypersensitivity ; drug therapy ; Male ; Maternal Deprivation ; Neurons ; drug effects ; Patch-Clamp Techniques ; methods ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Stress, Physiological ; physiology ; Visceral Pain ; chemically induced ; metabolism

Objective To explore the correlation between the methylation level of 5-hydroxytryptamine receptor 1A(HTR1A) gene promoter region and severity of symptom in the manic epi-sode patients with bipolar disorder type Ⅰ(BD-Ⅰ). Methods Fifty six manic episode patients with BD-Ⅰand fifty nine healthy controls were randomly included in the study. The level of HTR1A gene promoter meth-ylation was measured with pyrosequencing technique in both manic episode patients with BD-Ⅰ and the healthy controls. The severity of symptoms was assessed with score of Bech-Rafaelsen Mania Rating Scale (BRMS) in patients with BD-Ⅰ. Pearson correlation analysis was employed to explore the correlation be-tween the serum level of HTR1A promoter methylation and score of BRMS in BD-Ⅰgroup. Results In-creased serum level of HTR1A gene promoter methylation was found in manic episode patients with BD-Ⅰ((66. 55±10. 55)%) compared with that in healthy controls((54. 03±8. 85)%)(P<0. 01). Positive corre-lation was found between the serum level of HTR1A gene promoter methylation and total score of BRMS in manic patient with BD-Ⅰ(r=0. 534,P<0. 01). Conclusion The current findings suggest that the serum level of HTR1A gene promoter methylation can be an epigenetic indicator for severity of manic symptom in BD-Ⅰ.

OBJECTIVE:To establish the method for simultaneous determination of 6 residual organic solvents in Xingnaojing injection,such as methanol,ethanol,isopropanol,n-butanol,ethyl acetate and acetonitrile.METHODS:Headspace GC method was adopted.The determination was performed on DB-624 capillary column by temperature programming with the injector temperature of 200 ℃;flame ionization detector was adopted with the temperature of 250 ℃;carrier gas was nitrogen with flow rate of 25 mL/min and split ratio of 35 ∶ 1;headspace sampling size was 1 mL,and heating temperature of headspace sampling was 80 ℃;equilibrium time was 15 min.RESULTS:The linear ranges of methanol,ethanol,isopropanol,n-butanol,ethyl acetate and acetonitrile were 15.00-240.00 μg/mL (r =0.999 9),25.00-400.00 μg/mL (r =0.999 9),25.00-400.00 μg/mL (r =0.999 9),25.00-399.99 μg/mL(r=0.999 9),25.00-399.99 μg/mL(r=0.999 8) and 5.00-80.00 μg/mL(r=0.999 9).The LOQ were 5.98,3.94,2.05,2.13,1.39,1.24 μg/mL,and the LOD were 2.01,2.11,1.18,1.56,1.15,0.01 μg/mL,respectively.RSDs of precision tests were all less than 2.0％,stability and repetitive tests only ethyl acetate was detected,RSD＜2.0％;the recoveries were 93.59％-99.02％ (RSD=2.62％,n=6),92.42％-98.40％ (RSD=2.43％,n=6),94.81％-104.64％ (RSD=3.47 ％,n=6),94.56％-106.73％ (RSD=4.21％,n=6),97.04％-106.33％(RSD=3.50％,n=6)and 98.40％-107.97％ (RSD=3.37％,n=6).CONCLUSIONS:The method is specific,rapid,simple and accurate,and can be used for simultaneous determination of 6 residual organic solvents in Xingnaojing injection.

BACKGROUND/AIMS: This study was to investigate whether transforming growth factor-β1 (TGF-β1) plays a role in hyperalgesia in chronic pancreatitis (CP) and the underlying mechanisms. METHODS: CP was induced in male adult rats by intraductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen. Dil dye injected into the pancreas was used to label pancreas-specific dorsal root ganglion (DRG) neurons. Whole cell patch clamp recordings and calcium imaging were performed to examine the effect of TGF-β1 on acutely isolated pancreas-specific DRG neurons. Western blot analysis was carried out to measure the expression of TGF-β1 and its receptors. RESULTS: TNBS injection significantly upregulated expression of TGF-β1 in the pancreas and DRGs, and TGF-β1 receptors in DRGs (T9-T13) in CP rats. Intrathecal injection of TGF-β receptor I antagonist SB431542 attenuated abdominal hyperalgesia in CP rats. TGF-β1 application depolarized the membrane potential and caused firing activity of DRG neurons. TGF-β1 application also reduced rheobase, hyperpolarized action potential threshold, and increased numbers of action potentials evoked by current injection of pancreas-specific DRG neurons. TGF-β1 application also increased the concentration of intracellular calcium of DRG neurons, which was inhibited by SB431542. Furthermore, intrathecal injection of TGF-β1 produced abdominal hyperalgesia in healthy rats. CONCLUSIONS: These results suggest that TGF-β1 enhances neuronal excitability and increases the concentration of intracellular calcium. TGF-β1 and its receptors are involved in abdominal hyperalgesia in CP. This and future study might identify a potentially novel target for the treatment of abdominal pain in CP.
Abdomen ; Abdominal Pain ; Action Potentials ; Adult ; Animals ; Blotting, Western ; Calcium ; Diagnosis-Related Groups ; Fires ; Ganglia, Spinal ; Humans ; Hyperalgesia ; Injections, Spinal ; Male ; Membrane Potentials ; Neurons* ; Pancreas ; Pancreatitis, Chronic* ; Rats*

BACKGROUND/AIMS: Patients with long-standing diabetes often demonstrate intestinal dysfunction and abdominal pain. However, the pathophysiology of abdominal pain in diabetic patients remains elusive. The purpose of study was to determine roles of voltage-gated sodium channels in dorsal root ganglion (DRG) in colonic hypersensitivity of rats with diabetes. METHODS: Diabetic models were induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in adult female rats, while the control rats received citrate buffer only. Behavioral responses to colorectal distention were used to determine colonic sensitivity in rats. Colon projection DRG neurons labeled with DiI were acutely dissociated for measuring excitability and sodium channel currents by whole-cell patch clamp recordings. Western blot analysis was employed to measure the expression of NaV1.7 and NaV1.8 of colon DRGs. RESULTS: STZ injection produced a significantly lower distention threshold than control rats in responding to colorectal distention. STZ injection also depolarized the resting membrane potentials, hyperpolarized action potential threshold, decreased rheobase and increased frequency of action potentials evoked by 2 and 3 times rheobase and ramp current stimulation. Furthermore, STZ injection enhanced neuronal sodium current densities of DRG neurons innervating the colon. STZ injection also led to a significant upregulation of NaV1.7 and NaV1.8 expression in colon DRGs compared with age and sex-matched control rats. CONCLUSIONS: Our results suggest that enhanced neuronal excitability following STZ injection, which may be mediated by upregulation of NaV1.7 and NaV1.8 expression in DRGs, may play an important role in colonic hypersensitivity in rats with diabetes.
Abdominal Pain ; Action Potentials ; Adult ; Animals ; Architectural Accessibility ; Blotting, Western ; Citric Acid ; Colon* ; Diagnosis-Related Groups ; Female ; Ganglia, Spinal ; Humans ; Hypersensitivity* ; Injections, Intraperitoneal ; Membrane Potentials ; Neurons ; Rats* ; Sensory Receptor Cells* ; Sodium ; Sodium Channels ; Streptozocin ; Up-Regulation ; Voltage-Gated Sodium Channels*

Objective To investigate effect of different anesthesia on cesarean section perioperative coagula-tion function and D -dimer,to provide a reference for clinical treatment.Methods 120 cases of cesarean section patients were selected,according to the anesthesia they were divided into observation group and control group.Obser-vation group (70 cases) used combined spinal epidural anesthesia,the control group(50 cases) used epidural anes-thesia.The prothrombin time (PT),activated partial thromboplastin time (APTT),thrombin time (TT),fiber clinical indicators fibrinogen (Fbg),DD,analgesia and its complications were compared between the two groups.Results Before surgery,PT,APTT,TT,Fbg had no statistically significant differences between the two groups (P >0.05).6h, 24h after operation, PT,APTT,TT of the observation group were (13.23 ±1.86) s,(31.18 ±5.94) s,(15.52 ± 2.55)s;(12.85 ±1.94)s,(29.74 ±5.52)s,(14.68 ±3.15)s,which were lower than the control group,the differ-ences were statistically significant (t =3.294,4.546,4.143,3.656,3.435,3.115,all P <0.05).6h after operation, Fbg of the observation group was (3.17 ±0.48)g/L,which was lower than the control group,the difference was statis-tically significant (t =3.656,P <0.05);D -D of the observation group before surgery,immediately after surgery,24h after surgery were (0.28 ±0.04)mg/L,0.04mg/L,(0.33 ±0.07)mg/L,(0.33 ±0.07)mg/L,compared with the control group had no statistically significant differences (P >0.05).In the observation group,the incidence rates of pain level 2,3 were 41.43%,30.00%,compared to the control group showed no significant difference (P >0.05). Deep vein thrombosis was not found in the observation group,the control group confirmed one case of femoral vein thrombosis,the incidence of venous thrombosis in the two groups showed no significant difference ( P >0.05). Conclusion Combined spinal epidural anesthesia,epidural anesthesia can both prevent cesarean section patients from perioperative hypercoagulable state,reduce the incidence of thrombotic complications,epidural anesthesia is the preferred method.