Objective To study the effect of leucine rich repeat kinase 2(LRRK2)on pain sensitivity in neuro-pathic pain(NP)rats and explore its possible mechanism.Methods 48 SD rats were randomly divided into four groups:sham surgery(Sham),model,LRRK2 inhibitor(MLi-2),and LRRK2 inhibitor+p3 8 mitogen activated pro-tein kinase(MAPK)agonist(MLi-2+Anisomycin),with 12 rats in each group.The NP rat model was induced by chronic constriction injury(CCI)of the sciatic nerve.Intrathecal injection of MLi-2(1 mg/kg,10 μl)or Anisomy-cin(20 μmol/L,10 μl)was started from the 8th day after surgery,once a day for 7 consecutive days.Pain sensi-tivity tests were conducted before surgery(day 0)and on postoperative days 7 and 14,respectively.The changes in mechanical withdrawal threshold(MWT)and paw withdraw thermal latency(PWTL)were analyzed in each group of rats.ELISA was used to detect the levels of interleukin-1 β(IL-1β),IL-6 and tumor necrosis factor-α(TNF-α)in the dorsal horn of the rat spinal cord.Nissl staining was used to observe the pathological changes of neurons in rat spinal cord tissue.Immunofluorescence staining was used to observe the expression levels of ionized calcium-binding adapter molecule-1(Iba-1),a marker of microglia in the spinal cord of rats.Western blot was used to detect the protein expression levels of LRRK2,p-p38 mitogen activated protein kinase(MAPK),p38 MAPK,and Iba-1 in the dorsal horn of the rat spinal cord.Results Compared with the sham group,the model group showed a significant decrease in MWT and PWTL in the right hind limb of rats(P＜0.01).The levels of IL-1,IL-6,and TNF in the spi-nal dorsal horn tissue,as well as the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK pro-tein ratio significantly increased(P＜0.01).The proportion of Iba-1 positive cells in the spinal cord tissue signifi-cantly increased(P＜0.01),while Nissl bodies were significantly reduced(P＜0.01).Compared with the model group,the MLi-2 group showed a significant increase in MWT and PWTL in the right hind limb of rats(P＜0.01),a significant increase in Nissl bodies(P＜0.01),a significant decrease in the proportion of Iba-1 positive cells in the spinal cord tissue(P＜0.01),and a significant decrease in the levels of IL-1,IL-6,and TNF and the expression levels of LRRK2,Iba-1 proteins and p-p38 MAPK/p38 MAPK protein ratio(P＜0.01).However,Anisomychin in-tervention could activate the p38 MAPK signaling pathway and partially reverse the beneficial effects of MLi-2 on pain sensitivity and neuroinflammation in rats with neuropathic pain.Conclusion Inhibiting the expression of LRRK2 can alleviate pain sensitivity in NP rats induced by microglia activation mediated neuroinflammation,and its mechanism of action may be related to regulating the p38 MAPK signaling pathway.

Objective To investigate the role and mechanism of silent information regulator 1(SIRT1)-NOD-like receptor protein 3(NLRP3)axis in the effect of remifentanil against ischemia-reperfusion injury(IRI)in rat livers.SD rats were randomly divided into sham operation group(sham group),IRI group,IRI+remifentanil pretreatment group(IRI+RPC group),IRI+SIRT1 inhibitor EX-527 group(IRI+EX-527 group)and IRI+RPC+EX-527 group,with 8 rats in each group.The levels of serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),lactate dehydrogenase(LDH),interleukin(IL)-1β and IL-18 of rats in each group were detected.The liver tissue pathology was observed.The apoptosis rate of hepatocytes in rats was detected.The expressions of SIRT1,NLRP3,cleaved cysteinyl aspartate specific proteinase-1(Cleaved Caspase-1)and Gasdermin D(GSDMD)proteins in rat liver tissue were detected.Results Compared with the sham group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI group were increased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI group,the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+RPC group were decreased,the serum ALT,AST,LDH,IL-1β,and IL-18 levels were decreased,the relative expression of SIRT1 protein in liver tissue was increased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were decreased;the liver tissue pathological score and hepatocyte apoptosis rate of rats in the IRI+EX-527 group were increased,the ALT,AST,LDH,IL-1β,and IL-18 levels were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Compared with the IRI+RPC group,the liver tissue pathological score and hepatocyte apoptosis rate in the IRI+RPC+EX-527 group were increased,the levels of ALT,AST,LDH,IL-1β,and IL-18 were increased,the relative expression of SIRT1 protein in liver tissue was decreased,and the relative expression of NLRP3,Cleaved Caspase-1,and GSDMD proteins were increased(all P<0.05).Conclusions SIRT1 may participate in the regulation of remifentanil against rat liver IRI by inhibiting NLRP3 mediated cell pyroptosis.

Objective To assess the prevalence of mycoplasma genitalium(MG)in patients attending sexually transmitted disease(STD)clinic in Guangzhou,and to provide an epidemiological foundation for clinical treatment and laboratory diagnostics.Methods Utilizing real-time polymerase chain reaction(PCR),we analyzed MG DNA in 2,749 clinical specimens collected from 2,722 outpatients in the Dermatology Hospital of Southern Medical University from July 2019 to December 2021.Concurrent testing for MG,Chlamydia trachomatis(CT),and Neisseria gonorrhoeae(NG)was performed on 2,382 of these specimens.Patient data extracted from medical records were used to investigate the correlation between STD symptoms and MG infection.Results The investigation revealed that the overall prevalence of MG infection was 4.4%among the sampled patients(120 out of 2,722),with a higher prevalence in males(4.9%,or 87 out of 1,790)compared to in females(3.5%,or 33 out of 932).Notably,the prevalence decreased with increasing age.The highest incidence of MG infection was observed in females aged 18～25 years(6.4%,or 18 out of 281),while the lowest was in males aged 46 years and above(1.5%,or 5 out of 342),showing a statistically significant variation across age groups(P<0.05).Among males with urethritis symptoms,MG positive rate was significantly higher at 7.3%(42 out of 574).The rate of single MG infection was prominent,accounting for 89.9%(71 out of 79)in MG-positive male patients and 61.5%(16 out of 26)in MG-positive female patients.Co-infection rate of MG with CT was 1.2%in females and 0.3%in males,indicating a significant dif-ference(P<0.05).Conclusion The findings suggest a relatively high prevalence of MG infection and co-infection with CT among STD clinic attendees in Guangzhou,particularly in the younger demographic.The study underscores the need for early screening and vigilant surveillance of MG to mitigate its transmission among sexually active popula-tions at high risk.

Objective:To explore the effects of a structured exercise intervention on the healthy physical fitness in patients with leukemia receiving umbilical cord blood transplantation.Methods:It was a randomized controlled trial, conducted from August 2022 to October 2023 at the Department of Hematology of the First Affiliated Hospital of the University of Science and Technology of China (Anhui Provincial Hospital). Fifty leukemia patients undergoing umbilical cord blood transplantation were recruited and were randomly assigned to either the control group (24 cases) or the intervention group (26 cases) using a random number table method. The control group received routine nursing care, health education, and exercise guidance during hospitalization. The intervention group were given moderate-intensity structured exercise intervention, including aerobic, resistance exercises, and flexibility training, three times per week for 30 to 40 minutes per session, over a period of 6 to 8 weeks. During the study, 2 patients withdrew due to disease reasons, and finally, 22 patients in the control group and 26 patients in the intervention group were obtained. The paired t-test, Wilcoxon test, and covariance analysis were used to compare the indices of healthy physical fitness before and after the intervention between the two groups, aiming to explore the effects of a structured exercise intervention on the healthy physical fitness of leukemia patients undergoing umbilical cord blood transplantation. Results:Before the intervention, there was no significant differences in baseline characteristics, such as age, gender and disease status between the two groups (all P>0.05). During the hospitalization phase, the rate of exercise participation in the intervention group was 73.4%, the frequency of exercise was (2.20±0.41) sessions per week and the duration of each exercise session was (34.34±5.05) minutes, and the Borg′s rating of perceived exertion was (13.04±0.82) points. After intervention, the indicators including cardiovascular endurance, muscle fitness, and functional activity status in the two groups were all decreased, and the reduction degree of the indicators were all significantly lower in the intervention group when compared with those in the control group [6-minute walk distance (48.81±30.39) m vs (143.05±77.26) m, grip strength of left hand (2.57±1.30) kg vs (6.72±4.88) kg, grip strength of right hand (2.47±1.97) kg vs (6.34±5.70) kg, muscle strength of left upper limb (4.12±2.07) times vs (8.18±5.26) times, muscle strength of right upper limb (3.96±2.29) times vs (7.91±5.16) times, 30 second chair standing test (3.65±1.98) times vs (7.86±4.34) times, and timed-up-and-go test (0.65±0.53) s vs (2.35±1.79) s] (all P<0.05). The flexibility fitness was improved in the intervention group after the intervention [sit-and-reach 2.00(-4.75, 8.18) cm vs 0(-9.75, 6.43) cm] ( P=0.011), but no significant differences was found in the control group ( P>0.05). Conclusions:The structured exercise intervention has advantages in reducing the decline of healthy physical fitness in patients with leukemia receiving umbilical cord blood transplantation, and exerts a protective effect on healthy physical fitness.

Objective:To evaluate the role of spinal Leucine-rich Repeat Kinase 2 (LRRK2) in neuropathic pain in rats.Methods:Fifty SPF healthy male Sprague-Dawley rats, aged 6-7 weeks, weighing 210-245 g, were divided into 5 groups ( n=10 each) using a random number table method: control group (C group), neuropathic pain group (NP group), low dose GNE-7915 group (low-dose GNE-7915 group), medium-dose GNE-7915 group (medium-dose GNE-7915 group), and high-dose GNE-7915 group (high-dose GNE-7915 group). Neuropathic pain was induced by the spared nerve injury in anesthetized rats. At 7 days after developing the model, LRRK2 inhibitor GNE-7915 12.5, 25.0 and 50.0 mg/kg were intraperitoneally injected in low-, medium- and high-dose GNE-7915 groups, respectively. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before developing the model, at 7 days after developing the model, and at 4 h after injecting the inhibitor. After measurement of the pain threshold, the rats were sacrificed and the spinal cord tissues were taken for determination of the positive expression of ionized calcium-binding adapter molecule 1(Iba-1) (by immunofluorescence staining), contents of interleukin-1β (IL-1β), monocyte chemotactic protein-1 (MCP-1) and IL-18 (by enzyme-linked immunosorbent assay), positive expression of phosphorylated LRRK2 (p-LRRK2) (by immunofluorescence staining), and expression of LRRK2, IL-1β, MCP-1 and IL-18 (by immunoblotting). The ratio of p-LRRK2/LRRK2 was calculated. Results:Compared with C group, the MWT was significantly decreased, the TWL was shortened, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were increased, and the expression of IL-1β, MCP-1 and IL-18 proteins was up-regulated in NP group ( P<0.05). Compared with NP group, the MWT was significantly increased, the TWL was prolonged, the proportion of Iba-1 and p-LRRK2 positive cells in spinal cord tissues, contents of IL-1β, MCP-1 and IL-18, and p-LRRK2/LRRK2 ratio were decreased, and the expression of IL-1β, MCP-1 and IL-18 proteins was down-regulated in low-, medium- and high-dose GNE-7915 groups ( P<0.05). Conclusions:LRRK2 in the spinal cord may be involved in the pathophysiological mechanism of neuropathic pain by activating microglia and inducing inflammatory responses in rats.

Objective:To systematically analyze the efficacy of nasal endoscopic transsphenoidal decompression and glucocorticoid pulse therapy for traumatic optic neuropathy (TON).Methods:PubMed, Web of Science, Cochrane Library, ClinicalTrial.gov, CNKI, Wanfang, China Biomedical and other databases were searched to retrieve clinical studies on endoscopic surgery and hormone therapy for TON since their establishment to November 1, 2020.Two researchers screened the literature and evaluated the quality of the included literatures.The improvement of visual acuity before and after treatment was taken as an effective indicator.RevMan 5.3 statistical software was used for meta-analysis.The sensitivity of the results was analyzed atfer literature exclusion.The publication bias of each study was double checked by funnel plot and Begg test.Results:Eight studies were included, including 7 cohort studies and 1 randomized controlled trial.There was no significant difference between the endoscopic decompression group and glucocorticoid group in the efficiency of visual acuity improvement in the treatment of TON [odds ratio ( OR)=1.65, 95% confidence interval ( CI)∶0.75-3.66, P=0.22], neither in TON patients with residual vision before surgery ( OR=2.17, 95% CI: 0.94-4.98, P=0.07). For nasal endoscopic decompression surgery, early surgery (disease course<7 days) was more effective than late surgery (disease course>7 days) ( OR=4.73, 95% CI: 2.55-8.78, P<0.01). Sensitivity analysis suggested that the results of this literature analysis were not robust.The Begg test showed that there was no literature publication bias. Conclusions:There is no significant difference between nasal endoscopic surgery and glucocorticoid therapy in the treatment of TON.Early endoscopic surgery may help improve visual acuity in patients with residual vision.

Humans ; East Asian People ; Psoriasis/drug therapy* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Treatment Outcome ; Severity of Illness Index

The clinical manifestation of iodine-refractory differentiated thyroid cancer (RAIR-DTC)is resistance to iodine therapy, which can not achieve the therapeutic effect and affect the prognosis of patients. Iodine-refractory thyroid cancer is mainly due to the decrease or disappearance of the expression of sodium-iodine isotransporters, the expression of some thyroid specific genes and the change of signaling pathway caused by some gene mutations. In this paper, the molecular characteristics of RAIR-DTC will be introduced and expounded, hoping to enhance understanding of RAIR-DTC, and provide help for targeted drug therapy of it.

Secondary hyperparathyroidism (SHPT) is the most common complication of chronic kidney disease. It is usually manifested as a series of symptoms such as bone and joint pain, bone deformity, limb numbness and fatigue, which seriously affect the quality of patients’life. Effective therapeutic interventions are very important to reduce the mortality and morbidity of SHPT patients. For most early stage patients, durg therapy combined with adequate dialysis is very effective for disease control, but as the disease progresses, SHPT will enter the irrevesible stage and patients will become resistant to durg therapy. Surgery is the only effective treatment for advanced SHPT. However, there are still some problems such as different surgical methods, unclear surgical indications, higher perioperative risk and recurrence rate, surgery has not been widely used in clinical treatment. Now the present status of surgery treatment of SHPT is introduced in order to provide reference for the further research and development of surgery treatment.

The choice of females to accept or reject male courtship is a critical decision for animal reproduction. Serotonin (5-hydroxytryptamine; 5-HT) has been found to regulate sexual behavior in many species, but it is unclear how 5-HT and its receptors function to regulate different aspects of sexual behavior. Here we used Drosophila melanogaster as the model animal to investigate how 5-HT and its receptors modulate female sexual receptivity. We found that knockout of tryptophan hydroxylase (Trh), which is involved in the biosynthesis of 5-HT, severely reduced virgin female receptivity without affecting post-mating behaviors. We identified a subset of sexually dimorphic Trh neurons that co-expressed fruitless (fru), in which the activity was correlated with sexual receptivity in females. We also found that 5-HT_1A and 5-HT₇ receptors regulate virgin female receptivity. Our findings demonstrate how 5-HT functions in sexually dimorphic neurons to promote virgin female receptivity through two of its receptors.
Animals ; Male ; Female ; Drosophila/physiology* ; Drosophila melanogaster/physiology* ; Serotonin ; Drosophila Proteins/physiology* ; Sexual Behavior, Animal/physiology* ; Transcription Factors ; Nerve Tissue Proteins