Objective:To investigate the effect of dexmedetomidine(DEX)on the polarization of alveolar macrophages in-duced by lipopolysaccharide(LPS)and to explore the related mechanisms.Methods:Rat alveolar macrophages NR8383 were cul-tured in vitro.Experiment one was divided into control group,model group(1 μg/ml LPS),DEX low,medium and high dose groups(1,5,10 mg/kg DEX+10 mg/kg LPS).Experiment two was divided into DEX high dose group(10 mg/kg)and DEX high dose+Colive-lin(JAK2/STAT3 signaling pathway activator)group(10 mg/kg DEX+0.5 μmol/L Colivelin).The morphological changes of rat alveo-lar macrophages NR8383 were observed by inverted microscope;RT-PCR method was used to detect the expression levels of iNOS and Arg1 mRNA in NR8383 cells,and flow cytometry was used to detect the expression levels of CD86 and CD163 proteins in NR8383 cells;Western blot was used to detect the expression levels of surface marker proteins TNF-α,iNOS,SOCS,Arg1,TGF-β and JAK2/STAT3 signaling pathway related proteins in NR8383 cells.Results:Compared with control group,there were a lot of cell debris in the intercellular space of NR8383 in the model group,the proportions of iNOS mRNA,CD86 positive cells,and the expression levels of TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 were significantly increased,the proportions of Arg1 mRNA,CD163 positive cells,and the expression levels of SOCS and TGF-β were significantly reduced(P<0.05);compared with the model group,the NR8383 intercellular cell debris in the DEX low,medium,and high dose groups were decreased,the proportions of iNOS mRNA,CD86 positive cells,and the expression levels of TNF-α,p-JAK2/JAK2,p-STAT3/STAT3 were significantly reduced,the proportions of Arg1 mRNA,CD163 positive cells,and the expression levels of SOCS and TGF-β were significantly increased(P<0.05).The reactivation of the JAK2/STAT3 signal pathway by Colivelin could weaken the role of DEX in LPS induced NR8383 cell polarization.Conclusion:DEX can inhibit the M1 polarization of NR8383 cells induced by LPS,which may be achieved by inhibiting the JAK2/STAT3 signaling pathway.

Objective:To observe any effect of percutaneous tibial nerve stimulation (PTNS) combined with electro-acupuncture on detrusor overactivity after a spinal cord injury.Methods:Forty spinal cord injury survivors with neurogenic detrusor overactivity were randomly assigned to a control group or an observation group, each of 20. Both groups received routine bladder training and electro-acupuncture modulating 3 sacral spinal nerves. The observation group also received 20 minutes of bilateral PTNS five times a week for 8 weeks. The frequency was 10Hz with a pulse width of 200μs. Before and after the treatment, both groups′ urination frequency, incontinence and average daily urine volume were assessed using a urodynamics analyzer, bladder diaries and an incontinence quality of life questionnaire (I-QOL).Results:After treatment, the average involuntary detrusor contraction volume (IDCV), maximum detrusor pressure at filling time (P det·max), bladder compliance (BC), residual volume and the TL value of the electromyogram of the urethral sphincter (LgTLR) had all improved significantly in both groups. The 1st IDCV, BC and LgTLR of the observation group were then significantly better than in the control group, on average, with the average P det·max and residual volume significantly lower than in the control group. The average daily single urine output and I-QOL score of both groups had increased significantly, while the average daily urination frequency and frequency of urinary incontinence had decreased significantly. Both were again significantly better in the observation group. Conclusion:Combining percutaneous electrical stimulation of the tibial nerves with electro-acupuncture can effectively inhibit detrusor overactivity after a spinal cord injury, reducing urinary incontinence.

Objective To analyze the influence of drainage volume on prognosis of acute hydrocephalus(AHC)after aneurysmal subarachnoid hemorrhage(aSAH)by continuous lumbar drainage.Methods A retrospective trial was conducted on 82 AHC patients after aSAH admitted to the First Affiliated Hospital of Chongqing Medical University between January 2017 and January 2022.In 6 months after discharge,modified Rankin Scale(mRS)score was used to evaluate the prognostic outcomes.Univariate and multivariate logistic regression analyses were performed on demographic factors,severity of subarachnoid hemorrhage(SAH)at admission,medical history,cerebral vasospasm,and lumbar drainage data.Then a nomogram prediction model was constructed.Results Univariate analysis found that World Federation of Neurosurgical Societies(WFNS)score,Hunt-Hess grade,modified Fisher grade,time for continuous lumbar drainage,shunt dependence,cerebral vasospasm,and drainage volume were factors affecting the prognosis of the patients.Then logistic regression analysis revealed that high WFNS score(OR:3.25,95％CI:1.11～9.48),high modified Fisher grade(OR:3.66,95％CI:1.08～12.35),shunt dependence(OR:15.56,95％CI:1.22～198.57),and cerebral vasospasm(OR:22.24,95％CI:3.08～160.68)were independent predictors for mRS score,while volume of continuous lumbar drainage(OR:0.57,95％CI:0.40～0.82)was an independent protective factor.ROC curve analysis indicated a good predictive performance of the model(AUC=0.898,95％CI:0.935～0.861).Internal validation through Bootstrap method demonstrated excellent discriminatory ability of the model(C-index=0.950,95％CI:0.904～0.996;adjusted C-index:0.934).Conclusion Increased volume of lumbar drainage is an independent protective factor for poor prognosis following aSAH and can improve the prognosis of SAH patients.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Objective:To observe any effect of dynamic motor instability training on the balance and postural control of stroke survivors.Methods:Forty stroke survivors with poor balance were randomly divided into a control group and an observation group, each of 20. In addition to routine rehabilitation, the observation group was given 20 minutes of dynamic motor instability training, 5 days a week for 8 weeks, while the control group underwent routine rehabilitation for the same length of time. Before and after the intervention, surface electromyogram of the rectus femoris, biceps femoris, and erector spinae were recorded during perturbation. Activation time and the intensity of the anticipatory and complementary postural adjustments (APAs and CPAs) were also observed. Balance and lower limb motor functioning were assessed using the Berg balance scale (BBS), the Fugl-Meyer lower extremity assessment (FMA-LE), and GaitWatch analysis.Results:After the treatment the average activation time of the rectus femoris, biceps femoris in the affected side and those of the biceps femoris [(-84.31±5.74)s] and erector spinae in the intact side in APAs were all significantly shorter in the observation group than in the control group, while the average activation intensity of the rectus femoris and erector spinae was significantly greater. There was no significant difference in the activation intensity of each muscle group in CPAs after the treatment. After the intervention the average BBS score, FMA-LE score, stride length and walking speed of the observation group all were significantly better than the control group′s averages.Conclusions:Supplementing traditional rehabilitation training with dynamic motor instability training can further improve the posture control of stroke survivors and promote recovery of their balance and walking ability.

The prevalence of osteoporosis， osteoarthritis， gouty arthritis， rheumatoid arthritis， and intervertebral disc degeneration is increasing year by year with the growing number of elderly people， and the common clinical manifestations of these diseases include severe pain in different areas， which seriously affects the daily life of the patients. Therefore， how to relieve the pain and reduce the prevalence of bone and joint diseases and improve the quality of life of the patients is a hot spot in the medical field. Studies have confirmed that NOD-like receptor family， pyrin domain-containing protein 3 （NLRP3） inflammasomes， as pattern recognition receptors， are involved in the inflammation， chondrocyte proliferation， osteoblast and osteoclast differentiation， intervertebral disc cell inflammation and scorching， extracellular matrix degradation and apoptosis， mitochondrial dysfunction， endoplasmic reticulum stress， and reactive oxygen species damage， demonstrating close link with the development of bone and joint diseases. Chinese medicine has a long history and demonstrates remarkable therapeutic effects in the treatment of bone and joint diseases. It can mitigate the pathological changes of bone and joint diseases by inhibiting NLRP3 inflammasomes to alleviate the pain， playing a role in preventing and treating these diseases. Therefore， this paper briefly describes the relationship between NLRP3 inflammasomes and the development of bone and joint diseases by reviewing the latest research progress at home and abroad. We summarize the latest studies about the active components， extracts， and compound prescriptions of Chinese medicines in the treatment of bone and joint diseases via regulating NLRP3 inflammasomes. This review is expected to offer new insights into the in-depth research on the pathogenesis and drug treatment of bone and joint diseases and provide a basis for the clinical application of Chinese medicine in the prevention and treatment of such diseases.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

【Objective】 To observe the effect of Xiaozhongzhitong Mixture on ischemia-reperfusion injury of rat skin flaps and p38MAPK-PPARγ/NF-κB signaling pathway. 【Methods】 After flap operation, the survival of rat back flaps and flap survival rate were observed. HE staining, TUNEL staining, and qRT-PCR were used to detect the degree of nuclear destruction, as well as the distribution characteristics and mRNA expression levels of p38MAPK, PPARγ, and Nf-κB in vascular endothelial cells of rat flaps, respectively. 【Results】 The flap survival area in sham operation group was the largest, and it was the smallest in model control group and PPARγ inhibitor group. HE staining and TUNEL staining results showed that the flap tissue cells of rats in model control group and PPARγ inhibitor group were severely damaged and obvious apoptotic cells were seen. In model group, rats’ skin flap tissue cells were arranged in a single layer, and the nucleus was intact and clear. qRT-PCR experiment results showed that compared with model group, the expressions of p38MAPK and Nf-κb in the flap tissue of rats in Xiaozhong Zhicong Mixture group were inhibited (P<0.05), while the expression of PPARγ was increased (P<0.05). When the blocker was added, the expressions of p38MAPK, NF-κB and PPARγ in the flap tissue were further suppressed. 【Conclusion】 Xiaozhongzhitong Mixture can alleviate the infiltration of inflammatory cells in the rat model of skin flap ischemia-reperfusion injury, reduce inflammation and the production of apoptotic cells, thereby alleviating the ischemia-reperfusion injury of skin flaps and promoting the survival of the flaps. The mechanism may be related to the inhibition of p38MAPK-PPARγ/NF-κB signaling pathway.

Objective The purpose of this study was to investigate the protective effect of dexmedetomidine(DEX)on pathological car-diomyocyte hypertrophy.Methods An in vitro cell population was established in neonatal rats.The rats were divided into six groups:control group(C)without serum for 24 h,model group(A)with angiotensin Ⅱ(Ang Ⅱ)for 24 h,dexmedetomidine group(AD)with Ang Ⅱ+DEX(5μmol/L)for 24 h,C'group with serum-free culture for 48 h,A'group with Ang Ⅱfor 24 h,and AD'group with DEX+Ang Ⅱfor 24 h.The morphological changes of cells were observed by immunofluorescence.The protein expressions of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),and myosin heavy chain(β-MHC)were detected by western blot,and the cell activity was detected by CCK-8.Results Compared with group C,the size of cells in group A was larger,and that in group AD was even more significant.Simi-lar observations were found for hypertrophy related proteins.Compared with group C,the expression of ANP,BNP,and βMHC increased in group A,although the increase in AD group was more obvious.CCK-8 detection showed that compared with group C,the activity of group A decreased and that of group AD increased significantly.Compared with the C'group,the expression of hypertrophy-related pro-tein in the A'group was significantly increased,but the expression of ANP and BNP protein in the AD'group was significantly lower than that in the A'group.The differences were statistically significant(P<0.05).Conclusion Dexmedetomidine can alleviate the occur-rence of pathological hypertrophy through compensatory mechanisms similar to physiological myocardial hypertrophy,and may play a role in myocardial protection.

Objective:To discuss the feasibility and safety of modified side overlap with fundoplication by Yamashita (mSOFY) in laparoscopic proximal gastrectomy.Methods:Using the method of descriptive case series study, the clinical data of 9 patients with upper gastric cancer who successfully performed mSOFY anastomosis from March 2022 to October 2022 in the Affiliated Huaian No.1 People's Hospital of Nanjing Medical University were retrospectively analyzed.The reconstruction steps of mSOFY anastomosis are as follows: (1) Make a small incision on the right side of the esophageal stump and in front of the anterior wall of the gastric stump; (2) The 45mm linear cutting stapler is placed into the preset anastomosis of the esophagus and the remnant stomach, and the esophagus is rotated 90° counterclockwise along the axis, so that the right wall of the esophagus is anastomosed with the remnant stomach, and the stomach wall is sutured to the left side of the esophagus; (3) The common opening of esophagus and remnant stomach was sutured with inverted suture; (4)Suture the left and lower sides of the esophagus with the remnant stomach to make the esophagus flat against the stomach wall; (5) Open the sutured common opening: due to the pressure of the false dome, the posterior wall of the lower esophageal segment was compressed into a valve-like structure. We mainly observing the postoperative reflux and nutritional improvement of the patients, and recording the intraoperative situation and postoperative complications.Results:Nine patients with upper gastric cancer who completed laparoscopic proximal gastrectomy (mSOFY anastomosis) did not have conversion to laparotomy or intraoperative / postoperative complications. The operation time was (169.4±10.4) minutes, the anastomotic reconstruction time was (51.7±7.1) minutes, the intraoperative bleeding volume was (98.9±43.4) ml, and the number of lymph nodes dissected was (27.2±6.7). The patient recovered well after operation, without any complaints related to reflux esophagitis. Postoperative gastrointestinal radiography showed that the anastomosis was smooth, without stenosis and leakage. The serum albumin [(41.6±3.4) L vs. (39.9±2.6) L], prealbumin [(211.3±38.6) mg/L vs. (205.3±36.0) mg/L], and hemoglobin levels [(126.7±13.2) g/L vs. (121.0±9.7) g/L] of patients before and one month after surgery have no statistically significant differences (all P>0.05). Conclusion:mSOFY anastomosis can be used as one of the safe and feasible reconstruction methods in laparoscopic proximal gastrectomy.