Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

【Objective】 To statistically analyze the relationship between homologous recombination repair deficiency (HRD) score and clinicopathological characteristics, genomic mutations in patients with high-risk and metastatic hormone-sensitive prostate cancer (mHSPC) and the prognostic predictive value in mHSPC. 【Methods】 A total of 127 patients diagnosed with high-risk prostate cancer and mHSPC, treated at the Department of Urology of Chinese PLA General Hospital during Dec.2021 and Nov.2023 were enrolled.Homologous recombination repair (HRR) gene sequencing was performed, and the genomic scar score (GSS) algorithm were conducted to calculate the HRD score.The relationship between HRD scores and clinicopathological features, genomic alterations, and prognosis were analyzed. 【Results】 The median HRD score was 1.6(0.8, 5.2), 30(23.6%) patients’ HRD scores ≥10, and 11(8.7%) patients’ HRD scores ≥20.Clinicopathological features, including ISUP classification ≥4 (P=0.044) and metastatic status (P=0.008) were associated with high HRD score.Patients with mutations in the BRCA, TP53 and MYC systems had significantly higher HRD score than those with wild-type genes (P<0.05).In mHSPC, the risk of biochemical recurrence was 12.836 times higher in patients with HRD score ≥20 than in those with <20 [OR:12.836 (1.332-124.623), P=0.028]. 【Conclusion】 Baseline HRD score was lower in patients with high-risk prostate cancer and mHSPC.Patients with high HRD score may have higher histological grading (ISUP≥4) and later clinical stage.Further investigation is needed to determine the threshold of HRD scores as biochemical markers suggestive of a poor prognosis.

Humans ; Asthma/drug therapy* ; Biological Therapy

Humans ; Nitric Oxide ; Carcinoma, Non-Small-Cell Lung/drug therapy* ; Lung Neoplasms ; Lung ; Nitric Oxide Synthase ; Macrophages, Alveolar ; Pulmonary Alveoli

Objective:To explore the effect of enhanced recovery nursing based on traditional Chinese medicine nursing operation technology in the perioperative period of elderly patients with total hip arthroplasty.Methods:From January 2020 to December 2021, 90 patients with unilateral total hip arthroplasty in Wenzhou Traditional Chinese Medicine Hospital were selected by convenience sampling as research objects. The patients from January to December 2020 were taken as the control group ( n=43) , and the patients from January to December 2021 were taken as the observation group ( n=47) . The patients in the control group adopted the traditional orthopedic perioperative nursing, while the patients in the observation group received the enhanced recovery perioperative nursing based on traditional Chinese medicine nursing operation technology on the basis of the control group. The pain, postoperative recovery and complications were compared between the two groups. Results:The time of first exhaust, eating, getting out of bed and hospital stay after operation in the observation group were shorter than those in the control group, the Visual Analogue Scale (VAS) score at discharge was lower than that in the control group, and the incidence of postoperative gastrointestinal reactions and postoperative urinary retention were lower than those in the control group, with statistically significant differences ( P<0.01) . Conclusions:The enhanced recovery nursing based on traditional Chinese medicine nursing operation technology applied to elderly patients with unilateral total hip arthroplasty during perioperative period can reduce postoperative complications, pain and hospital stay, which is worthy of clinical promotion.

Objective:To evaluate the efficacy of holographic image technology in robot-assisted laparoscopic radical prostatectomy (RARP).Methods:The clinical data of 34 patients with prostate cancer who underwent RARP in our hospital during October 2020 and December 2020 was analyzed retrospectively. The average age of the patients was 67.8 (52-78) years. The mean BMI was 25.8 (18.0-32.3) kg/m 2. The median level of PSA before surgery was 13.4 (2-149) ng/ml. Median prostate volume was 31.7 (9.5-159.1) ml. EAU risk groups for biochemical recurrence of localised and locally advanced prostate cancer were list as below: 5 cases of low-risk, 7 cases of medium-risk, 22 cases of high-risk. There were 9, 16, 9 cases with the ASA score of 1, 2, 3 point, respectively. Preoperative Gleason score of 34 patients were list as below: 9 cases in score ≤6 group, 15 cases in score=7 group, 10 cases in score ≥8 group. For clinical stage before the surgery, 13 cases ≤T 2a stage, 1 case in T 2b stage, 20 cases ≥T 2c stage. The engineers established holographic images of 34 patients based on multiparametric magnetic resonance imaging (mpMRI) and the reports before the operation. Surgeons can obtain the size and location of tumors, surrounding neurovascular bundles visually by revolving, assembling, disassembling and concealing images, which was helpful for pre-surgery planning. By manipulating the holographic images extracorporeally, surgeons can discriminate Internal sphincter of urinary bladder and vesicoprostatic muscle, neurovascular bundles, membranous part, seminal vesicle easily, which improves the operation accuracy. Results:All 34 cases underwent operation successfully without transferring to open surgery. The median operative time was 157.5 (95-276) min with an estimated blood loss of 50 (20-300) ml. The median drainage removal time was 2 d and median hospitalization time was 3.5 d, respectively. The catheters were removed within an average time of 20.5 d. For postoperative Gleason score, there were 2 cases in score ≤6 group, 16 cases in score =7 group, 8 cases in score ≥8 group and 8 cases can’t make a score. For clinical stage after the surgery, 10 cases were ≤T 2a stage, 1 case was T 2b stage, 23 cases were ≥cT 2c stage. 22 cases underwent pelvic lymph node dissection, including a patient with right iliac fossa lymph node metastasis. There were 2 cases with positive surgical margin and 3 cases with Clavien-DindoⅠcomplications. The rate of 1-month and 3-month urinary continence were 47.1% and79.4%, respectively, 8 cases recovered erectile function after 3 month. Conclusions:Holographic image technology can promote cancer dissection completely, achieve urinary continence early and reduce perioperative complications tremendously. The technology is the "intraoperative security" for the accurate surgical treatment of prostate cancer.

PURPOSE: Details of patients hospitalized for asthma exacerbation in mainland China are lacking. To improve disease control and reduce economic burden, a large sample survey among this patient population is indispensable. This study aimed to investigate the clinical characteristics and outcomes of such patients.METHODS: A retrospective study was conducted on patients hospitalized for asthma exacerbation in 29 hospitals of 29 regions in mainland China during the period 2013 to 2014. Demographic features, pre-admission conditions, exacerbation details, and outcomes were summarized. Risk factors for exacerbation severity were analyzed.RESULTS: There were 3,240 asthmatic patients included in this study (57.7% females, 42.3% males). Only 28.0% used daily controller medications; 1,287 (39.7%) patients were not currently on inhaled corticosteroids. Acute upper airway infection was the most common trigger of exacerbation (42.3%). Patients with severe to life-threatening exacerbation tended to have a longer disease course, a smoking history, and had comorbidities such as hypertension, chronic obstructive pulmonary disease (COPD), and food allergy. The multivariate analysis showed that smoking history, comorbidities of hypertension, COPD, and food allergy were independent risk factors for more severe exacerbation. The number of patients hospitalized for asthma exacerbation varied with seasons, peaking in March and September. Eight patients died during the study period (mortality 0.25%).CONCLUSIONS: Despite enhanced education on asthma self-management in China during recent years, few patients were using daily controller medications before the onset of their exacerbation, indicating that more educational efforts and considerations are needed. The findings of this study may improve our understanding of hospital admission for asthma exacerbation in mainland China and provide evidence for decision-making.
Adrenal Cortex Hormones ; Asthma ; China ; Comorbidity ; Disease Progression ; Education ; Female ; Food Hypersensitivity ; Hospitalization ; Humans ; Hypertension ; Inpatients ; Medication Adherence ; Mortality ; Multivariate Analysis ; Pulmonary Disease, Chronic Obstructive ; Retrospective Studies ; Risk Factors ; Seasons ; Self Care ; Smoke ; Smoking

Objective To evaluate the general level of asthma management in urban areas of China and further promote the national asthma management plan. Methods A multi-center, cross-sectional survey was carried out in 30 provinces of China (except for Tibet) during Oct 2015 to May 2016. It's a questionnaire-based face-to-face survey which included asthma management using peak flow meter (PFM) and pulmonary function test,medication choice of maintenance therapy and asthma education.Results A total of 3 875 asthmatic outpatients were recruited including 2 347(60.6%)females and 1 528(39.4%)males. The mean age was(50.7±16.7)years ranging from 14 to 99.Only 10.1%(388/3 837)patients used PFM as monitoring, whereas 62.1%(2 405/3 874) patients underwent pulmonary function test during the past year. There were 57.4%(2 226/3 875) patients treated with inhaled cortical steroid plus long-acting β2-agonist combinations (ICS+LABA) as daily medication. 43.3%(1 661/3 836) patients were followed up by physicians. Among this population, 1 362 asthmatic outpatients were recruited, who also took part in the asthma control survey in 2007-2008 in 10 cities.In this subgroup,17.9%(244/1 360)were tested by PFM and 66.6%(907/1 362)by pulmonary function test during last year.As to the medication,63.1%(860/1 362) selected ICS+LABA for daily control. There were 50.4%(685/1 359) patients in the follow-up cohort by physicians.Compared to the similar survey conducted in 2007-2008,the proportion of patients with ICS+LABA regimen and follow-up by physicians were markedly higher,while the rate of PFM use did not have significant improvement. Conclusion Although the present level of asthma management in China is still far from ideal, asthma management has improved compared to 8 years ago. Yet the use of PFM does not significantly improve.Asthma action plan and application of PFM should be further promoted to improve the level of asthma management.

OBJECTIVETo establish a chronic obstructive pulmonary disease (COPD) model by passive cigarette smoking and (or) intratracheal instillation of lipopolysaccharide (LPS) in spontaneously hypertensive (SH) rats.

METHODSFifteen male SH rats were randomly divided into control group, cigarette smoking exposure (CS) group and CS+LPS (cigarette smoking exposure plus intratracheal instillation of LPS) group. After 8 weeks' treatment, the COPD model was validated by inspecting the general condition and examining lung function and pulmonary pathological changes. The expressions of surfactant-associated protein A (SP-A), NF-κB, histone, p-Iκ-Kα/β, Iκ-Kα/β, and IκB-α were determined with Western blotting, and the expression of TNF-α and IL-6 mRNA were measured using qRT-PCR.

RESULTSThe rats in both CS and CS+LPS groups were marantic with intermittent cough and tachypnea. Lung function test showed increased RI and lowered peak expiratory flow in CS group, which were more prominent in CS+LPS group (P<0.05). HE staining demonstrated typical chronic bronchitic inflammation and emphysema in the lungs of the two model groups with significantly decreased mean alveolar number and significantly increased mean lining intermittent and destruction index. The emphysema level was more serious in CS+LPS group than in CS group. Western blotting showed markedly decreased expressions of SP-A and IκB-α in CS group and CS+LPS , especially the latter group. The protein levels of NF-κB, Iκ-K phosphorylation and mRNA expressions of TNF-α and IL-6 increased obviously in the two model groups.

CONCLUSIONCOPD model can be established by passive smoking and (or) intratracheal instillation of LPS in SH rats, and the model induced by combined exposures is optimal.

Animals ; Disease Models, Animal ; Lipopolysaccharides ; adverse effects ; Male ; Pulmonary Disease, Chronic Obstructive ; etiology ; Rats ; Rats, Inbred SHR ; Tobacco Smoke Pollution ; adverse effects

Objective To establish a chronic obstructive pulmonary disease (COPD) model by passive cigarette smoking and (or) intratracheal instillation of lipopolysaccharide (LPS) in spontaneously hypertensive (SH) rats. Methods Fifteen male SH rats were randomly divided into control group, cigarette smoking exposure (CS) group and CS+LPS (cigarette smoking exposure plus intratracheal instillation of LPS) group. After 8 weeks' treatment, the COPD model was validated by inspecting the general condition and examining lung function and pulmonary pathological changes. The expressions of surfactant-associated protein A (SP-A), NF-κB, histone, p-Iκ-Kα/β, Iκ-Kα/β, and IκB-αwere determined with Western blotting, and the expression of TNF-αand IL-6 mRNA were measured using qRT-PCR. Results The rats in both CS and CS+LPS groups were marantic with intermittent cough and tachypnea. Lung function test showed increased RI and lowered peak expiratory flow in CS group, which were more prominent in CS+LPS group (P<0.05). HE staining demonstrated typical chronic bronchitic inflammation and emphysema in the lungs of the two model groups with significantly decreased mean alveolar number and significantly increased mean lining intermiment and destrction index. The emphysema level was more serious in CS+LPS group than in CS group. Western blotting showed markedly decreased expressions of SP-A and IκB-αin CS group and CS+LPS , especially the latter group. The protein levels of NF-κB, Iκ-K phosphorylation and mRNA expressions of TNF-α and IL-6 increased obviously in the two model groups. Conclusion COPD model can be established by passive smoking and (or) intratracheal instillation of LPS in SH rats, and the model induced by combined exposures is optimal.