Objective:To investigate the effect of methylene blue (MB) on motor dysfunction and its mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease (PD) mouse models.Methods:Forty healthy male C57BL/6 mice were randomly divided into 4 groups: control group, model group, low-dose treatment group and medium-dose treatment group ( n=10); PD mouse models were established by intraperitoneal injection of 25 mg/kg/d MPTP for a consecutive 7 d; low-dose treatment group and medium-dose treatment group were pretreated intraperitoneally with MB 2 mg/kg/d or MB 10 mg/kg/d for a consecutive 3 d, respectively; and then, MPTP 25 mg/kg/d+MB 2 mg/kg/d or MPTP 25 mg/kg/d+MB 10 mg/kg/d were injected intraperitoneally into the low-dose treatment group or medium-dose treatment group for a consecutive 7 d (MPTP and MB were given at 12 h of interval). Eight d after modeling, open field experiment, pole climbing experiment and rod rotating experiment were carried out to evaluate the spontaneous movement, coordination, endurance and motor ability. And then, the mice were sacrificed; immunofluorescent staining was used to observe tyrosine hydroxylase (TH) expression in the substantia nigra; Western blotting was used to detect the expressions of TH, α-synuclein, nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-Caspase-1 and Gasdermin D (GSDMD) in the striatum and substantia nigra of mice. Contents of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-18 in the substantia nigra and striatum of mice were detected by ELISA. Results:Compared with the control group, the model group had shortened residence time in rod rotating, prolonged descent time in rod climbing, reduced total movement distance in open field, decreased number of TH-positive cells in the substania nigra, decreased TH protein levels in the substania nigra and striatum, and increased NLRP3, ASC, cleaved-Caspase-1, GSDMD and GSDMD-N protein levels in the substania nigra and striatum, and increased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). Compared with the model group, low-dose treatment group and medium-dose treatment group had prolonged residence time in rod rotating, shortened descent time in rod climbing, increased total movement distance in open field, increased number of TH-positive cells in the substania nigra, and increased TH protein levels in the substania nigra and striatum, decreased NLRP3, ASC, and cleaved-Caspase-1 levels in the substania nigra and striatum, and decreased TNF-α, IL-1β and IL-18 contents in the substania nigra and striatum, with significant differences ( P<0.05). No statistical differences in the above indexes were noted between the low-dose treatment group and medium-dose treatment group ( P>0.05). Conclusion:Low-/medium-dose MB can ameliorate motor dysfunction in PD mouse models, whose mechanism may be related to downregulate NLRP3 inflammasome and inhibit neuroinflammatory response to reduce dopaminergic neuron pyroptosis.

BACKGROUND:Intervertebral disk degeneration is a pathological change caused by a series of complex molecular mechanisms that result in the aging and damage of intervertebral discs,ultimately leading to severe clinical symptoms.Traditional Chinese medicine has unique advantages in the treatment of intervertebral disk degeneration due to its low cost,non-addictive nature,multi-target effects,minimally toxic and side effects,and high patient acceptance. OBJECTIVE:To review the latest research results of traditional Chinese medicine monomer intervention-related signaling pathways in the treatment of intervertebral disk degeneration,describe and analyze the action mechanism of traditional Chinese medicine monomer on intervertebral disk degeneration,and provide a new approach and theoretical basis for future basic research and clinical treatment. METHODS:The first author searched for relevant literature from January 2018 to February 2023 in CNKI,PubMed,VIP,and WanFang using the search terms"intervertebral disc,signal pathway".The articles that did not meet the criteria were excluded after preliminary screening of the titles and abstracts.Finally,72 articles were selected for review and analysis. RESULTS AND CONCLUSION:Traditional Chinese medicine monomers can regulate multiple classical signaling pathways such as Wnt/β-catenin,PI3K/Akt,mTOR,NF-κB,and MAPK.They achieve this by regulating oxidative stress,adjusting the expression of pro/anti-apoptotic proteins in cells,stimulating cellular autophagy function,reducing stimulation of cell inflammatory factors,increasing the expression of extracellular matrix markers,reducing the production of matrix-degrading enzymes,maintaining the synthesis and stability of extracellular matrix,inducing differentiation of mesenchymal stem cells in the nucleus pulposus into nucleus pulposus cells,promoting endogenous repair and reconstruction,controlling apoptosis and aging of nucleus pulposus cells,and increasing the activity of nucleus pulposus cells.These actions improve the microenvironment within the intervertebral disc,maintain the normal physiological function of the intervertebral disc,and delay intervertebral disc degeneration.

Objective:To investigate the feasibility and safety of a treatment system for stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath.Methods:The clinical data of 72 patients with upper urinary calculi admitted to the Second Hospital of Tianjin Medical University from November 2022 to February 2023 were retrospectively analyzed. All patients achieved stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath. There were 50 males and 22 females. The average age was (54.7±12.1) years. Preoperative urine culture was positive in 14 cases, negative in 3 cases (4.2%)with nitrite positive, and 11 cases were negative for urine culture and nitrites but positive of white blood cells (+ + + ). There were 29 cases of renal calculi, 33 cases of upper ureteral calculi, and 10 cases of upper ureteral calculi combined with renal calculi.The mean stone diameter was 17.0(14.0, 24.0)mm. CT value was (1 049.3±258.6)HU. Twenty-four patients carried ureteral stents before operation. A total of 42 cases used ureteral sheaths with diameters of F11/13, and 30 cases used sheaths with diameters of F12/14.During the operation, an infusion pump was used to provide sufficient irrigation pressure. The negative pressure suction was attached to the distal end of the sheath. The flexible head of the sheath was guided to the target renal calyx, to completely aspirate stone fragments. Stone baskets was used in 11 cases during the procedure. The level of ureteral injury was assessed according to the Traxer grading system at the end of the operation. A ureteral stent with extraction string was retained.On the first day postoperatively, CT scanning was performed to evaluate the residual stone fragments. Patients were discharged on postoperative day 2-3 after the removal of the ureteral stent and catheter. Follow-up was conducted for 30 days postoperatively, during which the Ureteral Stent Symptom Questionnaire (USSQ) was used to assess voiding symptoms and pain. Painkiller usage and emergency revisit situations were recorded. CT scans were performed to evaluate the stone-free rate on postoperative day 30.Results:The average operation time was 30.0 (20.0, 44.5) minutes. A total of 70 cases had no ureteral injuries, and 2 cases had Grade 1 ureteral injuries (minor mucosal damage). Three cases developed fever within 72 hours postoperatively, with no cases of septic shock or fever after stent removal. Eight patients reported waist and abdominal discomfort after discharge and took oral pain medication. Among them, one patient returned to the emergency department for pain treatment. Five patients reported moderate or severe genitourinary symptoms (including voiding frequency, nocturia, urgency/incontinence, dysuria, hematuria, and incomplete emptying) based on subjective evaluation. All patients could work and recovered a normal daily life after discharge and there was no readmission or additional surgical procedures. There were 61 patients achieved immediate stone-free status on the first day after surgery, and 66 patients achieved stone-free status during follow-up at 30 days postoperatively.Conclusions:Stentless discharge after flexible ureteroscopic lithotripsy assisted by flexible negative pressure sheath is safe and feasible.

Objective:To establish an index system for frailty risk assessment of maintenance hemodialysis patients, and scientifically evaluate frailty risk status of maintenance hemodialysis patients.Methods:With the biopsychosocial medical model as the theoretical framework, semi-structured interview method and Delphi expert consultation method were used to establish and screen indicators and analytic hierarchy process was used to determine the weight of indicators, and an indicator system for frailty risk assessment of patients with maintenance hemodialysis was constructed.Results:The effective recovery rates of the two rounds of expert consultation questionnaires were respectively 100.00% (22/22) and 95.45% (21/22), the expert authority coefficients were respectively 0.85 and 0.84, the Kendall's harmony coefficients of the importance of expert opinions were respectively 0.149 and 0.201, and the Kendall's harmony coefficients of the feasibility of expert opinions were respectively 0.134 and 0.175. Finally, the frailty risk evaluation system for maintenance hemodialysis patients was established, including 3 primary indexes, 8 secondary indexes and 36 tertiary indexes.Conclusions:The established frailty risk evaluation index system for patients with maintenance hemodialysis is scientific and practical and comprehensive in content, which can better reflect the specialty characteristics and provide a basis for frailty risk assessment for maintenance hemodialysis patients.

Normal tension glaucoma (NTG) is almost the most difficult type of glaucoma to diagnose.The difficulty lies in the lack of specificity of the symptoms and signs of glaucomatous optic neuropathy (GON), so the reevaluation of NTG is a new understanding of GON.As a subtype of primary open-angle glaucoma (POAG), NTG is difficult to accurately conceptualize.One of the reasons is that the intraocular pressure (IOP) is closely linked to the occurrence of GON in POAG but not in NTG.GON seems to be secondary to a number of local or systemic disorders, including vascular dysfunction in the optic nerve head induced by compression (elevated IOP) or ischemia, hypoxia, migraine, Flammer syndrome, intracranial hypotension, low body mass index, low estrogen levels, nocturnal hypotension, obstructive sleep apnea-hypopnea syndrome, Alzheimer disease, Parkinson disease, and genetic background, which may influence the flow in the radial peripapillary capillaries (RPCs) and the underfilling of RPCs causing retinal ganglion cell damage.In some cases, GON does not progress with systemic diseases under control, and these systemic diseases are not risk factors for NTG but may be the cause of GON (or GON is one of the manifestations of these diseases). If these causes are not excluded and NTG is diagnosed only on the basis of GON, chamber angle opening, and normal IOP, it is easy to cause misdiagnosis, and the complete exclusion of these diseases is short of clinical significance in practice.In conclusion, the diagnosis of NTG may not be made before the other ocular or systemic disorders capable of presenting with GON are ruled out, and the concept and diagnostic criteria of NTG should be reconsidered.

Objective:To investigate the predictive value of serum albumin (Alb) levels in the early postoperative period (within 1 hour) for urosepsis after minimally invasive percutaneous nephrolithotomy (mPCNL).Methods:The clinical data of 160 patients treated by single channel holmium laser mPCNL in urolithiasis treatment center of the second hospital of Tianjin Medical University from January 2019 to January 2020 were retrospectively analyzed. The patients were divided into the sepsis group and the non-sepsis group according to whether the patients developed urosepsis after the operation. There were 110 cases of male, and 50 cases of female, with average age of(51.8±11.9), including 68 cases with hypertension, 26 cases with diabetes, 12 patients with history of preoperative fever, 16 cases with history of endoscopic lithotomy surgery, 6 patients with preoperative catheter, 24 patients with positive preoperative urine culture, 12 patients with positive preoperative nitrite volume, 32 cases with preoperative routine urine leucocyte(+ + + ). The operative time and infusion volume were recorded during the operation. Blood samples were collected from all patients within 1 hour after surgery to detect blood routine and serum albumin (Alb), and the change of haemorrhagic white blood cells and serum albumin were calculated. Univariate and multivariate analyses were used to statistically analyze the relevant clinical parameters to identify the independent risk factors for urosepsis after mPCNL surgery. The ROC curve was established and the area under the comparison curve was calculated to analyze the predictive value of independent risk factors for postoperative urosepsis.Results:There were 13 patients (8.1%) in the sepsis group, including 7 males and 6 females, with an average age of (53.1±8.2) years. There were 147 patients (91.9%) in the non-sepsis group, including 103 males and 44 females, with an average age of (51.7±12.1)years. Single factor analysis showed the infectious stones (38.5% and 8.8%), surgery duration [(94.6±26.2)min and(63.6±24.5)min], a positive urine culture (46.2% and 12.2%), positive urinary nitrite (30.8% and 5.4%), strong positive urinary leukocyte (61.5% and 11.3%), postoperative albumin levels [(34.2±2.7)g/L and(40.7±6.2)g/L]and changes of serum albumin levels within one hour after surgery [(18.3±4.6)% and(3.8±14.3)%] between the sepsis group and the non-sepsis group had significant differences ( P<0.05). Multiariable logistic regression analysis showed the strong positive urine leucocyte ( OR=57.704, 95% CI 2.407-1383.427, P=0.012), postoperative blood leucocyte level within one hour after surgery ( OR=2.406, 95% CI 1.154-3.627, P=0.014) and the change of serum albumin levels after surgery ( OR=1.373, 95% CI 1.083-1.740, P=0.009) were independent risk factors for sepsis. ROC curve analysis indicated that the AUC of the change amplitude of serum albumin level was 0.926, which was significantly higher than the AUC of the qualitative results of blood leukocyte and the AUC of urinary leukocyte( P<0.01). Conclusions:The positive urinary leucocyte, the change of serum albumin levels after surgery within one hour and the leucocyte level are independent risk factors for postoperative urosepsis after mPCNL. The change of serum albumin level in the early postoperative period has a strong predictive value for the early diagnosis of postoperative sepsis.

Objective: To make a preliminary assessment on the immunogenicity of a quadrivalence recombinant human papillomavirus (HPV) vaccine (6, 11, 16 and 18 types) (Hansenulapolymorpha) in healthy women aged 18-45 years in phaseⅠclinical study. Methods: It was a single-center, double-blind, randomized, placebo-controlled phaseⅠ clinical study. Women aged 18-45 years were randomized (2∶1) to receive HPV vaccine (n=60) or placebo control (n=30) at months 0, 2 and 6. Antibodies against HPV6/11/16/18 were detected by pseudovirus-based neutralisation assay in serum samples collected at 0 d, 180 d and 210 d. Seroconversion rates and geometric mean titres (GMT) of antibodies against the four types of antigens were calculated. Results: Seroconversion rates of the vaccination group at 180 d (before the third dose) and 210 d (one month after the third dose) were generally similar and between 85%-100% for all types of antibodies. The GMT of antibodies at one month after the last dose improved significantly compared with those before immunization. Conclusions These results showed that the HPV vaccine had good immunogenicity in the population of healthy women aged 18-45 years. Higher antibody titers were elicited by the vaccine compare with the tites before the first dose and in the placebo control group.

Objective To investigate intestinal cleaning status of the patients undergoing colonoscopy,and to analyze the potential influential factors.Methods A total of 340 patients undergoing colonoscopy in the endoscopy center of a Class Ⅲ Grade A hospital in Beijing from January to September 2017 were recruited into this study by convenience sampling method.The patients' general situation,disease condition,dietary and the implementation of bowel preparation were recorded.The intestinal cleaning status was scored according to the Boston Bowel Preparation Scale (BBPS).Results Of the 340 patients included in this study,67.9％ had adequate bowel preparation,and the other 32.1％ had not.Logistic regression analysis showed that male (OR=2.514),abdominal surgery history (OR=2.145),diabetes mellitus (OR=2.091),lunch at noon (OR=3.381) were the influential factors of intestinal cleanliness.Conclusions At present,the intestinal cleaning status is unsatisfactory.Medical staff should pay attention to male,patients with abdominal surgery history or diabetes mellitus,so as to have a better quality for the bowel preparation.

Objective To investigate the risk factors and prognosis of perioperative myocardial infarction in the patients undergoing noncardiac surgery. Methods Clinical data of 562 patients who had accepted non-cardiac surgery was collected and retrospectively analyzed. The risk factors, treatments and outcomes of all these patients were recorded and analyzed. Results A total of 19 out of the 562 patients had perioperative myocardial infarction ( PMI) . The incidence was 3. 4% . The mean occurrence time was (43. 5 ± 12. 7)h after operation. Eleven PMI patients (11 ∕ 19) were non-ST-segment elevation myocardial infarction and eight patients (8 ∕ 19) were ST-segment elevation myocardial infarction. Thirteen PMI patients were left coronary artery occlusion and six patients were right coronary artery occlusion. Advanced age, history of myocardial infarction, unstable angina, change of ST-T segment on electrocardiography (ECG), multivessel diseases, diabetes,hypertension,and high risk non-cardiac surgery were the risk factors of PMI and positively correlated to PMI. Sixteen PMI (16 ∕ 19) patients accepted PCI treatment and three patients (3 ∕ 19) accepted drug conservative treatment. Two patients had unstable angina attack after treatment and one patient had arrhythmia. The heart function in two patients decreased by one or more than one class within the follow up of 1 year. No patient had recurrent acute myocardial infarction or deceased during follow-up. Conclusions Many factors could lead to PMI. Making preoperative assessment, recognizing patients of high risks and dealing with patients who had PMI in time was necessary.

Objective To compare the rates of major adverse cardiovascular events(MACE)and bleeding events of three different antiplatelet strategies during temporary withdrawal of antiplatelet therapy for non-cardiac surgery within 1 year after drug-eluting stent (DES)implantation.Methods Retrospectively analyzed 42 patients who had accepted non-cardiac surgery and required temporary withdrawal of antiplatelet therapy within 1 year after drug-eluting stent implantation. The patients were divided into three groups according to the bridging antiplatelet strategies they received.All patients discontinued clopidogrel 5 to 7 days before the non-cardiac surgery. The tirofiban group was treated with intravenous tirofiban 0.4ug/kg·min in the first 30 min followed 0.1μg/(kg·min). The dosage was reduced by half for patients whose Creatinine clearance were less than 30 ml/min.The low molecular weight heparin group was treated with subcutaneous enoxaparin (Clexane 4000 AxaIU, once per day) .The asprin group was given only oral asprin(100 mg, once per day) . Tirofiban and low molecular weight heparin were continued until clopidogrel was resured. Perioperative cardiovascular events and serious bleeding were recorded. Results The rates of major adverse cardiac events in the tirofiban and the low molecular weight heparin group were lower than the aspirin group. Acute myocardial infarction caused by confirmed in-stent thrombosis was diagnosed in one patient in the aspirin group. One case of asymptomatic ST-T changes was found in the low molecular weight the aspirin group. 3 cases in the aspirin group presented ST-T changes on ECG and among them 1 case was STEMI due to LAD thrombosis requiring primary and 2 other cases were agina pectoris.There were no significant differences in bleeding events among the three groups.Conclusions Potential for the perioperative management with tirofiban or low molecular weight heparin is safe and feasible for patients who had recently undergone DES implantation and required noncardiac surgery with the interruption of antiplatelet therapies.