ObjectiveToll-like receptor 4 （TLR4）， a receptor for pathogen-associated molecular patterns of innate immunity， is associated with neurodegenerative diseases. Interleukin （IL）-6， IL-1β， and tumor necrosis factor-α （TNF-α） as common pro-inflammatory cytokines and high-sensitivity C-reactive protein （hs-CRP） are related to inflammatory responses. This study evaluated the clinical efficacy and possible mechanisms of therapeutic effects of Fengyintang on early and mid-stage PD with excessive heat generating wind by observing the effects of Fengyintang on the serum levels of TLR4， IL-6， IL-1β， TNF-α， and hs-CRP in the patients with PD. MethodsSixty-eight PD patients who met the inclusion criteria were randomly assigned into the control group and the observation group （n=34）. Both groups were treated with anti-PD Western medicine and the observation group was additionally treated with Fengyintang. Both groups were treated for 8 weeks. Before and after 8 weeks of treatment， the patients in the two groups were measured for their TCM symptom scores， International Movement Disorder Society Unified Parkinson's Disease Rating Scale （MDS-UPDRS） score， Parkinson's Disease Non-Motor Symptom Scale （NMSS） score， Patient Assessment of Constipation Symptom （PAC-SYM） score， Pittsburgh Sleep Quality Index （PSQI）， Hamilton Anxiety Scale （HAMA） score， Hamilton Depression Scale （HAMD） score， and changes in serum TLR4， IL-6， IL-1β， TNF-α， and hs-CRP levels. ResultsOne case in the control group was removed due to loss of visit， and a total of 67 PD patients （33 in the control group and 34 in the observation group） who met the criteria were included for analysis. After treatment， patients in the observation group showed decreases in scores of TCM symptoms， MDS-UPDRS， NMSS， PAC-SYM， PSQI， HAMA， and HAMD （P<0.05， P<0.01）. Moreover， the observation group had lower scores of TCM symptoms， MDS-UPDRS， NMSS， PAC-SYM， PSQI， HAMA， and HAMD than the control group （P<0.05， P<0.01）. The observation group showed higher efficacy in terms of TCM symptoms and MDS-UPDRS score than the control group （Z=-0.57， P<0.05）. The overall response rate was higher in the observation group than in the control group （Z=-0.62， P<0.05， P<0.01）. The serum TLR4， TNF-α， IL-1β， IL-6， and hs-CRP levels of the observation group were lower than those of the control group （P<0.05， P<0.01）. ConclusionFengyintang combined with Western medicine can safely and effectively alleviate the clinical symptoms， reduce the levels of inflammatory factors， improve the quality of life， and delay the disease progression of PD patients by inhibiting peripheral TLR4 expression and thus suppressing the downstream inflammatory response.

Background: Bushen Zhuanggu Formula (BZF), derived from the classic Yougui Pills, has shown favorable clinical efficacy in treating advanced nontraumatic osteonecrosis of the femoral head (NONFH), particularly by promoting bone repair. However, its underlying mechanisms remain unclear. Objective: This study aimed to explore the mechanisms by which BZF promotes bone repair in advanced NONFH. Materials and methods: A total of 518 potential BZF targets were identified from the ETCM v2.0 database. Transcriptomic profiling of clinical cohorts revealed 485 differentially expressed genes in advanced NONFH patients compared to healthy controls. A drug target-disease gene interaction network was constructed to identify candidate BZF targets involved in NONFH pathogenesis. In vivo experiments were conducted to validate the effects of BZF in a rat model of advanced NONFH. Results: Network analysis identified key pathways associated with blood circulation obstruction, immune-inflammatory imbalance, and abnormal bone metabolism. Protein kinase C alpha (PKCA), Ras proto-oncogene (RAS), mitogen-activated protein kinase 3(ERK), ETS proto-oncogene 1 (ETS1), and receptor activator of nuclear factor-κB ligand (RANKL) formed a signaling axis implicated in NONFH pathogenesis. BZF treatment alleviated joint inflammation, preserved trabecular bone morphology, reduced bone loss, and promoted bone repair. Mechanistically, BZF significantly downregulated the expression of PKCA, RAS, ERK, ETS1, and RANKL, improved blood circulation, and inhibited osteoclast activation while promoting osteoblast activation. Conclusion: BZF may promote bone repair in advanced NONFH by enhancing blood circulation and modulating the PKC-RAS-ERK-ETS1-RANKL signaling axis, thereby reversing dysregulated bone metabolism.

ObjectiveTo discuss the correlation between young patients’ adverse transfusion reaction and pre-transfusion C reactive protein （CRP） level and EO% （percentage of eosinophils） . MethodsThe observation group was chosen from among sixty-six young patients who experienced transfusion-related adverse events between January 2019 and December 2020. For each patient chosen to be included in the observation group， another patient from the same department， with the same disease and gender， who had been hospitalized in the same month and received the same type of blood product transfusion， but had not experienced any transfusion-related adverse effects， was chosen to be in the control group. We examined and compared their ages， transfusion experiences， allergy backgrounds， EO%， and CRP levels in peripheral blood prior to transfusion. A receiver operating characteristic （ROC） curve was used to examine the diagnostic value of EO% and CRP for transfusion-related adverse events. Simultaneously， a logistic analysis was performed on the risk factors for transfusion-related adverse events. ResultsPre-transfusion CRP was higher in patients with FNHTR in the observation group than it was in patients in the control group； pre-transfusion CRP was also higher in patients with ATR in the observation group than it was in patients in the control group. There were also statistically significant differences between these variables in the percentage of patients with transfusion history and pre-transfusion EO% （ P＜0.05）. For the transfusion of different blood types， there was statistical significance in the occurrence of ATR and FNHTR （ P＜0.05）. For the diagnosis of FNHTR， the CRP area under the ROC curve was 0.889， and the best cut-off value was 18.05 mg/L. For the diagnosis of ATR， the area under the ROC curve was 0.749， and the best cut-off values were 17.60 mg/L. ConclusionPre-transfusion C-reactive protein level is an independent risk factor for FNHTR and ATR in young patients； the predictive value of EO% for adverse blood transfusion reactions is insufficient.

Objective:To evaluate the effect of obesity on the dose-effect relationship of remimazolam when combined with alfentanil in painless gastroscopy.Methods:American Society of Anesthesiologists physical status Ⅰor Ⅱ patients of both sexes, scheduled for elective painless gastroscopy, aged 18-64 yr, were divided into 2 groups according to the body mass index (BMI): normal (BMI 19-24 kg/m 2) group and obese (BMI≥28 kg/m 2) group.Alfentanil 5 μg/kg combined with remimazolam was given intravenously in all the patients, and the dose of remimazolam was determined by the modified Dixon′s up-and-down method.The initial dose of remimazolam was 0.25 mg/kg, and each time the dose was increased or decreased by 0.05 mg/kg based on the sedative effect.The response was defined as positive when the responses that affected the operation of examination developed during insertion of the gastroscope and within the first 2 min of examination such as swallowing, bucking or body movement.This process was repeated until the seventh intersection occurred.The 50% effective dose (ED 50), 95% effective dose (ED 95), and 95% confidence interval ( CI) of remimazolam were calculated by probit method. Results:There were 26 patients in normal group and 18 patients in obese group.The ED 50 (95% CI) of remimazolam was 0.196 (0.087-0.274) mg/kg, and the ED 95 (95% CI) was 0.322 (0.256-1.397) mg/kg in normal group.The ED 50 (95% CI) of remimazolam was 0.125 (0.102-0.148) mg/kg, and the ED 95 (95% CI) was 0.161 (0.141-0.242) mg/kg in obese group.The ED 50 and ED 95 were significantly lower in obese group than in normal group ( P<0.001). Conclusions:Obesity increases the potency of remimazolam when combined with alfentanil 5 μg/kg in the patients undergoing painless gastroscopy.

Objective:To evaluate the efficacy of remimazolam-alfentanil-mivacurium for fiberoptic bronchoscopy.Methods:A total of 100 patients of both sexes, aged 18-64 yr, with body mass index of 18.5-28.0 kg/m 2, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective fiberoptic bronchoscopy, were divided into 2 groups ( n=50 each) using a random number table method: remimazolam-alfentanil-mivacurium group (group R) and propofol-alfentanil-mivacurium group (group P). Oxygen was inhaled by mask, and alfentanil 10 μg/kg was slowly injected intravenously in advance.One minute later, remimazolam 0.2 mg/kg was injected intravenously in group R, propofol 1.5-2.0 mg/kg was injected in group P until loss of consciousness, and mivacurium 0.14 mg/kg was then injected intravenously in 2 groups.When the bispectral index value was 40-60, mechanical ventilation was performed after laryngeal mask was placed by the same anesthesiologist.During the maintenance of anesthesia, remimazolam 1 mg·kg -1·h -1 was infused intravenously in group R, propofol 4-6 mg ·kg -1·h -1 was infused intravenously in group P, and mivacurium was intermittently injected in both groups to maintain muscle relaxation.Before induction (T 0), when the laryngeal mask was placed (T 1), immediately when fiber bronchoscope reached juga (T 2), at 10 min after the surgery (T 3), at the end of the surgery (T 4) and when patients regained consciousness (T 5), blood pressure (BP), (HR), pulse oxygen saturation (SpO 2), breathing at the end of the CO 2 partial pressure (P ETCO 2), BIS values and Modified Observer's Assessment/Alertness and Sedation (MOAA/S) score were recorded.The time from beginning of anesthesia to beginning of examination, total examination time, the time from the end of administration to laryngal mask airway removal, the time to recovery of spontaneous breathing and the time from emergence to discharge from postanesthesia care unit (PACU) were recorded.The occurrence of intraoperative and postoperative adverse reactions was recorded. Results:There was no significant difference in SpO 2, P ETCO 2, BIS values and MOAA/S score at each time pint and the time from beginning of anesthesia to beginning of examination, the time to recovery of spontaneous breathing and the time from emergence time to discharge from PACU between the 2 groups ( P>0.05). Compared with group P, systolic blood pressure and diastolic blood pressure were significantly increased at T 1, T 3 and T 4, the time from the end of administration to laryngal mask airway removal was prolonged, the incidence of intraoperative hypotension, postoperative cough and total adverse reactions were decreased in group R ( P<0.05). Conclusion:Remimazolam-alfentanil-mivacurium produces better efficacy than propofol-alfentanil-mivacurium for fiberoptic bronchoscopy.

Objective To evaluate the role of poly( ADP-ribose) polymerase-1 ( PARP-1) in lung ischemia-reperfusion ( I/R ) injury in rats and the relationship with autophagy. Methods Twenty-four clean-grade healthy male Sprague-Dawley rats, aged 8-12 weeks, weighing 200-240 g, were divided into 3 groups (n=8 each) using a random number table method: sham operation group (S group), lung I/R group ( I/R group) and lung I/R plus PARP-1 inhibitor PJ34 group ( I/R+PJ34 group) . The chest was only opened without clamping the left hilum of lung in group S. Lung I/R injury model was established by clam-ping the left hilum of lung for 45 min followed by 120 min reperfusion in I/R and I/R+PJ34 groups. PJ3410 mg/kg was intraperitoneally injected at 30 min before ischemia in group I/R+PJ34, while the equal volume of normal saline was injected in S and I/R groups. The rats were sacrificed at the end of reperfusion, and lungs were removed for microscopic examination of the pathological changes ( with a light microscope) which were scored and for determination of wet to dry weight ratio ( W/D ratio) , cell apoptosis ( by TUNEL) , ex-pression of PARP-1 activity markers ( PAR) , Bcl-2, Bax, microtubule-associated protein 1 light chain 3Ⅰ ( LC3-Ⅰ) , LC3-Ⅱ and Beclin-1 ( using Western blot ) . The apoptosis index, Bcl-2/Bax ratio and LC3-Ⅱ/LC3-Ⅰ ratio were calculated. Results Compared with S group, the W/D ratio, pathological scores, apoptosis index and LC3-Ⅱ/LC3-Ⅰ ratio were significantly increased, the expression of PAR and Beclin-1 was up-regulated, and Bcl-2/Bax ratio was decreased in I/R and I/R+PJ34 groups (P＜0. 05). Compared with I/R group, the W/D ratio, pathological scores, apoptosis index, and LC3-Ⅱ/LC3-Ⅰratio were significantly decreased, the expression of PAR and Beclin-1 was down-regulated, and Bcl-2/Bax ratio was increased in I/R+PJ34 group ( P＜0. 05) . Conclusion PARP-1 activation is involved in lung I/R inju-ry in rats, and the mechanism may be related to increasing autophagy and inducing cell apoptosis.

Objective: To evaluate the post-marketing safety profiles of the inactivated enterovirus type 71 (EV-A71) vaccine (Vero cell) after routine inoculation. Methods: Eleven cities of Zhejiang Province, Fengtai district of Beijing, Qinnan district, two counties as Pingle and Pingguo of Guangxi Zhuang Autonomous Region, and Dongtai city of Jiangsu Province were selected as the field sites. A total of 45 239 subjects were enrolled in this study from children who seeked the vaccination of EV-A71 vaccine during the period from July, 2016 to June, 2018. Different sampling method were adopted in different sites. All vaccinated children were invited to participate in the study in Fengtai and Dongtai, however, systematic sampling method were adopted in other sites. Active surveillance was conducted and information about adverse reactions (ARs) occurred in 30 min, 3 d and 30 d following each dose of EV-A71 immunization was collected by field observation, phone-call or face-to-face interview. The incidence of ARs in different types, symptoms and grades were described. Results: In total, there were 45 239 children who received 71 243 doses EV-A71 vaccine. The overall incidence of ARs was 1.079% (769 doses), with the highest incidence of 1.182% (177/14 973) in 5-11 month group and the lowest incidence of 0.849% (18/2 119) in ≥ 36 month group among different age groups. There was a higher incidence in solicited ARs, which was 1.047% (746 doses). The incidences of grade 1 and grade 2 ARs were also higher, which were 0.404% (288 doses) and 0.554% (395 doses), respectively. No grade 4 ARs occurred. The doses of the first and the second vaccination was 40 736 and 30 507, respectively, and the incidences of ARs were 1.281% (522 doses) and 0.810% (247 doses). Also, the incidences of ARs were 0.091% (37 doses) and 0.043% (13 doses) in local, and 1.168% (476 doses) and 0.760% (232 doses) in system. The symptoms of ARs after the two doses of vaccination were basically the same. Redness at the injection site was the most common local ARs after each dose vaccination, with doses of 24 and 11, while fever was the most common systemic ARs, with doses of 362 and 190. Moreover, ARs mainly occurred in 30 min to 3 d after each dose vaccination, with incidence of 1.016% (414 doses) and 0.698% (213 doses) in the first and second dose, respectively. Conclusion The ARs had a low incidence after vaccination in children and most were mild or moderate. EV-A71 vaccine with good safety is suitable for inoculation in a large scale.

Objective To evaluate the anesthetic efficacy of propofol used to supplement spinal anesthesia for sedation in the pediatric patients undergoing lower abdominal or lower extremity operations.Methods One hundred twenty pediatric patients of both sexes, aged 2-5 yr, weighing 11-21 kg, of ASA physical status Ⅰ or Ⅱ , scheduled for elective lower abdominal or lower extremity operations were randomly divided into 3 groups (n =40 each) using a random number table: general anesthesia group (group G), propofol used to supplement caudal block for sedation group (group PS+CB) , and propofol used to supplement spinal anesthesia for sedation group (group PS+SA).In group G, after induction of anesthesia, laryngeal mask airway was inserted, the patients were then mechanically ventilated, and anesthesia was maintained with iv infusion of propofol (5-7 mg· kg-1 · h-1), remifentanil (20-25 μg· kg-1 · h 1) and cisatracurium besylate (0.1 mg· kg-1 · h 1).In group PS+CB, caudal block was performed with the mixture 0.8 ml/kg of 1％ lidocaine and 0.25％ bupivacaine.In group PS+SA, spinal anesthesia was performed with isobaric bupivacaine 1.0 mg/age.Propofol was then infused at 3-5 mg · kg-1 · h-1 for sedation in PS+CB and PS+SA groups.Before anesthesia (baseline, T0) and at 1, 5 and 10 min after emergence from anesthesia (T1-3) , heart rate (HR), mean arterial pressure (MAP) and oxygen saturation (SpO2) were recorded.The emergence time, time for recovery of orientation, and duration of stay in postanesthesia care unit were recorded.Pain was assessed and scored, and agitation was graded at 5 min after emergence from anesthesia, and the occurrence of intraoperative traction reaction, body movement and nausea and vomiting within 24 h after operation was recorded.Results No intraoperative traction reaction and body movement was found in group PS+SA, and no patients stayed in postanesthesia care unit in PS+CB and PS+SA groups.HR and MAP were significantly higher at T1-3 than at T0 in group G (P＜0.05).Compare with group G, the HR, MAP at T1-3, pain scores, agitation scores, incidence of nausea and vomiting were significantly decreased, and the emergence time and time for recovery of orientation were shortened in groups PS+CB and PS+SA (P＜0.05).Conclusion Propofol used to supplement spinal anesthesia for sedation is effective and provides faster recovery from anesthesia with fewer complications in the pediatric patients undergoing lower abdominal or lower extremity operations.

Objective To record the drilling feed force on different layers of fresh porcine femur, so as to provide reference for collecting and outputting the feedback signals of drilling feed force for orthopedic virtual surgery system. Methods The biological bone drilling feed force testing system was established by modifying the universal material testing machine and adjustable speed electric drill (drill bit Φ5.0 mm). The feed forces on 6 fresh porcine femoral shafts with a total of 162 drilling markers were collected at 3 different rotate speeds (n＝500, 800, 1 200 r/min) and 3 feed speeds (v＝30, 50, 70 mm/min), and their variation with corresponding tissues and locations were also analyzed. Results At the same drill marker of the fresh porcine femur, the drilling feed force on bilateral cortical bone was the largest (fmax＝103.63~142.59 N), while that on marrow cavity was the smallest, which was almost close to zero, and the drilling feed force on the middle part (f4,5,6＝124.69 N) was larger than that at two ends (f1,2,3,7,8,9＝121.84 N); the drilling feed force was smallest (f＝106.04 N) at v＝30 mm/min, n＝1 200 r/min, while the largest drilling feed force (fmax＝139.84 N) appeared at v＝70 mm/min、n＝500 r/min. Conclusions The modified drilling feed force testing system could efficiently collect the biological bone drilling data. The drilling feed force had a close relationship with bone structure, feed speed and rotate speed of electric drill as well. A larger bone density, smaller rotate speed of electric drill and higher feeding speed would lead to a larger drilling feed force, and vice versa. The accurate drilling feed force data and its variation tendency on porcine femoral obtained in this experiment could provide a reliable basis for force-feedback signal output in the virtual orthopedic surgery system.

OBJECTIVETo introduce a method of three-column classifications for Pilon fractures and observe clinical utility on column fixation.

METHODSFrom June 2007 to March 2010,a total of 27 patients (29 ankles, 26 males and 1 female,ranging in age from 23 to 59 years, with an average of 33.1 years) with Pilon fractures were treated through column fixation by using semitubular plates or screws with anteromedial, anterior, posterolateral,posteromedial approach. And postoperative follow up were carried out.

RESULTSThe mean follow up was 17.5 months(ranged,5 to 33 months). According to the Mazur ankle grading system, the outcome was excellent in 20, good in 4 and fair in 5 ankles. Patients in this group did not have complications of wound dehiscence, deep infection, osteomyelitis, nonunion, ankylosis, and joint instability.

CONCLUSIONBased on the three-column classification, the clinical results for the treatment of Pilon fractures demonstrate the rationality and efficiency of this method.

Adult ; Female ; Humans ; Male ; Middle Aged ; Tibial Fractures ; classification ; diagnostic imaging ; surgery ; Tomography, X-Ray Computed