ObjectiveTo investigate the possible mechanism of action of Xibining Formula （膝痹宁） for cartilage damage in knee osteoarthritis （KOA） through the cyclic guanosine-adenosine monophosphate synthase （cGAS）- stimulator of interferon genes （STING） signaling pathway. MethodsFifty C57BL/6J mice were randomly divided into five groups （10 per group）， sham operation group， KOA model group， low-dose Xibining Formula group， high-dose Xibining Formula group， and high-dose Xibining Formula + agonist group. The KOA models were constructed using the destabilization of the medial meniscus （DMM） method in all groups but the sham surgery group. Two weeks after surgery， the low- and high-dose Xibining Formula groups were administered Xibining Formula at doses of 3.58 g/（kg·d） and 14.32 g/（kg·d） respectively via gavage. The high-dose Xibining Formula + agonist group received 14.32 g/（kg·d） of Xibining Formula via gavage followed by an intraperitoneal injection of Vadimezan （DMXAA） at 25 mg/kg. The sham surgery group and the KOA model group mice were given an equivalent volume of normal saline at 5 ml/（kg·d） via gavage， once daily for four consecutive weeks. Serum levels of tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） were measured by ELISA； pathological changes in cartilage tissue were observed using hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Pathological changes were scored according to the Mankin scoring system； the levels of cartilage tissue matrix regulation-related indicators such as matrix metalloproteinase 3 （MMP3）， matrix metalloproteinase 13 （MMP13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS）， type-Ⅱ collagen （CⅡ） and aggregated proteoglycan （Aggrecan）， and also cGAS-STING pathway-related protein and mRNA expression levels were detected by Western blot and qPCR methods. ResultsCompared with the sham surgery group， the KOA model group showed severe cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with the control group， serum level of IL-6， IL-1β， TNF-α in all the intervented groups decreased （P＜0.01）， while compared with high-dose Xibining Formula group， level of IL-6， IL-1β， and TNF-α in low-dose Xibining Formula group and high-dose Xibining Formula + agonist group increased （P＜0.01）. Compared with the KOA model group， all the intervention groups exhibited alleviated cartilage pathological changes， signi-ficantly reduced Mankin scores， significantly increased protein and mRNA expression levels of COLⅡ and Aggrecan， and significantly decreased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. Compared with high-dose Xibining Formula group， high-dose Xibining Formula + agonist group showed cartilage edge destruction， significantly increased Mankin scores， significantly decreased protein and mRNA expression levels of COLⅡ and Aggrecan， and increased protein and mRNA expression levels of cGAS， STING， MMP3， MMP13， and ADAMTS5 （P＜0.01）. ConclusionXibining Formula may improve KOA cartilage damage by inhibiting the cGAS-STING signaling pathway， decreasing matrix degradation-related proteins， and elevating matrix composition-related proteins.

Objective:To compare the efficacy of individualized PEEP determined by lung electrical impedance tomography (EIT) and dynamic lung compliance (Cdyn) during lung-protective ventilation strategies in the patients undergoing general anesthesia.Methods:Sixty patients of both sexes, aged 18-64 yr, of American Society of Anesthesiologists physical status Ⅰor Ⅱ, with body mass index of 18.5-28.0 kg/m 2, undergoing elective surgery with general anesthesia and endotracheal intubation in the Second Affiliated Hospital of Soochow University, were selected.Lung-protective ventilation strategy was applied in supine position after general anesthesia.The peak value of PEEP did not exceed 10 cmH 2O, with an increment/decrement of 2 cmH 2O for titration.The corresponding Cdyn value and lung EIT data were collected during titration.The patients were divided into 2 groups ( n=30 each) using a random number table method: titration first increased and then decreased group (group A) and titration first decreased and then increased group (group B). The determination method of individualized PEEP: Cdyn method was the PEEP corresponding to the maximum Cdyn value; EIT method was obtained through PV500 PC software analysis.The level and success rate of individualized PEEP determined by the Cdyn and EIT methods were compared, and the ICC consistency analysis of the determined individualized PEEP was performed. Results:Compared with the Cdyn method, the success rate of individualized PEEP determined by EIT method was significantly increased, and the level of individualized PEEP was decreased in the two group ( P<0.05). In group A, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.761, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.763, P<0.05). In group B, the individualized PEEP titrated by the EIT and Cdyn methods showed good agreement (the ICC value of the increment-Cdyn and increment-EIT methods was 0.809, P<0.05; the ICC value of the decrement-Cdyn and decrement-EIT methods was 0.797, P<0.05). Conclusion:The agreement between the individualized PEEP determined by lung EIT method and Cdyn method during lung-protective ventilation is good in the patients undergoing general anesthesia, and the success rate of EIT method is higher, and the level of individualized PEEP is lower.

Objective To evaluate the effect of nicotinamide adenine dinucleotide phosphate(NADPH)on myocardial ischemia-reperfusion(I/R)injury in rats.Methods Fifty-six SPF adult male Sprague-Dawley rats,weighing 220-320 g,aged 1-2 months,were divided into 4 groups(n＝14 each)using a random number table method: sham operation group(Sham group),myocardial I/R group(I/R group),NADPH group(N group)and diltiazem group(D group).The model of myocardial I/R injury was established by ligation of the left anterior descending branch for 30 min followed by 2-h reperfusion in anesthetized rats.NADPH 16 mg/kg was intravenously infused over 5 min starting from 5 min of reperfusion in N group.Diltiazem 5 mg/kg was infused through the internal jugular vein starting from 10 min before is-chemia until the end of ischemia.At 2 h of reperfusion,blood samples were taken from the internal jugular vein for measurement of serum LDH and cTnI concentrations,and myocardial tissues were taken for deter-mination of infarct size and ROS level.Results Compared with Sham group,the serum LDH and cTnI concentrations,myocardial infarction size and ROS levels were significantly increased in I/R group(P＜0.05).Compared with I/R group,the serum LDH and cTnI concentrations,myocardial infarction size and ROS levels were significantly decreased in N and D groups(P＜0.05).Compared with N group,the LDH concentration was significantly decreased(P＜0.05),and no significant change was found in the cTnI con-centration,myocardial infarction size or ROS level in D group(P>0.05).Conclusion NADPH can re-duce myocardial I/R injury through antioxidant effect in rats.

Objective To determine the optimal positive end-expiratory pressure (PEEP) for volume-controlled ventilation using pulmonary electrical impedance tomography in the patients undergoing surgery with general anesthesia.Methods Fifty patients of both sexes,aged 18-64 yr,of American Society of Anesthesiologists physical status Ⅰ or Ⅱ,with body mass index of 18.5-28.0 kg/m2,scheduled for surgery for ureteral calculi under general anesthesia,were enrolled in this study.The patients were tracheally intubated after anesthesia induction and mechanically ventilated in volume-controlled mode,with tidal volume 6 ml/kg,mean arterial pressure was recorded at 3 min of ventilation and served as the baseline value,and then PEEP was increased with an increment of 3 cmH2O every 3 min until PEEP reached 15 cmH2 O.The percentage of dorsal pulmonary ventilation and peak airway pressure were recorded at 3 min of ventilation with different PEEPs.When the decrease in mean arterial pressure was more than 20％ of the baseline value during ventilation,deoxyepinephrine 0.1 mg was injected intravenously,and the consumption of deoxyepinephrine was recorded within 3 min of ventilation with different PEEPs.Results Peak airway pressure was gradually increased with the increase of PEEP (P＜0.05),the percentage of dorsal pulmonary ventilation was gradually increased when PEEP was 6 cmH2O (P＜ 0.05),and the consumption of deoxyepinephrine was gradually increased when PEEP was 15 cmH2O (P＜0.05).Conclusion The optimal PEEP is 12 cmH2O during volume-controlled ventilation with tidal volume of 6 ml/kg in the patients undergoing surgery with general anesthesia.

Objective: To evaluate the effect of nicotinamide adenine dinucleotide phosphate (NADPH) on myocardial ischemia-reperfusion (I/R) injury in rats. Methods: Fifty-six SPF adult male Sprague-Dawley rats, weighing 220-320 g, aged 1-2 months, were divided into 4 groups (n=14 each) using a random number table method: sham operation group (Sham group), myocardial I/R group (I/R group), NADPH group (N group) and diltiazem group (D group). The model of myocardial I/R injury was established by ligation of the left anterior descending branch for 30 min followed by 2-h reperfusion in anesthetized rats.NADPH 16 mg/kg was intravenously infused over 5 min starting from 5 min of reperfusion in N group.Diltiazem 5 mg/kg was infused through the internal jugular vein starting from 10 min before ischemia until the end of ischemia.At 2 h of reperfusion, blood samples were taken from the internal jugular vein for measurement of serum LDH and cTnI concentrations, and myocardial tissues were taken for determination of infarct size and ROS level. Results: Compared with Sham group, the serum LDH and cTnI concentrations, myocardial infarction size and ROS levels were significantly increased in I/R group (P<0.05). Compared with I/R group, the serum LDH and cTnI concentrations, myocardial infarction size and ROS levels were significantly decreased in N and D groups (P<0.05). Compared with N group, the LDH concentration was significantly decreased (P<0.05), and no significant change was found in the cTnI concentration, myocardial infarction size or ROS level in D group (P>0.05). Conclusion NADPH can reduce myocardial I/R injury through antioxidant effect in rats.

Objective To investigate the double-lumen endobronchial intubation-related anatomical factors of respiratory tract in adult patients through measurement of the parameters of glottis and left main bronchus using computed tomography(CT). Methods A total of 206 patients of both sexes, aged 20-80 yr, of American Society of Anesthesiologists physical status Ⅰ-Ⅲ, scheduled for elective surgery, were enrolled in this study.The cervical and thoracic CT images were evaluated.The anteroposterior glottic diame-ter(AP-GD), anteroposterior tracheal diameter(AP-TD), transverse tracheal diameter(Tr-TD), left and right main bronchus diameters(LBD and RBD)and length between glottis and carina(G-TL)were measured.Multiple linear regression analyses were performed to detect the correlations between obtained pa-rameters and between obtained parameters and height. Results AP-GD was(19±3)mm, AP-TD(20± 4)mm, Tr-TD(16.6±2.4)mm, LBD(12.3±2.0)mm, RBD(13.7±2.0)mm and G-TL(126± 11)mm.AP-GD, height, AP-TD and Tr-TD were moderately correlated with LBD(r was 0.522, 0.584, 0.648 and 0.606, respectively, P<0.05).AP-TD +Tr-TD+AP-GD+height served as the inde-pendent variable, the fitting curve was confirmed, and the results showed that AP-TD, Tr-TD and height were the affecting factors for LBD, and the degree of correlation with LBD was as follows from high to low:Tr-TD(b′=0.334), AP-TD(b′=0.323), height(b′=0.243). When AP-GD served as the independ-ent variable and curve fitting was performed, there was no significant difference(P>0.05). Conclusion Tr-TD and AP-GD should be considered besides double-lumen endobronchial intubation-related anatomical factors such as LBD and height in adult patients.

Objective To explore the relations between pulse pressure and LDL-C for elderly patients with hyperten-sion. Methods A total of 451 elderly patients with hypertension were selected and divided into four groups. Group A was 65 to 69 years of age, group B was 70 to74 years of age, group C was 75 to 79 years of age, and group D was ≥80 years of age. They were also divided into four groups according to PP levels: PP1 group ≤40 mm Hg, PP2 group 41 to 60 mm Hg, PP3 group 61 to 80 mm Hg, and PP4 group>80 mm Hg. They were divided into LDL-C group 1 (≥2.6 mmol/L) and LDL-C group 2 (<2.6 mmol/L) according to their LDL-C levels. Distribution of different age groups in four PP groups and the effects of different levels of LDL-C on pulse pressure were analyzed. Results (1) The propor-tions of PP2 group among the four age groups were 59.41%, 48.84%, 55.45% and 51.67%. The proportions of PP4 a-mong the four age groups were 4.95%, 3.88%, 3.96% and 7.50%. (2) Compared with PP1 group, the proportion of LDL-C ≥2.6 mmol/L in PP2 group, PP3 group and PP4 group was significantly increased. Conclusion (1) PP levels in different ages groups are concentrated on 41-60 mmHg. Among elderly patients with hypertension>80 mmHg, the pro-portion of patients with advanced age (≥years of age) is relatively higher. (2) LDL-C is the risk factor of increased pulse pressure for elderly patients with hypertension.

Objective To investigate the effects of sevoflurane postconditioning on myocardial ischemiareperfusion (I/R)-induced oncosis of cardiomyocytes and the role of mitochondrial permeability transition pore (MPTP) in it.Methods Sixty male Sprague-Dawley rats,aged 3 months,weighing 280-360 g,were randomly divided into 5 groups (n =12 each):sham operation group (group S),group I/R,sevoflurane postconditioning group (group SP),sevoflurane postconditioning + atractyloside group (group SP + ATR) and atractyloside group (group ATR).Myocardial ischemia was induced by 30 min occlusion of left anterior descending branch (LAD) of coronary artery followed by 2 h reperfusion.2.5 ％ sevoflurane was inhaled for 5 min starting from 27 min of ischemia until 2 min after beginning of reperfusion in SP and SP + ATR groups,while 33 ％ oxygen was inhaled in the other groups.In SP + ATR and ATR groups,atractyloside 5 mg/kg was injected via the internal jugular vein at 15 min before ischemia.HR and systolic pressure were monitored and recorded and rate-pressure product (RPP) was calculated.At the end of reperfusion,the rats were sacrificed and the hearts removed for determination of myocardial infarct size.The myocardial ultrastrncture was observed by electron microscopy.The expression of Porimin (Pro-oncosis receptor inducing membrane injury) was measured by Western blot.Myocardial nicotinamide adenine dinucleotide (NAD+) content was determined by spectrophotometry.Results Compared with group S,the myocardial infarct size was significantly enlarged,the expression of Porimin was up-regulated,and NAD+ content and RPP were decreased in the other four groups (P ＜ 0.05).Compared with groups I/R and SP + ATR,the infarct size was significantly decreased,the expression of Porimin was down-regulated,and NAD+ content was increased in group SP (P ＜ 0.05),and no significant change was found in the indices mentioned above in group ATR (P ＞0.05).Conclusion Sevoflurane postconditioning can mitigate myocardial I/R injury by inhibiting MPTP opening and reducing oncosis of cardiomyocytes.

Objective To evaluate the role of the mitochondrial ATP-sensitive potassium (mito-KATP)channel in sevoflurane preconditioning-induced delayed cardioprotection against ischemia-reperfusion (I/R) injury in isolated rat hearts.Methods Seventy-two adult male Sprague-Dawley rats were randomly divided into 6 groups (n =12 each):control group (group CON),I/R group,sevoflurane control group (group SEVO),sevoflurane preconditioning group (group SWO P),5-hydroxydeconoate (5-HD) + sevoflurane preconditioning group (group 5-HD+ SWOP) and 5-HD control group (group 5-HD).The rats were exposed to 33％ pure oxygen for 1 h in groups CON and I/R.The rats were exposed to 2.5％ sevoflurane for 1 h in groups SEVO and SWOP.5-HD (a mito-KATP channel inhibitor) 10 mg/kg was injected intraperitoneally 30 min before sevoflurane preconditioning in group 5-HD + SWOP.5-HD 10 mg/kg was injected intraperitoneally in group 5-HD.The hearts were immediately removed and perfused in a Langendorff apparatus.The hearts were made globally ischemic for 30 min followed by 120 min reperfusion in groups I/R,SWOP,5-HD + SWOP and 5-HD.The expression of phosphorylated protein kinase C-epsilon (p-PKC-ε) and caspase-8 was measured by Western blot immediately before ischemia (T0) and at 120 min of reperfusion (T1).The myocardial infarct volume was measured by TTC staining.Results Compared with group CON,the myocardial infarct volume was significantly increased at T1 in groups I/R,SWOP,5-HD +SWOP and 5-HD,p-PKC-ε expression was up-regulated at T0 in groups SEVO and SWOP and at T1 in groups I/R,SWOP,5-HD + SWOP and 5-HD,and caspase-8 expression was down-regulated at T1 in group SEVO (P ＜0.05).Compared with group I/R,the myocardial infarct volume was significantly decreased at T1 in groups SWOP and 5-HD + SWOP,p-PKC-ε expression was up-regulated at T0 in groups SEVO and SWOP,and caspase-8 expression was down-regulated at T1 in group SWOP (P ＜ 0.05).Compared with group SWOP,the myocardial infarct volume was significantly increased,p-PKC-ε expression was down-regulated at T0,and caspase-8 expression was up-regulated at T1 in group 5-HD + SWOP (P ＜ 0.05).Conclusion The mito-KATP channel is involved in sevoflurane preconditioning-induced delayed cardioprotection against I/R injury in isolated rat hearts through upregulation of p-PKC-ε expression before ischemia and inhibition of cell apoptosis during reperfusion.

BACKGROUND:Studies have shown that Weilingxian can maintain and promote the synthesis of proteoglycan and collagen Ⅱ of chondrocyte,and protect artlcular cartilage and postpone the development of osteoarthdtis by inhibiting the level of intedeukin-1(1L-1)possibly.OBJECTIVE:Based on the previous studies,to observe the effect of Weilingxian on the proliferation of rabbit knee articular chondrocyte and transforming growth factor-β1 mRNA expression,and then to explore the role and possible mechanism of Weilingxian in the treatment of osteoarthdtis.METHODS:Knee cartilage was shredded after harvested from New Zealand white rabbits under sterile conditions,and chondrocytes were isolated and cultured by the way Of enzymatic digestion.After identifying by toluidine blue staining,the third-passage calls in the logarithmic growth phase were cultured in vitro and randomly divided into two groups after adherence.The experimental groups were cultured in DMEM with 0.01,0.05,0.1,0.5,and 1.0 mg/mL Weilingxian,while the control group was given with normal medium alone.Chondrecytes morphology was observed under an inverted phase contrast microscope,and the phenotype was identified by toluidine blue staining;Methyl Thiazolyl Tetrazolium(MTT)assay method was adopted to observe the influenca of Weilingxian with difierent concentrations on the proliferation of chondrocytes,and anti-transcription-polymerase chain-type reaction(RT-PCR)was used to assay the expression changes of transforming growth factor-β1 mRNA.RESULTS AND CONCLUSlON:Primary cultured chondrocyte was round-shaped,and most of It adhered after 24 hours,the appearance was polygonal and irregular-shaped;after passage,cell growth was faster than before,the typical appearance was slabstone-like;long spindle-shaped chondrocytes appeared after four generations;after six generations,most cells showed long spindle-shaped fibroblast-like appearance,the rate of growth also slowed down.Extracellular matrix of chondrocytes was stained to be blue by toluidine blue staining,and the nucleus was dark blue.Different concentrations of Weilingxian could promote the proliferation of chondrocytes,effect of 0.5 mg/mL group was significantly,and the peak of proliferation was on the third day.0.05,0.1,0.5,and 1.0 mg/mL Weilingxian group could promote the expression of transforming growth factor-β1 mRNA.and there was no significant difference between four groups(P＞0.05),but the peak was at 0.5 mg/mL group.Weilingxian can promote proliferation of chondrocyte and transfonlling growth factor-β1 mRNA expression,and these may be one of the possible mechanisms that Weilingxian can work in the treatment of osteoarthritis.