BACKGROUND:Muscle weakness is a common symptom after coronavirus disease 2019(COVID-19)infection and affects the ability to perform daily activities in humans during recovery.Low-frequency pulsed magnetic field stimulation at a strength of 1.5 mT and a frequency of 3 300 Hz can enhance the maximal voluntary contraction and strength endurance of human skeletal muscle by inducing and activating classical transient receptor potential channel 1(TRPC1),which produces a series of pathological support effects on muscle tissue.It has not been studied whether this means will improve muscle weakness in patients recovering from COVID-19. OBJECTIVE:To select the low-frequency pulsed magnetic field for magnetic stimulation of lower limb muscle groups in patients with COVID-19,in order to observe the effect of this stimulation on the improvement of muscle weakness of lower limb muscle groups in patients with COVID-19 during the recovery period. METHODS:Fourteen patients infected with COVID-19(Omicron strain)positive for Innovita COVID-19 Ab Test(Colloidal Gold)and accompanied by muscle weakness were recruited and randomly divided into two groups:a test group receiving magnetic field stimulation and a control group receiving sham treatment,respectively.The total duration of the trial was 3 weeks.The test group was given low-frequency pulsed magnetic stimulation of the lower limbs every 48 hours and the control group was given the same intervention procedure as the test group but with sham stimulation.Patients in both groups were not informed whether the magnetic stimulation apparatus was running or not.Nine sessions were performed in both groups and the changes in the maximum voluntary contraction,explosive leg force and strength endurance of the local muscle groups of the lower limbs were subsequently observed in both groups. RESULTS AND CONCLUSION:Among the eight local muscle groups collected,seven local muscle groups in the test group showed an increase in the maximum voluntary contraction value after 3 weeks of low-frequency pulsed magnetic field stimulation.In the control group,there were only three muscle groups with improvement in the maximum voluntary contraction.The rate of improvement in the anterior and posterior muscle groups of the left leg in the test group was significantly higher than that in the control group.The longitudinal jump height and peak angular velocity of the knee joint in both groups were improved compared with the pre-test measurement,and the elevation rate of jumping height in the test group was higher than that in the control group.Under the fatigue condition,the decline rates of peak angular velocity of the knee joint and jumping height in the test group decreased significantly,while those in the control group did not change significantly.The above data confirmed that the low-frequency pulsed magnetic field stimulation with the intensity of 1.5 mT and frequency of 3 300 Hz could improve the muscle strength of more local muscle groups in the lower limbs of patients with COVID-19 during the recovery period compared with the human self-healing process,and the whole-body coordination ability and functional status based on explosive leg force of the legs could be significantly improved.Therefore,low-frequency pulsed magnetic field stimulation can be used as an effective,non-exercise rehabilitation tool to improve muscle weakness in the lower limbs of patients with COVID-19.

Maturity-onset diabetes of the young 3 (MODY3) is an autosomal dominant monogenic diabetes mellitus characterized by defective β-cell function and non-insulin-dependent early-onset diabetes mellitus. The facts that patients with MODY3 are often misdiagnosed as type 1 and type 2 diabetes mellitus and genetic diagnosis is expensive, make its diagnosis very challenging. In this study, we reported a case of MODY3, which was verified to be caused by a mutation in hepatocyte nuclear factor 1α gene (c.598C>T, p.Arg200Trp). In addition, the patient had a neuroendocrine tumor simultaneously, and a KMT2D gene mutation (c.5587C>G, p.Pro1863Ala) might be associated with this leson.

Objective To evaluate the effect of pulsed radiofrequency (PRF) on spinal adenosine triphosphate (ATP)-P2X4-NLRP3 signaling pathway in rats with neuropathic pain.Methods Forty healthy clean-grade adult male Sprague-Dawley rats,aged 2-3 months,weighing 220-260 g,were divided into 4 groups (n =10 each) using a random number table method:sham operation group (group S),neuropathic pain group (group NP),sham PRF group (group SPRF) and PRF group.Neuropathic pain was induced by chronic constriction injury to the left sciatic nerve of anesthetized rats.Rats received PRF treatment on 7th day after establishing the model in group PRF.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured before establishing the model (T0) and at 3,7,10,14,21 and 28 days after establishing the model (T1-6).The rats were then sacrificed and the spinal cord was removed for determination of P2X4 and NLRP3 expression (by Western blot) and interleukin-1beta (IL-1β),IL-2,IL-6 and tumor necrosis factor-alpha (TNF-α) contents (by enzymelinked immunosorbent assay).Results Compared with group S,the MWT and TWL were significantly decreased at T1-6,the expression of P2X4 and NLRP3 was up-regulated,and the contents of IL-1β,IL-2,IL-6 and TNF-α were increased in NP,SPRF and PRF groups (P＜0.05).Compared with group NP and group SPRF,the MWT and MWT were significantly increased at T3-6,the expression of P2X4 and NLRP3 was down-regulated,and the contents of IL-1 β,IL-2,IL-6 and TNF-α were decreased in group PRF (P＜0.05).Conclusion The mechanism by which PRF alleviates neuropathic pain is related to inhibiting ATP-P2X4-NLRP3 signaling pathway in rats.

Objective To evaluate the role of protein kinase C in the maintenance of chronic inflammatory pain in rats and the relationship with the expression of Nav1.8 in the dorsal root ganglion (DRG).Methods Thirty pathogen-free healthy female Sprague-Dawley rats,weighing 180-220 g,were divided into 3 groups using a random number table:control group (group C),chronic inflammatory pain group (group CIP) and PKC inhibitor group (group P).Normal saline 20 μl was injected into the plantar surface of the right hindpaw every day for 14 consecutive days in group C.Prostaglandin E2 100 ng was injected into the plantar surface of the right hindpaw every day for 13 consecutive days to establish the model of chronic inflammatory pain,and dimethyl sulfoxide 20μl was injected into the plantar surface of the right hindpaw on 14th day in group CIP.Prostaglandin E2 100 ng was injected into the plantar surface of the right hindpaw every day for 13 consecutive days,and PKC inhibitor GF1O9203X 100 nmol/20 μl was injected into the plantar surface of the right hindpaw on 14th day in group P.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before injection (T0) and 1,3,7 and 14 days after the last injection (T1-4).The DRGs of the lumbar segment (L4.5) were removed for determination of Nav1.8 expression using immunofluorescence and Western blot.Results Compared with group C,the MWT was significantly decreased at T1-4 in CIP and P groups,and the expression of Nav1.8 in DRGs was significantly up-regulated in group CIP (P＜0.05).Compared with group CIP,the MWT was significantly increased at T4,and the expression of Nav1.8 in DRGs was down-regulated in group P (P＜0.05).Conclusion Up-regulated expression of Nav1.8 after PKC activation in DRGs is involved in the maintenance of chronic inflammatory pain in rats.

Objective To evaluate the effect of penehychdine hydrochloride pretreatment on nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway during myocardial ischemia-reperfusion (Ⅰ/R) in rats.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 2-3 months,weighing 220-240 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),myocardial Ⅰ/R group and penehyelidine hydrochloride pretreatment group (group PHC).Myocardial Ⅰ/R was induced by occlusion of the anterior descending branch of left coronary artery for 30 min followed by 120 min reperfusion.At 30 min before ischemia,penehyelidine hydrochloride 2 mg/kg was injected intraperitoneally in group PHC,and the anterior descending branch of left coronary artery was only exposed but not ligated in group S.Rats were sacrificed at the end of reperfusion,and hearts were removed for measurement of the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),cell apoptosis (by TUNEL) and expression of Nrf2,heme oxygenase-1 (HO-1),NQO1 and γ-glutamylcysteine synthetase (γ-GCS) protein and mRNA (by using Western blot or real-time fluorescence quantitative polymerase chain reaction).The percentage of myocardial infarct size and apoptosis index were calculated.Results Compared with group S,the percentage of myocardial infarct size and apoptosis index were significantly increased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was down-regulated in Ⅰ/R and PHC groups (P＜0.05).Compared with group l/R,the percentage of myocardial infarct size and apoptosis index were significantly decreased,and the expression of Nrf2,HO-1,NQO1 and γ-GCS protein and mRNA was up-regulated in group PHC (P＜0.05).Conclusion Penehyclidine hydrochloride pretreatment attenuates myocardial Ⅰ/R injury through activating Nrf2-ARE signaling pathway in rats.

Objective To evaluate the effect of prostaglandin E1 (PGE1) on propofol-induced neuroapoptosis in hippocampus of newborn rats.Methods Thirty-six clean-grade healthy newborn SpragueDawley rats,aged 7 days,weighing 11-16 g,were divided into 3 groups (n=12 each) using a random number table method:control group (group C),propofol group (group P) and group PGE1.Propofol 75 mg/kg was intraperitoneally injected once every other day for 7 consecutive days in P and PGE1 groups.PGE1 10 μg/kg was injected via the tail vein at 30 min before each injection of propofol in group PGE1.Normal saline 3 ml/kg was intraperitoneally injected once every other day for 7 consecutive days in group C.The rats were sacrificed at 60 min after emergence from the last injection.The hippocampi were harvested for determination of neuroapoptosis (by TUNEL),expression of caspase-3,Bcl-2 and Bax (by Western blot),and contents of intedeukin-1bota (IL-1β),IL-6 and tumor necrosis factor-alpha (TNF-α) (by enzyme-linked immunosorbont assay).Results Compared with group C,the contents of hippocampal IL-1β,IL-6 and TNF-α were significantly increased,apoptosis index was increased,the expression of caspase-3 and Bax was up-regulated,and the expression of Bcl-2 was down-regulated in P and PGE1 groups (P＜0.05).Compared with group P,the contents of hippocampal IL-1β,IL-6 and TNF-α were significantly decreased,apoptosis index was decreased,the expression of caspase-3 and Bax was down-regulated,and the expression of Bcl-2 was up-regulated in group PGE1 (P＜0.05).Conclusion PGE1 can reduce propofol-induced neuroapoptosis in hippocampus of newborn rats,and the mechanism may be related to inhibiting inflammatory responses of the hippocampus.

Objective To observe the effect of Hawthorn Jiangzhi powder on blood lipids in hyperlipidemia patients.Methods Four hundreds and eighty-four patients with hyperlipidemia were selected from Department of Cardiology in Huanghuai University Affiliated Hospital from January 2011 to June 2016,and they were divided into observation group and control group by random number table,each group 242 cases.The observation group took orally Hawthorn Jiangzhi powder (including ingredients:hawthorn 6 g,salvia miltiorrhiza 18 g,black soybean 16 g,hoelen 6 g,ganoderma lucidum 9 g,kudzuvine root 6 g,Chinese yam 6 g,fructus amomum 9 g,coix seed 16 g,cassia seed 6 g) once 6-9 g powder,twice a day,once in the morning and another in the evening;the control group was given simvastatin,20 mg each day during taking dinner;the therapeutic period lasted 2 months in both groups.The differences in serum lipid and serum inflammatory factor levels were compared before and after treatment in the two groups;the changes of lymphocyte subsets of the two groups were observed and compared with the changes of the subset results of 100 normal healthy subjects aged 35-80 years old in the same period in our hospital,and the total efficiency,the situations of adverse reactions and liver and kidney functions of two groups were observed.Results In the observation group and the control group,before treatment the levels of CD4+,CD8+,CD4+/CD8+ were lower than those of healthy control group,but after treatment the levels of CD4+,CD8+ and CD4+/CD8+ were higher than those before treatment,and the changes of the observation group were more significant than those of the control group(CD4+:0.47±0.11 vs.0.40±0.10,CD8+:0.28 ± 0.10 vs.0.26 ± 0.08,CD4+/CD8+:1.67 ± 0.79 vs.1.53 ± 0.45);After treatment,the levels of hypersensitive C-reactive protein (hs-CRP),interleukin-6 (IL-6),von Willebrand factor (vWF) and homocysteine (Hcy) in the two groups were significantly lower than those before treatment,and the levels of hs-CRP,IL-6 and vWF in the observation group were obviously lower than those in the control group [hs-CRP (mg/L):5.1 ± 1.8 vs.5.8 ± 1.7,IL-6 (ng/L):2.9 ± 1.6 vs.3.7 ± 1.8,vWF:(126.8 ± 12.8)％ vs.(156.5 ± 11.3)％,all P ＜ 0.05].After treatment,Hcy in the observation group was lower than that in the control group,but there was no significant difference between the two groups (μμmol/L:5.2 ± 1.8 vs.5.4 ± 2.6,P ＞ 0.05).In the observation group after treatment at each time point,the levels of total cholesterol (TC),triglyceride (TG) and low density lipoprotein cholesterol (LDL-C) were lower than those before treatment,while the levels of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein cholesterol/total cholesterol (HDL/TC) were higher than those before treatment;after treatment in the control group,the levels of TC,TG and LDL-C were decreased,and the levels of HDL-C and HDL/TC were obviously increased compared with those before treatment;The levels of TC,TG and LDL-C in the observation group after treatment for 2 months were significantly lower than those in the control group [TC (mmol/L):1.26 ± 0.57 vs.2.26 ± 0.56;TG (mmol/L):3.45 ± 0.78 vs.5.45 ± 0.75,LDL-C (mmol/L):2.40±0.65 vs.2.72±0.85;all P ＜ 0.05),and HDL/TC was obviously increased (1.19±0.15 vs.0.62±0.35,P ＜ 0.01).The total therapeutic effective rate of the observation group was significantly higher than that of the control group [90.1％ (218/242) vs.73.4％ (178/242),P ＜ 0.01].Adverse reactions and changes of liver and kidney functions during the period of treatment in the two groups were minimal.Conclusions Hawthorn Jiangzhi powder can effectively reduce the blood lipids and serum inflammation cytokines in patients with hyperlipidemia,improve blood rheological situation,reduce serum levels of inflammatory factors,inhibit the formation and development of atherosclerosis and enhance the immune function obviously in patients with high lipid abnormalities.

Objective To evaluate the effect of emulsified isoflurane postconditioning on mitophagy during myocardial ischemia-reperfusion (I/R) in rats.Methods Forty-eight pathogen-free healthy male Sprague-Dawley rats,aged 4-5 months,weighing 250-300 g,were divided into 4 groups (n=12 each) using a random number table:sham operation group (group S),group I/R,fat emulsion group (group F) and emulsified isoflurane postconditioning group (group EIP).Myocardial I/R was induced by occlusion of the anterior descending branch of the left coronary artery for 30 min followed by 120 min of reperfusion in pentobarbital sodium-anesthetized rats.Starting from 3 min before reperfusion,8％ emulsified isoflurane 2 ml/kg was intravenously infused over 8 min in group EIP,while 30％ fat emulsion 2 ml/kg was intravenously infused over 8 min in group F.Rats were sacrificed at the end of reperfusion,and hearts were removed for measurement of the myocardial infarct size (by 2,3,5-triphenyltetrazolium chloride staining),cell apoptosis (by TUNEL),mitochondrial membrane potential and expression of microtubule-associated protein 1 light chain 3 (LC3),Beclinl,P62,PINK1 and Parkin in cardiomyocytes (by using Western blot).Apoptosis index (AI) was calculated.Results Compared with group S,the myocardial infarct size and AI were significantly increased,the mitochondrial membrane potential was decreased,the expression of LC3,Beclinl,PINK1 and Parkin was up-regulated,and the expression of P62 was down-regulated in I/R,F and EIP groups (P＜0.05).Compared with group I/R,the myocardial infarct size and AI were significantly decreased,the mitochondrial membrane potential was increased,the expression of LC3,Beclinl,PINK1 and Parkin was down-regulated,and the expression of P62 was up-regulated in group EIP (P＜0.05).Compared with group F,the myocardial infarct size and AI were significantly decreased,the mitochondrial membrane potential was increased,the expression of LC3,Beclin1,PINK1 and Parkin was down-regulated,and the expression of P62 was up-regulated in group EIP (P＜0.05).Conclusion The mechanisin by which emulsified isoflurane postconditioning reduces myocardial I/R injury is related to inhibition of mitophagy in rats.

OBJECTIVE:To observe the influence and safety of dexmedetomidine (DEX) on intraoperative wake-up quality of patients underwent neurosurgical surgery. METHODS:126 patients with general anesthesia in neurosurgery were enrolled and randomized equally into observation group and control group,with 63 cases in each group. Control group was given target con-trolled infusion of propofol with plasma target concentration of 3-5 μg/ml and remifentanil with target effect site concentration of 2-6 ng/ml for anesthesia induction and maintenance,and then plasma target concentration of remifentanil decreased to 0.5 ng/ml 30 min before wake-up. Observation group received target controlled infusion of propofol with plasma target concentration of 3-5 μg/ml and remifentanil with target effect site concentration of 2-6 ng/ml for anesthesia induction and maintenance,and then given DEX 0.3 μg/kg intravenously 30 min before wake-up and maintained at 0.1 μg/(kg·h). MAP,HR,SBP,SaO2,serum levels of IgA,IgM,IgG,IL-6,IL-8 and TNF-α were observed in 2 groups 2 h before operation(T1)and after extubation(T2)as well as the occurrence of ADR during wake-up. RESULTS:There was no statistical significance in HR,MAP,SBP,SaO2,IgA,IgM, IgG,IL-6,IL-8 and TNF-α levels at T1 and SaO2 levels at T2 between 2 groups(P>0.05). HR,MAP,SBP,IL-6 and TNF-α lev-els of observation group decreased significantly at T2 and lower than those of control group;IgA,IgM and IgG increased signifi-cantly and higher than those of control group,with statistical significance (P<0.05). The incidence of bucking in observation group was significantly lower than control group,with statistical significance(P<0.05);there was no statistical significance in the incidence of ADR as dysphoria,awareness rate during operation,respiratory depression,body movement,bradycardia between 2 groups (P>0.05). CONCLUSIONS:DEX influence intraoperative wake-up quality of patients underwent neurosurgical surgery slightly,and can reduce inflammatory reaction with less ADR.

Objective To evaluate the effect of curcumin pretreatment on c-Jun N-terminal kinase (JNK) signaling pathway during one-lung ventilation (OLV)-induced acute lung injury in mice.Methods Ninety SPF male C57BL/6J mice,aged 6-9 weeks,weighing 18-24 g,were randomly divided into 6 groups (n=15 each) using a random number table:two-lung ventilation (TLV) group;OLV group;curcumin 100,150,200 and 250 mg/kg groups (C100,C150,C200 and C250 groups).The corresponding doses of curcumin were administered intraperitoneally at 2 h before one-lung ventilation in C100,C150,C200 and C250 groups.The animals were tracheally intubated and mechanically ventilated in volume-controlled mode.The ventilator settings were adjusted to maintain the end-tidal pressure of carbon dioxide at 35-45 mmHg.In OLV,C100,C150,C200 and C250 groups,unilateral lung was ventilated for 1.5 h followed by 0.5 h of TLV.Bilateral lungs were ventilated for 2.0 h in group TLV.Peak airway pressure and airway pressure were recorded at 1.5 h of OLV and 0.5 h of TLV.At the end of mechanical ventilation,left lungs were removed for microscopic examination of the pathologic changes,and the index of quantitative assessment for alveolar damage (IQA) was recorded.Wet/dry lung weight ratio (W/D ratio) was determined,and the cell apoptosis in lung tissues was detected using TUNEL.The apoptosis index (AI) was calculated.The expression of JNK mRNA was determined using real-time polymerase chain reaction.The expression of JNK and phosphorylated JNK was determined by Western blot.The phosphorylation of JNK was calculated.Results Compared with group TLV,the IQA,W/D ratio,AI,expression of JNK mRNA and phosphorylation of JNK were significantly increased in group OLV (P＜0.05).Compared with group OLV,the IQA,W/D ratio,AI,expression ofJNK mRNA and phosphorylation of JNK were significantly decreased in C150,C200 and C250 groups,the parameters mentioned above were significantly decreased in sequence in C100,C150,C200 and C250 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group C100 (P＞ 0.05).Compared with group OLV,the pathological changes were significantly attenuated in sequence in C150,C200 and C250 groups.Conclusion The mechanism by which curcumin pretreatment reduces cell apoptosis during OLV-induced acute lung injury is related to inhibition of JNK signaling pathway activation in mice.