Objective To preliminarily investigate the effect and possible mechanisms of Senecio cannabifolius Less.Ⅱ(FHC-Ⅱ) on perfluoroisobutylene (PFIB) inhalation-induced acute lung injury. Methods Totally 156 rats were randomly assigned to three groups: the control group, the PFIB group and the FHC-Ⅱ prevention group, with 32, 62 and 62 rats in each group respectively. The FHC-Ⅱprevention group were given FHC-Ⅱthree times per day at the dosage of 340 mg/kg before PFIB exposure. 1 h after the last time of FHC-Ⅱ administration, the FHC-Ⅱ prevention group were exposured to gaseous PFIB (0.2 mg/L) for 10 minutes in a static whole-body exposure inhalation system. The survival rate of the rats were recorded at 1, 2, 4, 8, 16, 24, 48 and 72 h post PFIB exposure;the lung index and total protein content in bronchoalveolar lavage fluid (BALF) were measured at 1 h, 2 h, 4 h, 8 h, 16 h and 24 h; IL-1β and IL-8 in sera were assayed by enzyme-linked immunosorbent assay (ELISA) at 1, 2, 4, 8 and 16 h post PFIB exposure and the histopathological examination of the lung tissue was performed at 8 h post PFIB exposure. Results FHC-II significantly reduced the content of the total protein in BALF, lung index and the levels of IL-1β and IL-8 in aera as well, and dramatically alleviated the histopathological changes in the lung tissue. Conclusion FHC-Ⅱ demonstrates some preventive effect on PFIB inhalation-induced acute lung injury in rats.

Objective By investigating the effects of AT1 and ERK2 signaling pathway in CHF,to study the effect of Guanxin-Shutong capsule on AT1,ERK2 expression in rats with chronic heart failure (CHF).Methods The CHF rat models were setup by coronary artery ligation,exhausting swimming and reducing feeding.Divided CHF rat methods into a model group,a lisinopril group,Qi-benefiting with Chinese medicine group,blood activating with Chinese medicine group,Qi benefiting and blood activating with Chinese medicine group(QBBA group) and Guanxin-Shutong capsule group.Rats without left coronary artery ligation were set for sham operated group.Real-time quantitative PCR technique and immunohistochemical method were adopted to detect AT1,ERK2 changes of CHF rats.Results AT1,ERK2 expression increased obviously in the model group compared with the sham operated group,and differences were statistically significant (P＜0.01).After treatment,AT1,ERK2 expression reduced significantly in QBBA group and Guanxin-Shutong capsule group than the lisinopril group.(P＞0.05).And therapeutic effect of Guanxin-Shutong capsule group was much better than other Chinese medicine treated group (P＜0.01).Conclusion Guanxin-Shutong capsule would achieve the goal of treating chronic heart failure By inhibiting the expression of AT1 and ERK2 in organizations,and inhibiting or reversing ventricular remodeling process.

OBJECTIVE:To systematically review the efficacy and safety of pirfenidone in the treatment of idiopathic pulmo-nary fibrosis (IPF),and provide evidence-based reference for clinical treatment. METHODS:Retrieved from Cochrane Library, PubMed,EMBase,CJFD,CBM,VIP Database and Wanfang Database,randomized controlled trials (RCT) about the efficacy and safety of pirfenidone (test group) versus placebo (control group) in the treatment of IPF were collected,and Meta-analysis was performed by using Rev Man 5.1.7 software after data extracting and quality evaluating by modified Jadad. RESULTS:Totally 4 RCTs were enrolled,involving 1 153 patients. Results of Meta-analysis showed the decrease value of lung capacity [WMD=0.39,95%CI(0.16,0.61), P<0.001] and decrease value of the percentage of forced vital capacity to expected value [RR=0.68, 95%CI(0.53,0.87),P=0.002] in test group were lower than control group,there was significant difference between 2 groups;there was no significant difference in the lowest oxygen saturation [WMD=0.53,95%CI(-0.78,1.84),P=0.43] between 2 groups,however,the results of subgroup analysis showed the remission degree of 1 200 mg/d PFD for the decrease of lowest oxy-gen saturation was superior to placebo group,there was significant difference between 2 groups [WMD=1.72,95%CI(1.33,2.10), P<0.001],but therewas no significant difference between the remission degree of 1800 mg/d and placebo;and there was no signifi-cant difference in the incidence of adverse reactions between 2 groups [RR=1.70,95%CI(0.46,6.31),P=0.43],but the incidence of photosensitivity veactions in test group was significantly higher than that of control group,there was significant difference [RR=9.35,95%CI(4.23,20.67),P<0.001]. CONCLUSIONS:The efficacy of pirfenidone in the treatment of IPF is good,but the inci-dence of photosensitivity reactions should be noticed.

Objective To investigate if the positive postnatal environment could modify the schizo-phrenia-related behaviors caused by early maternal immune activation,and the interaction of this two pre-and postnatal factors.Methods The pregnant mice were randomly divided into experimental and control groups.The experimental groups were injected with polynosinic-polycytidylic acid(Poly I : C)(5mg/kg),via intra-venous route,at gestational day 9.The control groups were injected with the same volume of normal saline (NS)at the same gestational day.All offspring were housed in groups of littermates until postnatal day (PND)21 when they were weaned.Between PND22-PND60,offspring were divided into dull or enriched en-vironment(DE or EE)groups by sex and treatment.Different toys were put into the cages of enriched envi-ronment group every week,such as running wheels,climbing materials,swings and rollers.The dull environ-ment(DE)groups were kept the normal housing environment only with sawdust.At PND60,behavioral tests were conducted,such as prepulse inhibition(PPI),open field test,novel object/location recognition,social interaction test,as well as water maze test,were conducted to evaluate the performance of all offspring.After behavioral tests,all offspring were killed and the hippocampus were dissected.The western blot was used to analyze the expression of myelin basic protein in the hippocampus.Results (1)The percentage of PPI with early maternal immune activation of Poly I : C were significantly reduced when compared with control groups (female offspring:F=28.12,P<0.001;male offspring:F=14.76,P<0.01),suggesting the schizophrenia-like behavioral deficit in the offspring induced by early prenatal Poly I : C challenge.(2)In open field test,early maternal immune activation increased the moved distance and speed of the offspring compared with the con-trol groups(female offspring:distances,F=5.10,P<0.05,speed:F=5.19,P<0.05;male offspring:distances:F=6.76,P<0.05,velocity:F=6.85,P<0.05,vs each corresponding control).(3)Enriched environment in-creased the social interaction time of offspring with strange mouse in the social interaction test(female off-spring:EE group(101.30±6.83)s,DE group(76.50±5.59)s,F=9.41,P<0.01;male offspring:EE group(98. 52±6.82)s,DE group(75.82±3.95)s,F=7.95,P<0.01).(4)Enriched environment decreased the time for offspring to find the platform in water maze test(P<0.05).(5)The expression of myelin basic protein in hip-pocampus in offspring which received early maternal immune activation by Poly I : C was lower than that in the control groups(P<0.05).Conclusion The postnatal enriched environment increased the social interac-tion and the learning abilities of the offspring with early maternal immune activation by Poly I : C in water maze,and even more improved the perseveration behavior of the offspring induced by the early maternal im-mune activation.

Objective To investigate the diagnostic efficacy and clinical value of GNB4 and Riplet gene methylation alone and in combination in the diagnosis of primary liver cancer.Methods A total of 313 patients were selected,including 78 patients with primary liver cancer,41 patients with other digestive system tumors,17 patients with non-digestive system tumors,20 patients with postoperative liver cancer,and 157 patients with benign liver disea-ses.The levels of GNB4 and Riplet gene methylation in plasma were detected using quantitative methylation-specific PCR(qMSP).Serum alpha-fetoprotein(AFP)levels were measured by direct chemiluminescence.Results The sensitivity and specificity of AFP in diagnosis were 51.3％and 94.3％,respectively;the sensitivity and specificity of GNB4 gene methylation in diagnosis were 83.3％and 99.4％,respectively;the sensitivity and specificity of Riplet gene methylation in diagnosis were 73.1％and 99.4％,respectively.The sensitivity and specificity of GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis were 92.3％and 98.7％,respectively;the sensitivity and specificity of combined diagnosis including age and gender were 93.6％and 97.5％,respective-ly.Conclusion The sensitivity and specificity of AFP in the diagnosis of primary liver cancer are limited,while the methylation levels of GNB4 and Riplet genes are higher,and the sensitivity and specificity of their combined de-tection are higher than those of AFP.The sensitivity and specificity of AFP,GNB4 and Riplet gene methylation combined diagnosis are significantly higher than those of AFP,GNB4 and Riplet gene methylation alone.

OBJECTIVE: To explore the expression, localization and regulatory effect on mitochondrial calcium signaling of Rictor in embryonic stem cell-derived cardiomyocytes (ESC-CMs). METHODS: Classical embryonic stem cell cardiomyogenesis model was used for differentiation of mouse embryonic stem cells into cardiomyocytes. The location of Rictor in ESC-CMs was investigated by immunofluorescence and Western blot. The expression of Rictor in mouse embryonic stem cells was interfered with lentiviral technology, then the superposition of mitochondria and endoplasmic reticulum (ER) in ESC-CMs was detected with immunofluorescence method; the cellular ultrastructure of ESC-CMs was observed by transmission electron microscope; the mitochondrial calcium transients of ESC-CMs was detected by living cell workstation;immunoprecipitation was used to detect the interaction between 1,5,5-trisphosphate receptor (IP3 receptor, IP3R), glucose-regulated protein 75 (Grp75) and voltage-dependent anion channel 1 (VDAC1) in mitochondrial outer membrane; the expression of mitochondrial fusion protein (mitonusin-2, Mfn2) was detected by Western blot. RESULTS: Rictor was mainly localized in the endoplasmic reticulum and mitochondrial-endoplasmic reticulum membrane (MAM) in ESC-CMs. Immunofluorescence results showed that Rictor was highly overlapped with ER and mitochondria in ESC-CMs. After mitochondrial and ER were labeled with Mito-Tracker Red and ER-Tracker Green, it was demonstrated that the mitochondria of the myocardial cells in the Rictor group were scattered, and the superimposition rate of mitochondria and ER was lower than that of the negative control group (<0.01). The MAM structures were decreased in ESC-CMs after knockdown of Rictor. The results of the living cell workstation showed that the amplitude of mitochondrial calcium transients by ATP stimulation in ESC-CMs was decreased after knockdown of Rictor (<0.01). The results of co-immunoprecipitation showed that the interaction between IP3R, Grp75 and VDAC1 in the MAM structure of the cardiomyocytes in the Rictor group was significantly attenuated (<0.01); the results of Western blot showed that the expression of Mfn2 protein was significantly decreased (<0.01). CONCLUSIONS Using lentiviral technology to interfere Rictor expression in mouse embryonic stem cells, the release of calcium from the endoplasmic reticulum to mitochondria in ESC-CMs decreases, which may be affected by reducing the interaction of IP3R, Grp75, VDAC1 and decreasing the expression of Mfn2, leading to the damage of MAM structure.
Animals ; Calcium Signaling ; genetics ; Gene Expression Regulation ; genetics ; Gene Knockdown Techniques ; Mice ; Mitochondria ; physiology ; Mouse Embryonic Stem Cells ; Myocytes, Cardiac ; physiology ; Protein Transport ; Rapamycin-Insensitive Companion of mTOR Protein ; genetics ; metabolism

Objective:To investigate the surgical method and clinical effect of O-arm navigation mini-open burring for osteoid osteoma.Methods:Eighteen patients with osteoid osteoma were treated with O-arm guided grinding drill from June 2021 to May 2022, including 15 males and 3 females, the age was (18.4 ±10.9) years (range 2 to 44 years), and the course of disease ranged from 1 week to 3 years (mean 14.2 months). The lesions sites included 6 cases of proximal femur, 3 cases of distal femur, 4 cases of proximal tibia, 1 case of distal tibia, 2 cases of proximal fibula and 1 case of distal and proximal humerus. During the operation, the O-arm navigation was used to determine the location of the focus, the muscle and soft tissue was peeled off to the bone surface through a 1-4 cm small incision, the channel retractor was placed, and the burr was registered as a navigation recognition device to gradually remove the bone on the surface of the tumor nest, and the tumor nest was scraped with a curette for pathological examination; according to the navigation image, the focus was enlarged removed with burr and the grinding range was confirmed by the O-arm X-ray machine before the end of the operation. The patients were followed up for 6 to 15 months (mean 9.5 months). CT scans were performed before and after surgery for imaging comparison in order to figure out whether it had residual lesions or recurrence. The visual analogue score (VAS) of pain was used as a parameter for evaluating the clinical efficacy.Results:The operation time of 18 cases was 40-175 min, with an average of 89.3 min. The time required to establish navigation image was 18.0 ±4.1 min (range 13 ~ 22 min). The length of the incision was 2.7±1.1 cm (range 1-4 cm). All patients achieved complete curettage of the lesions, and osteoid osteoma was confirmed by pathology after operation. All the patients could move to the ground 24 hours after operation, and the pain was significantly relieved from 3 to 7 d after operation, and the pain almost disappeared 3 months after operation. The VAS score of 18 cases was 5.33±1.24 before surgery, 2.79±1.32 on the 3rd day, 1.86±1.21 on the 7th day, 0.86±0.93 on the 1st month, 0.33±0.48 on the 3rd month, and 0.09±0.29 on the 6th month after operation, and the difference was statistically significant ( F=58.50, P<0.001). There were no serious complications during and after operation, and the success rate of treatment (no recurrence of symptoms, no residual recurrence of imaging lesions, no serious complications after operation) was 100%. Conclusion:Treatment of osteoid osteoma with mini-open excision using burrs under the navigation of O-arm is a simple, safe, minimally invasive and efficient technique. Intraoperative precise positioning and the use of burr with navigation to remove a larger area than the tumor nest are the keys to successful treatment.

Objective:To explore the risk factors of recurrence after resection of thigh soft tissue malignant tumors and the evaluation of the postoperative lower limb function.Methods:A total of 211 patients who underwent thigh soft tissue malignant tumor resection in the Department of Orthopaedics of the second affiliated Hospital of Medical College of Zhejiang University from May 2011 to May 2021 were retrospectively analyzed, including 117 males and 94 females, aged 53 (43, 65) years. There were 59 cases of atypical/well-differentiated liposarcoma, 30 cases of other types of liposarcoma, 33 cases of malignant fibrous histiocytoma, 19 cases of fibrosarcoma, 12 cases of rhabdomyosarcoma, 12 cases of leiomyosarcoma, 9 cases of synovial sarcoma, and 37 cases of others. The tumor involvement of muscle, bone, blood vessel, nerve tissue and intermuscular compartment, postoperative Musculoskeletal Tumor Society (MSTS) functional score and recurrence were recorded. The relationship between anatomical structure and postoperative recurrence was analyzed by Cox logistic regression to determine risk factors; the cumulative recurrence rate of different compartment groups (medial compartment, anterior compartment, and posterior compartment) were compared; The Box plot was used to compare the postoperative function of patients with resection of different anatomical structures (e.g., vastus lateralis, biceps femoris, femur, etc.).Results:A total of 34 out of 211 patients relapsed, with a recurrence rate of 16.1%. The recurrence time ranged from 2.6 months to 91.6 months after operation, with a median recurrence time of 37.0 (18.2, 52.8) months. Three independent risk factors were found to be associated with recurrence, namely: pathological grade [ HR=3.86, 95% CI(1.75, 8.51)], involvement of vastus intermedius [ HR=3.05, 95% CI(1.53, 6.06)], and involvement of vastus medialis [ HR=3.17, 95% CI(1.56, 6.41)]. The recurrence rate of patients with anterior chamber tumor resection was 35.3%, which was higher than that of patients without tumor resection (16.2%), and the difference was statistically significant ( P=0.020). There was no significant difference in recurrence rate between patients with medial chamber tumor resection and patients without tumor resection ( P>0.05). The recurrence rate of patients with posterior compartment tumor resection was 12.3%, which was lower than that of unresectable patients (37.6%), and the difference was statistically significant ( P=0.002).The postoperative MSTS score of 167 patients averaged 26±3.2 points (9-30 points). After intraoperative resection of part of the femur, vastus intermedius, vastus medialis, and rectus femoris, the patient's function was relatively poor [corresponding median MSTS score: 25 (23, 28), 26 (24 28), 26 (24,28), 26(24, 27)]. Conclusion:The risk factors for local recurrence after resection of thigh soft tissue malignant tumors include: pathological grade of the tumor, and whether the vastus intermedius or vastus medialis is involved. Anterior compartment tumors have a higher recurrence rate after surgery. If the tumor involves the above-mentioned anatomical structures, more attention should be paid to the risk of local recurrence after surgery.

Objective To study the status of diabetic foot and its related factors in Hanzhong area in recent years, and to provide a scientific basis for the prevention and management of diabetic foot complicated by type 2 diabetes. Methods A stratified sampling method was used to select 528 patients with type 2 diabetes among permanent residents in Hanzhong from April 2016 to April 2022. Relevant medical history and laboratory examination data were collected, and the incidence of diabetic foot was calculated. The influence of related factors on the risk of diabetic foot was analyzed by regression model. Results Among 528 subjects in this study, the disease course and body type of T2DM showed that male patients had significantly longer disease, and the proportion of overweight and obesity was higher, P<0.05. The incidence of diabetic foot was 16.29% (86 cases). The proportion of male patients and female patients was 24.66% and 5.93%（χ²=27.516，P<0.05）. The proportion of male patients complicated with diabetic foot was higher than that of female patients (P<0.05). At the same time, the incidence of Wagner Grade I was higher in males than in females (P<0.05). The effects of potential factors on the risk of diabetic foot were discussed by gender. Univariate analysis and multivariate logistic regression analysis indicated that the risk factors of diabetic foot in male T2DM patients included: Increased course of disease, increased age, poor blood glucose control, increased total cholesterol level, increased BMI level and increased platelet to lymphocyte ratio . Potential risk factors in women include increased course of disease, age, poor blood sugar control (increased glycosylated hemoglobin levels) and increased platelet to lymphocyte ratios in all cases（P<0.05）. Conclusion The current prevalence rate of type 2 diabetes patients complicated with diabetes foot in Hanzhong area is 16.29%, which is still high , and the prevalence rate of men is significantly higher than that of women. Older age, long duration of T2DM, poor blood glucose control, increased total cholesterol level, increased blood uric acid level, decreased urine pH value, and increased platelet lymphocyte ratio are potential risk factors for diabetes foot. Male patients should also pay attention to the occurrence of overweight and obesity tendency to reduce the risk of diabetes foot.

OBJECTIVE： To investigate the protective effect and its mechanism of thymoquinone （TQ） on myocardial fibrosis （MF） induced by lipopolysaccharide in rats. METHODS： Totally 40 male Wistar rats were randomly divided into control group， model group， TQ low-dose and high-dose groups [5， 10 mg/（kg?d）]， with 10 rats in each group. Except that control group was given constant volume of normal saline intraperitoneally， other groups were given LPS intraperitoneally to induce MF model， once a day， for consecutive 3 weeks. Since the first day of modeling， administration group was given relevant medicine intraperitoneally， once a day， for consecutive 3 weeks. After last medication， ELISA method was used to detect the contents of serum inflammation factors （IL-1β， IL-6， TNF-α） in rats. Cardiac mass parameters （HW/BM， LVW/BW） were weighed and calculated. HE staining was used to observe the histopathological changes of myocardial tissue. The contents or activities of oxidative stress indicators （MDA， SOD） and myocardial collagen indexes （HYP， Col-Ⅰ， Col-Ⅲ） were detected by chemical analysis， xanthine oxidase method or ELISA. mRNA expression of regulation genes （Col-Ⅰ， Col-Ⅲ， MMP-3， MMP-9， TGF-β1 and Smad3） related to myocardial fibrosis were determined by real-time fluorescence quantitative PCR. RESULTS： Compared with control group， there were swollen myocardial cells， disordered nuclei of different sizes and visible fiber hyperplasia in model group； the levels of serum inflammatory factors and LVW/BW， cardiac contents of MDA， HYP， Col-Ⅰand Col-Ⅲ， mRNA expression of Col-Ⅲ， TGF-β1 and Smad3 in model group were increased significantly （P＜0.05）， while SOD activity was decreased significantly （P＜0.05）. Compared with model group， the degree of myocardial fibrosis was improved in TQ groups to different extents； serum content of IL-1β and the contents of MDA， HYP and Col-Ⅰ in cardiac tissue in TQ low-dose group， serum contents of IL-1β， IL-6 and TNF-α， LVW/BW and the contents of MDA， HYP， Col-Ⅰ and Col-Ⅲ in cardiac tissue of TQ high-dose group as well as mRNA expression of Col-Ⅰ， Col -Ⅲ， TGF-β1 in TQ groups were decreased significantly （P＜0.05）. The activities of SOD in cardiac tissue were increased significantly in TQ groups （P＜0.05）. There was no statistical significance in other indexes among groups （P＞0.05）. CONCLUSIONS： TQ can protect against MF model rats to certain extent， the mechanism of which may be associated with the inhibition of inflammation reaction and oxidant stress reaction， and down-regulation of mRNA expression of Col-Ⅰ， Col-Ⅲ and TGF-β1.