ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

ObjectiveTo investigate the mechanism of Shenkang injection in delaying diabetic kidney disease by regulating endoplasmic reticulum stress and attenuating podocyte apoptosis through the Glucose regulated protein 78 （ GRP78 ） / transcription factor C / EBP homologous protein （ CHOP ） signaling pathway （GRP78/CHOP） signaling pathway. MethodsFor the animal experiment， 10 12-week-old db/m mice were selected as a normal group， and 30 12-week-old db/db mice were randomly divided into a model group， a Shenkang injection group （15.6 mL·kg^-1）， and a dapagliflozin group （1.6 mg·kg^-1）. To observe the general condition of mice， fasting blood glucose， urinary albumin/urine creatinine （ACR）， and 24 h urine protein quantification were detected in each group before drug administration. After 12 weeks of drug treatment， mice were tested for fasting blood glucose， total cholesterol （TC）， triglyceride （TG）， low-density cholesterol （LDL）， ACR， 24 h urine protein quantification， blood creatinine （SCr）， and blood urea （UREA）. Hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and transmission electron microscopy were used to observe the pathologic morphology in renal tissue. Immunohistochemistry was used to detect the expressions of nephroprotective marker protein （Nephrin）， glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in renal tissue. Western blot was used to detect the expressions of GRP78， CHOP， Bcl-2， Bax， and Nephrin proteins， and Real-time polymerase chain reaction （Real-time PCR） was employed to detect the expressions of Nephrin， GRP78， CHOP， Bcl-2， and Bax mRNAs in renal tissue. ResultsBefore drug administration， compared with those in the normal group， the body mass of db/db mice was significantly increased， and blood glucose， 24 h urine protein quantification， and ACR were significantly elevated in the Shenkang injection group and Dapagliflozin group （P<0.01）. After 12 weeks of administration， compared with those in the model group， the general state of mice in the Shenkang injection group was significantly improved， and the body mass was decreased. The blood glucose was significantly reduced （P<0.01）， and blood lipids TC， TG， and LDL were significantly decreased （P<0.05， P<0.01）. The 24 h urine protein quantification and ACR were significantly decreased （P<0.05）， and SCr and UREA were significantly reduced （P<0.01）. Compared with those of the model group， the pathologic results of the Shenkang injection group showed that proliferation of mesangial cells， reduction of inflammatory cell infiltration， and alleviation of renal tubular vacuolization and podocyte damage were observed in renal tissue of mice. Electron microscopy showed that fusion of the pedicle protruding and thickening of the basement membrane were reduced. Immunohistochemistry results showed that the expressions of GRP78， CHOP， and Bax proteins were significantly reduced （P<0.01）， and the expressions of Nephrin and Bcl-2 proteins were significantly increased （P<0.01） in renal tissue of the Shenkang injection group. Western blot results showed that the expressions of Nephrin and Bcl-2 in the Shenkang injection group were significantly increased （P<0.05， P<0.01）， and the expressions of GRP78， CHOP， and Bax proteins were significantly decreased （P<0.05， P<0.01）. Real-time PCR results showed that the expressions of GRP78， CHOP， and Bax mRNAs were down regulated in the Shenkang injection group （P<0.01）， and the expressions of Nephrin and Bcl-2 mRNAs were up regulated （P<0.01）. ConclusionShenkang injection inhibits endoplasmic reticulum stress response and podocyte apoptosis by regulating the GRP78/CHOP signaling pathway， which in turn ensures the integrity of glomerular filtration barrier， reduces the occurrence of proteinuria， improves renal function， and thus delays the progression of diabetic kidney disease.

Objective:To investigate the clinical efficacy and safety of non-invasive bilevel positive airway pressure (BiPAP) ventilator combined with oxygen atomization in the treatment of chronic obstructive pulmonary disease (COPD) complicated with type Ⅱ respiratory failure.Methods:A total of 80 patients with COPD complicated with type Ⅱ respiratory failure admitted to Haiyan County People′s Hospital from June 2019 to July 2021 were selected, and they were divided into the observation group and the control group by the random number table method, with 40 cases in each group. Patients in both groups received conventional treatment, while patients in the control group were connected with BiPAP non-invasive ventilator and received non-invasive mechanical ventilation in S/T mode; the observation group was given aerosol inhalation drugs during ventilation, and both groups were treated for 7 d. Blood gas indicators and vital signs were collected before treatment and 7 d after treatment. Clinical symptoms were investigated by COPD patient Caring Assessment Tool (CAT) and Dyspnea Scale (DECAF). Serum levels of interleukin (IL)-10, tumor necrosis factor (TNF-α) and CD 4+/CD 8+ were determined, and treatment outcomes and adverse reactions were compared between the two groups. Results:After treatment, the partial pressure of oxygen (PaO 2) and the oxygen saturation (SaO 2) in the observation group were higher than those in the control group: (73.41 ± 5.26) mmHg(1 mmHg = 0.133 kPa) vs. (65.11 ± 4.33) mmHg, 0.921 ± 0.052 vs. 0.884 ± 0.039; the arterial partial pressure of carbon dioxide (PaCO 2), heart rate (HR), respiratory rate (RR) were lower than those in the control group: (45.20 ± 5.33) mmHg vs. (50.52 ± 5.96) mmHg, (90.12 ± 8.56) times/min vs. (98.52 ± 9.63) times/min, (17.41 ± 2.26) times/min vs. (22.10 ± 3.05) times/min, there were statistical differences ( P<0.05). After treatment, CAT scores and DECAF scores in the observation group were lower than those in the control group: (8.45 ± 1.63) scores vs. (12.77 ± 2.36) scores, (0.89 ± 0.15) scores vs. (1.15 ± 0.19) scores, there were statistical differences ( P<0.05). After treatment, the levels of IL-10 and CD 4+/CD 8+ in the observation group were higher than those in the control group: (15.28 ± 3.12) ng/L vs. (13.41 ± 2.96) ng/L, 1.71 ± 0.38 vs. 1.54 ± 0.30; while the level of TNF-α was lower than that in the control group: (215.27 ± 33.96) ng/L vs. (251.11 ± 50.95) ng/L, there were statistical differences ( P<0.05). The hospitalization time in the observation group was shorter than that in the control group: (13.52 ± 3.96) d vs. (15.22 ± 2.74) d, there was statistical difference ( P<0.05). The rates of tracheal intubation and the incidence of adverse reactions between the two groups had no significant differences ( P>0.05). Conclusions:Non-invasive BiPAP ventilator combined with oxygen atomization can improve blood gas index, vital signs and clinical symptoms of COPD patients complicated with type Ⅱ respiratory failure and reduce inflammatory response.

Objective To investigate the intervention effect of Xuanfuhua decoction on mice with nonalcoholic steatohepatitis (NASH) induced by high-fat, high-fructose, and high-cholesterol diet. Methods A total of 32 male C57/BL6J mice were randomly divided into normal group, model group, Xuanfuhua decoction group, and obeticholic acid group, with 8 mice in each group. Since week 24 of modeling using high-fat, high-fructose, and high-cholesterol diet, each group was given the corresponding drug for intervention at a dose of 14.19 g/kg by gavage for the Xuanfuhua decoction group and 10 mg/kg by gavage for the obeticholic acid group and a volume of 20 mL/kg for gavage, once a day for 6 consecutive weeks. HE staining, oil red O staining, Sirius Red staining, and Masson staining were used to observe the pathological changes, lipid deposition, and collagen deposition of liver tissue; related kits were used to measure the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and glucose, as well as the content of TG and hydroxyproline (Hyp) in liver tissue; quantitative real-time PCR was used to measure the expression of genes associated with lipid metabolism, inflammation, and fibrosis in liver tissue; immunohistochemical staining was used to observe the positive expression of F4/80 and α-SMA in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t -test was used for further comparison between two groups. Results Compared with the normal group, the model group had significant increases in body weight, liver wet weight, and serum levels of AST, ALT, TC, TG, LDL-C and glucose (all P < 0.01). HE staining showed hepatocyte steatosis, a large number of fat vacuoles, hepatocyte ballooning degeneration, and inflammatory cell infiltration in liver tissue of the mice in the model group, and the model group had a significant increase in NAFLD activity score (NAS) compared with the normal group ( P < 0.01). Oil red O staining showed the deposition of a large number of red lipid droplets with different sizes in hepatocytes of the mice in the model group, and compared with the normal group, the model group had significant increases in the area percentage of oil red O staining and the content of TG in the liver ( P < 0.01). Sirius Red staining and Masson staining showed significant collagen fiber hyperplasia in the perisinusoidal area, the central vein, and the portal area in the model group, and the model group had a significant increase in the content of Hyp in liver tissue compared with the normal group ( P < 0.05). Compared with the model group, the Xuanfuhua decoction group had significant reductions in the serum levels of AST, ALT, TC, TG, LDL-C, and glucose (all P < 0.05), significant improvements in hepatic steatosis, inflammatory infiltration, lipid droplet deposition, and collagen fiber hyperplasia, and significant reductions in NAS score, area percentage of oil red O staining, and content of TG and Hyp in the liver (all P < 0.05). Compared with the normal group, the model group had significant increases in the mRNA expression levels of lipid metabolism-related genes (SREBP-1c, FASN, SCD-1, PPAR-γ, and CD36), inflammation-related genes (F4/80, TNF-α, CCL2, and CD11b), and the fibrosis-related gene α-SMA (all P < 0.05), and immunohistochemical staining showed significant increases in the positive expression of F4/80 and α-SMA ( P < 0.01). Compared with the model group, the Xuanfuhua decoction group had significant reductions in the mRNA expression levels of SREBP-1c, FASN, SCD-1, PPAR-γ, CD36, F4/80, TNF-α, CCL2, CD11b, and α-SMA in liver tissue (all P < 0.05), and immunohistochemical staining showed significant reductions in the positive expression of F4/80 and α-SMA ( P < 0.01). Conclusion Xuanfuhua decoction has a good intervention effect on mice with NASH induced by high fat, high fructose, and high-cholesterol diet and can significantly inhibit hepatic lipid deposition, inflammatory response, and liver fibrosis.

Most α2-AR agonists derived from dexme-detomidine have few structure differences between them and have no selectivity for α2A/2B-AR or Gi/Gs,that can lead to the side effect of drugs.To get novel and potent α2A-AR agonists,we built the homology model for human α 2A-AR and α2B-AR to find α2A-AR agonists with higher selectivity.Compound P300-2342 and its 3 analogs sig-nificantly decreased the locomotor activity of mice(P＜0.05).Furthermore,P300-2342 and its 3 analogs inhibited the binding of[3H]rauwolscine to α 2A-AR and α 2B-AR respectively.In α2A-AR-HEK293 cells,P300-2342 decre-ased forskolinstimulatedcAMPpruductionwithoutincreas-ing cAMP pruduction,that indicated the P300-2342 acti-vating α2A-AR coupling with Gαi/o pathway without Gαs coupling.P300-2342 had no agonistic and antagonistic activities on α 2B-AR.Similar results were shown in 3 analogs of P300-2342.The docking results showed that P300-2342 formed the π-hydrogen bonds with Y394,V114 of α2A-AR,and with V93 of α2B-AR.3 analogs of P300-2342 formed several π-hydrogen bonds with V114,Y196,F390 of α 2A-AR and with V93 of α 2B-AR.We believe that these molecules can serve as leads for fur-ther optimization of α2A-AR agonists with potentially few side effects.

Objective:To explore the risk factors of acute kidney injury (AKI) in acute respiratory distress syndrome (ARDS) patients with mechanical ventilation.Methods:A retrospective analysis was conducted. ARDS patients with mechanical ventilation admitted to ICU of Taizhou People's Hospital from January 2019 to December 2019 were enrolled. Patients were divided into the AKI group and non-AKI group according to whether the patients had AKI. Clinical characteristics and laboratory indicators of the two groups were compared. Risk factors of incidence of AKI in ARDS patients were analyzed. The Kaplan-Meier survival curve was drawn to evaluate the survival rates of the two groups.Results:A total of 120 ARDS patients with mechanical ventilation were included, and 57 patients (47.5%) developed AKI. Procalcitonin, increased basal creatinine, decreased pH and impaired consciousness were independent risk factors for AKI in ARDS patients with mechanical ventilation. Fifty-seven of the 120 patients died with a mortality of 38.3%. The Kaplan-Meier survival curve showed that the survival rate of the AKI group was significantly lower than that of the non-AKI group ( P<0.001). Conclusions:The incidence and mortality of AKI is high in ARDS patients with mechanical ventilation. Procalcitonin, increased basal creatinine, decreased pH and impaired consciousness are independent risk factors for AKI in ARDS patients with mechanical ventilation.

To investigate the neuroprotective effect and possible mechanism of masitinib on cerebral ischemia-reperfusion injury in rats, healthy adult male Sprague-Dawley rats were divided into sham group (n = 12), model group (n = 12), masitinib low dosage group (n = 12), masitinib middle dosage group (n = 12), and masitinib high dosage group (n = 12). All rats was subjected to middle cerebral artery occlusion (MCAO) for two hours and reperfusion except sham group, and received treatment twice per day for 7 days once reperfusion started.Neurological score, infarct volume, and brain water content were detected; some autophagic markers, apoptotic and inflammatory cytokines were evaluated by Western blot and PCR after 7 d of reperfusion. Treatment with masitinib significantly ameliorated neurologic deficit, infarct volume and brain water after I/R injury. Masitinib also decreased the ratio of LC3II/I and the expression of Beclin-1 and increased the expression of p62 in the brain tissues of rats with I/R injury.Furthermore, it could inhibit apoptosis-related proteins and NF-κB expression. Masitinib could relieve the cerebral ischemia-reperfusion injury in rats through inhibiting autophagy and apoptosis.

Objective:To study the treatment efficacy of percutaneous radiofrequency thermocoagulation in patients with hyperhidrosis of heads and palms.Methods:Thirty patients with primary hyperhidrosis of heads and palms, admitted to our hospital from June 2017 to May 2019, were chosen in our study. CT-guided percutaneous puncture of T 3 or T 4 and sympathetic ganglion radiofrequency thermocoagulation were given to all patients. The evaluation of curative effects and complications of these patients were summarized during the 12 months of follow up. Results:The symptoms of hyperhidrosis in 24 patients got significant improvement, enjoying postoperative satisfaction rate of 80%. During the surgery, 5 patients suffered thoracic and lung puncture injury, including 4 with pneumothorax and one with hemothorax. Seven patients experienced pain and numbness in the chest, back, armpit or upper arm after surgery; 10 patients developed compensatory hyperhidrosis of the back, and two patients developed compensatory hyperhidrosis of the back and bilateral feet.Conclusion:Percutaneous radiofrequency is an effective treatment for hyperhidrosis that provides excellent immediate and long-term effect, as well as low complication rate.

Objective:To investigate the expression change of blood plasma miRNA-210 (miR-210) in blood plasma for patients with esophageal squamous cell carcinoma (ESCC) before and after radiotherapy and its effect on cell proliferation, cycle, apoptosis of ESCC cells in vitro.Methods:The blood specimens from 22 patients with newly diagnosed ESCC (ESCC group) before and after radical radiotherapy between December 2013 and March 2015 in Linyi People's Hospital of Shandong Province as well as 15 healthy controls (the healthy control group) were collected. miRNA-21 (miR-21) was treated as the positive controls. The real-time polymerase chain reaction (RT-PCR) was used to detect the expression level of miR-210 and miR-21 in blood plasma before and after radiotherapy for patients, and the expression of miR-21 in ESCC Eca109 cells at normoxia and hypoxia time. The cell proliferation, cycle and apoptosis of Eca109 cells in untransfected group (the blank control group), miR-21 transfected mimics negative control RNA group (negative control group) and miR-210 transfected mimics RNA group (miR-210 group) were detected by using EdU cell proliferation assay and flow cytometry.Results:A total of 59 plasma samples from ESCC group and the healthy control group were collected. The relative expression level [median ( P25, P75)] of blood plasma miR-210 and miR-21 in ESCC group before radiotherapy was higher than that in the healthy control group, and the difference was statistically significant [4.04×10 -4 (2.06×10 -4, 6.68×10 -4) vs. 0.54×10 -4 (0.28×10 -4, 0.77×10 -4), 397.07×10 -4 (181.77×10 -4, 742.93×10 -4) vs. 127.43×10 -4 (21.97×10 -4, 184.65×10 -4); U value was 37.0, 49.0, respectively, all P < 0.01]. The expression level of miR-210 and miR-21 before radiotherapy in ESCC group was not related with tumor location and differentiation degree (all P > 0.05). After the radical radiotherapy one week later, the relative expression level of miR-210 and miR-21 in blood plasma of ESCC group was 65.33×10 -4 (22.15×10 -4, 160.87×10 -4), 437.23×10 -4 (327.18×10 -4, 749.09×10 -4), respectively, which was higher compared with that before radiotherapy ( U value was 32.0, 154.0, respectively, both P < 0.05), and the increase of miR-210 was more significant. The expression level of miR-210 after hypoxic cultured Eca109 cells for 12 h was increased compared with the normal oxygen with the peak value 12 h later, and the difference was statistically significant ( P < 0.01). EdU cell proliferation assay showed that the Eca109 cell proliferative activity after transfection of 24 h and 48 h in miR-210 group was decreased compared with the negative control group and the blank control group, and the difference was statistically significant (all P < 0.01). Flow cytometry analysis showed that the proportion of G 2/M phase of Eca109 cells in miR-210 group after transfection of 24 h was increased compared with the negative control group and the blank control group, and the difference was statistically significant ( P < 0.05). After transfection of 48 h, the increased proportion in G 2/M phase was more obvious ( P <0.01); there was no statistically difference in the apoptotic cell proportion among three groups after transfection of 24 h and 48 h (all P > 0.05). Conclusions:miR-210 is highly expressed in the blood plasma of ESCC patients, especially the significant increase in the expression level of miR-210 in blood plasma after radical radiotherapy. miR-210 is highly expressed in hypoxic ESCC Eca109 cells. The overexpression of miR-210 can inhibit cell proliferation and its mechanism may be related with cell arrest in G 2/M phase.

Objective To investigate the clinical efficacy of free flap transplantation in repairing the Gustilo type ⅢB and ⅢC fractures of tibia and fibula combined with soft tissue defects.Methods A retrospective case series study was conducted on the clinical data of 46 patients who had Gustilo type ⅢB and ⅢC fractures of tibia and fibula with soft tissue defects admitted from June 2013 to January 2017.There were 34 males and 12 females,aged 1-67 years (mean,39 years).The wound defect areas ranged from 6 cm × 20 cm to 7 cm × 38 cm.According to the Gustilo fracture classification,there were 31 cases of type ⅢB and 15 cases of type ⅢC.According to the AO fracture typing,there were five cases of type A,23 type B,and 18 type C.All patients were repaired with free flap transplantation,among which 40 patients were treated with anterolateral thigh flap and six with latissimus dorsi flap.The areas of anterolateral thigh flap ranged from 6 cm × 13 cm to 14 cm ×32 cm,and those of the latissimus dorsi flap from 6 cm × 22 cm to 7 cm × 40 cm.Efficacy was evaluated by flap survival rate,complications,fracture healing time,lower limb function scoring system (LEFS),and skin flap function.Results All limbs were salvaged successfully.One case of total flap necrosis and eight cases of postoperative crisis occurred.After active exploration and treatment,three cases were seen distal local necrosis,and the total survival rate was 91％.Infection at the donor site was found in two cases.The complication incidence rate was 4％.All patients were followed up for 7-42 months,with an average of 19 months.The fracture healing time averaged 43.5 weeks,and the LEFS score averaged 54 points.According to the seven indexes of flap function,the results were excellent in 1 1 cases,good in 29 cases,fair in four cases,and poor in two cases,with an excellent and good rate of 87％.Conclusion Free flap transplantation can achieve satisfactory efficacy in treating Gustilo type ⅢB and ⅢC of tibia and fibula combined with soft tissue defects,with high limb salvage rate and good function recovery.