Objective To construct an"Internet+TCM nursing service"talent cultivation model in Zhejiang Province and to evaluate its application effect.Methods Based on the literature review and expert panels,the"Internet+TCM nursing service"talent cultivation model was constructed in Zhejiang Province.A total of 63 trainees from 63 TCM and integrated traditional Chinese and Western medicine hospitals in the province were selected to carry out for 45 days of theoretical training and 9 days of clinical skills training.After the training,the training effect was evaluated by theoretical knowledge,TCM nursing skills,scenario simulation case assessment,trainees'satisfaction,as well as a survey on the results of practice.Results The constructed talent cultivation model contains course contents including theoretical learning,skill training and emergency home treatment management and corresponding assessment programs.Sixty-three trainees successfully completed the course with the theoretical score of(92.24±3.64),the skill score of(97.13±2.53),and the situational case score of(95.78±3.02).Fifty-five trainees(87.30％)were assessed as"excellent"and 8(12.70％)as"good".The trainees'satisfaction about the overall module design of the project was(4.93±0.23)and 415 cases of"Internet+TCM nursing service"were carried out.Conclusion The"Internet+TCM nursing service"talent cultivation model in Zhejiang Province has strong applicability and remarkable training effect,which can provide references for the implementation of"Internet+TCM nursing service"in other regions.

Objective To verify the function of exosomes from 293T cells over-expressing membrane-localized IL-3 in vitro,so as to lay a foundation for in vivo function verification in animal models of Alzheimer's disease.Methods Using the patented structure of the group,a recombinant IL-3 lentiviral vector was constructed and virus-infected 293T cells were packaged.Stable cell strain over-expressing IL-3 was screened.The membrane localization of IL-3 was verified by flow cytometry and immuno-fluorescence.Il-3-exosomes were purified by ultra filtration centrifugation,the exosmic morphology was observed by transmission electron microscope,the size distribution and concentration of exosomes were detected by nano-flow analysis,and the expression of IL-3 and exosome related marker proteins were detected by Western blot.The effect of BV-2 on the phagocytosis of Aβ amyloid was detected by immuno-fluores-cence.Results Through vector construction,virus infection,screening and verification of puromycin,293T cell strain with stable over-expression membrane-anchored IL-3 was obtained.The purified exosomes were collected and the structures of double-layer membrane vesicles with a diameter of 50-100 nm were observed under transmission electron microscope.Western blot results proved the presence of CD63,ALIX,TSG101 and other exosome marker proteins and these molecules were rich in IL-3 as compared with the control,that suggested the successful purifica-tion of IL-3-exosomes.The results of immuno-fluorescence assay showed that IL-3-exosomes promoted the phagocy-tosis of Aβ amyloid by BV-2 cells in vitro.Conclusions The gene modified 293T cell exosomes membrane-anchored expression of IL-3 can play a role of both IL-3 and exosomes in vitro,which promote the phagocytosis of microglia,there for provides a new idea for the clinical treatment of Alzheimer's disease.

Background::Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.Methods::TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results::TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion::TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. Fat accumulation "sensitizes" the liver to insult and leads to nonalcoholic steatohepatitis (NASH). G protein-coupled receptor 35 (GPR35) is involved in metabolic stresses, but its role in NAFLD is unknown. We report that hepatocyte GPR35 mitigates NASH by regulating hepatic cholesterol homeostasis. Specifically, we found that GPR35 overexpression in hepatocytes protected against high-fat/cholesterol/fructose (HFCF) diet-induced steatohepatitis, whereas loss of GPR35 had the opposite effect. Administration of the GPR35 agonist kynurenic acid (Kyna) suppressed HFCF diet-induced steatohepatitis in mice. Kyna/GPR35 induced expression of StAR-related lipid transfer protein 4 (STARD4) through the ERK1/2 signaling pathway, ultimately resulting in hepatic cholesterol esterification and bile acid synthesis (BAS). The overexpression of STARD4 increased the expression of the BAS rate-limiting enzymes cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and CYP8B1, promoting the conversion of cholesterol to bile acid. The protective effect induced by GPR35 overexpression in hepatocytes disappeared in hepatocyte STARD4-knockdown mice. STARD4 overexpression in hepatocytes reversed the aggravation of HFCF diet-induced steatohepatitis caused by the loss of GPR35 expression in hepatocytes in mice. Our findings indicate that the GPR35-STARD4 axis is a promising therapeutic target for NAFLD.

OBJECTIVE To study the effect and potential mechanism of eriodictyol on non-alcoholic fatty liver disease （NAFLD）. METHODS Sixteen C57BL/6J mice were randomly divided into control group， NAFLD model group， and eriodictyol low-dose and high-dose groups （50， 100 mg/kg）， with 4 mice in each group. Except for control group， the other groups were fed with high fat diet to induce NAFLD model. After four weeks of preprocessing， they were given relevant medicine intraperitoneally （0.01 mL/g）， once a day， for 6 consecutive weeks. The body weight and liver weight of mice were measured， and the pathological damage of liver tissue in mice was observed. The levels of aspartate aminotransferase （AST）， alanine aminotransferase（ALT）， and triglycerides （TG） in serum， as well as the protein expressions of nuclear factor-erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were determined. In vitro NAFLD model was established by using 0.5 mmol/L oleic acid （OA） in HepG2 cells. Normal control group， NAFLD model group and eriodictyol low-， medium- and high-concentration groups （50， 100， 150 μmol/L） were set up. HepG2 cells in drug groups were treated with eriodictyol for 24 h at the time of modeling. The lipid deposition was observed in cells， and the levels of TG， malondialdehyde （MDA） and reactive oxygen species （ROS） as well as the phosphorylation levels of the mitogen-activated protein kinase （MAPK） signal pathway related proteins [extracellular signal-regulated kinase （ERK）， c- Jun N-terminal kinase （JNK）] and the protein expressions of Nrf2 and HO-1 were all determined. RESULTS In the in vivo experiment， compared with the NAFLD model group， the body weight， liver weight， the serum levels of AST， ALT and TG were all decreased significantly in eriodictyol low- and high-dose groups （except for serum level of AST in eriodictyol low-dose group） （P＜0.01）； liver lipid deposition was reduced significantly and the protein expressions of Nrf2 and HO-1 in liver tissues were further up-regulated （P＜0.01）. In the in vitro experiment， compared with the NAFLD model group， the lipid deposition in hepatocytes was reduced in eriodictyol low-， medium- and high-concentration groups （P＜0.01）， and the levels of ROS， MDA and TG were down-regulated （P＜0.05 or P＜0.01）； the phosphorylation levels of ERK and JNK were significantly down-regulated （P＜0.01）， while the protein expressions of Nrf2 and HO-1 were up-regulated significantly （P＜0.01）. CONCLUSIONS Eriodictyol can inhibit MAPK signaling pathway and activate Nrf2/HO-1 signaling pathway to alleviate NAFLD.

Objective:To explore the relationship between aortic arch calcification (AoAC) and arteriovenous fistula (AVF) failure in maintenance hemodialysis (MHD) patients.Methods:The patients who underwent initial AVF and started MHD in the General Hospital of Ningxia Medical University from September 2016 to September 2017 were retrospectively recruited and prospectively followed up until two years after AVF surgery or withdrawal from MHD or death. Calcification of the aortic arch was estimated with plain chest radiology. The patients were divided into four groups (0-3 grade) according to the aortic arch calcification score (AoACs). Spearman correlation analysis was used to analyze the relationship between AoACs and AVF failure. Multivariate logistic regression was used to analyze the influencing factors of AVF failure.Results:A total of 165 MHD patients were included in this study, with age of (55.52±14.06) years old and 102 males (61.82%). Among 128 AoAC patients (77.6%), 45 patients were categorized as grade 1 (27.3%), 35 patients as grade 2 (21.2%) and 48 patients as grade 3 (29.1%). There was significant difference in the, age, pulse pressure, corrected calcium, phosphorus, diastolic blood pressure, intact parathyroid hormone and AVF failure between AoAC group and no AoAC group (grade 0 calcification) (all P<0.05). The results of Spearman correlation analysis showed that AoACs was positively correlated with AVF failure ( r=0.759, P=0.010), age ( r=0.407, P<0.001), pulse pressure ( r=0.575, P=0.006), and diabetes history ( r=0.848, P=0.049), blood calcium ( r=0.591, P=0.018), and blood phosphorus ( r=0.509, P=0.012), and negatively correlated with diastolic blood pressure ( r=-0.614, P=0.013). Multivariate logistic regression analysis showed that diabetes history ( OR=6.702, 95% CI 1.431-31.396, P=0.016), high corrected calcium ( OR=10.830, 95% CI 3.479-35.300, P=0.008), high phosphorus ( OR=3.792, 95% CI 1.128-12.750, P=0.031) and AoAC ( OR=4.473, 95% CI 1.490-13.428, P=0.008) were the independent influencing factors of AVF failure. Conclusions:AoAC is an independent risk factor for AVF failure in MHD patients. Evaluation of AoAC has predictive value for AVF failure.

Objective:To explore the characteristics and evolution trend of renal disease spectrum in Ningxia.Methods:The demographic, clinical manifestations and renal pathological examination results of patients who underwent renal biopsies in the General Hospital of Ningxia Medical University from August 1, 2008 to December 31, 2019 were collected and analyzed retrospectively. According to the time period of receiving renal biopsy, the patients were divided into 2008—2013 group and 2014—2019 group. The age and sex constituent, clinical manifestation, renal disease type, pathological types of primary and secondary glomerular disease and the main clinical manifestations of patients with diabetic nephropathy were compared between the two groups. The changing trend of renal disease spectrum in Ningxia from 2008 to 2019 was analyzed.Results:A total of 3 867 patients who underwent renal biopsies were enrolled in this study, with more males (53.71%, 2 077/3 867), and age of (39.59±14.05) years old. The most common clinical manifestation of patients receiving renal biopsies was nephrotic syndrome (36.33%, 1 405/3 867). Among them, primary glomerular diseases accounted for 78.79% (3047/3 867), followed by secondary glomerular diseases (18.57%, 718/3 867), renal tubulointerstitial diseases (1.45%, 56/3 867) and hereditary nephropathy (1.19%, 46/3 867). The most common primary glomerular disease was IgA nephropathy (44.60%, 1 359/3 047), followed by membranous nephropathy (30.75%, 937/3 047). The most common secondary glomerular disease was Henoch-Sch?nlein purpura nephritis (27.44%, 197/718), followed by lupus nephritis (25.07%, 180/718). Compared with the 2008—2013 group, the proportion of membranous nephropathy increased, the proportion of mesangial proliferative glomerulonephritis (non-IgA deposition) decreased (both P<0.001), the proportions of diabetic nephropathy and hypertensive renal damage increased, and the proportions of Henoch-Sch?nlein purpura nephritis and hepatitis B virus-associated glomerulonephritis decreased in 2014—2019 group (all P<0.01). Compared with the 2008—2013 group, the proportions of acute kidney injury, chronic renal failure, simple hematuria and urinary protein≤1.0 g/24 h increased in kidney biopsy patients in 2014—2019 group, while the proportion of nephrotic syndrome decreased (all P<0.05). Compared with the 2008—2013 group, the proportion of chronic renal failure in diabetic nephropathy patients increased during renal biopsy, and the proportion of albuminuria with hematuria decreased in 2014—2019 group (all P<0.05). Conclusions:Primary glomerular disease is the most common kidney disease in Ningxia. IgA nephropathy is the most common cause, and the proportion of membranous nephropathy is increasing year by year. Henoch-Sch?nlein purpura nephritis is the most common secondary glomerular disease, and the proportions of diabetic nephropathy and hypertensive renal damage are increasing year by year, suggesting that the screening of renal complications of metabolic diseases in Ningxia should be strengthened and pay more attention to the patients with mild abnormal urine test.

Objective:To evaluate the feasibility of Full-stack Smart Pelvic Floor Ultrasound (FSPFU) software in the acquisition and measurement of the minimal levator hiatus (LH).Methods:Transperineal pelvic floor ultrasonography was performed in 119 women of 6-month postpartum from Nov.2020 to Jan.2021 of Shenzhen Second People′s Hospital. Mid-sagittal plane of pelvic floor was set as the initial plane, and the three-dimensional volume data was acquired. The dataset was stored in the machine. The offline volume data was manually adjusted to obtain the minimal LH images and measured by four physicians (two junior physicians as the D1 group and two senior physicians as the D2 group). For comparison, the results were also obtained using the fully automated method—the FSPFU software by a junior physician (the D3 group). The obtained parameters of minimal LH included area, circumference, anterioposterior diameter, transverse diameter, left and right levator-urethral gap distance. Analysis time was recorded for each group. The contours of minimal LH were outlined by three groups and the overlapping rate was calculated. The quality of the resulted images was evaluated and scored by another two senior physicians(A and B) independently.Results:The D3 group had a significant shorter analysis time compared with the other two groups, and the D1 group took a longer time than the D2 group, regardless of the cystocele severity (D1: 82.97 s, D2: 62.51 s, D3: 2.71 s, all P<0.05). The intergroup agreements and correlations of the minimum LH area were good (all ICC>0.85, rs>0.70, P<0.001) and the outlined contours were largely overlapped (>92%). There was no significant difference in image quality among the three groups(all P>0.05). Conclusions:FSPFU software can automatically obtain and measure the minimum LH in an efficient and accurate way, which can improve the effectiveness of the present pelvic floor examination. FSPFU software can be an useful tool in the diagnosis of pelvic floor dysfunctional diseases.

Objective:To evaluate the clinical effect of total-model fractional CO 2 laser in the treatment of atrophic acne scar. Methods:A retrospective analysis was performed on the clinical data of patients with atrophic acne scar treated by total-model fractional CO 2 laser(Deep FX+ Active FX+ CW) in Laser Aesthetic Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2017 to September 2019. CW mode and/or Active FX mode was used to fine grinding of the scar edge, and Active FX mode and Deep FX mode were used to scan the whole area acne scar involved. The treatment was performed 3-5 times with an interval of more than 3 months. Two attending physicians who were not involved in the study evaluated the photos of patients before treatment and 3-5 times after treatment with the Global Aesthetic Improvement Scale (GAIS) and the Echelle d’Evaluation Clinique des Cicatrices d’acne (ECCA). Acne scar and overall facial skin quality were assessed with GAIS, a total score of 1 to 3, with a score 1 indicating deterioration and a score 3 indicating significant improvement. The severity and density of acne scarring were assessed with ECCA, with the higher the score, the more severe it is. The international numeric rating scale (NRS) was used to rate the pain immediately after treatment (0-10 points), with 0 indicating no pain and 10 indicating extreme pain. Side effects such as the occurrence of crusts, erythema, pigmentation and acne-like rash were observed. SPSS 24.0 was used for statistical analysis, and the measurement data were expressed by Mean±SD. Paired t-test was used for ECCA scores before and after treatment, and P<0.05 was considered as statistically significant difference. Results:A total of 75 patients were included in this study, including 16 males and 59 females, aged 27.2±6.2 years (19-49 years). Among them, the improvement in acne scar and overall facial skin quality were excellent in 12 cases, significant in 34 cases, median in 24 cases and poor in 5 cases. GAIS score was 1.62±0.77. The ECCA score was 157.20±18.89 before treatment and 138.93±23.62 after treatment, showing significant difference ( t=9.41, P<0.001). The pain score was 4.65±1.52 and disappeared spontaneously about 2-4 hours after operation. The scab stage was 6.65±0.89 days, and the erythema stage was 3.09±0.70 weeks. The post-inflammatory hyperpigmentation case occurred in 1.3% (1/75) and lasted for 4 months. Acne-like rash occurred in 16.0% (12/75), which relieved by external smear of fusidic acid. No blisters, hypopigmentation, bacterial or viral infection, scar formation and other adverse reactions happened. Conclusions:The total-mode fractional CO 2 laser is effective and safe in the treatment of facial atrophic acne scar.

Objective:To evaluate the clinical effect of total-model fractional CO 2 laser in the treatment of atrophic acne scar. Methods:A retrospective analysis was performed on the clinical data of patients with atrophic acne scar treated by total-model fractional CO 2 laser(Deep FX+ Active FX+ CW) in Laser Aesthetic Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2017 to September 2019. CW mode and/or Active FX mode was used to fine grinding of the scar edge, and Active FX mode and Deep FX mode were used to scan the whole area acne scar involved. The treatment was performed 3-5 times with an interval of more than 3 months. Two attending physicians who were not involved in the study evaluated the photos of patients before treatment and 3-5 times after treatment with the Global Aesthetic Improvement Scale (GAIS) and the Echelle d’Evaluation Clinique des Cicatrices d’acne (ECCA). Acne scar and overall facial skin quality were assessed with GAIS, a total score of 1 to 3, with a score 1 indicating deterioration and a score 3 indicating significant improvement. The severity and density of acne scarring were assessed with ECCA, with the higher the score, the more severe it is. The international numeric rating scale (NRS) was used to rate the pain immediately after treatment (0-10 points), with 0 indicating no pain and 10 indicating extreme pain. Side effects such as the occurrence of crusts, erythema, pigmentation and acne-like rash were observed. SPSS 24.0 was used for statistical analysis, and the measurement data were expressed by Mean±SD. Paired t-test was used for ECCA scores before and after treatment, and P<0.05 was considered as statistically significant difference. Results:A total of 75 patients were included in this study, including 16 males and 59 females, aged 27.2±6.2 years (19-49 years). Among them, the improvement in acne scar and overall facial skin quality were excellent in 12 cases, significant in 34 cases, median in 24 cases and poor in 5 cases. GAIS score was 1.62±0.77. The ECCA score was 157.20±18.89 before treatment and 138.93±23.62 after treatment, showing significant difference ( t=9.41, P<0.001). The pain score was 4.65±1.52 and disappeared spontaneously about 2-4 hours after operation. The scab stage was 6.65±0.89 days, and the erythema stage was 3.09±0.70 weeks. The post-inflammatory hyperpigmentation case occurred in 1.3% (1/75) and lasted for 4 months. Acne-like rash occurred in 16.0% (12/75), which relieved by external smear of fusidic acid. No blisters, hypopigmentation, bacterial or viral infection, scar formation and other adverse reactions happened. Conclusions:The total-mode fractional CO 2 laser is effective and safe in the treatment of facial atrophic acne scar.