Research report of living donor kidney harvesting in Bama miniature pigs with six gene modified / 器官移植

Objective To summarize the experience and practical value of living donor kidney harvesting in Bama miniature pigs with six gene modified. Methods The left kidney of Bama miniature pigs with six gene modified was obtained by living donor kidney harvesting technique. First, the ureter was occluded, and then the inferior vena cava and abdominal aorta were freed. During the harvesting process, the ureter, renal vein and renal artery were exposed and freed in sequence. The vascular forceps were used at the abdominal aorta and inferior vena cava, and the renal artery and vein were immediately perfused with 4℃ renal preservation solution, and stored in ice normal saline for subsequent transplantation. Simultaneously, the donor abdominal aorta and inferior vena cava gap were sutured. The operation time, blood loss, warm and cold ischemia time, postoperative complications and the survival of donors and recipients were recorded. Results The left kidney of the genetically modified pig was successfully harvested. Intraoperative bleeding was 5 mL, warm ischemia time was 45 s, and cold ischemia time was 2.5 h. Neither donor nor recipient pig received blood transfusion, and urinary function of the kidney transplanted into the recipient was recovered. The donor survived for more than 8 months after the left kidney was resected. Conclusions Living donor kidney harvesting is safe and reliable in genetically modified pigs. Branch blood vessels could be processed during kidney harvesting, which shortens the process of kidney repair and the time of cold ischemia. Living donor kidney harvesting contributes to subsequent survival of donors and other scientific researches.

Phosphatidic acid-enabled MKL1 contributes to liver regeneration: Translational implication in liver failure

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver function. In the present study we investigated the contribution of megakaryocytic leukemia 1 (MKL1), a transcriptional modulator, to liver regeneration. We report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure patients. Mice with MKL1 deletion exhibited defective regenerative response in the liver. Transcriptomic analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative transcription. MAPKAPK2 mediated phosphorylation primed MKL1 for its interaction with E2F1. Of interest, phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid (PA). PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver failure. Finally, PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure patients. In conclusion, our data reveal a novel mechanism whereby MKL1 contributes to liver regeneration. Screening for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

Establishment of animal models for depression in the elderly and progress on their application / 中华老年医学杂志

Geriatric depression in the elderly is becoming one of the most common psychiatric disorders affecting older people's mental and physical health.However, there is currently no systematic review on animal models for geriatric depression.Therefore, this paper analyzes and summarizes the animal models commonly used in geriatric depression studies and the application of antidepressants in geriatric depression models based on relevant national and international literature of recent years, aiming to provide insights on research approaches and considerations on study methods for geriatric depression.

Exploration on the blended learning reform in organ-systems based curriculum model of the endocrine system / 中华医学教育探索杂志

Since 2016, Binzhou Medical University began to carry out the blended learning reform in the organ-systems based curriculum (OSBC) of the experimental class of clinical medicine. Based on the traditional face-to-face teaching method, the blended learning mode of the integrated course of endocrine system under OSBC has been carried out by using the small private online course (SPOC) of MOOC platform of China universities. Many teaching methods have been adopted and formed, including case-based learning (CBL), problem-based learning (PBL), professional bilingual teaching, scientific research teaching and virtual simulation experiment teaching. The evaluation system for the combination of formative and summary assessment has been also adopted in the whole process to assess the students' academic achievement, and the teaching effect as well. The blended learning mode of the integrated course of the endocrine system under OSBC is still in the exploratory stage. There are some limitations, such as too high requirements for teachers' quality, long preparation time for teaching, and great difficulty in supervising online learning. However, the practice of teaching reform that has been carried out shows that it is effective, feasible, and worth popularizing.

The clinical effect of sacubitril valsartan combined with dapagliflozin in heart failure with reduced ejection fraction and non-diabetes patients / 西安交通大学学报(医学版)

【Objective】 To observe the clinical effect of combination therapy of sacubitril valsartan and dapagliflozin in heart failure with reduced ejection fraction (HFrEF) and non-diabetes patients. 【Methods】 This study involved 96 patients with HFrEF and non-diabetes. The patients were randomly divided into control group (50 cases) and observation group (46 cases). On the basis of routine treatment, the control group was treated with sacubitril valsartan, while the observation group was treated with sacubitril valsartan and dapagliflozin. After 1-month and 6-month treatment, we monitored blood pressure, N-terminal pro brain natriuretic peptide (NT-proBNP), high sensitivity troponin T (cTnT), fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), left ventricular ejection fraction (LVEF), left ventricular end diastolic diameter (LVEDd), left atrial diameter (LAD), left ventricular posterior wall thickness (LVPW), Minnesota soda heart failure life quality score (MLHFQ), the incidence of rehospitalization and death, and major adverse cardiovascular events (MACE) in the two groups. 【Results】 After 6 months, systolic blood pressure, cTnT, NT-proBNP, LVEDd, LVPW, and LAD of the observation group were significantly decreased compared with the control group (P0.05). 【Conclusion】 The combination treatment of sacubitril valsartan and dapagliflozin on HFrEF and non-diabetes patients can significantly improve cardiac function, inhibit myocardial remodeling, reduce the incidence of MACE, and improve the prognosis.

Mechanism study of Dangshen Pingfei Huoxue decoction in treatment of pulmonary fibrosis based on network pharmacology and molecular docking / 中国药理学通报

Aim To explore the potential mechanism of Dangshen Pingfei Huoxue decoction (DPHD) in the treatment of pulmonary fibrosis. Methods The common targets of DPHD and pulmonary fibrosis were obtained. Cytoscape software was used to construct " disease-drug-ingredients-targets " network diagram, and the common targets were imported into the STRING database for protein-protein interaction (PPI) analysis to screen out the core targets. In order to screen out key signaling pathways, the core genes were inputted into the DAVID platform for gene ontology (GO) and kyoto encyclopedia of genes genomes (KEGG) enrichment analysis. Then the molecular docking technology was used to verify the molecular docking between the core components and the key proteins in the signaling pathway. Finally, the molecular docking technology was used to verify the results of network pharmacology. Results A total of 176 active ingredients were obtained, and the top 5 was quercetin, kaempferol, luteolin, naringenin and p-sitosterol, respectively. A total of 116 common targets were obtained. A total of 21 core targets were finally obtained by PPI screening, and the top 5 was AKT1, CCND1, CASP3, MYC and IL1B, respectively. The results of GO enrichment analysis showed that DPHD was mainly involved biological processes of oxidative stress, proliferation and differentiation, transcriptional regulation, drug response and inflammatory response. The results of KEGG enrichment analysis indicated that the mainly signaling pathways included PI3K/Akt, MAPK, cellular senescence, AMPK, and TGF-beta. Molecular docking results showed that the binding energies of the top 5 active components of DPHD and the top 5 core targets were all less than-6.0 kcal • mo

Mechanism of ophiopogonin D in treatment of pulmonary fibrosis based on network pharmacology and experimental verification / 中国药理学通报

Aim To predict the potential mechanism of ophiopogonin D (OPD) against pulmonary fibrosis by network pharmacology, and further verify it by experiment in vivo. Methods This study found that ophiopogon was the most frequently used drug in the treatment of pulmonary fibrosis with deficiency of Qi and Yin through data mining. In order to explore its material basis, network pharmacology analysis was carried out. A model of pulmonary fibrosis was established by bleomycin, and different concentrations of ophiopogonin D were administered to verify the results of the pharmacological network. Results Firstly, through network pharmacology analysis, it was found that mitophagy might be the potential target for ophiopogon to exert anti-pulmonary fibrosis effect. Meanwhile, network topology analysis showed that OPD had the greatest relationship with mitophagy. Animal experiments showed that OPD could relieve pulmonary fibrosis and reduce collagen deposition in mice. At the same time, the detection of mitophagy related proteins showed that the compound could increase the expression of PINK1 and Parkin proteins, reduce the content of P62 protein in lung tissue, and reduce the intracellular ROS level. Conclusions OPD can improve mitochondrial function and play an anti-pulmonary fibrosis role by promoting PINKl/Parkin dependent mitophagy in lung tissue.

Preliminary report of perioperative monitoring of six-gene-edited pig-to-cynomolgus monkey kidney xenotransplantation / 器官移植

Objective To investigate the establishment of a six-gene-edited pig-to-non-human primate kidney xenotransplantation model. Methods The kidney of humanized genetically-edited pig (GTKO/β4GalNT2KO/CMAHKO/hCD55/hCD46/hTBM) was transplanted into a cynomolgus monkey. The survival of the recipient and kidney condition after blood perfusion were observed. The parenchymal echo, blood flow changes, and size of the kidney were monitored on a regular basis. Routine blood test, kidney function test and electrolyte assessment were carried out. Dynamic changes of urine, feces and body mass were monitored. At the end of life, the transplant kidney, heart, liver, spleen, lung, and cecum were collected for pathological examination. Results The recipient died at postoperative 7 d. After blood flow was restored, the kidney was properly perfused, the organ was soft and the color was normal. At the end of the recipient's life, a slight amount of purulent secretion was attached to the ventral side of the kidney, with evident congestion and swelling, showing the appearance of "red kidney". Postoperatively, the echo of renal parenchyma was increased, blood flow was decreased, the cortex was gradually thickened, and a slight amount of effusion surrounded the kidney and abdominal cavity over time. In the recipient, the amount of peripheral red blood cells, hemoglobin, albumin, and platelets was progressively decreased, and serum creatinine level was increased to 308 μmol/L at postoperative 7 d, whereas the K+ concentration did not significantly change. Light yellow urine was discharged immediately after surgery, diet and drinking water were resumed within postoperative 3 h, and light yellow and normal-shape stool was discharged. The reddish urine was gradually restored to normal color within postoperative 1 d, which were consistent with the results of the routine urine test. A large amount of brown bloody stool was discharged twice in the morning of 2 d after surgery. Omeprazole was given for acid suppression, and the stool returned to normal at postoperative 4 d. The β2-microglobulin level was increased to 0.75 mg/L at postoperative 7 d. The body mass was increased by 1.7 kg. Autopsy pathological examination showed interstitial edema and bleeding of the transplant kidney, a large amount of infiltration of lymphocytes and macrophages, infiltration of lymphocytes in the arteriole wall and arterial cavity, accompanied by arteritis changes, lymphocyte infiltration in the cecal stroma and congestion in the spleen tissues. No significant abnormal changes were observed in other organs. Conclusions The humanized genetically-edited pig-to-non-human primate kidney xenotransplantation model is successfully established, and postoperative survival of the recipient is 1 week.

Casticin Attenuates Stemness in Cervical Cancer Stem-Like Cells by Regulating Activity and Expression of DNMT1 / 中国结合医学杂志

OBJECTIVE@#To explore whether casticin (CAS) suppresses stemness in cancer stem-like cells (CSLCs) obtained from human cervical cancer (CCSLCs) and the underlying mechanism.@*METHODS@#Spheres from HeLa and CaSki cells were used as CCSLCs. DNA methyltransferase 1 (DNMT1) activity and mRNA levels, self-renewal capability (Nanog and Sox2), and cancer stem cell markers (CD133 and CD44), were detected by a colorimetric DNMT activity/inhibition assay kit, quantitative real-time reverse transcription-polymerase chain reaction, sphere and colony formation assays, and immunoblot, respectively. Knockdown and overexpression of DNMT1 by transfection with shRNA and cDNA, respectively, were performed to explore the mechanism for action of CAS (0, 10, 30, and 100 nmol/L).@*RESULTS@#DNMT1 activity was increased in CCSLCs compared with HeLa and CaSki cells (P<0.05). In addition, HeLa-derived CCSLCs transfected with DNMT1 shRNA showed reduced sphere and colony formation abilities, and lower CD133, CD44, Nanog and Sox2 protein expressions (P<0.05). Conversely, overexpression of DNMT1 in HeLa cells exhibited the oppositive effects. Furthermore, CAS significantly reduced DNMT1 activity and transcription levels as well as stemness in HeLa-derived CCSLCs (P<0.05). Interestingly, DNMT1 knockdown enhanced the inhibitory effect of CAS on stemness. As expected, DNMT1 overexpression reversed the inhibitory effect of CAS on stemness in HeLa cells.@*CONCLUSION@#CAS effectively inhibits stemness in CCSLCs through suppression of DNMT1 activation, suggesting that CAS acts as a promising preventive and therapeutic candidate in cervical cancer.

Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis

Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.

Satisfaction of Patients with Above-the-knee Amputation following Periprosthetic Joint Infection / 中山大学学报(医学科学版)

ObjectiveThe purpose of this study was to evaluate the functional outcomes and satisfaction in periprosthetic knee infection patients after above-the-knee amputation （AKA）. MethodsA review was performed in 13 patients who underwent AKA due to periprosthetic knee infection from October 2010 to August 2022， there were 7 females and 6 males with the median age of 69 （45~ 73） years. The mean number of surgical procedures between primary total knee arthroplasty and AKA was 2.9 times （range： 1 ~ 6）. Patients were segregated into non-elderly group （including patients <65 years old） and elderly group （involving patients ≥65 years old）. Functional outcomes were evaluated by SF-12 and Barthel activities daily living index （Barthel ADL index）. Patient satisfaction was accomplished through a questionnaire. ResultsFour patients died within 6 months after the amputation. Three patients received surgical procedures for recurrent infections after AKA. In the remaining 9 patients，the median time from AKA to the final follow-up was 4.2 （1.9~8.2） years， three patients received surgical procedures for recurrent infections after AKA. Patients in non-elderly group showed better functional outcomes than elderly patients after AKA （both P<0.05）. All patients in non-elderly group were fitted with a prosthesis. Whereas， elderly patients reported a better satisfaction after AKA than young patients. ConclusionYoung PJI patients seemed to have better function and ambulatory ability with high expectation and demand， which made them feel less satisfied about AKA. Meanwhile，despite poor function outcomes due to the less healthy physical condition， the alleviation of financial and psychological burdens resulting from reinfections and multiple surgeries and the less demand in function and daily activities made elderly patients have a good satisfaction after AKA.

Protective effect and mechanism of Maiwei Yangfei Decoction on pulmonary fibrosis mice based on Nrf2 regulation of oxidative stress / 中国中药杂志

This study explored the effect and mechanism of Maiwei Yangfei Decoction(MWYF) on pulmonary fibrosis(PF) mice. MWYF was prepared, and its main components were detected by ultra-high-performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS). Male C57BL/6J mice were randomly divided into a control group, a model group, a pirfenidone(PFD) group, and low-, medium-, and high-dose MWYF groups, with 10 mice in each group. The PF model was induced in mice except for those in the control group by intratracheal instillation of bleomycin(BLM), and model mice were treated with saline or MWYF or PFD by gavage the next day. The water consumption, food intake, hair, and activity of mice were observed daily. The pathological changes in lung tissues were observed by hematoxylin-eosin(HE) staining, Masson staining, and CT scanning. The level of hydroxyproline(HYP) in lung tissues was detected by alkaline hydrolysis. Immunohistochemistry was used to observe the expression of collagen type Ⅲ(COL3) and fibronectin. The mRNA expression levels of α-smooth muscle actin(α-SMA), type Ⅰ collagen α1(COL1α1), COL3, and vimentin were detected by reverse transcription real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). Superoxide dismutase(SOD) and malondialdehyde(MDA) kits were used to detect oxidative stress indicators in lung tissues and serum. The nuclear translocation of nuclear factor E2-related factor 2(Nrf2) protein was detected by immunofluorescence. The protein and mRNA expression levels of Nrf2, catalase(CAT), and heme oxygenase 1(HO-1) in lung tissues were detected by Western blot and RT-qPCR. Twelve chemical components were detected by UPLC-MS/MS. Animal experiments showed that MWYF could improve alveolar inflammation, collagen deposition, and fibrosis in PF mice, increase body weight of mice, and down-regulate the expression of fibrosis indexes such as HYP, α-SMA, COL1α1, COL3, fibronectin, and vimentin in lung tissues. In addition, MWYF could potentiate the activity of SOD in lung tissues and serum of PF mice, up-regulate the expression level of Nrf2, and promote its transfer to the nucleus, up-regulate the levels of downstream antioxidant target genes CAT and HO-1, and then reduce the accumulation of lipid metabolite MDA. In summary, MWYF can significantly improve the pathological damage and fibrosis of lung tissues in PF mice, and its mechanism may be related to the activation of the Nrf2 pathway to regulate oxidative stress.

Research progress in the proteomics of crystal-cell interaction in pathogenesis of calcium oxalate kidney stones / 国际生物医学工程杂志

Nephrolithiasis/urolithiasis have long been a global public health problem because of their high incidence. The most common chemical component causing nephrolithiasis/urolithiasis is calcium oxalate, which forms stone lesions through the processes of crystalline formation, crystal growth, aggregation, crystal-cell adhesion, and invasion of the interstitial extracellular matrix of the kidney. In these processes, crystal-cell interactions are crucial. Proteomics has been widely used in the study of nephrolithiasis/urolithiasis. In this paper, the progress of proteomics of calcium oxalate crystal-cell interaction in nephrolithiasis/urolithiasis was reviewed with the aim of better understanding the pathogenesis of kidney stones.

Clinical anatomy of cast specimens of the pancreatic duct / 解剖学报

Objective To explore the distribution and structure of pancreatic ducts and lobules in human pancreas and explore their clinical application value. Methods Three human pancreatic specimens were dissected, 2 of which were fresh whole pancreas samples which were collected from the donated human bod)' after dead,UW organ preservation solution was immediately perfused, and the pancreatic duct was rinsed at low pressure. The surface and internal structure of 1 case was observed as a fixed specimen. Paraffin sections were taken for HE staining to observe the structure of lobules and the distribution of catheters in the leaves. Results The gross specimen showed that the pancreas was composed of lobules of different sizes, with thin layers of connective tissue between the lobules. The pancreatic duct had a complete cast structure and could be clearly displayed to the main duct and the branches of the interlobular duct. The diameters of the interlobular ducts varied widely, and finally a main trunk flowed into the main duct. Each trunk was distributed independently, and the distal pancreatic duct formed a lobule-like structure with different sizes of lobules and no interlobular communication. HE staining showed that the pancreatic lobules were surrounded by connective tissue, in which vascular and ductal structures were visible. Intralobular duct could also be observed in the pancreatic lobules. Conclusion The cast specimen of the human pancreatic duct can clearly show the branch distribution of the pancreatic duct, and the study of the morphological of the pancreatic duct and lobular structure is of great reference value for understanding the clinical problems.

Cross lagged analysis of boredom proneness and smoking, drinking behavior among adolescents / 中国学校卫生

Objective@#To explore the development and interactive correlations between boredom proneness, smoking and drinking behavior.@*Methods@#A total of 416 adolescents from one senior high school and one college in the Inner Monggol Autonomous Region were recruited to complete the short version boredom proneness scale, as well as smoking and drinking behavior scale at baseline and in the 12 month follow up.@*Results@#There were significant and positive correlation between boredom proneness and smoking and drinking behavior at both cross sectional levels (T1 r =0.30, 0.34, T2 r =0.24, 0.45, P ＜0.01). Significant autoregressive coefficients were observed for boredom proneness, smoking and drinking behavior in adolescents ( β=0.53, 0.61, 0.45, P ＜ 0.01). Moreover, the cross lagged analyses revealed that the relationship between bordom proneness and smoking behavior was unilaterally influencing ( β=0.12, P＜0.01; β=0.03, P ＞0.05), the relationship between bordom proneness and drinking behavior was bidirectional over the 12 months ( β=0.21, 0.09, P ＜0.05).@*Conclusion@#Boredom proneness of adolescents is closely related to smoking and drinking behavior, boredom proneness can positively predict smoking and drinking behavior, and drinking behavior can positively predict boredom proneness.

Effect of lymphovascular invasion on biochemical recurrence in patients treated with radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the effect of lymphovascular invasion (LVI) on biochemical recurrence in patients treated with radical prostatectomy (RP).Methods:From June 2012 to November 2020, 403 cases treated with RP in the Second Hospital of Tianjin Medical University were analyzed retrospectively. Median age was 67 (range 47-81) years old. Median prostate specific antigen (PSA) was 18.0 (range 1.9-813.0) ng/ml. All patients received prostate biopsy and were confirmed with prostatic acinar adenocarcinoma according to pathology. The Gleason score of 44 (10.9%) cases were 6, 65 (16.1%) cases were 3+ 4, 62 (15.4%) cases were 4+ 3, and 232 (57.5%) cases were ≥8. 73 (18.1%) patients received neoadjuvant hormonal therapy. RP and pelvic lymph node dissection were carried out in all patients including 10 open surgery, 144 laparoscopic surgery and 249 robot-assisted laparoscopic surgery. The χ 2 test was used to analyze the correlation between LVI and clinicopathological characteristics. Kaplan-Meier method and log-rank test were used to summarize time-to-biochemical recurrence end point and compare biochemical recurrence-free survival between LVI positive and negative groups. Univariable and multivariable analyses were performed to test the possible factors of biochemical recurrence with Cox proportional-hazard model. Results:Of all 403 patients treated with RP, the final Gleason score of 68 (16.9%) cases were≤6, 87 (21.6%) cases were 3+ 4, 89 (22.1%) cases were 4+ 3, and 159 (39.5%) cases were≥8. 179 (44.4%) patients had positive surgical margins. The rate of seminal vesicle invasion was 23.6% (95 patients). There were 167 (41.4%) cases with T 1~2 and 236 (58.6%) cases with T 3~4 pathological stage. 39 (9.7%) patients had lymph node metastasis. 62 (15.4%) patients were LVI positive and 341 (84.6%) patients were LVI negative. There were statistically significant differences in biopsy and final Gleason score, pathological stage, rates of seminal vesicle invasion and rates of positive lymph node between LVI positive and negative patients ( P<0.05). 259 (64.3%) patients received adjuvant hormonal therapy and 70 (17.4%) patients received adjuvant hormonal plus radiation therapy. Median follow-up time was 22 (range 6-89) months. 23 (37.1%) occurred biochemical recurrence in LVI positive cases and median biochemical recurrence-free survival was 41 months. Meanwhile, 71 (20.8%) occurred biochemical recurrence in LVI negative cases and median biochemical recurrence-free survival was not reached, significantly longer than LVI positive cases ( P<0.001). Multivariable analysis showed that PSA level, biopsy gleason score, neoadjuvant hormonal therapy, pathological stage, positive surgical margins, seminal vesicle invasion, lymph node metastasis and LVI were significantly associated with prognostic prediction of biochemical recurrence. Conclusions:LVI implies shorter biochemical recurrence-free survival and could be an independent predictor on biochemical recurrence in patients treated with RP.

Clinical characteristics of idiopathic inflammatory myopathy patients with positive anti-melanoma differentiation-associated gene 5 antibody / 中华风湿病学杂志

Objective:To investigate the clinical characteristics and prognosis of idiopathic inflammatory myopathy (IIM) patients with positive anti-melanoma differentiation-associated gene 5 (MDA5) antibody.Methods:A total of 194 hospitalized IIM patients who were tested for myositis-specific autoantibodies (MSAs) in the Departments of Rheumatology and Immunology of Tianjin Medical University General Hospital from January 2015 to September 2020 were collected, including 29 cases with positive anti-MDA5 antibody and 165 cases with negative anti-MDA5 antibody. Their clinical data were analyzed retrospectively. T test was used for measurement data with normal distribution. Measurement data with non-normal distribution were tested by Mann-Whitney U rank sum test. χ2 test was used for counting data. Risk factors were analyzed by binary Logistic regression, survival analysis by Kaplan-Meier method and Cox regression analysis. Results:IIM patients with positive anti-MDA5 antibody had a high incidence of dermatomyositis specific skin rash, and the skin rash was the most common presenting symptom. In the positive anti-MDA5 antibody group, muscle symptoms were mild; and the patients were prone to have fever, arthritis, oral ulcer and weight loss. All patients were complicated with interstitial lung disease (ILD). In patients with negative anti-MDA5 antibody, white blood cell (WBC) count [7.59(5.61, 9.89)×10 9/L vs 4.07(3.17, 5.50×10 9/L, Z=-5.05, P<0.001], platelet (PLT) [249.00 (200.00, 302.00)×10 9/L vs 205.00 (178.00, 244.00)×10 9/L, Z=-2.59, P=0.010], lymphocyte (LY) [1.34(0.85, 1.94)×10 9/L vs 0.64(0.40, 0.83)×10 9/L, Z=-5.78, P<0.001), serum creatine kinase (CK) [558.00 (72.00, 2 959.00) U/L vs 64.00 (35.00, 149.50) U/L, Z=-3.97, P<0.001], creatine kinase isoenzymes (CK-MB) [38.00 (17.00, 127.00) U/L vs 16.00 (14.00, 25.00) U/L, Z=-3.84, P<0.001], myoglobin (MYO) [243.65 (60.50, 829.83) ng/ml vs 34.55(21.00, 104.23) ng/ml, Z=-3.98, P<0.001], troponin T (TnT) [0.09(0.03, 0.44) ng/ml vs 0.02(0.01, 0.04) ng/ml, Z=-4.17, P<0.001], albumin (ALB) [34.00(30.00, 38.00) g/L vs 31.00 (26.50, 36.00) g/L, Z=-2.68, P=0.007], cluster of differentiation 4 (CD4) + T cells [498.00(276.00, 752.00) cells/μl vs 259.50 (179.00, 498.25) cells/μl, Z=-2.79, P=0.005], partial pressure of carbon dioxide (PaCO 2) [39.00(36.13, 42.00) mmHg vs 35.35 (31.30, 38.88) mmHg, Z=-3.75, P<0.001], partial pressure of oxygen (PaO 2) [82.00(71.90, 90.20) mmHg vs 73.25(64.30, 84.05) mmHg, Z=-2.08, P=0.037], arterial oxygen saturation (SaO 2) [96.50% (95.05%, 97.30)% vs 95.80%(93.70%, 96.55%), Z=-2.11, P=0.035], diffusion capacity for carbon monoxide of the Lung (DLco) [(63±21) % vs (52±14)%, t=0.96, P=0.006] were significantly reduced, while UTP [260.50 (172.25, 401.25) g vs 331.00 (252.75, 666.25) g, Z=-2.18, P=0.029], alanine aminotransferase (ALT) [40.00 (21.00, 83.00) U/L vs 56.00(40.00, 107.50), Z=-2.27, P=0.023], glutamyltranspeptidas (GGT) [22.50(15.00, 42.00) U/L vs 57.00 (38.00, 101.50) U/L, Z=-4.98, P<0.001], D-Dimer [850.00 (485.00, 1 799.50) ng/ml vs 1 346.00 (896.50, 2 527.00) ng/ml, Z=-2.55, P=0.011], immunoglobulin (Ig)E [60.00 (25.60, 147.50) U/ml vs 173.00(68.25, 471.50) U/ml, Z=-3.06, P=0.002], C4[20.25(16.68, 25.03) mg/L vs 23.60(20.20, 28.35) mg/L, Z=-2.38, P=0.017], Fer [228.01 (115.40, 513.36) ng/ml vs 1 636.39 (851.80, 3 888.82) ng/ml, Z=-6.01, P<0.001], krebsvondenlungen-6 (KL-6) [365.00 (180.25, 1 018.75) U/ml vs 788.00 (406.00, 1 364.00) U/ml, Z=-2.10, P=0.035] were higher when compared to patients with positive anti-MDA5 antibody. In the anti-MDA5 antibody positive group, patients had high mortality rate [8.5%(14/165) vs 34.5%(10/29), χ2=13.07, P<0.001], and the use of intravenous immunoglobulin [32.7%(54/165) vs 65.5%(19/29), χ2=11.30, P=0.001] and steroid pulse therapy [4.8%(86/165) vs 27.6%(8/29), χ2=13.98, P<0.001] were more frequent. Patients in the positive anti-MDA5 antibody group were classified into two sub groups based on lung features: the rapidly progressive interstitial lung disease (RP-ILD) group (48.28%, 14/29) and the chronic interstitial lung disease (C-ILD) group (51.72%, 15/29). RP-ILD patients had significantly elder disease onset age, higher C-reaction protein (CRP), Fer, IgE levels and the positive rate of anti-Ro52 antibody, while ALT was lower. The difference was statistically significant. Regression analysis suggested that older onset age [ HR (95% CI)=1.154 (1.069, 1.246), P<0.001], male [ HR(95% CI)=6.383(1.038, 39.242), P=0.045], positive anti-MDA5 antibody [ HR(95% CI)=17.180 (2.900, 101.766), P=0.002], LY decrease [ HR (95% CI)=0.083 (0.008, 0.817), P=0.033], high serum Fer level [ HR (95% CI)=1.001(1.000, 1.001), P=0.016], increased D-Dimer [ HR(95% CI)=1.000(1.000, 1.001), P=0.004] and compicated with carcinoma [ HR (95% CI)=11.849 (1.978, 70.970), P=0.007] were independent risk factors for death in IIM patients. Binary logistic regression analysis suggested that late onset age [ OR(95% CI)=1.090 (1.005, 1.183), P=0.038], high Fer level [ OR (95% CI)=1.001 (1.000, 1.001), P=0.022] and decreased ALB [ OR (95% CI)=0.818 (0.696, 0.963), P=0.016] might be risk factors for RP-ILD in patients with positive anti-MDA5 antibody. Conclusion:In patients with positive anti-MDA5 antibody group, typical skin damage, mild muscle symptoms, high proportion of ILD and poor prognosis are chardcteristic when compared to patients without this autoantibody. It is necessary to monitor the disease activity closely and explore the treatment strategy.

Evaluation of therapeutic markers and mechanism of Shuganjieyu capsule in treatment of depression / 中华行为医学与脑科学杂志

Objective:To compare the expression levels of candidate genes before and after Shuganjieyu capsule treatment, to analyze their correlation with depression symptoms and cognitive function, and to find and clarify the biomarkers related to the efficacy of Shuganjieyu capsule.Methods:Among 27 patients with mild to moderate depression (MMD), 24 items Hamilton depression rating scale (HAMD-24) was used to assess the severity of depression, Chinese revised Wechsler adult intelligence scale(WAIS-RC) and Chinese revised Wechsler memory scale(WMS) were used to assess cognitive function, and qRT-PCR was used to detect the expression levels of candidate genes in peripheral blood of patients with depression before and after treatment with Shuganjieyu capsule.SPSS 25.0 software was used for statistical analysis, paired t-test, non-parametric test, Spearman correlation analysis and receiver operating characteristic curve were used for data statistics. Results:The symptoms of MMD patients were relieved after Shuganjieyu capsule treatment(HAMD scores: baseline 14.00(9.75, 18.25), 8-week 4.00(2.00, 7.25), Z=-4.462, P<0.01), and the verbal intelligence quotient(VIQ) of WMS was puomoved (VIQ scores: baseline (123.00±10.24), 8-week (128.00±6.77), t=4.372, P<0.01). The level of gene expression brain derived neurotrophic factor(BDNF) (baseline 1.68(0.92, 2.63), 8-week 2.30(1.47, 4.34), Z=-2.781, P=0.005), glial cell derived neurotrophic factor(GDNF) (baseline 0.74(0.31, 1.15), 8-week 0.97(0.50, 1.71), Z=-2.159, P=0.031), 5-hydroxytryptamine receptor 2A(HTR2A) (baseline 0.60(0.39, 1.60), 8-week 0.98(0.44, 2.29), Z=-1.994, P=0.046) and glutamate ionotropic receptor AMPA type subunit 1(GRIA1) (baseline 1.19(0.66, 2.40), 8-week 1.76(0.86, 4.13), Z=-2.756, P=0.006) was up-regulated after treatment.The change rate of BDNF expression were correlated with the score of HAMD-24 ( r=-0.35, P=0.038) and performance intelligence quotient of WMS ( r=0.40, P=0.022). Conclusions:BDNF may be used as a therapeutic marker of Shuganjieyu capsule in the treatment of clinical symptoms and cognitive function of MMD patients, which is used to evaluate the efficacy of antidepressants.

Study on the influencing factors of teaching quality in standardized training of psychiatry specialists / 中华医学教育探索杂志

Objective:To explore the influencing factors of teaching quality in standardized training of psychiatry specialists, and to provide evidence for improving the training quality.Methods:Both qualitative and quantitative methods were combined in the study. First, information was collected by stratified random sampling and individual interviews, and NVivo 11.0 was used in coding the information and reducing the information to the main concepts. Then, the qualitative research results were compiled into a questionnaire Investigation on Influencing Factors of Standardized Training of Specialists to investigate and analyze all previous specialized training doctors and teaching teachers. SPSS 23.0 was used to perform Mann-Whitney U test. Results:①The teaching abilities of teachers, the attitudes on study and work of the specialists, the teaching initiative of teachers were found to be the important influencing factors of teaching quality. The recognition degree of the specialists was 89.5%, 57.9% and 55.3%, while that of the teachers was 68.4%, 66.7% and 52.6%. ②The teachers' attitudes, the busy degree of the teachers' work and policy orientation were found to be the important influencing factors of teaching initiative. The recognition degree of the specialists was 68.4%, 57.9% and 47.7%, while that of the teachers was 68.4%, 59.6% and 47.4%. ③The mentors' reserve of professional knowledge and skills, the reserve of educational knowledge and skills and the study and exploration in education were found to be the important influencing factors of teaching ability. The recognition degree of the specialists was 89.5%, 81.6% and 57.9%, while that of the teachers was 82.5%, 82.5% and 68.4%.Conclusion:The early cultivation of teaching attitude should be emphasized; the workload of the teachers should be distributed reasonably; the training on both the teaching ability and professional ability should be paid attention to.

The hypothalamus for whole-body physiology: from metabolism to aging

Obesity and aging are two important epidemic factors for metabolic syndrome and many other health issues, which contribute to devastating diseases such as cardiovascular diseases, stroke and cancers. The brain plays a central role in controlling metabolic physiology in that it integrates information from other metabolic organs, sends regulatory projections and orchestrates the whole-body function. Emerging studies suggest that brain dysfunction in sensing various internal cues or processing external cues may have profound effects on metabolic and other physiological functions. This review highlights brain dysfunction linked to genetic mutations, sex, brain inflammation, microbiota, stress as causes for whole-body pathophysiology, arguing brain dysfunction as a root cause for the epidemic of aging and obesity-related disorders. We also speculate key issues that need to be addressed on how to reveal relevant brain dysfunction that underlines the development of these disorders and diseases in order to develop new treatment strategies against these health problems.