Effect of neurally adjusted ventilatory assist ventilation in severe neurological cerebrovascular diseases patients undergoing mechanical ventilation / 中华危重病急救医学

Objective:To explore the prognostic effect and safety of neurally adjusted ventilatory assist (NAVA) mode on the patients with severe neurological cerebrovascular disease undergoing mechanical ventilation.Methods:A prospective study was conducted. Fifty-four patients with cerebrovascular disease undergoing mechanical ventilation admitted to the neurosurgery intensive care unit (NSICU) of the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital) from December 2020 to May 2022 were enrolled. They were divided into NAVA group and pressure support ventilation (PSV) group by computer random number generator with 27 patients in each group. The ventilation time of the two groups was ≥72 hours. The general basic data of the two groups were recorded. The time without mechanical ventilation 28 days after enrollment, total length of mechanical ventilation, survival rate of 90 days after enrollment, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, Glasgow outcome score (GOS), complications related to mechanical ventilation, and changes of respiratory mechanics indexes, arterial blood gases, vital signs, and diaphragm function indexes were observed.Results:The time without mechanical ventilation 28 days after enrollment in the NAVA group was significantly longer than that in the PSV group [days: 22 (15, 26) vs. 6 (0, 23), P < 0.05]. However, there were no significant differences in the total length of mechanical ventilation, 90-day survival rate, length of NSICU stay, total length of hospital stay, NSICU mortality, in-hospital mortality, GOS score, and incidence of mechanical ventilator-related complications between the two groups. In terms of respiratory mechanics parameters, the expiratory tidal volume (VTe) on 3 days after mechanical ventilation of patients in the NAVA group was significantly lower than that on 1 day and 2 days, and significantly lower than that in the PSV group [mL: 411.0 (385.2, 492.6) vs. 489.0 (451.8, 529.4), P < 0.01]. Minute ventilation (MV) at 2 days and 3 days in the NAVA group was significantly higher than that at 1 day, and significantly higher than that in the PSV group at 2 days [L/min: 9.8 (8.4, 10.9) vs. 7.8 (6.5, 9.8), P < 0.01], while there was no significant change of MV in the PSV group. At 1 day, peak airway pressure (Ppeak) and mean airway pressure (Pmean) in the NAVA group were significantly lower than those in the PSV group [Ppeak (cmH 2O, 1 cmH 2O≈0.098 kPa): 14.0 (12.2, 17.0) vs. 16.6 (15.0, 17.4), Pmean (cmH 2O): 7.0 (6.2, 7.9) vs. 8.0 (7.0, 8.2), both P < 0.05]. However, there was no significant difference in the Ppeak or Pmean at 2 days and 3 days between the two groups. In terms of arterial blood gas, there was no significant difference in pH value between the two groups, but with the extension of mechanical ventilation time, the pH value at 3 days of the two groups was significantly higher than that at 1 day. Arterial partial pressure of oxygen (PaO 2) at 1 day in the NAVA group was significantly lower than that in the PSV group [mmHg (1 mmHg≈0.133 kPa): 122.01±37.77 vs. 144.10±40.39, P < 0.05], but there was no significant difference in PaO 2 at 2 days and 3 days between the two groups. There was no significant difference in arterial partial pressure of carbon dioxide (PaCO 2) or oxygenation index (PaO 2/FiO 2) between the two groups. In terms of vital signs, the respiratory rate (RR) at 1, 2, and 3 days of the NAVA group was significantly higher than that of the PSV group [times/min: 19.2 (16.0, 25.2) vs. 15.0 (14.4, 17.0) at 1 day, 21.4 (16.4, 26.0) vs. 15.8 (14.0, 18.6) at 2 days, 20.6 (17.0, 23.0) vs. 16.7 (15.0, 19.0) at 3 days, all P < 0.01]. In terms of diaphragm function, end-inspiratory diaphragm thickness (DTei) at 3 days in the NAVA group was significantly higher than that in the PSV group [cm: 0.26 (0.22, 0.29) vs. 0.22 (0.19, 0.26), P < 0.05]. There was no significant difference in end-expiratory diaphragm thickness (DTee) between the two groups. The diaphragm thickening fraction (DTF) at 2 days and 3 days in the NAVA group was significantly higher than that in the PSV group [(35.18±12.09)% vs. (26.88±8.33)% at 2 days, (35.54±13.40)% vs. (24.39±9.16)% at 3 days, both P < 0.05]. Conclusions:NAVA mode can be applied in patients with neuro-severe cerebrovascular disease, which can prolong the time without mechanical ventilation support and make patients obtain better lung protective ventilation. At the same time, it has certain advantages in avoiding ventilator-associated diaphragm dysfunction and improving diaphragm function.

Research progress on the characteristics and rapid diagnostic tools of early lung adenocarcinoma subtypes / 中国胸心血管外科临床杂志

@#Lung adenocarcinoma has become the most common type of lung cancer. According to the 2015 World Health Organization histological classification of lung cancer, invasive lung adenocarcinoma can be divided into 5 subtypes: lepidic, acinar, papillary, solid, and micropapillary. Relevant studies have shown that the local lobectomy or sublobectomy is sufficient for early lepidic predominant adenocarcinoma, while lobectomy should be recommended for tumors containing micropapillary and solid ingredients (≥5%). Currently, the percentage of micropapillary and solid components diagnosed by frozen pathological examination is 65.7%, and the accuracy of diagnosis is limited. Therefore, to improve the accuracy of diagnosis, it is necessary to seek new methods and techniques. This paper summarized the characteristics and rapid diagnosis tools of early lung adenocarcinoma subtypes.

Current status of surgery for portal hypertension in China: a national multi-center survey analysis / 中华器官移植杂志

Objective:To explore the current status of surgery for portal hypertension to grasp current status and future development of surgery in China.Methods:This study is jointly sponsored by China Hepatobiliary & Pancreatic Specialist Alliance & Portal Hypertension Alliance in China (CHESS).Comprehensive surveying is conducted for basic domestic situations of surgery for portal hypertension, including case load, surgical approaches, management of postoperative complications, primary effects, existing confusion and obstacles, liver transplantation(LT), laparoscopic procedures and transjugular intrahepatic portosystemic shunt(TIPS), etc.Results:A total of 8 512 cases of portal hypertension surgery are performed at 378 hospitals nationwide in 2021.Splenectomy plus devascularization predominated(53.0%)and laparoscopy accounted for 76.1%.Primary goal is preventing rebleeding(67.0%) and 72.8% of hospitals used preventive anticoagulants after conventional surgery.And 80.7% of teams believe that the formation of postoperative portal vein thrombosis is a surgical dilemma and 65.3% of hospitals practiced both laparoscopy and TIPS.The major reasons for patients with portal hypertension not receiving LT are due to a lack of qualifications for LT(69.3%)and economic factors(69.0%).Conclusions:Surgery is an integral part of management of portal hypertension in China.However, it is imperative to further standardize the grasp of surgical indications, the handling of surgical operation and the management of postoperative complications.Moreover, prospective, multi-center randomized controlled clinical studies should be performed.

Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

A medium-and long-term comparative observation on volumetric changes of cervical disc herniation after symmetrically or asymmetrically decompression and conservative treatment for cervical spondylotic myelopathy / 中华外科杂志

Objective: To compare the volumetric changes of cervical disc herniation (CDH) after cervical microendoscopic laminoplasty(CMEL),expansive open-door laminoplasty (EOLP) and conservative treatment. Methods: A retrospective study was conducted involving 101 patients with cervical spondylotic myelopathy(CSM),at the Department of Orthopaedics,the First Affiliated Hospital of Zhengzhou University from April 2012 to April 2021. The patients included 52 males and 49 females with an age of (54.7±11.8) years(range:25 to 86 years). Among them, 35 patients accepted CMEL treatment,33 patients accepted EOLP treatment,while 33 patients accepted conservative treatment. Volume data of CDH were measured by three-dimensional analysis of the initial and follow-up MRI images. The absorption rate and reprotrusion rate of CDH were calculated. The happening of resorption or reprotrusion was defined when the ratio was greater than 5%. The clinical outcomes and quality of life were evaluated by the Japanese Orthopaedic Association (JOA) score and the neck disability index (NDI).Quantitative data was analyzed by one-way ANOVA with post LSD-t test (multiple comparison) or Kruskal-Wallis test. Categorical data was analyzed by χ2test. Results: The follow-up time of the CMEL group,EOLP group and the conservative treatment group were (27.6±18.8)months,(21.6±6.9)months and(24.9±16.3)months respectively with no significant difference(P>0.05). Changes of CDH volume in patients:(1) There were 96 CDH of 35 patients in the CMEL group,among which 78 showed absorption. The absorption frequency was 81.3%(78/96) and the absorption rate was ranged 5.9% to 90.9%;9 CDH showed reprotrusion,the reprotrusion frequency was 9.4% (9/96) and the reprotrusion rate was 5.9% to 13.3%;(2) There were 94 CDH of 33 patients in the EOLP group,of which 45 showed absorption. The absorption prevalence was 47.9% (45/94) and the absorption rate was 5.0% to 26.7%;20 CDH showed reprotruded,with the reprotrusion frequency of 21.3% (20/94) and the reprotrusion rate was 5.8% to 28.3%;(3) There were 102 CDH in 33 patients of the conservative group. Among them, 5 showed absorption. The absorption frequency was 4.9% (5/102),and the absorption rate was 7.2% to 14.3%;58 CDH showed reprotruded with the re-protrusion ratio of 56.9% (58/102) and the re-protrusion rate was 5.4% to 174.1%. The absorption ratio and reprotrusion ratio of the CMEL group were statistically different from EOLP group or the conservative group (P<0.01).The absorption ratio and reprotrusion ratio of the EOLP group was different from conservative group (P<0.01). In terms of clinical outcomes, the excellent/good rate of the JOA score and NDI scores in the CMEL group were different from that of conservative group (P<0.01) but not from that of the EOLP group(P>0.05). Conclusions: CMEL is an effective method for the treatment of CSM,making CDH easier to resorption compared to the EOLP or conservative treatment,thus making a better decompression effect on the nerves. This study enlightened on a new strategy for the clinical treatment of CSM.

Ameliorative Effect of Gramine on 2，4-Dinitrochlorobenzene-Induced Atopic Dermatitis in Mice / 中国实验方剂学杂志

ObjectiveTo explore the pharmacodynamic effect of gramine on 2，4-dinitrochlorobenzene （DNCB）-induced atopic dermatitis （AD） in mice and its potential mechanism. MethodThe mice were divided into the normal control group， model group， dexamethasone （0.05 g·kg-1） group， and high- and low-dose （0.12，0.06 g·kg-1） gramine groups. Mice in all groups except for the normal control group were stimulated with DNCB， followed by medication 13 d later. The changes in skin lesions were then observed， and the skin thickness， moisture content， and transepidermal water loss （TWEL） in each group were measured. The pathological changes in skin lesions were observed by hematoxylin-eosin （HE） staining， and the effects of drugs on CD4+/CD8+T-cell ratio in the spleen were detected by flow cytometry. The levels of immunoglobulin E （IgE）， interleukin （IL）-4， and IL-6 in serum were detected by enzyme-linked immunosorbent assay （ELISA）， and the changes in serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， blood urea nitrogen （BUN）， and creatinine （CRE） by microplate method. The mRNA expression levels of inflammatory cytokines γ-interferon（IFN-γ）， IL-13， IL-17， IL-1β， IL-6， and tumor necrosis factor-α （TNF-α） in skin lesions were assayed by real-time polymerase chain reaction （Real-time PCR）， and the protein expression levels of nuclear transcription factor -κB (NF-κB) and NF-κB inhibitory protein α (IκBα) in skin lesions by Western blot. ResultCompared with the normal control group， the model group showed skin edema， erythema， scab， scratch， and lymphocyte and neutrophil infiltration， decreased skin moisture content， as well as increased skin thickness， TWEL （P<0.01）， spleen index， CD4+/CD8+ T-cell ratio in the spleen （P<0.05）， mRNA expression of IFN-γ， IL-13， IL-17， IL-1β， IL-6， and TNF-α in the skin lesions （P<0.05）， serum contents of IgE， IL-4， and IL-6 （P<0.05）， and protein expression of IκBα and NF-κB in skin lesions （P<0.05）. Compared with the model group， dexamethasone and gramine at different doses alleviated skin erythema， scale， scab， and inflammatory cell infiltration， elevated skin moisture content， inhibited skin thickening and TWEL， and decreased spleen index， CD4+/CD8+T-cell ratio in the spleen， mRNA expression of inflammatory factors in the skin lesions， serum contents of IgE and inflammatory factors， and protein expression of IκBα and NF-κB in skin lesions， especially in the dexamethasone group and the high- dose gramine group（P<0.05，P<0.01）. ConclusionGramine can inhibit the expression of related inflammatory factors and regulate the immune function of AD mice via the IκBα/NF-κB pathway， enabling it become a potential drug for treating AD.

Repurposing econazole as a pharmacological autophagy inhibitor to treat pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterized by the highest mortality among carcinomas. The pathogenesis of PDAC requires elevated autophagy, inhibition of which using hydroxychloroquine has shown promise. However, current realization is impeded by its suboptimal use and unpredictable toxicity. Attempts to identify novel autophagy-modulating agents from already approved drugs offer a rapid and accessible approach. Here, using a patient-derived organoid model, we performed a comparative analysis of therapeutic responses among various antimalarial/fungal/parasitic/viral agents, through which econazole (ECON), an antifungal compound, emerged as the top candidate. Further testing in cell-line and xenograft models of PDAC validated this activity, which occurred as a direct consequence of dysfunctional autophagy. More specifically, ECON boosted autophagy initiation but blocked lysosome biogenesis. RNA sequencing analysis revealed that this autophagic induction was largely attributed to the altered expression of activation transcription factor 3 (ATF3). Increased nuclear import of ATF3 and its transcriptional repression of inhibitor of differentiation-1 (ID-1) led to inactivation of the AKT/mammalian target of rapamycin (mTOR) pathway, thus giving rise to autophagosome accumulation in PDAC cells. The magnitude of the increase in autophagosomes was sufficient to elicit ER stress-mediated apoptosis. Furthermore, ECON, as an autophagy inhibitor, exhibited synergistic effects with trametinib on PDAC. This study provides direct preclinical and experimental evidence for the therapeutic efficacy of ECON in PDAC treatment and reveals a mechanism whereby ECON inhibits PDAC growth.

Dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy / 中华流行病学杂志

Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /106 PBMCs) before ART, and droped rapidly (<400 copies /106 PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/106 PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.

Application of enhanced recovery after surgery concept in laparoscopic radical cystectomy and ileal conduit diversion under modular operation / 国际外科学杂志

Objective:To explore the application value of enhanced recovery after surgery (ERAS) in laparoscopic radical resection of bladder cancer and ileal bladder surgery under modular operation procedures.Methods:A retrospective selection of 42 cases of laparoscopic radical radical resection of bladder cancer and ileal bladder surgery performed by the Department of Urology, General Hospital of Southern Theater Command from January 2017 to December 2019 were divided into two groups according to the different management methods adopted during the perioperative period: ERAS management group and conventional management group, each with 21 cases. Among them, patients in the ERAS management group were managed by ERAS during the perioperative period, and patients in the conventional management group were managed by conventional management during the perioperative period. The postoperative hospital stay, first exhaust time, first defecation time, first time to get out of bed, first liquid food time, postoperative visual analogue scale (VAS) score, as well as transferrin, upper arm circumference, body mass index, plasma albumin, total protein, and total protein were compared between the two groups of patients after surgery. The measurement data conforming to the normal distribution were expressed as mean±standard deviation ( Mean± SD), and the in dependent t-test was used for comparison between groups; the measurement data of non-normal distribution were expressed as the median (interquartile range) [ M( P25, P75)], the independent sample Mann-Whitney U test was used for comparison between groups; the Chi-square test was used for comparison of enumeration data between groups. Results:The postoperative hospital stay in the ERAS group was (8.9±1.8) d, the first exhaust time was (33.4±3.2) h, the first defecation time was (60.3±7.8) h, the first time to get out of bed was (23.1±6.7) h, the first liquid food time was (82.7±18.5) h and postoperative VAS was (1.3±0.6), that were significantly reduced compared with the conventional treatment group [(12.3±2.3) d, (51.4±5.2) h, (73.0±8.1) h, (34.7±8.2) h, (109.7±21.6) h, (3.6±0.8)], the difference were statistically significant ( P<0.05). In the ERAS group, the decreased value of transferrin was [0.8 (-0.4, 2.2) g/L], the decreased value of body mass index was[1.61±0.73], the decreased value of plasma albumin was [3.5±1.5 g/L], the decrease value of total protein was[10.1±5.6 g/L] and the decrease value of prealbumin was [90.5±11.3 mg/L] were significantly lower than those of the conventional management group[(1.9(0.9, 3.6) g/L, (2.32±1.05) kg/m 2, (9.6±2.0) g/L, (16.3±4.9) g/L, (131.3±7.4) g/L], and the difference were statistically significant ( P<0.05). Conclusion:Modular laparoscopic precision resection of bladder cancer and ERAS concept after ileal bladder surgery is beneficial to shorten the hospital stay, reduce postoperative pain, have less impact on the patient′s body loss and immune function, and can speed up the patient′s postoperative recovery.

Mechanism of Fuzheng Qufeng Prescription in Suppressing Epithelial-mesenchymal Transition of Podocytes in Membranous Nephropathy Rats via TGF-β1/Smad Pathway / 中国实验方剂学杂志

Objective:To study the effect of Fuzheng Qufeng prescription （FZQP） on transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）/Smad signaling pathway and epithelial-mesenchymal transition of podocyte in membranous nephropathy （MN） rats and to explore its molecular mechanism for podocyte protection. Method:The rats were randomly divided into normal control group （NC） and modeling group. Rats in modeling group induced by bovine serum albumin （C-BSA） were randomly divided into model group （MN）， losartan potassium group （LP， 0.05g·kg^-1）， and FZQP high dose （FZQPH， 41 g·kg^-1）， medium dose （FZQPM， 20.5 g·kg^-1）， and low dose （FZQPL， 10.25 g·kg^-1） groups. The administration lasted for 4 weeks. In week 0， 2， and 4 of administration， the levels of 24 hours urine protein （24 h-Upro） were tested. At the end of 4th week， the levels of blood urea nitrogen （BUN） and serum creatinine （SCr） were detected， and the rats in each group were sacrificed and the renal pathological morphology changes were observed by light microscope with hematoxylin-eosin （HE）， Masson and periodic acid-silver metheramine （PASM） staining. The deposition of immune complex， the thickening of glomerular basement membrane （GBM） and podocyte foot process were observed by transmission electron microscope （TEM）. The distribution and expression intensity of Desmin in renal tissues were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of TGF-<italic>β</italic>₁， Smad2/3， phospho（p）-Smad2/3， Smad7 and Desmin in renal tissues were respectively detected by Western blot （WB） and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. Result:Compared with NC group， the levels of 24 h-Upro， BUN and SCr significantly increased in model group （<italic>P</italic><0.01）， with increased deposition of immune complex， significantly thickened GBM and fusion of foot processes， significantly increased Desmin mRNA and protein expression （<italic>P</italic><0.01） and increased TGF-<italic>β</italic>₁， Smad2， and Smad3 mRNA and protein expression （<italic>P</italic><0.05）， and decreased Smad7 mRNA and protein expression （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with model group， 24 h-Upro and BUN decreased in FZQP groups and LP group （<italic>P</italic><0.05）， levels of serum SCr in FZQPM group decreased （<italic>P</italic><0.05）， deposition of immune complex， thickening of GBM and fusion of foot process were all alleviated in FZQP groups and LP group. Distribution of Desmin along GBM decreased in FZQPH group， FZQPM group and LP group （<italic>P</italic><0.05）. Both mRNA and protein expression levels of TGF-<italic>β</italic>₁ and p-Smad2/Smad2 in FZQPM group decreased， while mRNA and protein expression levels of Smad7 increased （<italic>P</italic><0.05）. Both mRNA and protein expression levels of p-Smad3/Smad3 in FZQPH group decreased （<italic>P</italic><0.05）. Both mRNA and protein expression levels of Desmin in podocyte in FZQPH group， FZQPM group and LP group decreased （<italic>P</italic><0.05）. Conclusion:FZQP might realize podocyte protection effect in MN via suppressing EMT mediated by overactivated TGF-<italic>β</italic>₁/Smad signaling pathway.

Effects of alginate/chondroitin sulfate-based hydrogels on bone defects healing.

Repairing bone defects remains challenging in orthopedics. Here, strontium (Sr) alginate hydrogels containing chondroitin sulfate (CS) were fabricated for enhancing bone defects repair. The effects of CS incorporation ratio on the morphology, structure, thermal stability, water uptake and mechanical performance of Sr-CS/alginate hydrogels were also evaluated. Increasing CS incorporation ratio, Sr-CS/alginate hydrogels exhibit decreasing mechanical properties and lower water retention capacity. In vitro results suggest that Sr-CS/alginate hydrogels with higher CS ratio facilitate the proliferation of osteoblasts. Additionally, the osteogenic genes expressions were investigated by real-time quantitative polymerase chain reaction (RT-qPCR). The results reveal that Sr-CS/alginate hydrogels should have positive effects on modulating the osteogenic factors. Moreover, by employing repair femoral cylindrical defects rabbit model, the efficiency of as-fabricated Sr-CS/alginate hydrogels in bone regeneration was evaluated. The animal study suggests that Sr-CS/alginate hydrogel could significantly facilitate bone defects repair and therefore should potentially be useful for osteochondral tissue engineering.

Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus in China (SARS-CoV-2)

A new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-{gamma}-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-{gamma}-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides. ImportanceSo far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.

Study on patient-ventilator synchrony of neurally adjusted ventilatory assist ventilation in severe neurological diseases patients with tracheotomy / 中华危重病急救医学

Objective:To explore the patient-ventilator interaction of neurally adjusted ventilatory assist (NAVA) in patients with severe neurological diseases.Methods:A prospective study was conducted. Sixteen severe neurological patients with tracheotomy admitted to neurosurgery intensive care unit (NSICU) of Yijishan Hospital of the First Affiliated Hospital of Wannan Medical College from September 2019 to February 2020 were enrolled. According to the random number table method, they were treated with pressure support ventilation (PSV) mode followed by NAVA mode or NAVA mode followed by PSV mode mechanical ventilation. Each mode was ventilated for 24 hours. The number of auto-triggering, ineffective trigger, double trigger, inspiratory trigger delay, premature cycling, late cycling, and patient-ventilator asynchronous time (inspiratory trigger delay time, premature cycling time, and late cycling time) within 1 minute were recorded every 8 hours for 3 minutes. The average number of asynchronies per minute, asynchrony index (AI), total AI, asynchrony time, arterial blood gas analysis, and coefficient variation (CV%) of respiratory mechanics parameters of each asynchrony type between the two modes were compared.Results:There were significant decrease in the number or AI of auto-triggering, ineffective trigger, inspiratory trigger delay, premature cycling, and late cycling with NAVA mode ventilation compared with PSV mode ventilation [auto-triggering times (times/min): 0.00 (0.00, 0.00) vs. 0.00 (0.00, 0.58), auto-triggering AI: 0.00 (0.00, 0.00) vs. 0.00 (0.00, 0.02), ineffective trigger times (times/min): 0.00 (0.00, 0.33) vs. 1.00 (0.33, 2.17), ineffective trigger AI: 0.00 (0.00, 0.02) vs. 0.05 (0.02, 0.09), inspiratory trigger delay times (times/min): 0.00 (0.00, 0.58) vs. 0.67 (0.33, 1.58), inspiratory trigger delay AI: 0.00 (0.00, 0.02) vs. 0.05 (0.02, 0.09), premature cycling times (times/min): 0.00 (0.00, 0.33) vs. 0.33 (0.08, 1.00), premature cycling AI: 0.00 (0.00, 0.01) vs. 0.02 (0.00, 0.05), late cycling times (times/min): 0.00 (0.00, 0.00) vs. 1.17 (0.00, 4.83), late cycling AI: 0.00 (0.00, 0.00) vs. 0.07 (0.00, 0.25), all P < 0.05]. But there was significant increase in the number or AI of double trigger with NAVA mode ventilation as compared with PSV mode ventilation [times (times/min): 1.00 (0.33, 2.00) vs. 0.00 (0.00, 0.00), AI: 0.04 (0.02, 0.11) vs. 0.00 (0.00, 0.00), both P < 0.05]. Total AI and incidence of total AI > 0.1 showed significant decrease during NAVA mode ventilation as compared with PSV mode ventilation [total AI: 0.08 (0.04, 0.14) vs. 0.22 (0.18, 0.46), incidence of total AI > 0.1: 37.50% (6/16) vs. 93.75% (15/16), both P < 0.01]. There was no significant difference in asynchronous time or arterial blood gas analysis between the two modes. There were significant increases in variances of peak airway pressure (Ppeak) and expiratory tidal volume (VTe) during NAVA mode ventilation as compared with PSV mode ventilation [Ppeak coefficient of variation (CV%): 11.25 (7.12, 15.17)% vs. 0.00 (0.00, 2.82)%, VTe CV%: (8.93±5.53)% vs. (4.71±2.61)%, both P < 0.05]. Conclusions:Compared with PSV mode, NAVA mode can reduce the occurrence of patient-ventilator asynchronous events, reduce the AI and the occurrence of serious patient-ventilator asynchronous events, so as to improve the patient-ventilator interaction. NAVA and PSV modes can achieve the same gas exchange effect. At the same time, NAVA mode has potential advantages in avoiding insufficient or excessive ventilation support, diaphragm protection and prevention of ventilator-induced lung injury.

Using metabolism related factors constructing a predictive model for the risk of cardiovascular diseases in Xinjiang Kazakh population / 中华内分泌代谢杂志

Objective@#To construct and confirm a predictive model for the risks of cardiovascular diseases (CVD) with metabolic syndrome (MS) and its factors in Xinjiang Kazakh population.@*Methods@#A total of 2 286 Kazakh individuals were followed for 5 years from 2010 to 2012 as baseline survey. They were recruited in Xinyuan county, Yili city, Xinjiang. CVD cases were identified via medical records of the local hospitals in 2013, 2016 and 2017, respectively. Factor analysis was performed on 706 MS patients at baseline, and main factors, age, and sex were extracted from 18 medical examination indexs to construct a predictive model of CVD risk. After excluding the subjects with CVD at baseline and incomplete data, 2007 were used as internal validation, and 219 Kazakhs in Halabra Township were used as external validation. Logistic regression discriminations were used for internal validation and external validation, as well as to calculate the probability of CVD for each participant and receiver operating characteristic curves.@*Results@#The prevalence of MS in Kazakh was 30.88%. Seven main factors were extracted from the Kazakh MS population, namely obesity factor, blood lipid and blood glucose factor, liver function factor, blood lipid factor, renal metabolic factor, blood pressure factor, and liver enzyme factor. The area under the curve (AUC) for predicting CVD in the internal validation was 0.773 (95%CI 0.754-0.792). In the external validation, the AUC for predicting CVD was 0.858 (95%CI 0.805-0.901).@*Conclusions@#The CVD risk prediction model constructed by 7 main factors extracted from Kazakh MS patients has high validation efficiency and can be used for risk assessment of CVD in Xinjiang Kazakh population.

Changes of awareness of tuberculosis and access to tuberculosis-related information among students in Zhejiang Province in the year of 2014 and 2018 / 中国学校卫生

Objective@#To explore the changes of awareness of tuberculosis and access to tuberculosis-related information among students in Zhejiang Province.@*Methods@#There were 554 students younger than 30 y were included in the study during April to sept. of 2014 and during sept. to Nov. of 2018. Univariate and multivariate Logistic regression were conducted to find the related factors of knowing about tuberculosis and related knowledge. Chi-square test was used to analyze the changes of ways access to tuberculosis-related information.@*Results@#There were 440 participants (79.4%) aware of tuberculosis, including 215(85.7%) in 2014 and 225(74.3%) in 2018. The factors affecting awareness on tuberculosis were female ( AOR=1.60, 95%CI =1.04-2.47) vs male; and junior middle school( AOR=1.99, 95%CI =1.03-3.85), high school( AOR=3.27, 95%CI =1.57-6.81), college or higher ( AOR=6.73，95%CI =2.55-17.76) vs primary school or lower; year 2018 ( AOR=0.50, 95%CI =0.31-0.80) vs 2014. There was no significant statistical difference in the overall knowledge scores of tuberculosis between the students in the two surveys. In 2018, the proportion of tuberculosisrelated information accessed from the Internet (forum, WeChat, Weibo.) and community activities (assembly promotion)(75.10%, 26.70%) was higher than that of 2014(36.20%, 13.10%)( χ 2=68.88, 12.79, P <0.05).@*Conclusion@#The proportion of students aware of tuberculosis and TB control in Zhejiang Province were not significantly improved. Higher proportion of students get tuberculosis-related information from the new media. Therefore, it is necessary to strengthen health education of tuberculosis in schools, especially through the usage of new media apart from traditional pathways.

Role of growth arrest-specific protein 6 in migration and osteogenic differentiation of human periodontal ligament cells / 北京大学学报(医学版)

OBJECTIVE@#To investigate the role of growth arrest-specific protein 6 (Gas6) in the process of the migration and osteogenic differentiation of human periodontal ligament cells (hPDLCs).@*METHODS@#After different concentrations of recombinant human Gas6 (rhGas6) were added to hPDLCs, cell prolife-ration experiment (CCK-8) was taken to observe the effect of rhGas6 on hPDLCs cell proliferation. Scratch test and cell migration test (Transwell) were taken to analyze the migratory ability of hPDLCs in different concentrations of rhGas6 groups. After osteogenic induction, real-time quantitative polymerase chain reaction (real-time PCR) was taken to detect the expression of the Runt-related transcription factor 2 (Runx2) and alkaline phosphatase (ALP). ALP staining was used to detect the amount of mineralized nodules.@*RESULTS@#After adding different concentrations of rhGas6, there were no statistically significant differences in hPDLCs cell proliferation among the experimental groups and the control group at 24, 48 and 72 hours (P>0.05). After 24 h of scratch, the healing area in the 800 μg/L of the rhGas6 group was greater than that in the control group, but without statistically significant difference (31.06%±13.70% vs. 21.79%±9.51%, P>0.05). In the migration test, after 24 h, the number of hPDLCs cells which penetrated through the membrane in the 800 μg/L rhGas6 group was significantly higher than that in the control group (P < 0.01). After rhGas6 was added and osteogenic induction, Runx2 and ALP gene expressions of hPDLCs in the 800 μg/L group were significantly higher than those in the control group (1.60±0.30 vs. 0.91±0.10, 2.81±0.61 vs. 0.86±0.12, P < 0.01). After Gas6 was knocked down, the ALP expression of hPDLCs was significantly lower than that of the control group (0.39±0.07 vs. 0.92±0.14, P < 0.01). There was no significant change in Runx2 expression (P>0.05). After 7 days of osteogenic induction, the mineralized nodules formed in the Gas6 knockdown group were significantly less than those in control group (0.25±0.04 vs. 1.00±0.11, P < 0.001). After 14 days of induction, the staining degree of the Gas6 knockdown group was lower than that of the control group, but there was no significant difference (0.86±0.04 vs. 1.00±0.16, P>0.05).@*CONCLUSION@#After downregulation of Gas6 gene, mineralized nodule formation was reduced and ALP gene expressions were decreased in the early stage of osteogenic induction (7 days). After addition of rhGas6, Runx2 and ALP gene expressions were increased and the number of cell migration was increased, suggesting that Gas6 might play a promoting role in the migration and osteogenic differentiation of human periodontal ligament cells.

Using metabolism related factors constructing a predictive model for the risk of cardiovascular diseases in Xinjiang Kazakh population / 中华内分泌代谢杂志

Objective:To construct and confirm a predictive model for the risks of cardiovascular diseases (CVD) with metabolic syndrome (MS) and its factors in Xinjiang Kazakh population.Methods:A total of 2 286 Kazakh individuals were followed for 5 years from 2010 to 2012 as baseline survey. They were recruited in Xinyuan county, Yili city, Xinjiang. CVD cases were identified via medical records of the local hospitals in 2013, 2016 and 2017, respectively. Factor analysis was performed on 706 MS patients at baseline, and main factors, age, and sex were extracted from 18 medical examination indexs to construct a predictive model of CVD risk. After excluding the subjects with CVD at baseline and incomplete data, 2007 were used as internal validation, and 219 Kazakhs in Halabra Township were used as external validation. Logistic regression discriminations were used for internal validation and external validation, as well as to calculate the probability of CVD for each participant and receiver operating characteristic curves.Results:The prevalence of MS in Kazakh was 30.88%. Seven main factors were extracted from the Kazakh MS population, namely obesity factor, blood lipid and blood glucose factor, liver function factor, blood lipid factor, renal metabolic factor, blood pressure factor, and liver enzyme factor. The area under the curve (AUC) for predicting CVD in the internal validation was 0.773 (95% CI 0.754-0.792). In the external validation, the AUC for predicting CVD was 0.858 (95% CI 0.805-0.901). Conclusions:The CVD risk prediction model constructed by 7 main factors extracted from Kazakh MS patients has high validation efficiency and can be used for risk assessment of CVD in Xinjiang Kazakh population.

Endoscopic resection and salvage surgery for early gastric cancer / 中国实用外科杂志

Endoscopic resection(ER) is playing an increasingly important role in treatment of gastric cancer. However,many patients received endoscopic resection turned out to be non-curative. Thus, the following treatment after ER is worthy of discussion. Reviewing the recomandations of guidelines published by European Society for Medical Oncology(ESMO), National Comprehensive Cancer Network(NCCN) and Japanese Gastric Cancer Association(JGCA) and relevant articles, and also retrospectively analysis of cases in our center. In conclusion, for patients of eCura-C, surgery is recommended after considering relevant risks. Gastrectomy type and lymph node dissection range may refer to those for early gastric cancer.Further research is needed to predict lymph node metastasis more accurately. With the development of minimal invasive surgery, sentinel node navigation surgery and laparoscopic and endoscopic cooperative surgery will gain more and more attention.

Discovery and functional analysis of a cytochrome P450 gene involved in C-28 oxidation of the triterpenoids from Ilex pubescens / 中国药科大学学报

@#The main components of the medicinal plant Ilex pubescens Hook. et Arn. are the pentacyclic triterpenoids with various chemical structures. The modification of the triterpenoid skeleton is closely related to a class of key enzymes downstream of the biosynthetic pathway, cytochrome P450 monooxygenase(CYP450). In this study, unigenes with a length of more than 1100 bp were retrieved from the previously obtained Ilex pubescens transcriptome data, and a cytochrome P450 gene(Unigene 0036170)proposed to have the oxidative function of pentacyclic triterpene C-28 was screened through phylogenetic tree analysis. The gene was named as IpAO2. The open reading frame of IpAO2 is 1443 bp, encoding 480 amino acids. RNA was extracted from the tender leaves of Ilex pubescens, and cDNA was obtained by reverse transcription using the RNA as the template. The specific primers AO2-F and AO2-R were designed according to the DNA sequence of IpAO2, and the IpAO2 gene was amplified by PCR using high fidelity enzyme. The IpAO2 gene was ligated into the pEASY cloning vector to obtain pEASY-IpAO2 plasmid. The ligation product was transformed into E. coli Trans1-T1 competent cells and positive clones were screened. The pESC-TRP plasmid was digested with restriction endonucleases to obtain a linearized vector. Primers V-AO2-F and V-AO2-R were designed and the DNA fragment was amplified by PCR using the pEASY-IpAO2 plasmid as template. The DNA fragment was ligated to the vector pESC-TRP to obtain pESC-TRP-IpAO2 recombinant plasmid. The pESC-TRP-IpAO2 plasmid was transformed into a strain of S. cerevisiae capable of efficiently synthesizing amyrin, and the expression of IpAO2 protein was induced with galactose. After extracting the total protein of recombinant S. cerevisiae, Western blot analysis was carried out through the 6×His antigen tag linked to the C-terminus of the target protein. The results showed that the recombinant protein was synthesized in accordance with the expected size. After 7 days of induction and cultivation, the cells of recombinant yeast were collected. The metabolites of cells were extracted and detected by GC-MS after silanization. Through GC-MS analysis of recombinant yeast metabolites, it was found that the protein encoded by the IpAO2 gene can oxidize α-amyrin and β-amyrin to ursolic acid and oleanolic acid, respectively, indicating that IpAO2 is a pentacyclic triterpene C-28 oxidase gene. Meanwhile, the transmembrane domain and protein tertiary structure of the IpAO2 were predicted using the Phyre2 online tool, the results showing that IpAO2 is a transmembrane protein. This study is of great significance to elucidate the biosynthetic mechanism of triterpenoids of Ilex pubescens, and lays a foundation for the further utilization of the metabolic engineering to produce triterpenoids of Ilex pubescens in S. cerevisiae.