Purpose This study aimed to investigate the expression and clinical significance of TLDC2 in colorec-tal adenocarcinoma.Methods Data from the human protein atlas(HPA)and the cancer genome atlas(TCGA)indi-cated that TLDC2 was highly expressed in colorectal adenocarcinoma.We further analyzed the expression of TLDC2 in 400 colorectal adenocarcinomas and 447 other solid tumors using tissue microarrays and immunohistochemical(IHC)staining.Result The positive expression rate of TLDC2 was significantly higher than that of SATB2 in colorectal ade-nocarcinomas(96.5％vs 87.0％,P＜0.000 1).TLDC2 positivity exceeded that of SATB2 in both low-or high-grade colorectal adenocarcinoma(99.4％vs 88.7％,P＜0.000 1;83.3％vs 79.2％,P=0.669 9).In addition,the expression of TLDC2 and SATB2 was evaluated in 447 cases of other types of solid tumors.TLDC2 was expressed in neuroendocrine tumors as well as in gastric and appendiceal adenocarcinomas,whereas SATB2 was detected in a small number of melanomas,ovarian cancers,breast cancers and gallbladder cancers.The positive and specificity of TLDC2 for colorectal adenocarcinoma were 97％(95％CI=0.94-0.98)and 85％(95％CI=0.81-0.88),respectively.Combined detection of TLDC2 and SATB2 yielded a sensitivity of 96％(95％CI=0.93-0.97)and a specificity of 93％(95％CI=0.90-0.95).Conclusion Analysis of large-scale datasets and IHC staining demonstrated that TLDC2 is a highly sensitive and specific biomarker for colorectal adenocarcinoma.

Purpose This study aimed to investigate the expression and clinical significance of TLDC2 in colorec-tal adenocarcinoma.Methods Data from the human protein atlas(HPA)and the cancer genome atlas(TCGA)indi-cated that TLDC2 was highly expressed in colorectal adenocarcinoma.We further analyzed the expression of TLDC2 in 400 colorectal adenocarcinomas and 447 other solid tumors using tissue microarrays and immunohistochemical(IHC)staining.Result The positive expression rate of TLDC2 was significantly higher than that of SATB2 in colorectal ade-nocarcinomas(96.5％vs 87.0％,P＜0.000 1).TLDC2 positivity exceeded that of SATB2 in both low-or high-grade colorectal adenocarcinoma(99.4％vs 88.7％,P＜0.000 1;83.3％vs 79.2％,P=0.669 9).In addition,the expression of TLDC2 and SATB2 was evaluated in 447 cases of other types of solid tumors.TLDC2 was expressed in neuroendocrine tumors as well as in gastric and appendiceal adenocarcinomas,whereas SATB2 was detected in a small number of melanomas,ovarian cancers,breast cancers and gallbladder cancers.The positive and specificity of TLDC2 for colorectal adenocarcinoma were 97％(95％CI=0.94-0.98)and 85％(95％CI=0.81-0.88),respectively.Combined detection of TLDC2 and SATB2 yielded a sensitivity of 96％(95％CI=0.93-0.97)and a specificity of 93％(95％CI=0.90-0.95).Conclusion Analysis of large-scale datasets and IHC staining demonstrated that TLDC2 is a highly sensitive and specific biomarker for colorectal adenocarcinoma.

Objective:To evaluate the effects of different doses of sivelestat sodium on perioperative acute lung injury (ALI) in the patients undergoing emergency surgery for acute Stanford type A aortic dissection (AAAD).Methods:A total of 120 patients of both sexes, aged 30-64 yr, with body mass index of 18.5-24.9 kg/m 2, of American Society of Anesthesiologists Physical Status classification Ⅲ or Ⅳ, scheduled for emergency AAAD surgery, were divided into 3 groups using a random number table method: low-dose sivelestat sodium group (SL group), medium-dose sivelestat sodium group (SM group)and high-dose sivelestat sodium group (SH group), with 40 patients in each group. Sivelestat sodium 4.8, 6.0 and 7.2 mg/kg were intravenously infused starting from 10 min before anesthesia until 24 h after surgery in SL, SM and SH groups, respectively. Blood samples from the radial artery were collected for blood gas analysis after anesthesia induction and before skin incision (T 1), immediately after the end of surgery (T 2), at 24 h after surgery (T 3), and 72 h after surgery (T 4), the alveolar-arterial oxygen tension difference (PA-aDO 2), oxygenation index (OI)and respiratory index (RI) were calculated. The duration of postoperative mechanical ventilation, length of stay in the intensive care unit (ICU) and length of postoperative hospital stay were recorded. Central venous blood samples were collected at T 1-T 4 to measure serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6)and IL-8. Peripheral venous blood samples were collected on preoperative day 1 and postoperative days 1 and 3 to measure white blood cell (WBC) count, neutrophil (NEUT) count, neutrophil percentage (NEUT%), and C-reactive protein (CRP) concentration. The occurrence of postoperative pulmonary complications (PPCs)and 90-day all-cause mortality were recorded. Results:Compared with the baseline at T 1, PA-aDO 2 and RI were significantly increased, OI was decreased, and the serum concentrations of TNF-α, IL-6 and IL-8 were increased at T 2-T 4 in all the three groups ( P<0.05). WBC, NEUT, NEUT% and concentrations of CRP were significantly higher on postoperative days 1 and 3 than on 1 day before surgery in the three groups ( P<0.05). Compared with SL and SM groups, PA-aDO 2 and RI were significantly decreased, OI was increased, and the serum concentrations of TNF-α, IL-6 and IL-8 were decreased, the WBC count, NEUT count, NEUT% and concentrations of CRP were decreased, the incidence of postoperative hypercapnia, hypoxemia, emerging lung rales and bronchospasm was decreased, and the duration of postoperative mechanical ventilation and length of intensive care unit stay were shortened( P<0.05), and no significant change was found in the postoperative length of hospital stay and 90-day all-cause mortality rate in SH group ( P>0.05). Conclusions:Sivelestat sodium 7.2 mg/kg can significantly inhibit the inflammatory responses, alleviate perioperative ALI, and improve early prognosis in the patients undergoing AAAD surgery.

Objective:To investigate the relationship between lncRNA H19 gene and transforming growth factor (TGF)-β1 in polycystic ovary syndrome (PCOS) granulosa cells and their effects on the proliferation and apoptosis of granulosa cells. Methods:Human ovarian granulosa cell line KGN was treated with TGF-β1 of 2 μg/L, 4 μg/L, and 10 μg/L, and the expression level of H19 was detected by Q-PCR method, and the H19 overexpression plasmid pcDNA3.0-H19 and siH19-1617 were transfected into KGN, the expression of TGF-β1 was detected by Western blotting, the proliferation of granulosa cells was detected by CCK8 method, and the apoptosis of granulosa cells was detected by flow cytometry.Results:After adding TGF-β1, the expression of H19 increased compared with untreated cells. When the concentration of TGF-β1≥4 μg/L, the expression of H19 increased significantly, and the difference was statistically significant ( P=0.023). After H19 was overexpressed, the expression of TGF-β1 was significantly higher than that of control group KGN+pcDNA3.0-NC transfected with empty plasmid ( P=0.017), and the expression of TGF-β1 after H19 silencing was significantly lower than that of control group KGN+NC ( P<0.001). After H19 overexpression, the proliferation ability of KGN cells was enhanced at 48 h and 72 h, but the apoptosis ability was weakened. After H19 was silenced, the proliferation ability of KGN cells was weakened at 48 h and 72 h, but the apoptosis ability was enhanced. Conclusion:H19 can regulate the expression of downstream protein TGF-β1, promote the proliferation of PCOS ovarian granulosa cells, and inhibit cell apoptosis.

Objective:To investigate the relationship between lncRNA H19 gene and transforming growth factor (TGF)-β1 in polycystic ovary syndrome (PCOS) granulosa cells and their effects on the proliferation and apoptosis of granulosa cells. Methods:Human ovarian granulosa cell line KGN was treated with TGF-β1 of 2 μg/L, 4 μg/L, and 10 μg/L, and the expression level of H19 was detected by Q-PCR method, and the H19 overexpression plasmid pcDNA3.0-H19 and siH19-1617 were transfected into KGN, the expression of TGF-β1 was detected by Western blotting, the proliferation of granulosa cells was detected by CCK8 method, and the apoptosis of granulosa cells was detected by flow cytometry.Results:After adding TGF-β1, the expression of H19 increased compared with untreated cells. When the concentration of TGF-β1≥4 μg/L, the expression of H19 increased significantly, and the difference was statistically significant ( P=0.023). After H19 was overexpressed, the expression of TGF-β1 was significantly higher than that of control group KGN+pcDNA3.0-NC transfected with empty plasmid ( P=0.017), and the expression of TGF-β1 after H19 silencing was significantly lower than that of control group KGN+NC ( P<0.001). After H19 overexpression, the proliferation ability of KGN cells was enhanced at 48 h and 72 h, but the apoptosis ability was weakened. After H19 was silenced, the proliferation ability of KGN cells was weakened at 48 h and 72 h, but the apoptosis ability was enhanced. Conclusion:H19 can regulate the expression of downstream protein TGF-β1, promote the proliferation of PCOS ovarian granulosa cells, and inhibit cell apoptosis.

Bacitracin is a broad-spectrum antibiotics mainly produced by Bacillus, and is used as veterinary medicine in the fields of livestock and poultry breeding. Insufficient supply of precursor amino acids might be an important factor that hinders high-level microbial production of bacitracin. We investigated the effect of strengthening L-cysteine supply on bacitracin production by an industrial bacitracin producer, Bacillus licheniformis DW2. Overexpression of cysK encoding L-cysteine synthase led to a 9.17% increase of the bacitracin titer. Moreover, overexpression of cysE encoding L-serine acetyltransferase and cysP encoding thiosulfate/sulfate intracellular transporter increased the bacitracin titers by 7.23% and 8.52%, respectively. Moreover, overexpression of a putative cystine importer TcyP led to a 29.19% increase of intracellular L-cysteine, and bacitracin titer was increased by 7.79%. Subsequently, the strong promoter PbacA was used to replace the promoters of genes cysP, cysE and tcyP in strain DW2::ysK, respectively. The resulted strain CYS4 (DW2::cysK-PbacA-(cysP)-PbacA(cysE)- PbacA(tcyP) produced 910.02 U/mL bacitracin, which was 21.10% higher than that of the original strain DW2 (747.71 U/mL). Together with the experiments in 3 L fermenters, this research demonstrated that enhancing intracellular L-cysteine supply is an effective strategy to increase bacitracin production of B. licheniformis.
Amino Acids ; Bacillus licheniformis/genetics* ; Bacitracin ; Cysteine ; Metabolic Engineering

Objective:To investigate the clinical characteristics and related risk factors of sarcopenia in elderly patients undergoing maintenance hemodialysis.Methods:This was a retrospectively study involving 135 elderly hemodialysis patients aged(70.6±7.7)years, with 46(34.1%)females and a mean hemodialysis duration of(3.2±2.9)years, at Shanghai Sixth People's Hospital.The incidence of sarcopenia in patients was examined by measuring handgrip strength, walking speed and muscle mass of the limbs using bioelectrical impedance analysis.Related risk factors were analyzed with univariate and multivariate logistic regression analysis.Results:Among 135 elderly hemodialysis patients, the incidence of sarcopenia was 62.9%(85 cases), and severe sarcopenia cases accounted for 44.4%(60 cases). Compared with the non-sarcopenia group, patients with sarcopenia were older, had lower body mass index(BMI)and handgrip strength, walked more slowly and had less muscle mass in their limbs.Advanced age, low BMI and long dialysis duration were correlated with the high incidence of sarcopenia in elderly dialysis patients.The odds ratio( OR)for sarcopenia increased by 12% per year, and the OR decreased by 32% with an increase of 1.0 kg/m 2 in BMI.Advanced age and lower BMI were also correlated with a high incidence of severe sarcopenia( OR=1.12, 95% CI: 1.05~1.18; OR=0.84, 95% CI: 0.74~0.95; all P<0.01). Conclusions:The incidence of sarcopenia is high in elderly hemodialysis patients and is closely related to advanced age and low body weight.Improving nutritional status and avoiding low body weight will help reduce the occurrence and development of sarcopenia in elderly hemodialysis patients.

This paper aimed at exploring methods and their effectiveness of cultivating the scientific research quality in medical undergraduates in the early stage of. In combination with teachers' scientific research projects, 3 to 5 medical undergraduates in 3rd grade who applied for the projects initiatively were selected every year to enter into different research groups in the department. According to students' wishes, they may participate in some experiments in scientific research projects, or complete small projects independently, or write a review on a certain topic under teachers' guidance. In the past 10 years, 25 students participated in the program of our section and published 19 papers in total. Most students who participated in the experimental research program were able to carry out some scientific experiments independently with improved scientific research ability and practical ability. Students who wrote reviews not only broadened their knowledge, but also developed the skills of literature search, reading, comprehensive writing and critical thinking. Therefore, it was concluded that the cultivation of scientific research quality in students in the early stage could motivate students to actively participate in scientific research; both scientific experiments and themed reviews could enhance the scientific research ability and scientific research quality of undergraduates from different angles.

OBJECTIVE： To investigate the effects of different polar parts of 5 kinds of Alpinia on the function of sympathetic-adrenal system in gastric ulcer model rats with cold syndrome， such as the root of Alpinia officinarum， the rhizome and fruit of Alpinia galangal， the seed of Alpinia katsumadai， and the fruit of Alpinia oxyphylla. METHODS： SD rats were given Anemarrhena asphodeloides decoction at 4 ℃ and Glacial acetic acid solution intragastrically to induce gastric ulcer model with cold syndrome； the model rats were randomly divided into model group， Fuzi lizhong pills group （positive control， 9.0 g/kg）， cimetidine group （positive control， 0.003 3 g/kg）， low-dose and high-dose groups of petroleum ether， ethyl acetate， n-butanol and water extraction parts from 5 medicinal materials （hereinafter referred to as “gaoshidi” “gaoshigao” “dashidi” “dashigao” “hongshidi” “hongshigao” “caoshidi” “caoshigao” “yishidi” “yishigao” “gaoyidi” “gaoyigao” “dayidi” “dayigao” “hongyidi” “hongyigao” “caoyidi” “caoyigao” “yiyidi” “yiyigao” “gaozhengdi” “gaozhenggao” “dazhengdi” “dazhenggao” “hongzhengdi” “hongzhenggao” “caozhengdi” “caozhenggao” “yizhengdi” “yizhenggao” “gaoshuidi” “gaoshuigao” “dashuidi” “dashuigao” “hongshuidi” “hongshuigao” “caoshuidi” “caoshuigao” “yishuidi” “yishuigao”， 0.064/0.256， 0.032/ 0.128， 0.008/0.032， 0.075/0.3， 0.1/0.4， 0.064/0.256， 0.108/0.432， 0.16/0.64， 0.064/0.25， 0.125/0.5， 0.056/0.224， 0.108/0.432， 0.08/0.32， 0.2/0.8， 0.3/1.2， 0.14/0.56， 0.032/0.128， 0.028/0.112， 0.05/0.2， 0.087/0.348 g/kg， by mass of extraction parts）， with 10 rats in each group； and the blank group （normal temperature water） was set up. Next day after modeling， blank group and model group were given constant volume of normal temperature water intragastrically； administration group was given relevant solution 2 mL/100 g intragastrically， q12 h， 4 times in total. After last medication， urine contents of 17-OHCS， CAs substances （A， NE， DA） and serum contents of ACTH and D-β-H were determined by ELISA. RESULTS： Compared with blank group， the contents of 17-OHCS， A， NE and DA in urine， the contents of ACTH and D-β-H in serum were decreased significantly in model group （P＜0.01）. Compared with model group， the contents of 17-OHCS （Fuzi lizhong pills group， cimetidine group， gaoshidi， gaoshigao， dashigao， hongshigao， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， gaoshuigao， dashuigao and hongshuigao groups）， A （Fuzi lizhong pills group， cimetidine group， gaoshigao， dashigao， hongshidi， hongshigao， caoshidi， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhengdi， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group）， NE （Fuzi lizhong pills group， cimetidine group， petroleum ether part， ethyl acetate part and n-butanol part groups of 5 medicinal materials， gaoshuigao， dashuigao and hongshuigao groups）， DA [Fuzi lizhong pills group， cimetidine group， petroleum ether part （except for gaoshidi group） and ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group] in urine， serum contents of ACTH [Fuzi lizhong pills group， petroleum ether part （except for gaoshidi， dashidi and caoshidi groups） and ethyl acetate part （except for dayidi and hongyidi groups） groups of 5 medicinal materials， hongzhenggao group， dashuigao group]， and D-β-H [Fuzi lizhong pills group， gaoshigao， dashigao， hongshidi， hongshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials （except for dayidi， hongyidi and yiyidi groups）， dazhenggao and hongzhenggao groups， hongshuigao group] were increased significantly （P＜0.05 or P＜0.01）. The contents of 17-OHCS and D-β-H in dashigao group， the contents of ACTH and D-β-H in caoshigao group and the contents of D-β-H in gaoshigao and yishigao groups were significantly lower than hongshigao group. The contents of DA in gaoyigao， caoyigao and yiyigao groups as well as the contents of D-β-H in gaoyigao， hongyigao， caoyigao and yiyigao groups were significantly lower than dayigao group； the contents of DA in gaoyigao and caoyigao groups were significantly lower than hongyigao group， the contents of ACTH in gaoyigao， dayigao， caoyigao and yiyigao groups were significantly higher than hongyigao group. The contents of 17-OHCS， DA and ACTH in gaozhenggao， dazhenggao， caozhenggao and yizhenggao groups， the contents of A in dazhenggao， caozhenggao and yizhenggao groups as well as the contents of D-β-H in gaozhenggao， caozhenggao and yizhenggao groups were significantly lower than hongzhenggao group. The contents of 17-OHCS and D-β-H in caoshuigao and yishuigao groups were significantly lower than dashuigao group. The contents of 17-OHCS， DA and D-β-H in caoshuigao and yishuigao groups as well as the contents of DA and D-β-H in gaoshuigao groups were significantly lower than hongshuigao group （P＜0.05 or P＜0.01）. CONCLUSIONS： Different polar parts of 5 kinds of Alpinia can improve gastric ulcer model rats with cold syndrome to different extents； among them， the fruit of A. galangal is the best， followed by the root of A. officinarum. Above medicinal materials can regulate the function of sympathetic-adrenal system by increasing the contents of 17-OHCS， CAs and D-β-H.

Objective To investigate the effect of hypertension on white matter microstructure and its correlation with cognitive function using automated fiber-tract quantification.Methods Consecutive subjects visited Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School between January 2017 and July 2018 were collected.They were divided into hypertension without cognitive impairment (HTN-nonCI) group (n =44),hypertension with cognitive impairment (HTN-CI) group (n =50),and control group (n =25).The imaging data and neuropsychological scale test results of the subjects were collected.The automated fiber-tract quantification was used to obtain the diffusion parameters of 100 nodes on 20 fiber tracts in the whole brain.The differential segments of each fiber tract diffusion parameter between the control group and HTN-nonCI group,and the HTN-nonCI group and HTN-CI group were compared.Correlation analysis was performed in white matter fiber tracts with significant differences and each cognitive domain between the HTN-nonCI group and the HTN-CI group.Results The fractional anisotropy (FA) of white matter fiber tracts in 3 groups showed a decreasing trend,and the mean diffusion diffusivity (MD) showed an increasing trend.The comparison between the control group and the HTN-nonCI group showed that there were significant differences in the FA values of the midpoint of left thalamic radiation tract partial to brainstem,the genus of corpus callosum near brainstem,and frontal part and and proximal ventricle of splenium of corpus callosum (all P＜0.05);there were significant differences in the MD values of the middle part of left thalamic radiation tract and near the brainstem,the right thalamic radiation tract near the brainstem,the top of left corticospinal tract and near brainstem,the middle hippocampus of right cingulate tract,the middle part of genu of corpus callosum,the splenium of the corpus callosum near the lateral ventricle,the left uncinate tract near the forehead (all P ＜ 0.05).A comparison between the HTN-nonCI group and the HTN-CI group showed that there was significant difference in the FA value between the distributed segments of cingulate gyrus of left cingulate tract and the left inferior fronto-occipital tract near the occipital lobe,in which cingnlate gyrus of left cingulate tract was significantly correlated with the Montreal Cognitive Assessment Scale score (standardized3 =0.268,P =0.029);there were significant differences in the right thalamic radiation tract near the brainstem,the forehead and proximal ventricle of splenium of the corpus callosum,and the scattered distribution segments of the right inferior longitudinal fasciculus,in which the right inferior longitudinal fasciculus was significantly correlated with memory (standardizedβ=-0.243,P=0.047) and executive function (standardizedβ=-0.284,P=0.021).Conclusions Microstructural integrity of white matter was generally destroyed in patients with hypertension,but some segments were more susceptible to hypertension.The integrity of cingnlate gyrus of cingulate tract was significantly correlated with the overall cognitive function.The integrity of inferior iongitudinal fasciculus was significantly correlated with the executive function and memory.