[Tyro3 and CDK9 as biomarkers for drug resistance to breast cancer anti-PD-1 therapies].

Objective: PD-1/PD-L1 immune checkpoint treatment is effective for some triple-negative breast cancer populations with PD-L1 expression, but the response rate is still not satisfactory. This study aims to explore the mechanism of drug resistance to breast cancer anti-PD-1 therapies and the strategies for overcoming the resistance to PD-1therapies. Methods: By constructing a human triple-negative breast cancer drug-resistant cell line called BT-549R5 and a mouse breast cancer drug-resistant cell line called 4T1R3, and applying the whole-gene shRNA library screening, candidate drug resistance-associated molecules were obtained and verified by cytological experiments. The expression of Tyro3, Axl and MerTK of the TAM family in the 4T1R3 group was tested using the Western blot method. The down-regulation of CDK9 on the effect of T cells killing the BT-549R5 cells was observed through T cell killing tests, while the down-regulation of Tyro3 and CDK9 on the effect of anti-PD-1 therapies for transplanted breast tumors was observed in mouse tumor formation experiments. Results: The cell lines and animal models of breast cancer resistant to PD-1 treatment were successfully constructed. Tyro3, Axl and MerTK were highly expressed in 4T1R3 cells. Whole genome sequencing showed that Tyro3 and CDK9 were highly expressed in BT-549R5 cells. T cell killing experiment showed that the survival rate of BT-549R5 cells in the CDK9 down-regulated group and the control group decreased gradually with the increase of T cells, but the survival rate of BT-549R5 cells in the CDK9 down-regulated group decreased rapidly. Tumor formation experiment in mice showed that under anti-PD-1 treatment, the transplanted tumor in the 4T1R3 cell group grew rapidly compared with the 4T1 cell group (P<0.05), and the tumor volume of the 4T1R3 group was larger than that of the 4T1 group on Day 20. Nevertheless, the tumor growth rates in the CDK9-knockdown 4T1R3 cell group and the Tyro3-knockdown 4T1R3 cell group were similar to that of the 4T1 cell group, and the tumor volumes at day 20 were signiference lower than that of 4T1R3 cell group(P<0.05). Conclusions: Tyro3 and CDK9 are associated with the drug resistance to anti-PD-1 therapies for breast cancer. Inhibiting the expression of Tyro3 and CDK9 can reverse the drug resistance to breast cancer treatment.

[Relationship between blood uric acid levels and body composition in patients with polycystic ovary syndrome].

Objective: To analyze the difference in blood uric acid levels between patients with polycystic ovary syndrome (PCOS) and healthy women of childbearing age, and to investigate the correlation between body composition and blood uric acid levels. Methods: A total of 153 eligible childbearing age patients with PCOS treated at Tianjin Medical University General Hospital from January 2018 to March 2022 were selected, and 153 healthy women with normal menstruation were selected as the control group. Fasting blood uric acid levels were measured by venous blood test, and body composition was measured by a body composition analyzer. Group comparisons were made to analyze the correlation between body composition and blood uric acid levels. Results: The incidence of hyperuricemia was higher in patients with PCOS than that in the control group [30.1% (46/153) vs 2.0% (3/153)], with a statistically significant difference (χ2=44.429, P<0.001). Blood uric acid level was also significantly higher in patients with PCOS than that in the control group [(371±98) vs (265±67) µmol/L; t=11.170, P<0.001]. Among PCOS patients, there were statistically significant differences in weight, body mass index (BMI), body fat mass, skeletal muscle mass, percent body fat, lean body weight, fat mass/lean body weight, percent skeletal muscle, and visceral fat level between the hyperuricemia group and the normal blood uric acid group (all P<0.001), but no significant difference was observed in waist-hip ratio (P=0.348). The following body composition indicators: weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, visceral fat level, lean body weight, and fat mass/lean body weight in all subjects, the PCOS patients and the control group, were positively correlated with blood uric acid levels (all P<0.01). The blood uric acid level in PCOS obese patients was higher than that in non-obese PCOS patients, and the difference was statistically significant [(425±83) vs (336±91) µmol/L; t=6.133, P<0.001]. The blood uric acid level in central obesity PCOS patients was also higher than that in non-central obesity PCOS patients [(385±95) vs (299±79) µmol/L], the difference was statistically significant (t=4.261, P<0.001). The blood uric acid level in normal-weight obese PCOS patients was higher than that in normal-weight non-obese PCOS patients [(333±73) vs (277±54) µmol/L], and the difference was statistically significant (t=2.848, P=0.006). Blood uric acid levels in normal-weight [(315±74) vs (255±67) µmol/L], overweight [(362±102) vs (276±57) µmol/L], and obese PCOS patients [(425±83) vs (303±74) µmol/L] were all higher than those in the corresponding control groups, with statistically significant differences (all P<0.001). Conclusions: PCOS patients have a higher incidence of hyperuricemia than healthy women of childbearing age. Blood uric acid levels are closely correlated with body composition indicators, such as weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, and visceral fat level. Body composition analysis of women with PCOS could help identify potentially obese people more accurately and carry out individualized treatment, thereby reducing the risk of metabolic abnormalities.

[Current status of influencing factors for postoperative anastomotic leakage in low rectal cancer].

The incidence of anastomotic leakage, a common and serious postoperative complication of low rectal cancer, remains high. Clarifying the risk factors for anastomotic leakage in patients with low rectal cancer after surgery can help guide clinical treatment and help patients improve their prognosis. The current literature suggests that the risk factors affecting the occurrence of anastomotic leakage after low rectal cancer include three aspects: (1) individual factors: male gender, high body mass index, malnutrition, smoking, alcoholism, and metabolic diseases; (2) tumor factors: the lower margin of tumor <5 cm from the anal verge, tumor diameter >2.5 cm, late tumor stage, high level of tumor markers and preoperative intestinal obstruction; (3) surgical factors: long operative time (>180 min), intraoperative bleeding (≥70 ml), more than 2 cartridges of stapling for anastomosis, contamination of the operative field, epidural analgesia and intraoperative hypothermia. Notably, the surgical approach (laparoscopic, open and hand-assisted laparoscopic surgery) was not a factor influencing the occurrence of postoperative anastomotic leakage in low rectal cancer. The findings on the effects of receiving neoadjuvant therapy, gut microbiota,intestinal bowel preparation, insufficient time for preoperative antibiotic prophylaxis, left colonic artery dissection, intraoperative blood transfusion, pelvic drainage, transanal drainage and combined organ resection, and postoperative diarrhea on postoperative anastomotic leakage in low rectal cancer are controversial. However, clinical workers can still take measures to reduce the risk of anastomotic leakage according to the above risk factors by making a good assessment before surgery, actively avoiding them during and after surgery, and taking measures for each step, so as to bring maximum benefits to patients.

[Epidemiological characteristics and treatment outcome analysis of 229 patients with hydrofluoric acid burns in hands].

Objective: To explore the epidemiological characteristics and treatment outcomes of patients with hydrofluoric acid burns in hands. Methods: A retrospective observational study was conducted. The medical records of 229 patients with hydrofluoric acid burns in hands who were admitted to Zhejiang Quhua Hospital from January 2008 to December 2020 and met the inclusion criteria were collected. The following statistical data of patients were collected, including gender, age, type of affiliated enterprise, hydrofluoric acid mass fraction, injury site, total burn area, prehospital time, length of hospital stay, length of wound healing, whether hypocalcemia and hypomagnesemia occurred or not on admission, whether surgery intervention was performed or not, and whether scar sequelae occurred or not. Single factor and multivariate logistic regression analysis were used to screen out the risk factors impacting surgery intervention and scar sequelae of all the patients and patients whose hydrofluoric acid mass fraction was known. Single factor and multivariate linear regression analysis were used to screen out the risk factors impacting the length of wound healing of all the patients and patients whose hydrofluoric acid mass fraction was known. Results: The 229 patients included 206 males and 23 females, with the majority aged 30 to 50 years (139 patients). The type of affiliated enterprise of majority patients was non-fluorine chemical enterprise. The hydrofluoric acid mass fraction was known in only 91 patients, mainly medium. The majority injury site was in the middle and end of finger. The total burn area was below or equal to 1% total body surface area. The prehospital time was 19 (9, 29) h. The length of hospital stay was 2 (1, 7) d. The length of wound healing was 12 (8, 18) d. The proportions of hypocalcemia and hypomagnesemia were 0.9% (2/229) and 1.3% (3/229) on admission, respectively. Thirty-six patients had surgeries and 83 patients had scar sequelae. In 229 patients, single factor logistic regression analysis showed that both type of affiliated enterprise and prehospital time were the factors impacting surgery intervention (with odds ratio values of 7.86 and 51.35, respectively, 95% confidence intervals of 1.83-33.76 and 11.89-221.78, respectively, P<0.01) and scar sequelae of patients (with odds ratio values of 3.62 and 27.40, respectively, 95% confidence intervals of 1.76-7.43 and 13.25-56.68, respectively, P<0.01); multivariate logistic regression analysis showed that prehospital time was the independent risks factor impacting surgery intervention and scar sequelae of patients (with odds ratio values of 43.00 and 24.55, respectively, 95% confidence intervals of 9.89-187.03 and 11.78-51.16, respectively, P<0.01); single factor linear regression analysis showed that both type of affiliated enterprise and prehospital time were the factors impacting the length of wound healing of patients (with ß values of 6.16 and 12.83, respectively, 95% confidence intervals of 3.38-8.93 and 10.72-14.93, respectively, P<0.01); multivariate linear regression analysis showed that both type of affiliated enterprise and prehospital time were the independent risk factors impacting the length of wound healing of patients (with ß values of 2.81 and 12.16, respectively, 95% confidence intervals of 0.50-5.13 and 10.00-14.31, respectively, P<0.05 or P<0.01). In 91 patients whose hydrofluoric acid mass fraction was known, single factor logistic regression analysis showed that type of affiliated enterprise, hydrofluoric acid mass fraction (low and high), and prehospital time were all the factors impacting surgery intervention of patients (with odds ratio values of 9.10, 11.25, 10.69, and 0.04, respectively, 95% confidence intervals of 1.15-72.25, 1.39-90.93, 1.32-86.59, and 0.01-0.19, respectively, P<0.05 or P<0.01), type of affiliated enterprise, hydrofluoric acid mass fraction, and prehospital time were all the factors impacting scar sequelae of patients (with odds ratio values of 0.32, 0.21, and 36.80, respectively, 95% confidence intervals of 0.11-0.92, 0.06-0.73, and 11.03-122.79, respectively, P<0.05 or P<0.01); multivariate logistic regression analysis showed that both hydrofluoric acid mass fraction and prehospital time were the independent risk factors impacting surgery intervention of patients (with odds ratio values of 11.51 and 0.04, respectively, 95% confidence intervals of 1.22-108.26 and 0.01-0.25, respectively, P<0.05 or P<0.01), prehospital time was the independent risk factor impacting scar sequelae of patients (odds ratio=37.71, with 95% confidence interval of 9.97-142.69, P<0.01); single factor linear regression analysis showed that type of affiliated enterprise, hydrofluoric acid mass fraction (low and high), and prehospital time were all the factors impacting the length of wound healing of patients (with ß values of 7.12, -5.63, -9.74, and 13.50, respectively, 95% confidence intervals of 2.43-11.81, -10.59--0.68, -14.78--4.70, and 10.14-16.86, respectively, P<0.05 or P<0.01); multivariate linear regression analysis showed that both hydrofluoric acid mass fraction and prehospital time were the independent risk factors impacting the length of wound healing of patients (with ß values of -5.84 and 0.09, respectively, 95% confidence intervals of -10.59--1.08 and 0.05-0.12, respectively, P<0.05 or P<0.01). Conclusions: The majority of patients with hydrofluoric acid burns in hands are young and middle-aged males. Type of affiliated enterprise, hydrofluoric acid mass fraction and prehospital time are the risk factors that affect the treatment outcomes of patients with hydrofluoric acid burns in hands.

[Anatomical controversies involved in radical resection of rectal cancer].

The concept of total mesorectal resection provides a quality control standard that can be followed for radical resection of rectal cancer, but some anatomical problems are still controversial. Compared with traditional open surgery, laparoscopic radical rectal surgery has better surgical vision, better neurological protection, better operating space. However, if the surgeon has insufficient understanding of the anatomy, collateral damage may occur, such as uncontrollable bleeding during the operation, postoperative urination and defecation dysfunction and so on. Based on the interpretation of the researches at home and abroad, combined with the clinical experience, we elucidate some associated issues, including anatomic variation of inferior mesenteric vessels, the controversy of inferior mesenteric artery ligation plane, the controversy of lymph node dissection in No. 253, the anatomical variation of middle rectal artery, and the anatomical controversy of lateral lymph node dissection in rectal cancer, in order to provide better cognitive process for the clinical front-line surgeons.

[Analysis of perioperative complications and influencing factors of complications in 1 000 cases of robotic gynecological surgery].

Objective: To investigate the occurrence and influencing factors of perioperative complications after robotic gynecologic surgery. Methods: The clinical data and occurrence of perioperative complications in 1 000 cases robotic surgery completed in the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Results: (1) Clinical data: the average age of the patients was (50.2±10.4) years old, and the average body mass index (BMI) was (24.4±3.6) kg/m2. Among 1 000 cases, 811 cases of them were malignant tumors, including 405 cases of cervical cancer, 279 cases of endometrial carcinoma, 112 cases of epithelial ovarian cancer (EOC), 15 cases of vulvar cancer; 189 cases of them were benign diseases, including 43 cases of uterine prolapse, 57 cases hysterectomy of uterine leiomyoma and adenomyosis of the uterus ≥12 weeks, 84 cases myomectomy of uterine leiomyoma, and 5 cases of fallopian tubal ligation requiring anastomosis. Surgical methods: in patients with malignant tumors, cervical cancer, hysterectomy plus salpingectomy or salpingo-oophorectomy for stage Ⅰa1, and radical hysterectomy plus pelvic lymphatic dissection plus salpingectomy or salpingo-oophorectomy for stage Ⅰa2-Ⅱb. Endometrial carcinoma, performed by staging surgery. Staging surgery for EOC with early stage and cytoreductive surgery with advanced EOC. Vulvar cancer, extensive vulvar resection plus inguinal lymphadenectomy. In patients with benign diseases, uterine prolapse, hysterectomy plus salpingectomy or salpingo-oophorectomy plus sacrocolpopexy. Uterine leiomyoma or adenomyosis with uterus ≥ 12 weeks, hysterectomy plus salpingectomy or salpingo-oophorectomy. Myomectomy for patients requiring uterine preservation with uterine leiomyoma. Tubal anastomosis for patients with fallopian tubal ligation. (2) Surgical complications: intraoperative complications occurred in 25 patients (2.5%, 25/1 000), including 11 patients with vascular laceration, 11 patients with ureteral injury, 2 patients with bladder injury, and 1 patient with intestinal injury. Postoperative complications occurred in 130 patients (13.0%, 130/1 000), including 66 cases of lower limb venous thrombosis, 20 cases of lymphatic cyst, 8 cases of hydronephrosis, 9 cases of ileus, 16 cases with infection, 6 cases with genital fistula, 4 cases with trocar site herniation and 1 case with subcutaneous emphysema. The incidence of intraoperative complications was 3.1% (25/811) in malignant tumors and no case in benign diseases, the incidence rate in malignant tumors was significantly higher than that in benign diseases (χ²=4.778, P=0.029). The incidence rate in cervical cancer (4.2%, 17/405) and EOC (3.6%, 4/112) were significantly higher than those in endometrial carcinoma (1.4%, 4/279) and vulvar cancer (0/15; P<0.05). The incidence of postoperative complications was 15.2% (123/811) in malignant tumors and 3.7% (7/189) in benign diseases. The incidence rate in malignant tumors was significantly higher than that in benign diseases (χ²=17.807, P<0.01), but there were no significant difference among different malignant tumors (χ²=4.318, P=0.229). (3) The correlative factors affecting the occurrence of surgical complications: patient's age, BMI, previous pelvic or abdominal surgery history, the nature of disease (malignant or benign), operation time, and comorbidities had a significant impact on the incidence of postoperative complications (P<0.05). Multivariate logistic regression analysis showed that the patient's age ≥40 years old, BMI ≥25 kg/m2, previous pelvic or abdominal surgery history, malignant tumors and comorbidities were independent influential factors of the postoperative complications (P<0.05). Conclusions: Perioperative complications vary according to the type of the surgery. The age, BMI, previous pelvic or abdominal surgery history, malignant tumors, and comorbidities are influential factors of postoperative complications.

[Clinical characteristics of elderly and younger onset rheumatoid arthritis].

Objective: To compare the clinical and laboratory characteristics and therapy methods of elderly onset rheumatoid arthritis (EORA) and younger onset rheumatoid arthritis (YORA). Methods: The clinical, laboratory and therapeutic data of 481 RA patients in the Department of Rheumatology and Immunology in Peking University Third Hospital from January 2013 to December 2018 were collected and used to analyze the difference of characteristics between EORA group and YORA group, which might be useful for better diagnosis and treatment of EORA patients. Quantitative data of normal distribution were compared with t test between the two groups. Results: There were 481 patients in this cohort, of which 137(28.5%) were EORA, 344(71.5%) were YORA, with a mean age of (59±14) years (19-87 years). There were 358 females (74.4%) and 123 males (25.6%). The percentage of male patients was obviously higher in EORA group (36.5% vs 21.2%, χ(2)=12.012, P<0.01), and the average disease course was obviously shorter (Z=-7.985, P<0.01). Disease Activity Score 28 (DAS28) score was higher in EORA group (5.6±1.3 vs 5.2±1.6, t=2.549, P<0.05), meanwhile the incidences of pleural effusion and interstitial lung disease (ILD) were higher (6.6% vs 1.7%, 29.9% vs 18.3%, respectively; χ(2)=7.550, 7.797, both P<0.05). The incidences of venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, coronary heart disease (CHD), peripheral atherosclerosis and cataract in EORA group were all significantly higher than those in YORA group (all P<0.05). Erythrocyte sedimentation rate (ESR) and D-Dimer in EORA group were all remarkably higher (both P<0.05). The rate of using glucocorticoid in EORA group was higher but the rate of using methotrexate and anti-tumor necrosis factor-α agents were lower (χ(2)=5.271, 8.407, 9.356, all P<0.05). Conclusion: Compared to YORA group, the percentage of male patients and disease activity of EORA group are higher. The occurrence of pleural effusion, ILD, venous thrombosis, primary hypertension, diabetes mellitus, cerebrovascular disease, CHD, peripheral atherosclerosis and cataract in EORA group are higher than those in YORA group.

[Analysis of new HIV-1 infection in MSM with seroconversion determined by limiting antigen avidity enzyme immunoassay].

Objective: To evaluate the applicability of limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA, LAg for short) in determining the new HIV-1 infection status of MSM population with seroconversion and make correlation analysis of other biological indicators. Methods: The 15 cases with HIV seroconversion were found in a MSM observation cohort for calculating the HIV prevalence in Zhejiang.The subjects were conducted epidemiological investigation and sampled.The interval of infection time was estimated according to the exposure history and the time of HIV-positive confirmation.LAg, immunoblotting, CD4 cell counting and viral load test were applied in the testing of the related blood samples. McNermar test was conducted for consistency of the two methods. Results: Of 15 cases, the average age was (31.5±8.0) years old, ranging from 24 to 57 years old. The interval of infection time ranged from 40 days to 366 days, and the median was 134 days, with inter-quartile range from 89 to 180 days. A total of 7 cases were classified as new HIV-1 infection by LAg, and 8 cases were classified as chronic infection.The consistent rate was high to 86.67%, and kappa value was 0.73.The samples lacking at least two bands in p31, p51, p66 and gp120 by immunoblotting were determined as recent infection, of which the new infection proportion was significantly higher than that of other samples (P=0.029).There was no statistical difference in the distribution of CD4 counts (P=0.533) and viral loads (P=0.467) between the new infection and chronic infection groups that divided by LAg. Conclusion: By combining with exposure history, the limiting antigen avidity enzyme immunoassay can be used to estimate the new HIV-1 infection.The other biological indicators such as immunoblotting bands, CD4 cell counts and viral loads, can be used as accessory indicators in evaluating the status of new HIV-1 infection.

Effects of taurine on growth performance, antioxidant capacity, and lipid metabolism in broiler chickens.

To investigate the effects of dietary taurine supplementation on growth performance, antioxidant status, and lipid metabolism in broilers, 384 male broilers (Arbor Acres, 1 D of age) were randomly allocated into 4 groups with 8 replicates of 8 birds. Dietary treatments were supplemented with taurine at the level of 0.00, 2.50, 5.00, and 7.50 g/kg of the diet (denoted as CON, TAU1, TAU2, TAU3, respectively). The BW gain from 1 to 21 D and from 22 to 42 D were all increased linearly (linear, P < 0.001) by taurine supplementation. Throughout the trial period, the highest BW gain and favorable gain-to-feed ratio were observed in the TAU2 group. Taurine supplementation increased the antioxidant enzyme activities and decreased (linear, P < 0.001) the content of malondialdehyde in both serum and the liver of broilers and alleviated oxidative damage through enhancing (P < 0.05) the hepatic genes expression of nuclear factor erythroid-2-related factor 2 (NRF2), glutathione peroxidase (GPX), and heme oxygenase-1 (HO-1). Correspondingly, in serum, the activities of hepatic lipase and total lipase were decreased linearly and quadratically (linear and quadratic, P < 0.001) with the increasing inclusion of taurine in the diet. Meanwhile, in serum, the content of triglycerides was significantly decreased (P < 0.05), and except for TAU3, the total cholesterol content was also significantly decreased (P < 0.05) by taurine supplementation. In addition, the hepatic content of triglycerides was significantly decreased (P < 0.05) in the TAU1 and TAU2 groups. Compared with the CON group, the hepatic genes expression of adenosine monophosphate-activated protein kinase alpha (AMPKα), silent 1, (SIRT1) and carnitine palmitoyltransferase 1 (CPT-1) were all increased (P < 0.05), and sterol regulatory element-binding protein-1 (SREBP-1) expression was decreased (P < 0.05) in the TAU2 group. These results indicated that taurine supplementation improved the growth performance, antioxidant capacity, and lipid metabolism of broilers.

[Treatment strategies for colorectal cancer patients in tumor hospitals under the background of corona virus disease 2019].

In December 2019, a new outbreak of corona virus disease 2019 began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies (including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.

[Thinking of treatment strategies for colorectal cancer patients in tumor hospitals under the background of coronavirus pneumonia].

In December 2019, a new outbreak of coronavirus pneumonia began to occur. Its pathogen is 2019-nCoV, which has the characteristics of strong infectivity and general susceptibility. The current situation of prevention and control of new coronavirus pneumonia is severe. In this context, as front-line medical workers bearing important responsibilities and pressure, while through strict management strategy, we can minimize the risk of infection exposure. By summarizing the research progress and guidelines in recent years in the fields of colorectal cancer disease screening, treatment strategies(including early colorectal cancer, locally advanced colorectal cancer, obstructive colorectal cancer, metastatic colorectal cancer and the treatment of patients after neoadjuvant therapy), the choice of medication and time limit for adjuvant therapy, the protective measures for patients undergoing emergency surgery, the re-examination of postoperative patients and the protection of medical staff, etc., authors improve treatment strategies in order to provide more choices for patients to obtain the best treatment under the severe epidemic situation of new coronavirus pneumonia. Meanwhile we hope that it can also provide more timely treatment modeling schemes for colleagues.

[The analysis of the relationship between the fungal microbiota from soil and tongue coating of 18 patients with precancerous lesions of upper gastrointestinal].

The fungal microbiota from self-retained soil and tongue coating of 18 patients with precancerous lesions of upper gastrointestinal (PLUG) were sequenced. The diversity of α, ß in and the structure of the microbial community were analyzed, and the association of them was quantified by using the Spearman rank correlation method. The richness index (1.67±2.79) and the diversity index (0.25±0.10) of the fungal microbiota from tongue coating of PLUG patients were significantly lower than those from soil (4.00±4.69; 0.99±0.18) (all P values<0.001). The relative abundance of 11 taxa from tongue coating of these PLUG patients was positively associated with that from soil (all P values<0.05).

[Application of nuclear magnetic dispersion weighted imaging and apparent diffusion coefficient in the identification of benign].

Objective:To determine the diagnostic role of diffusionweighted imaging(DWI) and apparent diffusion coefficient（ADC） under different b values in differentiating benign and malignant thyroid nodules by using postoperative histopathological results were taken as the reference standard. Method: From January 2017 to June 2018, 64 patients with thyroid nodules diagnosed by ultrasound in the head and neck surgery of Shanxi Cancer Hospital were collected, and a total of 80 nodules were collected. The Philips 3.0T superconducting magnetic resonance imaging system was used for T1 weighting, T2 weighting, and DWI horizontal axis scanning imaging. The b values were 300, 500, 800 and 1 000 s/mm², respectively. Taking postoperative histopathological results as the reference standard, the ADC values of thyroid nodules of all subjects were calculated and compared, and the working characteristics(ROC) curves of all subjects with b values were drawn, the area under the curve was calculated, and the threshold value of differentiating benign and malignant thyroid nodules was obtained. Result:A total of 80 nodules, 33 malignant and 43 benign were excluded, including 1 diffuse b-cell non-hodgkin's lymphoma, 2 parathyroid cysts, and 1 pure cystic patient. A total of 76 nodules were included. When b values were 300, 500, 800 and 1 000 s/mm²î€‰, the average ADC values of malignant nodules were(1.498±0.210) ×10⁻³mm²î€‰/s, (1.311±0.190) ×10⁻³î€‰mm²/s, (1.134±0.170) ×10⁻³mm²î€‰/s, (0.972±0150) ×10⁻³mm²/s. The mean ADC values of benign nodules were(2.207±0.390) ×10⁻³mm²/s, (1.928±0.430) ×10⁻³î€‰mm²/s, (1.702±0.410) ×10⁻³mm²/s,(1.557±0.420) ×10⁻³mm²/s. At the same b value, the average ADC value of malignant nodules was lower than that of benign nodules, and the difference was statistically significant(t values were 9.279,7.641,7.301,7.569, P values were 0.000,0.000,0.000,0.000,0.000). The average ADC values of the benign and malignant nodules decreased with the increase of b value, and the difference was statistically significant(the F values of the benign and malignant groups were 210.091 and 353.822, respectively，P values are 0.000, 0.000). Under different b values, the area(AUC) of ROC curve is 0.927,0.884,0.878,0.901,and 95%CI are 0.862-0.993,0.804-0.956,0.794-0.962 and 0.829-0.972, respectively. When b value is 300 s/mm², AUC is the largest, indicating that it is the best indicator to distinguish benign and malignant thyroid nodules. The diagnostic threshold of benign and malignant nodules is 1.802×10⁻³mm²/s. Specificity, sensitivity, accuracy, positive predictive value, and negative predictive value were 95.00%,86.11%,90.79%,93.94% and 88.37%, respectively. Conclusion: DWI is a noninvasive diagnostic tool used to identify benign and malignant thyroid nodules. It can help to make a definite diagnosis before surgery and reduce the unnecessary burden of surgery.

Effect of fermented Ginkgo biloba leaves on nutrient utilisation, intestinal digestive function and antioxidant capacity in broilers.

1. A total of 648 one-day-old broiler chicks were randomly allocated into six equal groups to investigate the effect of diet supplemented with fermented Ginkgo biloba leaves (FGBL) at different levels on nutrient utilisation, intestinal digestive function and antioxidant activity. 2. Broilers in the six groups were offered basal diet supplemented with either 0, 1.5, 2.5, 3.5, 4.5 and 5.5 g/kg FGBL during the 42-d experiment, respectively. 3. Birds fed with 3.5 g/kg FGBL diet exhibited increased (P < 0.05) body weight gain, feed intake, apparent total tract retention (ATTR) of ether extract (EE) and relative weight of duodenum. Diets supplemented with FGBL increased (P < 0.05) antioxidant and digestive enzyme activities, and decreased malondialdehyde (MDA) concentrations at different degrees in pancreas and small intestine. The expression of antioxidant related genes was up-regulated (P < 0.05) by the transcription factor Nrf2 in small intestine, especially with supplementation of 3.5 and 4.5 g/kg FGBL in the diet. However, 5.5 g/kg diet significantly decreased (P < 0.05) feed conversion ratio and catalase activity (CAT) in the duodenum. 4. Body weight, relative weight of duodenum, amylase and trypsin activities in ileum, total antioxidant capacity (T-AOC) and CAT in duodenum, and glutathione peroxidase (GSH-PX) in ileum increased linearly and quadratically with FGBL content. Activities of amylase in pancreas, trypsin in jejunum, lipase in ileum, and GSH-PX in duodenum and jejunum increased linearly with FGBL content. Body weight gain, ATTR of EE, activities of trypsin in pancreas and amylase in jejunum, total superoxide dismutase activity in duodenum, T-AOC level and concentrations of MDA in the jejunum and ileum showed a quadratic (P < 0.05) dose response as supplemental FGBL level increased. 5. In conclusion, the addition of FGBL had the potential to improve nutrient utilisation, intestinal digestive function and antioxidant activity of broilers. The optimal dietary supplementation dose for broiler production seemed to be 3.5 to 4.5 g/kg.

Suppressing the secretion of exosomal miR-19b by gw4869 could regulate oxaliplatin sensitivity in colorectal cancer.

Oxaliplatin is commonly used in managing malignancy, including colorectal cancer. While treatment often fails due to decreased drug sensitivity, the mechanisms involved are not clear. In this study, we investigate how exosomal miR-19b participates in oxaliplatin sensitivity and then prove that miR-19b down-regulates oxaliplatin sensitivity of sw480 cells. We found that suppressing the secretion of exosomal miR-19b with gw4869 promotes sw480 cell oxaliplatin sensitivity. Our combined results demonstrate for the first time that miR-19b regulates the oxaliplatin sensitivity of sw480 cells and provides a unique mechanism mediated by gw4869 to modulate oxaliplatin sensitivity by suppressing exosomal miR-19b release.

Effect of anti-mullerian hormone on stem cell factor in serum, follicular fluid and ovarian granular cells of polycystic ovarian syndrome patients.

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a common disorder in gynecological practice. Anti-mullerian hormone (AMH) and ovarian granular stem cell factor (SCF) participate in the occurrence and progression of PCOS. This study aimed to investigate the expression of AMH and SCF in PCOS patients and attempt to analyze the effect of AMH on SCF. PATIENTS AND METHODS: Both PCOS and non-PCOS patients who received in vitro fertilization (IVF) in our hospital were recruited for measuring AMH and SCF levels in serum, ovarian follicular fluid and granular cells by using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry (IHC) and Real-time PCR were employed to quantify mRNA and protein levels of SCF in ovarian granular cells after treatment using different dosages of AMH. RESULTS: AMH levels in serum, follicular fluid and granular cells in PCOS patients were significantly elevated, whilst SCF level was significantly decreased (p<0.05 in both cases). Therefore, there was a negative correlation between AMH and SCF level (p<0.05). In 5 ng/ml, 10 ng/ml and 15 ng/ml group, SCF protein positive rate was gradually decreased and was significantly lower compared to that of blank control (p<0.05). After treatment using AMH for 12, 24 and 48 h, SCF mRNA expression in the granular cell was significantly decreased (p<0.05). With higher dosage, SCF mRNA was gradually down-regulated in granular cells (p<0.05). CONCLUSIONS: High level of AMH and low level of SCF existed in serum, follicular fluid, and granular cells in PCOS patients. AMH exhibited negative regulatory effects on SCF.

[Mutation analysis and early pregnancy prenatal diagnosis for two families affected with non-syndromic hearing loss].

Objective:The aim of this study is to identify the pathogenic genes of two non-syndromic hearing loss families, provide accurate genetic counseling and early pregnancy prenatal diagnosis services for second birth families, which determine the genotype of the fetus, early diagnosis and early intervention to prevent the birth of deaf children. Method:Two families with a severe sensorineural hearing loss were enrolled in this study. Genomic DNA was extracted from the peripheral venous blood of the proband and parents. The mutations of the four hearing loss susceptibility genes were analyzed by the hereditary hearing loss gene detection kit (PCR reverse hybridization) and Sanger sequencing. After confirming the genotype of the subject, the genotype of the fetus was examined for the fetus with 10 to 12 weeks of gestation, and the neonates were diagnosed with prenatal diagnosis. Result:In the two families, the No. 1 family proband was the compound heterozygous mutation of SLC26A4 gene c.IVS72A＞G/c.2177insCTAT, and parents were carriers. The prenatal diagnosis showed that the fetal genotype of No. 1 family was a compound heterozygous mutation, and the fetus was not born. The No. 2 family proband genotype was the compound heterozygous of GJB2 gene c.605ins46/c.512insAACG, and the parents were both carriers. The No. 2 family, the prenatal diagnosis showed the fetal genotype of No. 2 family GJB2 gene sequence was normal, the newborn passed the hearing screening. Conclusion:Genetic testing of hereditary hearing loss combined with prenatal diagnosis plays a significant role in guiding deaf children with re-fertility needs, especially prenatal diagnosis in early pregnancy, which can achieve early diagnosis, early detection and early intervention, effectively reducing the birth rate of children with deafness.

[Effects of oblique lateral interbody fusion and transforaminal lumbar interbody fusion for lordosis correction in degenerative lumbar diseases].

Objective: To compare the operation time, estimated blood loss, clinical outcome and correction of lumbar lordosis between oblique lateral interbody fusion (OLIF) and transforaminal lumbar interbody fusion (TLIF) in patients with degenerative lumbar diseases. Methods: Seventy-three patients who underwent OLIF or TLIF surgery from January 2016 to December 2017 in Sir Run Run Shaw Hospital Zhejiang University were analyzed in this retrospective case-control study. The patients included 31 males and 42 females, with a mean age of 65.8 years (range, 36-88 years). Of the patients, there were 9 cases of calcified disc herniation, 34 cases of spinal stenosis, 17 cases of degenerative spondylolithesis, 12 cases of degenerative scoliosis and 1 case of isthmic spondylolithesis. According to the type of surgery, patients were divided into OLIF group (34 cases) and TLIF group (39 cases). The operation time, estimated blood loss and transfusion were recorded, pre-and post-operative visual analogue scale (VAS) for back pain and Oswestry Disability Index (ODI) were evaluated, and pre- and post-operative lumbar lordosis (LL) and fused segment lordosis (FSL) were measured. Student t test were used in comparison between groups. Results: Ten (29.4%) patients in OLIF group and all 39 (100%) patients in TLIF group were supplemented with posterior instrumentation (χ(2)=41.013, P<0.05). The average operation time and estimated blood loss was significantly lower in OLIF group than in those in TLIF group[(163±68) vs (233±79) min, (116±148) vs (434±201) ml, t=4.019, 6.964, both P<0.05]. There was no significant differences in decreases value in VAS and ODI after surgery between the two groups (t=1.716, 0.522, both P>0.05). The correction of LL was 4.0°±10.0° in the OLIF group and 4.2°±6.1° in the TLIF group; the correction of FSL was 4.1°±7.0° in the OLIF group and 5.2°±4.6° in the TLIF group, with no significant differences between the two groups too (t=0.139, 0.805, both P>0.05). The correction of LL was significantly higher in OLIF group with posterior instrumentation than that in TLIF group (9.9°±11.1° vs 4.2°±6.1°, t=2.180, P<0.05). Conclusions: Both OLIF and TLIF can restore LL to some extent, but OLIF has obvious advantages in the operation time and blood loss during surgery. When supplemented with posterior instrumentation, OLIF can achieve better correction of LL than TLIF.