Mechanism of Qizhu Kang'ai Prescription for Inhibiting Proliferation of Hepatocellular Carcinoma by Regulating Tumor Metabolic Reprogramming via PCK1/Akt/p21 Signal Axis / 中国实验方剂学杂志

ObjectiveTo study the effect of Qizhu Kang'ai prescription （QZAP） on the gluconeogenesis enzyme phosphoenolpyruvate carboxykinase 1 （PCK1） in the liver of mouse model of liver cancer induced by diethylnitrosamine （DEN） combined with carbon tetrachloride （CCl4） and Huh7 cells of human liver cancer， so as to explore the mechanism on regulating metabolic reprogramming and inhibiting cell proliferation of liver cancer cells. MethodDEN combined with CCl4 was used to construct a mouse model of liver cancer via intraperitoneal injection. A normal group， a model group， and a QZAP group were set up， in which QZAP （3.51 g·kg-1） or an equal volume of normal saline was administered daily by gavage， respectively. Serum and liver samples were collected after eight weeks of intervention. Serum alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyltransferase （γ-GT）， and alpha-fetoprotein （AFP） in mice were detected to evaluate liver function changes of mice in each group. Hematoxylin-eosin （HE） staining and Sirius red staining were used to observe pathological changes in liver tissue. In the cell experiment， Huh7 cells were divided into blank group， QZAP low， medium， and high dose groups and/or PCK1 inhibitor （SKF-34288 hydrochloride） group， and Sorafenib group. The corresponding drug-containing serum and drug treatment were given， respectively. Cell counting kit-8 （CCK-8） method， colony formation experiment， Edu fluorescent labeling detection， intracellular adenosine triphosphate （ATP） content detection， and cell cycle flow cytometry detection were used to evaluate the proliferation ability， energy metabolism changes， and change in the cell cycle of Huh7 cells in each group. Western blot was used to detect the protein expression levels of PCK1， serine/threonine kinase （Akt）， phosphorylated Akt （p-Akt）， and cell cycle-dependent protein kinase inhibitor 1A （p21）. ResultCompared with the model group， the pathological changes such as cell atypia， necrosis， and collagen fiber deposition in liver cancer tissue of mice in the QZAP group were alleviated， and the number of liver tumors was reduced （P<0.01）. The serum ALT， AST， γ-GT， and AFP levels were reduced （P<0.01）. At the cell level， compared with the blank group， low， medium， and high-dose groups of QZAP-containing serum and the Sorafenib group could significantly reduce the survival rate of Huh7 cells （P<0.01） and the number of positive cells with Edu labeling （P<0.01） and inhibit clonal proliferation ability （P<0.01）. The QZAP groups could also reduce the intracellular ATP content （P<0.05） and increase the distribution ratio of the G0/G1 phase of the cell cycle （P<0.05） in a dose-dependent manner. Compared with the model group and blank group， PCK1 and p21 protein levels of mouse liver cancer tissue and Huh7 cells in the QZAP groups were significantly reduced （P<0.05，P<0.01）， and the p-Akt protein level was significantly increased （P<0.01）. Compared with the blank group， the ATP content and cell survival rate of Huh7 cells in the SKF-34288 hydrochloride group were significantly increased （P<0.05）， but there was no statistical difference in the ratio of Edu-positive cells and the proportion of G0/G1 phase distribution. Compared with the SKF-34288 hydrochloride group， the QZAP combined with the SKF-34288 hydrochloride group significantly reduced the ATP content， cell survival rate， and Edu-positive cell ratio of Huh7 cells （P<0.05） and significantly increased the G0/G1 phase distribution proportion （P<0.05）. ConclusionQZAP may induce the metabolic reprogramming of liver cancer cells by activating PCK1 to promote Akt/p21-mediated tumor suppression， thereby exerting an anti-hepatocellular carcinoma proliferation mechanism.

Photonic-assisted fast broadband microwave vector network analyzer based on FMCW.

In the paper, we propose a photonic-assisted fast broadband microwave vector network analyzer (FB-VNA) based on frequency modulated continuous wave (FMCW). A photonic recirculating frequency shift (RFS) loop is used to extend the bandwidth of optical FMCW. The bandwidth-extended optical FMCW beats with the continuous wave (CW) light to generate the broadband electrical FMCW, which serves as the incident signal of the device under test (DUT). The response signals of the DUT are modulated on the bandwidth-extended optical FMCW to perform de-chirping. After coherently beating the de-chirped light with the CW light, the broadband response signals of DUT are down-converted to a single-tone intermediate frequency (IF) signal carrying the frequency response of DUT, and the scattering parameters of DUT can be obtained. The single-tone IF signal relaxes the demand on the bandwidth and sampling rate of the electrical backend. Thanks to the RFS loop and the short period of FMCW, the measurement frequency range is highly extended and measurement speed is greatly accelerated at the same time, which can be applied in monitoring sudden changes of DUT features. A bandwidth multiplication of the FMCW from 6-18 GHz to 6-498 GHz is experimentally implemented. With available photodetectors (PDs) and Mach-Zehnder modulators (MZMs), a 6-54 GHz FB-VNA is demonstrated, and the S parameters of a 25-GHz low-pass filter (LPF) is measured within 6 µs. The sudden changes of S21 parameter of DUT simulated by fast adjusting the bias voltage of the MZM used for de-chirping are also characterized by the proposed FB-VNA. The sudden changes as short as 0.01 µs can be captured.

Role of P2X4R in maintenance of trigeminal neuralgia in rats: relationship with p38 MAPK/BDNF signaling pathway / 中华麻醉学杂志

Objective:To evaluate the role of P2X4 receptor (P2X4R) in the maintenance of trigeminal neuralgia and the relationship with p38 mitogen-activated protein kinase (p38 MAPK)/brain-derived neurotrophic factor (BDNF) signaling pathway in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, weighing 190-230 g, aged 2-3 months, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), trigeminal neuralgia group (TN group), trigeminal neuralgia+ dimethylsulfoxide (DMSO) group (TN+ DMSO group), and trigeminal neuralgia+ P2X4R specific antagonist 5-BDBD group (TN+ 5-BDBD group). The model was developed by chronic constriction of the infraorbital nerve. The infraorbital nerve was only exposed without ligation in group S. At 3, 7, 10 and 14 days after developing the model, 5 μg/μl 5-BDBD 10 μl was intrathecally injected in TN+ 5-BDBD group, and 2% DMSO 10 μl was intrathecally injected in TN+ DMSO group. The facial mechanical pain withdrawal threshold (MWT) was measured at 1 day before developing the model and 1, 3, 7, 10, 14 and 28 days after developing the model (T 0-6). The rats were sacrificed and the trigeminal ganglia were taken for determination of the expression of P2X4R, p38 MAPK, phosphorylated p38 MAPK (p-p38 MAPK) and BDNF (by Western blot) and contents of tumor necrosis factor (TNF)-α and interleukin (IL)-1β and IL-6 (by enzyme-linked immunosorbent assay). Results:Compared with group S, the MWT was significantly decreased at T 1-6, the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was up-regulated, and the contents of TNF-α, IL-1β and IL-6 were increased in TN group ( P<0.05). Compared with TN group, the MWT was significantly increased at T 3-6, and the expression of P2X4R, p-p38 MAPK and BDNF in trigeminal ganglion was down-regulated, and the contents of TNF-α, IL-1β and IL-6 were decreased in TN+ 5-BDBD group ( P<0.05), and no significant change was found in the indexes mentioned above in TN+ DMSO group ( P>0.05). Conclusions:P2X4R is involved in the maintenance of trigeminal neuralgia in rats, which may be related to the activation of p38 MAPK/BDNF signaling pathway and the increase in inflammatory mediator release.

The preliminary safety and immunogenicity results of a randomized, double-blind, placebo-controlled Phase I trial for a recombinant two-component subunit SARS-CoV-2 vaccine ReCOV

BackgroundThe ReCOV is a recombinant trimeric two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03. We report the preliminary safety and immunogenicity results for the ReCOV. MethodsThis first in human, randomized, double-blind, placebo-controlled phase I study, was conducted at 2 study sites in New Zealand. Subjects were stratified into two age cohorts (18-55 years and 56-80 years old) and then randomly assigned in a 4:1 ratio to receive two 0.5 mL intramuscular doses of the ReCOV vaccine (20{micro}g or 40{micro}g, adjuvanted with BFA03 in each) or placebo, 21 days apart. The primary endpoints were incidence of solicited local and systemic adverse events (AEs) and unsolicited AEs after each dose; incidence of serious adverse events (SAEs) up to 30 days after the second dose; changes in clinical laboratory tests from baseline up to 7 days after each dose; and changes in vital signs from baseline up to 30 days after the second dose. The key secondary endpoints for immunogenicity were neutralizing antibody titers against SARS-CoV-2, S1 receptor binding domain (RBD) and N-terminal domain (NTD) IgG titers post-vaccination. The T cell-specific immune response elicited by ReCOV were also evaluated. The trial was registered with ClinicalTrials.gov (NCT04818801). FindingsOne hundred participants (50 for each age group) were randomized. The incidence of solicited local AEs in 20g ReCOV, 40g ReCOV, and pooled placebo group among younger adults were 60.0%, 70.0%, and 10.0%, respectively, while among older adults were 55.0%, 84.2%, and 10.0%, respectively. The incidence of solicited systemic AEs in 20g ReCOV, 40g ReCOV, and pooled placebo group among younger adults were 60.0%, 60.0%, and 30.0%, respectively, while among older adults were 50.0%, 52.6%, and 50.0%, respectively. All solicited AEs and unsolicited AEs were mild. No vaccination-related SAE, adverse events of special interest, and AE leading to early discontinuation were reported. ReCOV elicited SARS-CoV-2 neutralizing antibody after the first vaccination, which were increased further after the second vaccination irrespective of dose and age groups. The neutralizing antibody against wild-type SARS-CoV-2 peaked at 14 days post the second vaccination in both 20{micro}g and 40{micro}g ReCOV groups, with GMT of 1643.17 IU/mL and 1289.21 IU/mL among younger adults, and 1122.32 IU/mL and 680.31 IU/mL among older adults, respectively. Similarly, both anti-RBD and anti-NTD specific IgG were elicited after the first vaccination, and peaked at 14 days after the second vaccination. T helper 1 biased cellular responses were observed after ReCOV vaccinations. InterpretationBoth 20 and 40{micro}g ReCOV showed good safety profiles and elicited strong immune responses in the younger and the older adults. The results of this study support the accelerated development of ReCOV. FundingJiangsu Recbio Technology Co., Ltd.

Lyophilized mRNA-lipid nanoparticles vaccine with long-term stability and high antigenicity against SARS-CoV-2

Advanced mRNA vaccines play vital roles against SARS-CoV-2. However, due to their poor stability, most current mRNA delivery platforms need to be stored at -20{degrees}C or -70{degrees}C, which severely limits their distribution. Herein, we present lyophilized SARS-CoV-2 mRNA-lipid nanoparticle vaccines, which can be stored at room temperature with long-term thermostability. In the in vivo Delta virus challenge experiment, lyophilized Delta variant mRNA vaccine successfully protected mice from infection and cleared the virus. Lyophilized omicron mRNA vaccine enabled to elicit both potent humoral and cellular immunity. In booster immunization experiments in mice and old monkeys, lyophilized omicron mRNA vaccine could effectively increase the titers of neutralizing antibodies against wild-type coronavirus and omicron variants. In humans, lyophilized omicron mRNA vaccine as a booster shot could also engender excellent immunity and had less severe adverse events. This lyophilization platform overcomes the instability of mRNA vaccines without affecting their bioactivity, and significantly improved their accessibility, particularly in remote regions.

Efficacy of prostatic arterial interventional embolization in the treatment of benign prostatic hyperplasia patients with prostatic volume greater than 80 milliliter / 中国医师进修杂志

Objective:To investigate the effect of interventional embolization of prostate artery in patients with benign prostatic hyperplasia with prostatic volume>80 ml.Methods:A total of 56 patients with BPH combined with hypertension, diabetesand heart disease with prostate volume>80 ml in Meizhou People′s Hospital from April 2018 to November 2020 were selected. They were divided into the study group and the control group according to a simple random number table, 28 cases in each group. The patients in the study group were performed prostatic arterial embolization, and the patients in the control group were performed transurethral resection of the prostate. The efficacy, perioperative conditions, preoperative and 1 month after operation serum total prostate specific antigen (TPSA) level, free prostate specific antigen (FPSA) level, prostate volume, and international prostate symptom score (IPSS) were compared between the two groups. The sexual life quality after operation for 6 months was compared between the two groups.Results:The efficacy of the two groups had no significant difference ( P>0.05). The intraoperative blood loss, postoperative catheterization, postoperative hospital stay in the study group were less than those in the control group: (10.65 ± 1.89) ml vs. (119.64 ± 23.60) ml, (2.16 ± 0.39) d vs. (3.05 ± 0.61) d, (3.03 ± 1.82) d vs. (7.10 ± 2.39) d, the differences were statistically significant( P<0.05). The levels of serum TPSA, FPSA and prostate volume, IPSS at the first month after surgery in the two groups had no significant differences ( P>0.05). After operation for 6 months, the scores of Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) and International Index of Erectile Function (IIEF-5) in the study group were higher than those in the control group: (18.63 ± 2.51) scores vs. (15.71 ± 2.29) scores, (16.38 ± 4.14) scores vs. (13.98 ± 3.82) scores, the differences were statistically significant ( P<0.05). Conclusions:Prostate arterial embolization is effective in BPH patients with prostate volume>80 ml and underlying diseases. Compared with transurethral prostatectomy, it has the advantage of faster recovery after surgery, and it has an ideal effect in controlling diseases, improving urination function, and quality of sexual life.

Fecal Microbiota Transplantation Controls Progression of Experimental Autoimmune Hepatitis in Mice by Modulating the TFR/TFH Immune Imbalance and Intestinal Microbiota Composition.

Intestinal microbiota (IM) dysbiosis contributes to the development of autoimmune hepatitis (AIH). This study aimed to investigate the potential effect of fecal microbiota transplantation (FMT) in a murine model of experimental AIH (EAH), a condition more similar to that of AIH patients. Changes in the enteric microbiome were determined in AIH patients and EAH mice. Moreover, we established an experimental model of secondary EAH mice harboring dysbiosis (ABx) to analyze the effects of therapeutic FMT administration on follicular regulatory T (TFR) and helper T (TFH) cell imbalances and IM composition in vivo. Alterations of the IM composition and bacterial translocation occurred in AIH patients compared to nonalcoholic fatty liver disease patients and healthy controls (HCs). Therapeutic FMT significantly attenuated liver injury and bacterial translocation and improved the imbalance between splenic TFR cells and TFH cells in ABx EAH mice. Furthermore, therapeutic FMT also partially reversed the increasing trend in serum liver enzymes (ALT and AST) of CXCR5-/-EAH mice on the 28th day. Finally, therapeutic FMT could effectively restore antibiotic-induced IM dysbiosis in EAH mice. Taken together, our findings demonstrated that FMT was capable of controlling hepatitis progression in EAH mice, and the associated mechanism might be involved in the regulation of the TFR/TFH immune imbalance and the restoration of IM composition.

A trimeric NTD and RBD SARS-CoV-2 subunit vaccine induced protective immunity in CAG-hACE2 transgenic mice and rhesus macaques

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to significant public health, economic and social problems. Development of effective vaccines is still a priority to contain the virus and end the global pandemic. In this study, we reported that ReCOV, a recombinant trimeric NTD and RBD two-component SARS-CoV-2 subunit vaccine adjuvanted with BFA03 (an AS03-like squalene adjuvant), induced high levels of neutralizing antibodies against SARS-CoV-2 and the circulating variants in mice, rabbits and rhesus macaques. Notably, two-dose immunizations of ReCOV provided complete protection against challenge with SARS-CoV-2 in hACE2 transgenic mice and rhesus macaques, without observable antibody-dependent enhancement of infection. These results support further clinical development of ReCOV and the vaccine is currently being evaluated in a phase I clinical trial in New Zealand (NCT04818801).

The effects of anticoagulant therapy re-initiation after gastrointestinal bleeding: A systematic review and meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Long-term anticoagulant/antithrombotic therapy is widely used for the management of thromboembolic conditions. Gastrointestinal bleeding is a common collateral manifestation of anticoagulant/antithrombotic therapy that complicates its administration. The continuation or discontinuation of anticoagulant/antithrombotic therapy after an episode of gastrointestinal bleeding has been a matter of debate. Despite recent positive reports from retrospective cohort studies suggesting a reduction in morbidity- and mortality-related outcomes with continued administration of anticoagulant/antithrombotic agents (even after gastrointestinal bleeding), no consensus or comparisons about the efficacies of continued or discontinued antithrombotic administration exist. Therefore, we developed this current state-of-evidence analysis evaluating the comparative effects of continuation and discontinuation of anticoagulant/antithrombotic drugs after gastrointestinal bleeding on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. METHODS: We performed a systematic academic literature search according to the PRISMA guidelines across five databases: Web of Science, Embase, CENTRAL, Scopus and MEDLINE. Moreover, we conducted a random effect meta-analysis to compare the effects of continuation and discontinuation of anticoagulant/antithrombotic drugs after an event of gastrointestinal bleeding on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. RESULTS: We found seven eligible studies (from 1397 candidates) with 2532 participants (mean age, 73.1 ± 4.1 years). Our meta-analysis revealed lower odds of thromboembolic events (OR, -0.21), mortality outcomes (OR, -0.39) and an increase in the incidence of gastrointestinal bleeding (OR, 2.4) in the group with continued anticoagulant/antithrombotic therapy than in the group discontinuing the therapy. WHAT IS NEW AND CONCLUSION: We provide an updated evidence on the comparative effects between continuation and discontinuation of anticoagulant/antithrombotic drugs after gastrointestinal bleeding events based on the overall incidences of gastrointestinal bleeding, thromboembolic events and mortality events. This study reports confirm an overall lower incidence of thromboembolic events and mortality outcomes for the continuation group than for the discontinuation group.

Ultrasound combined with X-ray-guided precise implantation of totally implantable access ports in the chest wall / 中国基层医药

Objective:To investigate the success rate, operation time and complications of ultrasound combined with X-ray-guided precise implantation of totally implantable access port (TIAP) in the chest wall.Methods:A total of 623 patients who underwent implantation of totally implantable venous access ports in the chest wall in Meizhou People's Hospital, China between January 2015 and August 2018 were included in this study. In group A ( n = 320), jugular or subclavian access ports were precisely implanted in the chest wall under the guidance of ultrasound combined with X-ray. During the surgery, color Doppler ultrasound was used to guide the puncture and a C-arm machine was used to locate the position of catheter tip. In group B ( n = 303), venous access ports were implanted using the conventional method. Subclavian vein puncture was performed using anatomic landmarks and the depth of catheterization was estimated by experience. The success rate of the first implantation, operation time, and complications (pneumothorax, hemothorax, catheter displacement, poor position of catheter tip, skin infection, and thrombosis) were compared between the two groups. Results:There were no statistical differences in baseline data between the two groups ( P > 0.05). The success rate of the first implantation in the group A was significantly higher than that in the group B [100% (320/320) vs. 93.06% (282/303), χ2 = 22.95, P < 0.01]. The operation time in the group A was significantly shorter than that in the group B [(26.48 ± 5.49) minutes vs. (35.51 ± 14.37) minutes, t = -10.25, P < 0.01]. In group A, 2 patients developed pneumothorax and healed after conservative treatment, 6 patients had thrombosis, and the incidence of complications was 2.5% (8/320). In group B, complications occurred in 67 patients, including pneumothorax in 9 patients, poor catheter tip position in 17 patients, thrombosis in 36 patients, and skin infection in 1 patient, and the incidence of complications was 22.11% (67/303). There was significant difference in the incidence of complications between the two groups ( χ2 = 56.53, P < 0.01). In group B, 6 out of 9 patients developing pneumothorax were healed after closed thoracic drainage, and 4 patients underwent a secondary surgery because of catheter displacement into the internal jugular vein. Conclusion:Precise implantation of venous access ports in the chest wall guided by ultrasound combined with X-ray has the advantages including 100% success rate of first precise implantation, few complications, short operation time, high comfort, safety and efficacy.

Establishment of prediction model for predicting the death risk in patients with sepsis in 30 days / 中华急诊医学杂志

Objective:To predict the sepsis patients with bad outcomes in short term and help clinical physicians to take intervention measures to reduce the mortality.Methods:A total of 900 patients with sepsis who were hospitalized in the Dongyang Peoples’ Hospital between 1st Jan 2013 and 30th Mar 2021 had been involved in this study. Information including gender, age and examination results of first time within 24 hours following hospitalization were collected. Independent risk factors of death in 30 days were screened by logistic regression analysis and further confirmed by stepwise regression analysis. Based on the screened variables, nomogram prediction model was established. Finally, the prediction model was evaluated for its prediction power by the area under the curve of receiver operating characteristic (AUC), calibration accuracy by GiViTI calibration curve and clinical effectiveness by decline curve analysis (DCA). The established prediction model was validated by using bootstrap assay.Results:Stepwise regression analysis results showed that B-type natriuretic peptide, lactic acid, albumin, oxygenation index, mean artery pressure, hematocrit and heart rate within 24 hours after hospitalization were significantly associated with death in 30 days among patients with sepsis. The AUC of prediction model was 0.846, with P of 0.886 in calibration curve, calibration slope of 1.0, R2 of 0.385, brier scaled value of 0.092 and DCA curve above the two extreme curves. In validation using bootstrap, the prediction model owned an AUC of 0.854, a P of 0.994 in calibration curve, a brier scaled value of 0.090, a calibration slope of 1.0 and a R2 of 0.389. Also, its DCA curve was above the two extreme curves. Conclusions:B-type natriuretic peptide, Lactic acid, albumin, oxygenation index, mean artery pressure, hematocrit and heart rate within 24 hours after hospitalization were independent risk factors of death in 30 days among patients with sepsis. The established prediction model in this study owned good prediction power of sepsis patients who owned high risk of death in 30 days.

Analysis of early complications of free gracilis muscle transfer in reconstruction of brachial plexus injury / 中华显微外科杂志

Objective:To explore the causes and preventive measures of early complications after free gracilis muscle transfer in reconstruction of brachial plexus injury, and to improve the postoperative function of the transferred gracilis muscle.Methods:Patients were recruited from August, 2005 to December, 2016. All 111 patients of brachial plexus injury underwent reconstructive surgery using 122 free gracilis flaps. Early postoperative complications, including recipient site, donor site and systemic complications, were closely observed and recorded. Outcome measurements included incidence and timing of flap compromise, type of flap compromise, causes of vascular occlusion and salvage rate. The postoperative strength of gracilis was evaluated according to the BMRC score. The data were statistically analyzed. The difference was statistically significant if P<0.05. Results:The survival rate of 122 free gracilis transfers was 98.4% (120/122). Early complications occurred in 32 cases (including 2 complications in 6 patients) : 27 cases with recipient site complications (84.4%), 4 with donor site complications and 7 with systemic complications. Among the 32 cases of complications, 17 flap compromises caused by vascular obstruction and 15 of them were salvaged completely after exploration. Flap crisis was the main issue that affected the postoperative function of gracilis muscle, and 58.8% (10/17) of patients with vascular crisis showed muscle strength above M 3 after surgery. The main causes of vascular crisis were venous tortuosity and venous thrombosis, which had nothing to do with operation time and intraoperative blood loss. Conclusion:Flap crisis is the main factor affecting the postoperative function of gracilis. The rate of flap salvage can be tremendously increased by early detection, re-exploration and effective management of the flap crisis.

Application analysis of sentinel area lymph node biopsy in early breast cancer / 国际外科学杂志

Objective:To explore the correlation between the number of sentinel regional lymph node (SALN) and non-sentinel regional lymph node (NSALN) metastasis in patients with early breast cancer after sentinel regional lymph node (SALN) biopsy.Methods:Retrospectively selected 400 female patients with early breast cancer who underwent SALN biopsy at the Department of Thyroid and Breast Surgery, Yijishan Hospital of Wannan Medical College from January 2016 to July 2021, and summarized and analyzed their clinical case data. The Chi-square test or Fisher exact probability method was used to compare the count data between groups. Perform single-factor analysis on the research indicators, then screen out indicators with statistically significant differences, then perform multi-factor Logistic regression analysis, draw a receiver operating characteristic curve, and combine the area under the curve to establish a predictive model.Results:SALN biopsy was performed in 400 patients with early breast cancer. A total of 1 504 lymph nodes were detected in 320 cases of total mastectomy, with an average of 4.7, 47 cases of macrometastasis, and 2 cases of postoperative macrometastasis. The false negative rate was 4.3%. Among 400 cases, 67 cases were positive for SALN, and the positive rate was 16.75% (67/400). The results of univariate analysis showed that the number of tumor thrombus in the vessel, the number of positive SALN and the metastasis of NSALN were closely related ( χ2=8.775, 16.53, P=0.003). The results of multivariate Logistic regression analysis showed that the number of tumor thrombi and SLN-positive ≥3 in the vessel were independent predictive risk factors for NSLN metastasis ( OR=16.149, 95% CI: 3.016-86.473, P<0.001; OR=31.76, 95% CI: 5.242-192.43, P<0.001). SALN positive was closely related to NSALN metastasis, but as the number of SALN detected increases (more than 6) and when only 1 to 2 SALN was positive, the probability of NSALN metastasis was significantly reduced ( P<0.05). Conclusions:The positive number of SALN and intravascular tumor thrombolus were closely related to NALN metastasis. SALN positive number ≥3 was the most important independent predictor of NSALN metastasis. The recurrence risk of sentinel lymph node can be reduced by increasing the number of SALN detected, when 1-2 positive sentinel lymph node are detected and the number of sentinel lymph node detected >6, axillary lymph node dissection can be exempted as appropriate.

A case report of endoscopic resection for the treatment of duodenal Brunner's gland adenoma with upper gastrointestinal bleeding.

RATIONALE: Gastrointestinal bleeding as the first sign of Brunner's gland adenoma (BGA) is an extremely rare, and its clinical features and treatment methods have not been well described. PATIENT CONCERNS: We described a 81-year-old female patient with coronary artery disease and chronic atrial fibrillation presenting with presenting with gastrointestinal bleeding requiring blood transfusion. DIAGNOSES: The diagnosis of our case mainly refered to radiologic imaging and endoscopic examination. Histological result was compatible with BGA. INTERVENTIONS: This mass lesion (6 × 7 cm diameter) was successfully totally removed by endoscopic submucosal dissection (ESD) for more than three hours. OUTCOMES: The patient was followed up for 6 months to date without recurrence. LESSONS: Endoscopic removal is considered as a safe and low-risk treatment for elderly patients with severe underlying diseases presenting with gastrointestinal bleeding.

Endoscopic submucosal dissection of coexisting early esophageal carcinoma and leiomyoma: a case report and review of the literature.

The occurrence of early esophageal cancer located within an area of leiomyoma is extremely rare, and its clinical features and treatment methods have not been well described. We herein report the clinical characteristics, diagnosis, and treatment methods of early esophageal cancer that developed on top of a leiomyoma in the upper third of the esophagus in a 78-year-old woman. All tumor marker concentrations were normal. The leiomyoma was correctly diagnosed as a submucosal tumor by endoscopy and endoscopic ultrasonography. Endoscopic biopsy revealed esophageal squamous cell carcinoma. Both lesions were successfully treated by endoscopic submucosal dissection. The patient was followed up for 6 months without recurrence. Endoscopic submucosal dissection was a successful initial treatment method for esophageal carcinoma coexisting with esophageal leiomyoma in this case.

Dysregulated TFR and TFH cells correlate with B-cell differentiation and antibody production in autoimmune hepatitis.

Follicular helper T (TFH) cell provides germinal centre (GC) B cell with critical signals for autoantibody production in the immunopathogenesis and progression of autoimmune hepatitis (AIH). However, the immunoregulatory functions of follicular regulatory T (TFR) cell in AIH are still unclear. The numbers of circulating TFR/TFH cells were measured in AIH patients. Moreover, we established experimental autoimmune hepatitis (EAH) model to examine the function of TFR cells on B-cell differentiation and autoantibody production in vivo and vitro. AIH patients had significantly increased numbers of TFH cells and decreased numbers of TFR cells as well as imbalanced TFR/TFH-type cytokines (IL-10, TGF-ß1 and IL-21) compared with healthy controls (HCs). In addition, TFR cell numbers negatively correlated with TFH cell numbers. Also, serum hypergammaglobulinaemia (IgG and IgM) concentration negatively correlated the levels of serum IL-21, but positively correlated with the levels of serum IL-10 in AIH patients. Furthermore, in comparison with control group, significantly higher frequencies of spleen TFR cells but lower frequencies of spleen TFH cells were detected in the EAH group. Further analysis found that TFR cells simultaneously express the phenotypic characteristics of Treg and TFH cells, but exercise as negative regulators of autoantibody production in vitro culture. Our findings demonstrated that dysregulated between TFR and TFH cells might cause excessive production of autoantibodies and destruction of the immune homeostasis, leading to the immunopathological process in AIH.

Study on Vascular Protection Effect and Mechanism of Timosaponin B Ⅱ Based on Zebrafish Model / 中国药房

OBJECTIVE：To study the protective effect of timosaponin BⅡ（TB-Ⅱ）on blood vessels and explore its possible mechanism. METHODS ：Using aquaculture water as blank control ，the effects of 100，200 and 400 μg/mL TB-Ⅱ treatment for 48 h on the situation of subintestinal veins （SIVs）in normal zebrafish embryos 24 h after fertilization （24 hpf）were investigated. PTK787（0.06 μg/mL），a tyrosine kinase inhibitor ，was used to induce the model of zebrafish intestinal vascular injury ；using combing with 0.1％ dimethyl sulfoxide but no PTK 787 as blank control ，combing with PTK 787 but no drug as model control ，the effects treatment of 100，200 and 400 μg/mL TB-Ⅱ for 48 h on the SIVs of zebrafish model with vascular injury were investigated. Relative expressions of fam-like tyrosine kinase 1（Flt-1），kinase insert domain containing receptor （Kdr），kinase insert domain containing receptor l （Kdr-l），vascular endothelial growth factor A （VEGF-A），tumor necrosis factor α（TNF-α）and interleukin 6 （IL-6）mRNA were detected by RT-PCR. RESULTS ：100 μg/mL TB-Ⅱ could significantly increase the sprouting vessel of normal zebrafish SIVs sprouting vessel number （P＜0.05），and 200 μg/mL TB-Ⅱ could significantly increase SIVs number of normal zebrafish （P＜0.05）. Compared with blank control ， SIVs treatment （P＜0.01），and the relative expressions of Flt-l ， Kdr，Kdr-l，VEGF-A，TNF-α and IL-6 mRNA were alse decreased significantly （P＜0.05 or P＜0.01）. After treated 化。E-mail：pn333@163.com with different concentrations of TB- Ⅱ ，SIVs number of vascular injury model zebrafish increase d to different extents ；relative expressions of Flt-l ，Kdr，Kdr-l，VEGF-A，TNF-α and IL-6 mRNA were increased to different extents. There was no significant difference in SIVs number and the expression of Flt-l ，TNF-α mRNA in zebrafish treated with 100 μg/mL TB-Ⅱ and the expression of TNF-α mRNA in zebrafish treated with 400 μg/mL TB-Ⅱ， but there was statistical significance in other indexes （P＜0.05 or P＜0.01）. CONCLUSIONS ：TB-Ⅱ has a certain function of promoting angiogenesis and repairing damaged blood vessels ，and its mechanism is related to the up-regulation of vascular endothelial growth factor receptor and pro-inflammatory cytokine expression.

First-trimester uterine artery Doppler pulsatility index for prediction of preeclampsia in twin pregnancies: a prospective cohort study / 中华围产医学杂志

Objective:To investigate the value of first-trimester uterine artery Doppler pulsatility index (PI) in the prediction of preeclampsia (PE) in twin pregnancies.Methods:From April 2014 to October 2016, women with twin pregnancies undergoing Down's screening at 11 +0-13 +6 gestational weeks in Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine were recruited in this prospective cohort study. Bilateral uterine artery PI values were measured by Doppler ultrasound at the first trimester. Pregnancy outcomes and the incidence of PE were followed up. The participants were classified into four groups according to their pregnancy outcomes: early-onset PE (<34 weeks), late-onset PE (≥34 weeks), gestational hypertension and normal groups. Differences in the multiples of median of uterine artery PI (PI MoM) and rates of abnormal PI MoM (≥ P90) were compared among the four groups using the Kruskal-Wallis test, Chi-square test or Fisher exact test. The performance of uterine artery PI in the prediction of PE was evaluated using receiver operating characteristic (ROC) curve. Results:A total of 1 223 twin pregnancies were recruited and 185 of them were excluded for not meeting the eligibility criteria. The 1 038 cases enrolled successfully were 231 monochorionic diamniotic (MCDA) and 807 dichorionic diamniotic (DCDA) twin pregnancies. The incidences of early-onset PE, late-onset PE and gestational hypertension were 3.47% (36/1 038), 7.03% (73/1 038) and 2.79% (29/1 038), respectively. No significant difference was observed in PI MoM [ M( P25~ P75), 1.06 (0.80-1.32), 1.05 (0.75-1.30), 0.99 (0.73-1.23), 1.03 (0.80-1.27); χ2=0.396, P=0.941] or the rates of abnormal PI MoM [8.33% (3/36), 6.85% (5/73), 13.79% (4/29), 10.11% (91/900); Fisher's exact test, P=0.703] among the four groups. Furthermore, there was no significant difference in PI MoM between normal MCDA and DCDA twin pregnancies [1.04 (0.81-1.29) vs 1.03 (0.79-1.27), χ2=0.095, P=0.758]. The area under the ROC curve showed that first-trimester uterine artery PI had limited value in the prediction of early-onset PE (0.514, 95% CI: 0.413-0.615), late-onset PE (0.499, 95% CI: 0.428-0.570) and gestational hypertension (0.530, 95% CI:0.418-0.643) in twin pregnancies. Conclusion:First-trimester uterine artery PI has limited value in predicting early- or late-onset PE in twin pregnancies.

A rare case report of fungal esophagitis combined with giant gastric ulcer in an immunocompetent patient.

RATIONALE: Fungal infection of gastrointestinal (GI) tract is usually seen in immunocompromised patients, but can rarely occur in immunocompetent people in whom no permissive factor is present. PATIENT CONCERNS: We describe a 68-year-old male immunocompetent patient presenting with simultaneous fungal esophagitis and giant gastric ulcer. DIAGNOSES: Repeated endoscopic biopsies were taken from the giant gastric ulcer edge and base and histology demonstrated granulation tissue and pseudohyphal fungal forms. INTERVENTIONS: The patient was treated with fluconazole and omeprazole for 8 weeks. OUTCOMES: After antifungal treatment with fluconazole, the patient's clinical symptoms gradually disappeared with the healing of gastric ulcer, which never recurred in this patient until 3 months after follow-up. LESSONS: Nonhealing gastroesophageal ulcers highlights the importance of repeated endoscopies and biopsies.