ADC189 is a novel drug of cap-dependent endonuclease inhibitor. In our study, its antiviral efficacy was evaluated in vitro and in vivo, and compared with baloxavir marboxil and oseltamivir. A first-in-human phase I study in healthy volunteers included single ascending dose (SAD) and food effect (FE) parts. In the preclinical study, ADC189 showed potent antiviral activity against various types of influenza viruses, including H1N1, H3N2, influenza B virus, and highly pathogenic avian influenza, comparable to baloxavir marboxil. Additionally, ADC189 exhibited much better antiviral efficacy than oseltamivir in H1N1 infected mice. In the phase I study, ADC189 was rapidly metabolized to ADC189-I07, and its exposure increased proportionally with the dose. The terminal elimination half-life (T_1/2) ranged from 76.69 to 98.28 hours. Of note, food had no effect on the concentration, clearance, and exposure of ADC189. It was well tolerated, with few treatment-emergent adverse events (TEAEs) reported and no serious adverse events (SAEs). ADC189 demonstrated excellent antiviral efficacy both in vitro and in vivo. It was safe, well-tolerated, and had favorable pharmacokinetic characteristics in healthy volunteers, supporting its potential for single oral dosing in clinical practice.
Humans ; Antiviral Agents/therapeutic use* ; Animals ; Male ; Adult ; Mice ; Female ; Endonucleases/antagonists & inhibitors* ; Influenza, Human/drug therapy* ; Young Adult ; Dibenzothiepins/pharmacology* ; Oseltamivir/pharmacology* ; Middle Aged ; Triazines/pharmacology* ; Thiepins/pharmacology* ; Influenza B virus/drug effects* ; Influenza A Virus, H1N1 Subtype/drug effects* ; Pyridines/pharmacology* ; Morpholines ; Pyridones

Nuclear medicine imaging has the advantage of assessing the status of organs and tissues from the perspective of function and metabolism,and has become an indispensable tool in tumor diagnosis and treatment.Tumor immunotherapy is therapy after surgery,chemotherapy,radiotherapy and molecular targeted therapy.Accurate assessment of tumor status and identification of benefit population are the prerequisite and guarantee for achieving precise and individualized tumor immunotherapy.This review summarizes the clinical utilization and prospect of nuclear medicine imaging in tumor immunotherapy.

【Objective】 To investigate the clinical characteristics and treatment strategy of giant multilocular prostatic cystadenoma(GMPC). 【Methods】 The clinical data of a GMPC patient treated in our hospital in July 2021 were retrospectively analyzed. The patient was 73 years old. The clinical manifestations were urgent urination and frequent urination. The prostate specific antigen (PSA) increased slightly. MRI showed giant cystic solid space occupying lesion of the prostate. Domestic and foreign cases of prostate cystadenoma from 2000 to 2021 were retrieved for literature review. 【Results】 Transabdominal laparoscopic radical prostatectomy was performed successfully. The postoperative pathological diagnosis was GMPC. Two weeks after operation, the urinary catheter was removed, and there was no discomfort such as urinary frequency or urinary incontinence. After follow-up for more than 8 months, there was no tumor recurrence or metastasis. 【Conclusion】 There are still some disputes about the oncological characteristics and diagnosis and treatment of GMPC, and there is a lack of long-term follow-up results. Laparoscopic prostatectomy is safe and feasible. Most patients have a good prognosis after surgical treatment. It is necessary to formulate an individualized standard treatment plan based on surgery combined with different patients’ conditions to actively improve the prognosis.

Metastasis is an important factor for the high recurrence and mortality rates of hepatocellular carcinoma (HCC), and epithelial-mesenchymal transition (EMT) is an important mechanism of HCC metastasis. EMT is regulated by the transcription factors such as Snail, Twist, and ZEB which are mediated by a variety of signaling pathways including TGF-β, Wnt/β-catenin, and Notch. Inhibition of EMT-related molecules and signal pathways in HCC is considered as an important approach to inhibit the invasion and metastasis of HCC. Recent studies have shown that a variety of compound traditional Chinese medicine (TCM) formula or their effective constituents can inhibit the invasion and metastasis of HCC by arresting or reversing EMT in HCC. This article reviews the role and mechanism of EMT and recent studies on TCM drugs and their derived natural compounds in inhibiting the invasion and metastasis of HCC by regulating cell EMT, so as to provide a scientific basis for the TCM prevention and treatment of HCC metastasis and new ideas for HCC treatment.

Objective:To explore the effect of serum lactic acid (Lac) level on acute kidney injury (AKI) in patients with sepsis and whether Lac level affects the in-hospital mortality of patients with sepsis-associated AKI.Methods:A retrospective cohort study was conducted. Clinical data of patients with sepsis admitted to the internal intensive care unit (ICU) of the First Affiliated Hospital of Guangxi Medical University from March 2014 to June 2019 and the ICU of the Second Affiliated Hospital of Guangxi Medical University from January 2017 to June 2020 were collected. According to the first quartile of Lac within 24 hours of admission to ICU, the patients were divided into Lac ≤ 1.4 mmol/L group (group Q1), Lac 1.5-2.4 mmol/L group (group Q2), Lac 2.5-4.0 mmol/L group (group Q3), and Lac ≥ 4.1 mmol/L group (group Q4). The incidence of sepsis-associated AKI after admission to ICU and hospital mortality were compared among four groups. The effect of elevated Lac on the incidence and mortality of sepsis-associated AKI was investigated by binary Logistic regression analysis. The receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of Lac on the incidence and mortality of sepsis-associated AKI, and the cut-off value was obtained to analyze the incidence and death risk of sepsis-associated AKI at different Lac levels. Results:A total of 655 sepsis patients were enrolled, of which 330 patients (50.4%) developed AKI and 325 patients (49.6%) did not. Among 330 patients with sepsis-associated AKI, 134 (40.6%) died and 196 (59.4%) survived. With the increase of Lac level, the incidence of sepsis-associated AKI increased gradually (34.5%, 41.0%, 58.4%, 66.3%, respectively, in group Q1- Q4), meanwhile, the in-hospital mortality also increased gradually (23.4%, 29.2%, 33.1%, 43.4%, respectively, in group Q1- Q4), the differences were statistically significant (both P < 0.01). Compared with the non-AKI group, the Lac level in the AKI group was significantly increased [mmol/L: 3.08 (1.84, 5.70) vs. 1.91 (1.20, 3.10), P < 0.01]. After adjustment for factors such as gender (male), site of infection (abdominal cavity), vasoactive drugs, basal mechanical ventilation, mean arterial pressure (MAP), basal renal insufficiency, uric acid, procalcitonin (PCT), platelet count (PLT), basal serum creatinine (SCr) and basal estimated glomerular filtration rate (eGFR), and other influencing factors, multivariate Logistic regression analysis showed that elevated Lac was an independent risk factor for sepsis-associated AKI [odds ratio ( OR) = 1.096, 95% confidence interval (95% CI) was 1.022-1.175, P = 0.010]. Compared with the survival group, the Lac level in the death group was significantly increased [mmol/L: 3.55 (2.00, 6.76) vs. 3.00 (1.70, 4.50), P < 0.01]. After adjusting for age, diabetes, vasoactive drugs, basal eGFR, and other factors, multivariate Logistic regression analysis suggested that increased Lac was an independent risk factor for in-hospital mortality in sepsis-associated AKI patients ( OR = 1.074, 95% CI was 1.004-1.149, P = 0.037). ROC curve analysis showed that the area under the ROC curve (AUC) of Lac for predicting the incidence and mortality of sepsis-associated AKI was 0.653 (95% CI was 0.611-0.694) and 0.593 (95% CI was 0.530-0.656, both P < 0.01), respectively, and the cut-off values were 2.75 mmol/L (sensitivity was 57.8%, specificity was 69.2%) and 5.95 mmol/L (sensitivity was 56.7%, specificity was 83.7%). When the Lac ≥ 2.75 mmol/L, the risk of sepsis-associated AKI was 2.772 times higher than that of < 2.75 mmol/L ( OR = 2.772, 95% CI was 1.754-4.380, P < 0.001). When the Lac ≥ 5.95 mmol/L, the patients with sepsis-associated AKI had a 2.511 times higher risk of in-hospital death than those with Lac < 5.95 mmol/L ( OR = 2.511, 95% CI was 1.378-4.574, P = 0.003). Conclusions:Elevated Lac level is an independent risk factor for the incidence and mortality of sepsis-associated AKI. When Lac ≥ 2.75 mmol/L, the risk of AKI in patients with sepsis increased by 1.772 times; when Lac ≥ 5.95 mmol/L, the risk of in-hospital death in patients with sepsis related AKI increased by 1.511 times.

Objective:To investigate the risk factors for anastomotic leakage after laparo-scopic lower anterior resection (LAR) of rectal cancer, and the application value of its risk assess-ment scoring model.Methods:The retrospective case-control study was conducted. The clinico-pathological data of 539 patients who underwent laparoscopic LAR of rectal cancer in 13 medical centers, including 248 cases in Renji Hospital of Shanghai Jiaotong University School of Medicine, 35 cases in Ningbo First Hospital, 35 cases in Changzhou Second People's Hospital, 32 cases in the First People's Hospital of Nantong, 32 cases in Linyi People's Hospital, 31 cases in Changzhou Wujin People's Hospital, 28 cases in Jiading District Hospital of Traditional Chinese Medicine, 27 cases in the First Hospital of Taizhou, 26 cases in Shanghai Pudong Gongli Hospital, 21 cases in the People's Hospital of Rugao, 11 cases in Central Hospital of Fengxian District, 7 cases in Ningbo Hangzhou Bay Hospital and 6 cases in Jiangsu jianhu People's Hospital, from January 2016 to November 2020 were collected. There were 157 males and 382 females, aged (62.7±0.5)years. Observation indicators: (1) follow-up; (2) risk factors for anastomotic leakage after laparoscopic LAR; (3) establishment of risk assessment scoring model for anastomotic leakage after laparoscopic LAR. Follow-up was conducted by outpatient examination or telephone interview. Patients were followed up at 1 week after discharge or 1 month after the operation to detect the anastomotic leakage. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were represented as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis was conducted using the chi-square test and multivariate analysis was conducted usong the Logistic regression model. The area under curve of receiver operating characteristic curve was used to estimate the efficiency of detecton methods. The maximum value of the Youden index was defined as the best cut-off value. Results:(1) Follow-up: 539 patients were followed up at postoperative 1 week and 1 month. During the follow-up, 79 patient had anastomotic leakage, with an incidence of 14.66%(79/539). Of the 79 patients, 39 cases were cured after conservative treatment, 40 cases were cured after reoperation (ileostomy or colostomy). (2) Risk factors for anastomotic leakage after laparoscopic LAR. Results of univariate analysis showed that sex, age, body mass index, smoking and/or drinking, tumor diameter, diabetes mellitus, hemoglobin, albumin, grade of American Society of Anesthesio-logists (ASA), neoadjuvant chemoradiotherapy, distance from anastomotic level to dentate line, the number of pelvic stapler, reinforced anastomosis, volume of intraoperative blood loss, placement of decompression tube, preservation of left colic artery, operation time and professional doctors were related factors for anastomotic leakage after laparoscopic LAR ( χ2=14.060, 4.387, 5.039, 4.094, 17.488, 33.485, 25.066, 28.959, 34.973, 34.207, 22.076, 13.208, 16.440, 17.708, 17.260, 4.573, 5.919, 5.389, P<0.05). Results of multivariate analysis showed that male, tumor diameter ≥3.5 cm, diabetes mellitus, hemoglobin <90 g/L, albumin <30 g/L, grade of ASA ≥Ⅲ, neoadjuvant chemoradiotherapy, distance from anastomotic level to dentate line <1 cm, the number of pelvic stapler ≥3, non-reinforced anastomosis, volume of intraoperative blood loss ≥100 mL and no placement of decom-pression tube were independent risk factors for anastomotic leakage after laparoscopic LAR ( odds ratio=2.864,3.043,12.556,7.178,8.425,12.895,8.987,4.002,3.084,4.393,3.266,3.224,95% confidence interval as 1.279?6.411, 1.404?6.594, 4.469?35.274, 2.648?19.459, 2.471?28.733, 4.027?41.289, 3.702?21.777, 1.746?9.171, 1.365?6.966, 1.914?10.083, 1.434?7.441, 1.321?7.867, P<0.05). (3) Establishment of risk assessment scoring model for anastomotic leakage after laparoscopic LAR. based on the results of univariate analysis, clinicopathological factors with χ2>20, χ2>10 and ≤20 or χ2≤10 were defined as scoring of 3, 2, 1, respectively. The cumulative clinicopatho-logical factors scoring ≥6 was defined as an effective evaluating indicator for postoperative anastomotic leakage. The risk assessment scoring model (6-321) for anastomotic leakage after laparoscopic LAR was established. The cumulative value ≥6 indicated high incidence of anastomotic leakage, and the cumulative value <6 indicated low incidence of anastomotic leakage. Conclusions:Male, tumor diameter ≥3.5 cm, diabetes mellitus, hemoglobin <90 g/L, albumin <30 g/L, grade of ASA ≥Ⅲ, neo-adjuvant chemoradiotherapy, distance from anastomotic level to dentate line <1 cm, the number of pelvic stapler ≥3, non-reinforced anastomosis, volume of intraoperative blood loss ≥100 mL and no placement of decompression tube are independent risk factors for anastomotic leakage after laparoscopic LAR. The risk assessment scoring model (6-321) is established according to the above results.The cumulative value ≥6 indicates high incidence of anastomotic leakage and the cumulative value <6 indicates low incidence of anastomotic leakage.

Objective:To investigate the correlation of blood pressure variability within 24 h after thrombolysis with symptomatic intracerebral hemorrhage (sICH) and 90 d outcome in patients with acute ischemic stroke.Methods:Patients with acute ischemic stroke treated with recombinant tissue plasminogen activator in the Department of Neurology, Jinshan Branch, Shanghai Sixth People's Hospital from January 2017 to May 2019 were enrolled prospectively. The baseline data of the patients were collected. The patients were divided into sICH group and non-sICH group according to the changes of head CT and the National Institutes of Health Stroke Scale (NIHSS) score after thrombolysis. At 90 d after thrombolysis, the modified Rankin scale was used to evaluate the outcomes, and the patients were divided into a good outcome group (0-2) and a poor outcome group (3-6). The blood pressure within 24 h after thrombolysis was monitored and the parameters related to blood pressure variability in 5 time periods (0-2 h, 2-6 h, 6-12 h, 12-18 h, and 18-24 h) were calculated, including systolic blood pressure (SBP) and diastolic blood pressure (DBP) maximum (max), minimum (min), maximum and minimum difference (max-min) and mean (mean). The differences between the adjacent blood pressures were calculated, the standard deviation (SD), successive variation (SV), rise successive variability (SVrise), drop successive variability (SVdrop), the maximum squared difference in blood pressure rise (SVrisemax), the maximum squared difference in blood pressure drop (SVdropmax) were calculated and recorded, respectively. Multivariate logistic regression analysis was used to evaluate the effect of various blood pressure variability parameters on sICH and the outcomes after intravenous thrombolysis. Results:A total of 112 patients receiving intravenous thrombolysis were included in the study. Their median age was 71 years (range, 38-92 years), 66 were males (58.9%); median baseline NIHSS score was 10. Seventeen patients (15.2%) developed hemorrhagic transformation, 10 of them (8.9%) were sICH. The 90-d follow-up showed that 73 patients (65.2%) had a good outcome, 39 (34.8%) had a poor outcome and 7 of them (6.3%) died. There were significant differences in hypertension ( P=0.029), ischemic heart disease ( P=0.012), total cholesterol ( P=0.033), baseline NIHSS score ( P=0.003) between the sICH group and the non-sICH group. There were significant differences in age ( P=0.025), gender ( P=0.005), atrial fibrillation ( P=0.003), etiologic classification of stroke ( P=0.003), baseline NIHSS score ( P<0.001) and sICH ( P=0.003) between the poor outcome group and the good outcome group. In addition, there were significant differences in multiple blood pressure variability parameters among the above groups (all P<0.05). Multivariate logistic regression analysis showed that DBP SVdropmax, 6-12 h DBP SV, 12-18 h DBP SV, 6-12 h DBP SVdrop, 12-18 h DBP SVdrop were the independent risk factors for sICH after intravenous thrombolysis (all P<0.05); 2-6 h SBP SV, 2-6 h SBP SVrise, 2-6 h SBP SVdrop, 2-6 h DBP SV, 2-6 h DBP SVrise and 2-6 h DBP SVdrop were the independent risk factors for poor outcome after intravenous thrombolysis (all P<0.05). Conclusions:Early blood pressure and some blood pressure variability parameters are closely related to sICH and outcomes after intravenous thrombolysis in acute ischemic stroke. Closely monitoring of blood pressure and its variability can help clinical management and outcome prediction after intravenous thrombolysis.

Objective To investigate the epidemic situation of children with respiratory viruses in zhongs-han ,Guangdong to provide evidence for the diagnosis of respiratory virus infections in children .Methods 55 240 cases were collected in a hospital from November 25 ,2011 to September 30 ,2016 ,Influenza virus(IFA , IFB) ,parainfluenza virus (PIV1 ,PIV2 ,PIV3) ,respiratory syncytial virus (RSV) and adenovirus (ADV) were detected by direct immunofluorescent ,and analyzed the results .Results The positive rate of virus infection in 55 240 children was 23 .25%,of which RSV 53 .75%,IFA 13 .83%,ADV10 .81%,PIV3 10 .77%,IFB 6 .49%, PIV1 2 .37%,PIV2 1 .14% and mixed infection 0 .84% .There were statistical significance between male and female (P＜0 .05) .The positive rates of virus infection in children 0- ≤1 years and 1- ≤3 years were higher than those in the other age groups ,the difference was statistically significant (P＜0 .05) .The positive rate of RSV was higher in both age groups (71 .92%,46 .23%) The positive rate of these 7 viruses infection in winter and spring was higher than that in summer and autumn ,the difference was statistically significant (P＜0 .05) , and the positive rate of RSV was the highest .The positive rate of these 7 viruses patients with bronchitis was higher than that of the other patients ,the difference was statistically significant (P＜0 .05) and in 108 patients with mixed infections ,the most cases was patients with RSV (90 cases) .Conclusion The main pathogen is RSV .The infection rate of children under 3 years old is the highest .Winter and spring are the high incidence of respiratory virus infection in children in Guangdong zhongshan district .

Objective To study the current situation of migrant children' s social adaptation and ex?plore its influencing factors. Methods The study population was 1547 children aged 10?16 years recruited from Shijiazhuang city. Social adaptation was collected through social adaptation questionnaire,whereas self?control was measured by children' s self?control investigating questionnaire. The data were statistically ana?lyzed with the ANOVA and stepwise regression analysis. Results ①There was no significant difference on social adaptation scores between migrant children and urban children (3.71±0.65,3.70±0.69, P>0.05). ②Among migrant children,girls scored significantly higher than boys(3.80±0.59,3.63±0.69, P<0.01). And as the grade of the migrant children increased,the social adaptation scores decreased (3.82±0.68,3.72±0.64, 3.58±0.60, P<0.01). ③The poor control system had a significantly negative prediction on migrant children' s social adaptation ( β=-0.299, P<0.01),whereas the good self?control system had a significantly positive prediction on migrant children' s social adaptation ( β=0.243, P<0.01) . Both parent?child relationship and peer relationship significantly positively predicted migrant children ' s social adaptation ( β=0. 179, β=0.092, P<0.01) . There was no significant correlation between the proportion of the migrant children in the classes and migrant children's social adaptation (P>0.05). Conclusion There is no significant difference on social adaptation between migrant children and urban children. Children' s self?control,parent?child rela?tionship and peer relationship have significant influence on social adaptation of migrant children .

Objective To observe the changes of serum complements and proinflammatory cytokines in rats with sepsis, and to explore the possible mechanism.Methods 120 healthy male Wistar rats were randomly divided into three groups: normal control group (n = 15), sham operation group (n = 15) and sepsis group [cecum ligation and puncture (CLP) operation,n = 90]. The sepsis rats were sacrificed on 24, 48 and 72 hours after modeling. The level of serum complements (C5, C5a) and cytokines tumor necrosis factor-α (TNF-α), interleukin (IL-1, IL-6), high mobility group box 1 (HMGB1), macrophage migration inhibitory factor (MIF) were detected by enzyme linked immunosorbent assay (ELISA).Results Compared with normal control group and sham operation group, the levels of serum complements C5, C5a and IL-1β were significantly increased at 24 hours after CLP in sepsis group [C5 (ng/L): 1.60±0.19 vs. 1.04±0.20, 1.09±0.09; C5a (ng/L): 0.20±0.02 vs. 0.18±0.01, 0.18±0.02; IL-1β (ng/L): 700.20±111.41 vs. 475.87±108.96, 592.29±121.57; allP < 0.05]; then the levels of C5, C5a and IL-1β declined, the level of serum C5 were also higher than normal control group at 48 hours and 72 hours after CLP (ng/L: 1.17±0.24, 1.27±0.24 vs. 1.04±0.20, bothP < 0.05). In sepsis group the level of serum TNF-α (ng/L: 51.33±1.96, 51.06±1.64) was lower than that in normal control group (59.53±3.06) and sham operation group (57.91±2.72) at 48 hours and 72 hours (allP < 0.05). There was a time dependent rise of serum HMGB1 in sepsis group, which level was much higher than that in normal control group and sham operation group at 72 hours after CLP (ng/L: 472.21±20.94 vs. 406.00±43.16, 404.41±35.39, bothP < 0.05). There were no significant differences of MIF, and IL-6 level between groups at each time points.Conclusions Complement system led to uncontrolled inflammatory response and immune dysfunction through the release of proinflammatory cytokines and inflammatory mediators, which maybe one of the important mechanism of the pathology of sepsis.