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 analyze the clinical efficacy of percutaneous kidney-sparing surgery(PCKSS)for the treatment of upper tract urothelial carcinoma(UTUC).Methods A retrospective analysis was conducted on clinical data and oncological characteristics of 11 cases of UTUC treated with PCKSS at our hospital from January 2018 to December 2023.After establishing a percutaneous renal working channel,a laser fiber or plasma resection device was inserted through the nephroscope to remove the tumor piece by piece along the edge of the tumor by 0.5 cm.Results All the 11 cases of PCKSS surgery were successfully completed,with 3 cases having multiple tumors.The surgical time was 75-216 min(median,150 min),and the intraoperative bleeding volume was 20-400 ml(median,150 ml).Postoperative pathological diagnosis showed 9 cases of high-grade UTUC,including 3 cases of G2 grade and 6 cases of G3 grade,with 5 cases in pTa phase and 4 cases in pT1 phase.In 2 cases with preoperative ureteroscopic biopsy showing high-grade pTa phase UTUC,no definite tumor was found during the PCKSS due to shallow sampling and obvious tissue burning.The average postoperative hospitalization time was(6.9±2.6)d.The 1 1 cases were followed up for 2-55 months(median,12 months),and there were 4 cases of recurrence,including 2 deaths,and 7 cases of recurrence free survival.Conclusions PCKSS has certain application value for treating UTUC with renal insufficiency.However,it is necessary to carefully select suitable patients before surgery,and strict and regular follow-up is required after surgery.

Objective To analyze the clinical efficacy of percutaneous kidney-sparing surgery(PCKSS)for the treatment of upper tract urothelial carcinoma(UTUC).Methods A retrospective analysis was conducted on clinical data and oncological characteristics of 11 cases of UTUC treated with PCKSS at our hospital from January 2018 to December 2023.After establishing a percutaneous renal working channel,a laser fiber or plasma resection device was inserted through the nephroscope to remove the tumor piece by piece along the edge of the tumor by 0.5 cm.Results All the 11 cases of PCKSS surgery were successfully completed,with 3 cases having multiple tumors.The surgical time was 75-216 min(median,150 min),and the intraoperative bleeding volume was 20-400 ml(median,150 ml).Postoperative pathological diagnosis showed 9 cases of high-grade UTUC,including 3 cases of G2 grade and 6 cases of G3 grade,with 5 cases in pTa phase and 4 cases in pT1 phase.In 2 cases with preoperative ureteroscopic biopsy showing high-grade pTa phase UTUC,no definite tumor was found during the PCKSS due to shallow sampling and obvious tissue burning.The average postoperative hospitalization time was(6.9±2.6)d.The 1 1 cases were followed up for 2-55 months(median,12 months),and there were 4 cases of recurrence,including 2 deaths,and 7 cases of recurrence free survival.Conclusions PCKSS has certain application value for treating UTUC with renal insufficiency.However,it is necessary to carefully select suitable patients before surgery,and strict and regular follow-up is required after surgery.

【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.

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.

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.

Transcranial direct current stimulation (tDCS) is a well-tolerated, safe and noninvasive physical brain stimulation method, which has been widely used in the treatment of some common mental disorders and neurological diseases and has achieved certain clinical effects. It is necessary to develop expert consensus on clinical treatment to improve the use norms in related fields. According to the clinical research published before August 2021 and the method of evidence-based medicine, we published an expert consensus on tDCS in the treatment of depressive disorders, schizophrenia, substance use-related disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, anxiety disorders, post-traumatic stress disorder, sleep disorders, pain, Parkinson′s disease, stroke, and epilepsy. The consensus also introduced the safety and efficacy of the clinical use of tDCS, and standardized the treatment process and operation technology, aiming to provide guidance for the clinical application of tDCS and promote the standardized development of this treatment technology in the future.

Transcranial direct current stimulation (tDCS) is a well-tolerated, safe and noninvasive physical brain stimulation method, which has been widely used in the treatment of some common mental disorders and neurological diseases and has achieved certain clinical effects. It is necessary to develop expert consensus on clinical treatment to improve the use norms in related fields. According to the clinical research published before August 2021 and the method of evidence-based medicine, we published an expert consensus on tDCS in the treatment of depressive disorders, schizophrenia, substance use-related disorders, obsessive-compulsive disorder, attention deficit hyperactivity disorder, autism, anxiety disorders, post-traumatic stress disorder, sleep disorders, pain, Parkinson′s disease, stroke, and epilepsy. The consensus also introduced the safety and efficacy of the clinical use of tDCS, and standardized the treatment process and operation technology, aiming to provide guidance for the clinical application of tDCS and promote the standardized development of this treatment technology in the future.

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.