With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.
Humans ; Aged ; Aged, 80 and over ; Biliary Tract Surgical Procedures ; Gallstones ; Laparoscopy ; Treatment Outcome ; Aging ; Retrospective Studies

OBJECTIVE To mine adverse drug event （ADE） signals related to baloxavir marboxil， and to provide reference for clinically safe drug use. METHODS The ADE signals related to baloxavir marboxil from January 1， 2018 to May 31， 2022 in the US FDA adverse event reporting system （FAERS） were mined using the proportional reporting odds ratio （PRR） method. ADE with report number≥3， PRR≥2 and χ2≥4 was defined as a positive signal， and PRR method was used to analyze the ADE signal. RESULTS A total of 1 424 ADE reports with baloxavir marboxil as the main suspected drug were collected， involving 460 ADE signals. The femininity and patient under 18 years old were reported more， the country with the highest number of reports was the United States， and the main indication of drug reported was influenza. A total of 37 ADE positive signals were obtained after PRR calculation and screening exclusion， the first three ADE signals in the list of the reported number were diarrhea， vomiting and immediate hypersensitivity， and the first three ADE signals in the list of PRR value were febrile delirium， ischaemic colitis and hemorrhagic cystitis. Compared with the instructions of baloxavir marboxil， 18 ADE signals had not yet been included， such as abnormal liver function， hematuria， hemorrhagic cystitis， etc. Five new SOCs were involved， such as kidney and urinary system diseases， hepatobiliary system diseases， investigations， nervous system disorders and musculoskeletal and connective tissue disorders. CONCLUSIONS When clinical application of baloxavir marboxil， in addition to the adverse drug reactions mentioned in the drug instructions， attention should be paid to abnormal liver function， hematuria， hemorrhagic cystitis， etc， so as to guarantee the safety of drug use.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

Objective:To analyze the effects of microvascular invasion (MVI) and anatomical hepatectomy on early recurrence and survival of patients with hepatocellular carcinoma (HCC).Methods:The data of 246 patients with HCC admitted to 215 Hospital of Shaanxi Nuclear Industry, Chinese PLA General Hospital and Beijing Tsinghua Chang Gung Hospital from July 2008 to June 2019 were retrospectively analyzed, including 208 males and 38 females, aged (53.8±9.6) years. According to the occurrence of MVI, 246 patients were divided into the MVI group ( n=83) and control group ( n=163, without MVI). Hepatitis B virus (HBV) infection, preoperative alpha-fetoprotein (AFP), maximum tumor diameter, intraoperative blood loss were compared between the two groups. The recurrence-free survival and cumulative survival were compared between the two groups before and after the inverse probability weighted correction for propensity score. Results:The propensity score was calculated by logistic regression model. After inverse probability weighted correction, the virtual sample size was 247 cases (82 cases in MVI group and 165 cases in control group). The proportion of HBV infection, with a serum level of AFP > 200 μg/L, the maximum diameter of tumor and the intraoperative blood loss were higher in MVI group (all P<0.05). The risk of early recurrence in patients undergoing anatomical hepatectomy ( n=107) was lower than that in patients undergoing non-anatomical hepatectomy ( n=139) (univariate Cox regression analysis of HR=1.60, 95% CI: 1.06 to 2.42, P=0.020), but the overall survival was comparable (univariate Cox regression analysis of HR=1.66, 95% CI: 0.80 to 3.42, P=0.200). The recurrence-free survival (RFS) of MVI group was lower than that of the control group, and the postoperative cumulative survival rate was also lower before the inverse probability weighted correction of the tendency score. The RFS in MVI group was lower than that in control group after the tendency score was adjusted by inverse probability weighting ( HR=2.62, 95% CI: 1.61 to 4.27, P<0.001). There was no significant difference in the cumulative survival between the MVI and control group ( HR=2.09, 95% CI: 0.89 to 4.93, P=0.050). Conclusion:MVI is associated with early postoperative recurrence in patients with HCC, and the early recurrence rate after anatomical hepatectomy is lower than that after non-anatomical hepatectomy.

Objective:To evaluate the effect of anatomic resection (AR) and nonanatomic resection (NAR) on the prognosis of hepatocellular carcinoma (HCC) patients of China Liver Cancer Staging (CNLC) Ⅰa.Methods:PubMed, Embase and Cochrane Library databases were searched for articles on AR and NAR of CNLC Ⅰa stage HCC from January 2000 to March 2021. A meta-analysis was performed on patient characteristics, tumor characteristics, surgical procedures, postoperative pathological characteristics and long-term prognosis.Results:Of 9 case-control studies were included in this study, there were 2761 patients, with 1727 cases in the AR group and 1034 cases in the NAR group. When compared with the NAR group, the AR group had lower proportion of liver cirrhosis, lower ICG R15 value, higher proportion of Child-Pugh A grade, larger tumor diameter, higher proportion of microvascular invasion, longer operation time and higher intraoperative blood loss. The AR group had a better postoperative 5-year disease-free survival rate [ OR=1.54, 95% CI: 1.30-1.82, P<0.001] and a higher postoperative 5-year overall survival rate [ OR=1.27, 95% CI: 1.04-1.55, P=0.018]. Conclusion:AR is significantly better than NAR for preventing long-term recurrence and improving long-term survival in patients with CNLC Ⅰa stage HCC.

Senescence of activated hepatic stellate cells (aHSCs) is a stable growth arrest that is implicated in liver fibrosis regression. Senescent cells often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). But little is known about how alanine-serine-cysteine transporter type-2 (ASCT2), a high affinity glutamine transporter, affects HSC senescence and SASP during liver fibrosis. Here, we identified ASCT2 is mainly elevated in aHSCs and positively correlated with liver fibrosis in human and mouse fibrotic livers. We first discovered ASCT2 inhibition induced HSCs to senescence in vitro and in vivo. The proinflammatory SASP were restricted by ASCT2 inhibition at senescence initiation to prevent paracrine migration. Mechanically, ASCT2 was a direct target of glutaminolysis-dependent proinflammatory SASP, interfering IL-1α/NF-κB feedback loop via interacting with precursor IL-1α at Lys82. From a translational perspective, atractylenolide III is identified as ASCT2 inhibitor through directly bound to Asn230 of ASCT2. The presence of -OH group in atractylenolide III is suggested to be favorable for the inhibition of ASCT2. Importantly, atractylenolide III could be utilized to treat liver fibrosis mice. Taken together, ASCT2 controlled HSC senescence while modifying the proinflammatory SASP. Targeting ASCT2 by atractylenolide III could be a therapeutic candidate for liver fibrosis.

Objective:To investigate the prognostic value of preoperative inflammatory indicators for hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 73 patients with primary HCC who underwent radical partial hepatectomy in the Beijing Tsinghua Changgung Hospital of Tsinghua University from December 2014 to July 2019 were collected. There were 57 males and 16 females, aged from 33 to 81 years, with a median age of 58 years. Results of blood examination indicators at the first time in hospital were determined for patients. Observation indicators: (1) the best cut-off values of?? preoperative inflammatory indicators calculated by the maximally selected rank statistics; (2) follow-up; (3) influencing factors for prognosis of HCC patients; (4) comparison of clinicopathological parameters of HCC patients; (5) comparison of predictive value for overall survival. Follow-up was conducted using outpatient examination and telephone interview to determine postoperative survival of patients up to September 2019. Measurement data with normal distribution were represented as Mean±SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M (range). The best cut-off values ??for continuous variables were obtained using the maximally selected rank statistics based on survival at endpoint of follow-up. Count data were represented as absolute numbers, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Kaplan-Meier method was used to calculate survival rates, and Log-rank test was used for survival analysis. Univariate analysis was performed using the Log-rank test. Multivariate analysis was performed using the COX proportional hazard model. The time-dependent receiver operating characteristic curve (ROC) was used to compare the predictive value of independent prognostic factors. Results:(1) The best cut-off values of?? preoperative inflammatory indicators calculated by the maximally selected rank statistics: the best cut-off values of neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutrition index (PNI) were 3.46, 131.05, and 45.65. (2) Follow-up: 73 patients were followed up for 31 months (range, 2-57 months). Twenty patients died during the follow-up. (3) Influencing factors for prognosis of HCC patients: results of univariate analysis showed that NLR, PNI, tumor diameter, and tumor differentiation degree were related factors affecting prognosis of patients ( χ2=10.213, 4.434, 5.174, 4.306, P<0.05). Results of multivariate analysis showed that NLR and tumor differentiation degree were independent factors affecting prognosis of patients ( hazzard ratio=4.429, 13.278, 95% confidence interval as 1.662-11.779, 1.056-10.169, P<0.05). (4) Comparison of clinicopathological parameters of HCC patients: of 73 patients, 64 cases had NLR<3.46 and 9 cases had NLR≥3.46. Cases with tumor length >5 cm or ≤5 cm, neutrophils, lymphocytes were 23, 41, (2.9±1.2)×10 9/L, (1.7±0.6)×10 9/L for 64 patients with NLR<3.46, versus 8, 1, (5.8±2.9)×10 9/L, (1.0±0.3)×10 9/L for 9 patients with NLR≥3.46; there were significant differences in above indicators between the two groups ( χ2=7.017, t=2.982, -3.168, P<0.05). (5) Comparison of predictive value for overall survival: time-dependent ROC curves of NLR and tumor differentiation degree for 1-, 2-, 3-, 4-year survival rates had the area under curve of 0.735,0.611, 0.596, 0.574 and 0.554, 0.583, 0.572, 0.556, respectively. NLR had better predictive value for overall survival of patients than tumor differentiation degree. Conclusion:Preoperative NLR is an independent factor affecting prognosis patients, and its predictive efficacy is better than tumor differentiation degree.

The current epidemic of Corona Virus Disease 2019 (COVID-19) poses a serious threat to people′s health and lives. Following the national policies and deployment, medical community in China invests large amounts of medical resources to help Hubei. However, some hospitals nationwide have suspended outpatient and inpatient services. The authors analyze the underlying causes of suspension of medical services and its harm to patients, and summarize the optimization of disease diagnosis and treatment during the COVID-19 outbreak. In further, they propose reasonable suggestions on safe medical management in general hospitals outside the epidemic area, in order to attract the attention of medical institutions and medical colleagues.

Objective:To evaluate the efficacy of erector spinae plane block (ESPB) for transforaminal endoscopic surgery.Methods:Sixty patients of both sexed, aged 20-45 yr, with body mass index of 17.5-29.0 kg/m 2, of American Society of Anesthesiologists physical status ⅠorⅡ, undergoing percutaneous transforaminal endoscopic lumbar discectomy, were divided into 2 groups ( n=30 each) by using a random number table method: ESPB group (E group) and local infiltration anesthesia group (L group). Group E received the ultrasound-guided ESPB, group L received layer-by-layer-assisted local infiltration anesthesia (including subcutaneous layer and fascia, muscular layer and superior articular process) according to the location of operation, and 0.5% ropivacaine 20 ml was used as local anesthetic in both groups.Operation time and C-arm X-ray localization time were recorded.Visual analogue scale score and Ramsay sedation score were recorded at skin incision (T 1), muscle separation (T 2), foraminoplasty (T 3), nerve root decompression (T 4) and skin suture (T 5). The effective analgesia and satisfaction with sedation were recorded.Patients were followed up postoperatively for patient satisfaction, lower extremity motor block, development of nausea and vomiting, dizziness, hematoma at puncture site, nerve damage and etc.Functional status was assessed using the Oswestry Disability Index. Results:Compared with group L, visual analogue scale scores were significantly decreased at T 2-4, Ramsay sedation scores were increased at T 3, 4, patient′s satisfaction was increased, operation time and C-arm X-ray localization time were shortened ( P<0.05), and no significant change was found in Oswestry Disability Index score or rate of satisfactory analgesia in group E ( P>0.05). No motor block, nausea and vomiting, dizziness, hematoma at puncture site and nerve damage was found in both groups. Conclusion:ESPB can provide satisfactory analgesia with a higher safety when used for trasforaminal endoscopic surgery.