ObjectiveTo investigate the mortality level and leading causes of death among the registered residents in Taishun County, Zhejiang Province from 2016 to 2023, as as to provide evidence for the formulation of relevant disease prevention and control strategies. MethodsDeath data of the registered residents in Taishun County were collected from the population death information registration and management system of Zhejiang Province Chronic Disease Surveillance Information Management System and Wenzhou City Disease Prevention and Control Information System. Excel 2021 software was used to calculate the mortality rates and cause-specific rankings of different genders, age groups, and surveillance years. ResultsDuring 2016‒2023, the crude mortality rate (CMR) of the registered residents in Taishun County was 663.97/10⁵, with a standardized mortality rate of 448.33/10⁵. The CMR for males (833.15/10⁵) was 1.73 times higher than that for females (480.77/10⁵). The mortality rate tended to decrease and then increase with age increased, with 78.25% of deaths occurring among individuals aged ≥65 years. The top five causes of death were malignant tumors, cerebral vascular diseases , cardiovascular diseases, chronic respiratory diseases, and injuries/poisoning, collectively accounting for 73.69% of the total deaths. The ranking orders for males and females were not exactly the same. Chronic diseases dominated the causes of death, accounting for 83.85% of the total deaths, from which, malignant tumors and cerebral vascular diseases accounted for 24.45% and 17.79%, respectively. ConclusionStatistically significant differences of mortality rates are observed among individuals from different ages and genders in Taishun County. Chronic diseases, particularly malignant tumors and cerebral vascular diseases, are the main causes of death among the registered residents in Taishun County. Therefore, it is needed to place weight on the prevention and management of chronic diseases, to alleviate the disease burden caused by premature deaths, and to promote the health of the whole population.

OBJECTIVE To explore the anti-liver fibrosis effect and mechanism of Atractylenolide Ⅲ-induced hepatic stellate cell(HSC)senescence.METHODS ASCT2 siRNA and Atractylenolide Ⅲ(40 μmol·L-1)acted on human hepatic stellate cells LX2 respectively to inhibit ASCT2,MTT was used to evaluate cell viability,EdU method was used to detect cell proliferation,and se-nescence associated-β-galactosidase(SA-β-Gal)staining was used to detect cell senescence;Western blot was used to detect chan-ges in the LC3-Ⅱ/Ⅰ ratio in LX2 cells,laser confocal detection was used to detect changes in LC3 autophagy flow and error protein accumulation,and the fluorescence of the lysosomal marker LAMP1 was also observed to detect lysosomal function and quantity;kits were applied to detect ROS and MDA levels as well as SOD activity in LX2 cells,and flow cytometry was used to analyze mitochondrial ROS levels and membrane potential.A CCl4-induced mouse liver fibrosis model was constructed.Atractylenolide Ⅲ was administered at 20,30,or 40 mg·kg-1.HE,Masson,and Sirius Red staining were used to observe liver tissue damage and collagen deposition.Western blot was used to detect the expression levels of P21 and P16 in mice in each group,and SA-β-Gal staining and immunohistochemistry were used to analyze the situation and origin of senescent cells.RESULTS After inhibiting ASCT2,the viabil-ity of LX2 cells decreased and senescence increased(P<0.01).Meanwhile,the autophagy function was enhanced and the number of lysosomes was increased but the function was weakened.After adding chloroquine(CQ)to clear lysosomes,the cell viability and auto-phagy function increased(P<0.01).After inhibiting ASCT2,the levels of MDA and ROS in LX2 cells increased,and the activity of SOD decreased(P<0.01).Among them,the level of mitochondrial ROS increased and the membrane potential decreased(P<0.01).After adding rotenone,the cellular redox homeostasis was improved,and the number of lysosomes was restored(P<0.01).In vivo experimental results showed that compared with the model group,Atractylenolide Ⅲ improved liver tissue structural damage and collagen deposition,induced HSC senescence in liver tissue of mice with liver fibrosis,and inhibited HSC activation marker α-smooth muscle actin(α-SMA),promoted the expression of senescence indicators P16 and P21(P<0.01).CONCLUSION Atractylenol-ide Ⅲ induces an increase in mitochondrial ROS and a decrease in membrane potential by inhibiting ASCT2,which further promotes the enhancement of HSC autophagy function,increases the number of lysosomes and weakens their function,thereby inducing the se-nescence of activated HSCs.

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

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 explore the clinical application of portable head and neck magnetic resonance imaging (MRI) device in neurosurgery.Methods:A total of 213 patients with brain diseases who were scanned by portable head and neck MRI device in Center of Neurosurgery, Zhujiang Hospital, Southern Medical University from June to September 2022 were selected. The portable head and neck MRI images and 3.0T conventional MRI images of 10 randomly selected patients were compared; the differences in signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of different sequences were analyzed. Thirty-one patients accepted tracheal intubation/tracheotomy, or ventilator-assisted breathing were selected as special patient group, and another 30 patients were as general patient group; the differences in comprehensive diagnostic scores of portable head and neck MRI images were compared. Noise intensity differences in different sequences between 3.0T conventional MRI and portable head and neck MRI were statistically compared. Twenty hospitalized volunteers with normal hearing in our center from July to August 2022 were selected, conventional 3.0T MRI and portable head and neck MRI were performed successively, and the noise intensity of different sequences in them was evaluated by using a 5-point system.Results:Compared with those in 3.0T conventional MRI images, the SNR and CNR of T1WI, T2WI, and Liquid attenuated reverse recovery sequence (FLAIR) sequences in portable head and neck MRI images were significantly lower ( P<0.05). No significant difference was noted in the comprehensive diagnostic scores of portable head and neck MRI images between special patients and general patients ( P>0.05). Compared with that in the 3.0T conventional MRI, the noise intensity of different sequences in portable head and neck MRI was significantly reduced ( P<0.05). These volunteers had significantly reduced noise intensity scores of different sequences in portable head and neck MRI compared with that in conventional 3.0T MRI ( P<0.05). Conclusion:Portable head and neck MRI device is easy to use, enjoying high safety, imaging quality and suitability, which meets the clinical needs for neurosurgery patients.

Aim To explore the factors on behavior patterns of light/dark box(LDB)as an animal model of state anxiety in Kunming mice.Methods The behavior of adult,male,Kunming mice in LDB was recorded for five minutes,respectively.The following parameters were evaluated:percentage of time in the light area(Ltime%),percentage of squares crossing in the light area(Lcross%),percentage of rears in the light area(Lrear%),total number of squares crossing in the whole apparatus(Cross),total number of rears in the whole apparatus(Rear),total(Cross plus Rear),transitions between two areas(Transition),and number of fecal bolis in light box and dark box(Fbs).Subsequently,the factors,such as day-night rhythm,illumination area(L3/5 or L2/5 for ratio between Light box and Dark box:3:2 or 2:3,respectively),illumination color(in Dark box)and illumination intensity(in Light box),were investigated to screen the best experimental conditions.Results t-test showed that compared with night cycle,there was no significant difference in all LDB parameters during day cycle(P>0.05),while compared with 3/5 and 2/5,LDB parameters during day cycle such as Lcross%(t=5.363,P<0.01)in big area light box(L3/5),Lrear%(t=3.211,P<0.05)in small area light box(L2/5)increased statistically.The factorial design ANOVA showed that there was no significant difference in day-night rhythm on all LDB parameters(P>0.05),but a statistical influence of illumination area on Ltime%(F(1,20)=18.361,P<0.01),Lcross%(F(1,20)=49.148,P<0.01)and Lrear%(F(1,20)=8.424,P<0.01).The single factor ANOVA showed that there was significant influence of illumination color in dark box on Real(F(3,20)=3.746,P<0.05),Fbs(F(3,20)=3.585,P<0.05),and illumination intensity in light box on Cross(F(4,25)=2.569,P<0.05)and Total(F(4,25)=2.588,P<0.05).The Dunnett t test showed that compared with red color group,Rear(MD=-30.833,P<0.05)was significantly lower in yellow color group; while Cross(MD=-173.167,P<0.05)and Total(MD=-93.667,P<0.05)in 100 W group declined statistically compared with 15 W Group.Kruskal-Wallis test showed that there was no significant difference in illumination color and intensity on Fbs(P>0.05).Conclusions LDB as an animal model of state anxiety in Kunming mice can evaluate anxiety-,locomotion-exploration and emotionality- related behaviors,which cannot be affected by day-night rhythm,but illumination area(Ltime%,Lcross%,Lrear%),illumination color(Rear)and illumination intensity(Cross,Total).So it is recommended to adopt the uniform and fixed conditions,such as illumination area,color and intensity(less than 100 W).

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.