Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

Objective:To describe the trend of changes in the disease burden of age-related hearing loss in China and globally from 1990 to 2021,to forecast the prevalence and years lived with disability(YLD)rates of age-related hearing loss from 2022 to 2036,and to provide a reference for the prevention and control of the disease burden associated with age-related hearing loss.Methods:Using the Global Burden of Disease 2021(GBD2021)data,this study selected age-standardized prevalence rate(ASPR)and YLD as indicators.The disease burden and long-term trends of age-related hearing loss in China and globally from 1990 to 2021 were described by different socio-demographic index(SDI)and gender.Joinpoint regression was used to calculate the average annual percent change(AAPC)to assess the trend changes in the disease burden.Decomposition analysis was applied to explore the relative im-pacts of aging,population growth,and epidemiological changes on the variation in disease burden.An autoregressive integrated moving average(ARIMA)model was used to forecast the age-standardized pre-valence rate and YLD rates from 2022 to 2036.Results:The prevalence of age-related hearing loss in China in 2021 was 82 162.49(73 288.08-89 187.21)per 100 000,higher than the global SDI level of 66 238.16(59 982.54-72 669.82)per 100 000,the high SDI region's level of 57 650.42(52 059.12-63 889.02)per 100 000,the upper-middle SDI region's level of 69 115.59(62 494.18-75 340.64)per 100 000,the middle SDI region's level of 72 365.56(65 181.43-78 912.01)per 100 000,the lower-middle SDI region's level of 64 439.66(58 368.22-71 468.27)per 100 000,and the low SDI region's level of 61 725.25(55 749.18-68 477.67)per 100 000.The age-related hearing loss YLD rate in China was 2 762.98[95％uncertainty interval(UI):1 855.28-3 880.68]per100000,higher than the global SDI level of 2 236.75(95％UI:1 511.56-3 155.88)per 100 000,the high SDI region's level of 1 805.79(95％UI:1 212.69-2 577.17)per 100 000,the upper-middle SDI re-gion's level of 2 316.58(95％UI:1 557.53-3 274.87)per 100 000,the middle SDI region's level of 2 480.99(95％UI:1 678.17-3 489.24)per 100 000,the lower-middle SDI region's level of 2 313.28(95％UI:1 578.35-3 271.50)per 100 000,and the low SDI region's level of 2 383.55(95％UI:1 623.66-3 365.68)per 100 000.From 1990 to 2021,both the prevalence and YLD rate of age-related hearing loss in China showed an increasing trend,rising by an average of 0.18％(95％CI:0.16％-0.19％)and 0.29％(95％CI:0.27％-0.30％)per year,respectively.The rates of in-crease in prevalence were the same for both men and women,with men showing a 0.18％increase(95％CI:0.17％-0.19％,P＜0.001)and women showing a 0.18％increase(95％CI:0.16％-0.19％,P＜0.001).However,the YLD rate increase was faster in men than in women,with men experiencing a 0.32％increase(95％CI:0.27％-0.37％,P＜0.001)and women experiencing a 0.27％increase(95％CI:0.26％-0.28％,P＜0.001).Decomposition analysis showed that population growth was the main factor driving the increase in prevalence and YLD rate globally and across different SDI regions.However,aging was the primary factor contributing to the increase in prevalence and YLD rate in China.ARIMA model predictions suggested that the prevalence and YLD rate of age-related hearing loss would continue to rise from 2022 to 2036,with the predicted prevalence and YLD rate in 2036 reaching 89 723.99 per 100 000 and 2 872.47 per 100 000,respectively.Conclusion:The prevalence and disease burden of age-related hearing loss in individuals aged 60 and above in China rank first globally.From 1990 to 2021,both the prevalence and YLD rate of age-related hearing loss have shown a continuous upward trend,consistently surpassing the levels observed in various SDI regions worldwide.The prevalence and disease burden of age-related hearing loss are particularly significant among elderly men.Moreover,projections indicate that the disease burden of age-related hearing loss will continue to rise over the next 15 years.Therefore,it is urgent to pay close attention to age-related hearing loss in this specific population,and early intervention measures are crucial to reduce the disease burden associated with age-related hearing loss.

Objective:To describe the trend of changes in the disease burden of age-related hearing loss in China and globally from 1990 to 2021,to forecast the prevalence and years lived with disability(YLD)rates of age-related hearing loss from 2022 to 2036,and to provide a reference for the prevention and control of the disease burden associated with age-related hearing loss.Methods:Using the Global Burden of Disease 2021(GBD2021)data,this study selected age-standardized prevalence rate(ASPR)and YLD as indicators.The disease burden and long-term trends of age-related hearing loss in China and globally from 1990 to 2021 were described by different socio-demographic index(SDI)and gender.Joinpoint regression was used to calculate the average annual percent change(AAPC)to assess the trend changes in the disease burden.Decomposition analysis was applied to explore the relative im-pacts of aging,population growth,and epidemiological changes on the variation in disease burden.An autoregressive integrated moving average(ARIMA)model was used to forecast the age-standardized pre-valence rate and YLD rates from 2022 to 2036.Results:The prevalence of age-related hearing loss in China in 2021 was 82 162.49(73 288.08-89 187.21)per 100 000,higher than the global SDI level of 66 238.16(59 982.54-72 669.82)per 100 000,the high SDI region's level of 57 650.42(52 059.12-63 889.02)per 100 000,the upper-middle SDI region's level of 69 115.59(62 494.18-75 340.64)per 100 000,the middle SDI region's level of 72 365.56(65 181.43-78 912.01)per 100 000,the lower-middle SDI region's level of 64 439.66(58 368.22-71 468.27)per 100 000,and the low SDI region's level of 61 725.25(55 749.18-68 477.67)per 100 000.The age-related hearing loss YLD rate in China was 2 762.98[95％uncertainty interval(UI):1 855.28-3 880.68]per100000,higher than the global SDI level of 2 236.75(95％UI:1 511.56-3 155.88)per 100 000,the high SDI region's level of 1 805.79(95％UI:1 212.69-2 577.17)per 100 000,the upper-middle SDI re-gion's level of 2 316.58(95％UI:1 557.53-3 274.87)per 100 000,the middle SDI region's level of 2 480.99(95％UI:1 678.17-3 489.24)per 100 000,the lower-middle SDI region's level of 2 313.28(95％UI:1 578.35-3 271.50)per 100 000,and the low SDI region's level of 2 383.55(95％UI:1 623.66-3 365.68)per 100 000.From 1990 to 2021,both the prevalence and YLD rate of age-related hearing loss in China showed an increasing trend,rising by an average of 0.18％(95％CI:0.16％-0.19％)and 0.29％(95％CI:0.27％-0.30％)per year,respectively.The rates of in-crease in prevalence were the same for both men and women,with men showing a 0.18％increase(95％CI:0.17％-0.19％,P＜0.001)and women showing a 0.18％increase(95％CI:0.16％-0.19％,P＜0.001).However,the YLD rate increase was faster in men than in women,with men experiencing a 0.32％increase(95％CI:0.27％-0.37％,P＜0.001)and women experiencing a 0.27％increase(95％CI:0.26％-0.28％,P＜0.001).Decomposition analysis showed that population growth was the main factor driving the increase in prevalence and YLD rate globally and across different SDI regions.However,aging was the primary factor contributing to the increase in prevalence and YLD rate in China.ARIMA model predictions suggested that the prevalence and YLD rate of age-related hearing loss would continue to rise from 2022 to 2036,with the predicted prevalence and YLD rate in 2036 reaching 89 723.99 per 100 000 and 2 872.47 per 100 000,respectively.Conclusion:The prevalence and disease burden of age-related hearing loss in individuals aged 60 and above in China rank first globally.From 1990 to 2021,both the prevalence and YLD rate of age-related hearing loss have shown a continuous upward trend,consistently surpassing the levels observed in various SDI regions worldwide.The prevalence and disease burden of age-related hearing loss are particularly significant among elderly men.Moreover,projections indicate that the disease burden of age-related hearing loss will continue to rise over the next 15 years.Therefore,it is urgent to pay close attention to age-related hearing loss in this specific population,and early intervention measures are crucial to reduce the disease burden associated with age-related hearing loss.

Objective:To explore genomic features associated with gemcitabine sensitivity, patient-derived organoid models of biliary tract cancer (BTC) were established and characterized.Methods:This is an experimental study. The tissue specimens of BTC were collected from patients who underwent surgical resection at the Department of Hepatobiliary and Pancreatic Surgery,the Second Affiliated Hospital of Zhejiang University School of Medicine between January 2020 and December 2023. The tumor organoids were cultured in vitro and histologically characterized. Drug sensitivity testing was performed using gemcitabine,cisplatin,paclitaxel,fluorouracil,and lenvatinib etc. to evaluate cell viability. The correlation between the drug sensitivity of organoids and clinical therapeutic response was analyzed.Results:Thirty-eight patient-derived organoids (PDO) models were successfully established from 43 biliary tract malignancy patients with complete follow-up data,including gallbladder cancer PDO 14 cases,distal bile duct cancer PDO 16 cases,intrahepatic cholangiocarcinoma PDO 8 cases,achieving an overall success rate of 88.4%. Drug sensitivity testing (DST) was performed on the successfully generated PDO,with 35 models successfully completing DST experiments. The overall consistency rate between drug responses in PDOs and clinical survival outcomes in corresponding patients was 8/14. Transcriptomic analysis of gemcitabine-sensitive vs. gemcitabine-resistant PDO identified 71 differentially expressed genes in the resistant group,the significantly up-regulated genes including GLDC, LINC01595, IL-27, ANGPTL3, CYP7A1,and AKR1C1;the significantly down-regulated genes including P2RY2,LIPC,and ECHDC3. Conclusion:A biobank of patient-derived organoids of BTC has been established,which demonstrates its potential as preclinical models and tools for predicting chemotherapy responses for BTC patients.

Objective:To explore the current situation and influencing factors of quality of life of septic patients in intensive care unit (ICU) after discharge, and to provide theoretical basis for clinical early psychological intervention and continuity of care.Methods:A prospective observational study was conducted. The septic patients who were hospitalized in the department of critical care medicine of the Affiliated Hospital of Jining Medical University and discharged with improvement from January 1 to December 31, 2022 were selected as the research objects. The demographic information, basic diseases, infection site, vital signs at ICU admission, severity scores of the condition within 24 hours after ICU admission, various biochemical indexes, treatment process, and prognostic indexes of all the patients were recorded. All patients were assessed by questionnaire at 3 months of discharge using the 36-item short-form health survey scale (SF-36 scale), the activities of daily living scale (ADL scale), and the Montreal cognitive assessment scale (MoCA scale). Multiple linear regression was used to analyze the factors influencing the quality of life of septic patients after discharge from the hospital.Results:A total of 200 septic patients were discharged with improvement and followed up at 3 months of discharge, of which 150 completed the questionnaire. Of the 150 patients, 57 had sepsis and 93 had septic shock. The total SF-36 scale score of septic patients at 3 months of discharge was 81.4±23.0, and the scores of dimensions were, in descending order, role-emotional (83.4±23.0), mental health (82.9±23.6), bodily pain (82.8±23.3), vitality (81.6±23.2), physical function (81.4±23.5), general health (81.1±23.3), role-physical (79.5±27.0), and social function (78.8±25.2). There was no statistically significant difference in the total SF-36 scale score between the patients with sepsis and septic shock (82.6±22.0 vs. 80.7±23.6, P > 0.05). Incorporating the statistically significant indicators from linear univariate analysis into multiple linear regression analysis, and the results showed that the factors influencing the quality of life of septic patients at 3 months after discharge included ADL scale score at 3 months after discharge [ β= 0.741, 95% confidence interval (95% CI) was 0.606 to 0.791, P < 0.001], length of ICU stay ( β= -0.209, 95% CI was -0.733 to -0.208, P = 0.001), duration of mechanical ventilation ( β= 0.147, 95% CI was 0.122 to 0.978, P = 0.012), total dosage of norepinephrine ( β= -0.111, 95% CI was -0.044 to -0.002, P = 0.028), mean arterial pressure (MAP) at ICU admission ( β= -0.102, 95% CI was -0.203 to -0.007, P = 0.036) and body weight ( β= 0.097, 95% CI was 0.005 to 0.345, P = 0.044). Conclusions:The quality of life of patients with sepsis at 3 months after discharge is at a moderately high level. The influencing factors of the quality of life of patients with sepsis at 3 months after discharge include the ADL scale score at 3 months after discharge, the length of ICU stay, the duration of mechanical ventilation, the total dosage of norepinephrine, MAP at ICU admission and body weight, and healthcare professionals should enhance the treatment and care of the patients during their hospitalization based on the above influencing factors, and pay attention to early psychological intervention and continued care for such patients.

Objective To analyze the genetic characteristics of chromosomes and related fusion genes in acute myeloid leukemia (AML) (non-M3), and to evaluate the prognosis of patients with chemotherapy of DA regimen with different doses of daunorubicin. Methods Fifty-six patients with newly diagnosed non-M3 AML from January 2013 to January 2015 were collected. Adopted short-term culture method was used to treat bone marrow, R-binding chromosome karyotyping was used to detect cytogenetic. Thirty-one types of fusion gene were identified by PCR and 10 % agarose gel electrophoresis. All patients treated by DA regimen were divided into group A, group B and group C according to different dosage of daunorubicin. Then, complete remission (CR) rate and survival time in the 3 groups were observed. The effect of cytogenetic and molecular biology abnormality on the chemotherapy, CR rate and overall survival (OS) of the 3 groups were analyzed by the chi-square test. Results Among the 56 patients, 18 cases (32.1%) had abnormal chromosome karyotype, 6 cases (10.7 %) had abnormal number of chromosome, 16 cases (28.6 %) had abnormal structure of chromosome, and 4 cases (7.1 %) had both abnormal number and structure of chromosome. Meanwhile, the most common abnormal structure was t(8;21), and the most common abnormal quantity were+8, -Y. Detective rate of genetic abnormality was raised to 62.00 % through fusion gene and chromosome karyotype analysis. The total CR rate of DA-induced chemotherapeutic regimen was 73.2 %, and the two-year OS rate was 42.9%. The remission rate of chemotherapy in the middle-risk group was significantly lower than that in the low-risk group (χ 2 = 8.976, P = 0.002), but there was no significant difference between the low-dose chemotherapy group and the standard dose chemotherapy group (P>0.05). The standard dose group showed a significant advantage in the OS rate (χ2= 8.045, P= 0.005). Conclusions Adult acute leukemia has its unique cytogenetic characteristics, which can assist in guiding clinical diagnosis, classification and prognosis. The prognosis of middle-risk patients is significantly lower than the low-risk group. Low-risk patients could benefit from a reduced dose of DA regimen, but the standard dose DA regimen has a significant advantage in long-term survival.

Objective: To investigate the gene frequency of HLA-B* 5801 in the population of Chinese Minnan region.Methods:In this study,we enrolled 178 patients requiring allopurinol therapy( including 40 patients with gout,89 patients with hyperuricemia and 49 patients with gouty arthritis) and 100 healthy people.We isolated genomic DNA from their blood and screened for HLA-B*5801 with both PCR and gene sequencing.Results:We found 22%patients and 16%healthy people with HLA-B*5801.The frequencies of HLA-B*5801 in patients and healthy people are 0.13 and 0.09,respectively.The results from PCR and gene sequencing were consistent.Conclusion:The frequency of HLA-B*5801 in the population of Chinese Minnan region is relatively high.Therefore,it is necessary to screen for HLA-B*5801 in allopurinol users before taking the medicine.

Objective To investigate the effect of anti-epileptic soup on the levds of interleukin-2 (IL-2) and interleukin-6 (IL-6) in pentylenetetrazol-induced rats and its mechanism.Methods Healthy adult male SD rats were injected intraperitoneally with pentylenetetrazol kindling 35.0mg/kg to induce a rat epilepsy model.After successful construction of the epilepsy model,the rats were divided into four the groups:blank group,model group,anti -epileptic soup group and sodium valproate (VPA) group.All of the treatments were performed three times a day continuously for 28 days.The rats in the anti-epileptic soup group were given 6ml of anti-epileptic soup.The rats in the VPA group were given 400mg/kg of sodium valproate by garage.The rats in blank group and model group received 6ml of normal saline.After treatment,the seizures level was recorded by using the Diehl six point grading scale,and the expression of serum IL-2 and IL-6 were detected by the enzyme linked immunoassay (ELISA).Results The seizure level of the model group was (4.23 ± 0.43),while that of the anti-epileptic group was (3.47 ± 0.39),indicated that the anti-epileptic soup can reduce the seizures level.The expressions of IL-2 (4.18 ± 0.41)pg/mL and IL-6 (350.0 ± 82.5) pg/mL of the model group were higher than those of the blank group [IL-2 (3.20 ± 0.36) pg/mL,IL-6 (260.2 ± 69.0) pg/mL,P ＜ 0.01],while the expressions of IL-2 (3.48 ± 0.44) pg/mL and IL-6 (287.5 ±74.6) pg/mL of the anti-epileptic group were lower compared with the control group (P ＜0.01).No significant difference was found between the anti-epileptic group and VPA group IL-2 (3.35 ± 0.56) pg/mL and IL-6 (253.8 ± 59.8) pg/mL(P ＞ 0.05).Conclusion The anti-epileptic soup is effective for treating epilepsy in rats,the possible mechanism may be related with downregulating the expression of IL-2 and IL-6.

A 74-year-old man presenting with general fatigue and dyspnea was admitted to another hospital. He was transferred to our hospital because his symptoms deteriorated and pericardial fluid increased. The symptoms did not improve even after percutaneous pericardial drainage. On a diagnosis of heart failure due to pericardial constriction, he underwent pericardiectomy. No hemodynamics improvement was found despite subtotal pericardiectomy. Multiple longitudinal and transverse incisions like a waffle were made in the thickened epicardium and improved the hemodynamics. The symptoms improved after sugery. Steroid therapy was effective after pathological examination of the excised epicardium that confirmed an emerging manifestation of hyper-IgG4 disease. We report a waffle procedure with good results for a constrictive pericarditis with hyper-IgG4 disease.

Objective The purpose of this investigation was to investigate the neuroprotective effects of rhubarb for ICH,as well as its mechanism.Methods ICH was produced in adult Spargue-Dawley rats by injection of collagenase IV(0.05U/0.5uL).Intraperitoneal injection of rhubarb (70mg/kg) or saline,was started at 3,6 or 12 hours post-ICH respectivdy.Casepase-3 activity.TUNEL and neurological behavior function were performed 24hours after ICH.Results Rhubarb siven at 3 or 6 hours can inhibit casepase-3 activity(P<0.001),reduce TUNEL positive cells(P<0.05) and attenuate apomorphine-induced rotation(P<0.05) at 24 hours after ICH.However,the animals which were treated 12 hours showed no improvement.Conclusion Rhubarb may be a potential drug for ICH patients for its possible effect of inhibiting apoptosis.