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.

Purpose To explore the forensic pathological features of deaths caused by craniocerebral injury in traf-fic accidents,in order to provide forensic practitioners with a more rigorous approach to identification.Methods A retrospective analysis was performed on 225 autopsy reports of traffic accident fatalities resulting from craniocerebral in-jury.The causes of death were classified,tabulated,and analyzed.Results Among the 225 autopsy reports,the main causes of death included primary brain injury,secondary brainstem injury,and complications.The main types of injuries craniocerebral injuries observed were skull fractures,cerebral hemorrhage,cerebral contusion,cerebral edema and so on.Conclusion The occurrence of craniocerebral injury is related to factors such as age,vehicle,collision speed,and road conditions,and there is an inherent regularity to these factors.Forensic practitioners should combine comprehesive and systematic pathological examinations,clinical data,and the inherent regularities of related factors to make objective,comprehensive,and accurate determinations of the cause of death in traffic accident-related craniocere-bral injuries.

Purpose To explore the forensic pathological features of deaths caused by craniocerebral injury in traf-fic accidents,in order to provide forensic practitioners with a more rigorous approach to identification.Methods A retrospective analysis was performed on 225 autopsy reports of traffic accident fatalities resulting from craniocerebral in-jury.The causes of death were classified,tabulated,and analyzed.Results Among the 225 autopsy reports,the main causes of death included primary brain injury,secondary brainstem injury,and complications.The main types of injuries craniocerebral injuries observed were skull fractures,cerebral hemorrhage,cerebral contusion,cerebral edema and so on.Conclusion The occurrence of craniocerebral injury is related to factors such as age,vehicle,collision speed,and road conditions,and there is an inherent regularity to these factors.Forensic practitioners should combine comprehesive and systematic pathological examinations,clinical data,and the inherent regularities of related factors to make objective,comprehensive,and accurate determinations of the cause of death in traffic accident-related craniocere-bral injuries.

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 evaluate the quality of coenzyme Q₁₀ emulsion with improved formulation and technology and establish an assay method. Methods Coenzyme Q₁₀ emulsion with a high oil concentration was prepared and analyzed by HPLC. The physical and chemical properties of the emulsion were characterized, and the entrapment efficiency was determined. The stability of sterilization, freeze-thaw and dilution was investigated. The photodegradation test as well as the influencing factors, acceleration and long-term stability tests were carried out. Results The particle size, Zeta potential, pH value, content and entrapment efficiency of coenzyme Q₁₀ emulsion were (239.5±0.8) nm、(−32.28±2.04) mV、(5.86±0.02)、 (100.59±1.24) % and (98.5±1.1) %, respectively. The stability of sterilization, freeze-thaw and dilution was good. The photolysis rate was directly proportional to the dilution ratio and inversely proportional to the drug loading. Coenzyme Q₁₀ emulsion should be prepared in light free environment and stored at a low temperature. The pH value dropped 0.61 when it was kept in darkness at (40±2) ℃ for 10 days. It exhibited good stability both in the accelerated and long-term test. Conclusion The physicochemical properties of coenzyme Q₁₀ emulsion with a high oil concentration meet the quality requirements for intravenous injection with good stability.

Objective: To understand the clinical features and pathogenic spectrum of encephalitis and meningitis syndrome in children. Methods: A total of 667 cases of children with encephalitis or meningitis diagnosed and documented at Changchun Children′s Hospital from May 2012 to July 2015 were enrolled.A variety of samples in diffe-rent types were collected and presented, including 335 cerebrospinal fluid specimens, 530 blood samples, and 332 stool samples.All the samples were collected from the patients within 72 hours on admission.Moreover, these samples are analyzed and tested, including PCR for enterovirus(EV), herpesvirus(HSV), mycobacterium tuberculosis(TB) and Mycoplasma pneumoniae(MP) nucleic acid in cerebrospinal fluid samples; fecal specimens were tested for EV, enterovirus 71 (EV71), coxsackievirus A6 (CA6), coxsackievirus A16 (CVA16), coxsackievirus A10 (CVA10) nucleic acids; degenerate primers to amplify Echovirus 30 (Echo30). Clinical data of children were collected. Results: The peak incidence of encephalitis and meningitis syndrome was from June to August, age distribution was from 0 to 15 years old, the proportion of children aged from 0-6 accounted for 81.41%; the highest proportion was among 0-1 years old infants, occupying 32.38%; 408 males and 259 females; the main symptoms were fever(586 cases), apathy(337 cases), vomiting (307 cases) and headache(203 cases). And clinical signs included drowsiness (103 cases), neck stiffness (71 cases), meningeal irritation (12 cases), and pathological reflex (313 cases), etc.The clinical diagnosis included 272 cases of viral encephalitis, 332 cases of severe hand, foot and mouth disease complicated by encephalitis, 30 cases of bacterial meningitis, and 33 other cases; the etiological detection included: the positive rates of EV, EBV and Echo30 in cerebrospinal fluid specimens were 59.72%, 3.16% and 70.00%, respectively.And EV71, CVA16, CVA6, EV71+ CA16 and EV71+ CVA16+ CVA6 nucleic acids were detected in fecal samples, in which the highest detection rate was EV71(98.96%). Conclusions In Changchun Children′s Hospital, the children with encephalitis and meningitis are mainly viral encephalitis.The main symptoms were fever, apathetic, drowsiness, vomiting and headache.Signs included, neck stiffness, meningeal irritation, and pathological reflexes, etc.The main pathogen of the disease is EV71.

Objective To observe the influence of renal sympathetic denervation (RSD) on renal interstitial fibrosis and transforming growth factor beta 1(TGF-β1) and microRNA-21 (miR-21) in rats with unilateral ureteral obstruction(UUO).Methods 40 male Wistar rats were randomly divided into UUO group (A group,n=10),sham UUO group (B group,n=10),RSD+UUO group (C group,n=1O) and RSD + sham UUO group (D group,n=10).Rats in A group and C group underwent unilateral ureteral ligation,while those in B group and D group underwent sham operation.Rats in C group and D group were followed by RSD.Rats were sacrificed at 21 days after the operation to evaluate the fibrosis by Masson staining.Immunohistochemical staining and Western blotting were used to detect the expressions of collagen I (COL-Ⅰ),collagen Ⅲ (COL-Ⅲ) and TGF-β1 in four groups.The expression of miR-21 was detected by fluorescence in situ hybridization (FISH) and quantitative real-time PCR (RT-qPCR).Results A large amount of collagen deposition was observed in the renal interstitial area in A and C group compared to either B or D group (P ＜ 0.05),but the change in C group was decreased significantly than that in A group (P ＜ 0.05).Similarly,the expressions of COL-Ⅰ,COL-Ⅲ,TGF-β1and miR-21 were obviously higher in A and C group compared to either B or D group (P ＜ 0.05),but those change in C group were decreased significantly than those in A group (P ＜ 0.05).The above indexes were not significantly different between B group and D group (P ＞ 0.05).Conclusion RSD may relieve the renal interstitial fibrosis in UUO rats,and down-regulate the expression of TGF-β1 and miR-21.

Objective To analyze the effect of different concentrations of tacrolimus on nephrotic syndrome.Methods A total of 90 kidney disease cases in our hospital from May 2012 to May 2016 were as research objects,the tacrolimus blood concentration was determined by ELISA method when blood concentration reached steady state after taking tacrolimus.All patients were followed up for 3 months to observe the efficacy,dosage and concentration of the drugs,and the incidence of adverse reactions was analyzed.Results After treatment,there were 76 cases with complete remission (84.4%),9 cases (10%) with partial remission,5 cases (5.6%) in invalid.The complete remission group,partial remission group and ineffective group dosage were (0.05±0.01) mg/(kg·d),(0.06±0.01) mg/(kg·d),and (0.07±0.02) mg/(kg·d),respectively.The concentration of drug in blood were (8.44±3.25) ng/mL,(5.92±1.53) ng/mL,and (3.34±0.86) ng/mL.Adverse reaction rates were 45.6% and 44.4% in complete remission group and partial remission group,which were significantly higher than 20.0% in the invalid group,the differences were statistically significant (P<0.05).Conclusion Different concentrations of tacrolimus have an effect on the treatment of nephrotic syndrome,the whole blood concentration of tacrolimus controlled in 5.19~11.69 ng/mL can reach satisfactory effect.

Objective To analyze the effect of different concentrations of tacrolimus on nephrotic syndrome.Methods A total of 90 kidney disease cases in our hospital from May 2012 to May 2016 were as research objects,the tacrolimus blood concentration was determined by ELISA method when blood concentration reached steady state after taking tacrolimus.All patients were followed up for 3 months to observe the efficacy,dosage and concentration of the drugs,and the incidence of adverse reactions was analyzed.Results After treatment,there were 76 cases with complete remission (84.4%),9 cases (10%) with partial remission,5 cases (5.6%) in invalid.The complete remission group,partial remission group and ineffective group dosage were (0.05±0.01) mg/(kg·d),(0.06±0.01) mg/(kg·d),and (0.07±0.02) mg/(kg·d),respectively.The concentration of drug in blood were (8.44±3.25) ng/mL,(5.92±1.53) ng/mL,and (3.34±0.86) ng/mL.Adverse reaction rates were 45.6% and 44.4% in complete remission group and partial remission group,which were significantly higher than 20.0% in the invalid group,the differences were statistically significant (P<0.05).Conclusion Different concentrations of tacrolimus have an effect on the treatment of nephrotic syndrome,the whole blood concentration of tacrolimus controlled in 5.19~11.69 ng/mL can reach satisfactory effect.

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Neck Injuries ; therapy ; Young Adult