Objective:This study aimed to investigate the role of mitochondrial fusion protein 2 (Mfn2) in chronic renal injury caused by cyclosporine A (CSA) and the possible mechanism.Methods:The model of chronic CSA nephropathy was established in rats. The rats were divided into solvent control group, CSA model group and normal control group. Serum creatinine and urinary protein levels were detected. The tubulointerstitial injury was observed by light microscopy. The changes of mitochondrial structure were observed by electron microscope, and the expression of Mfn2 was detected by Western blot.Results:The levels of serum creatinine and urinary protein in CSA model group at 2 and 4 weeks were significantly higher than those in control group and solvent group ( P<0.05). In CSA model group, tubulointerstitial injury was obvious, mitochondria swelling and deformation were found in tubular epithelial cells, and ridge disappeared. Compared with normal control group and solvent control group, the expression of Mfn2 in CSA model group was significantly decreased at 2 and 4 weeks ( P<0.05), and the expression of Mfn2 in CSA model group at 4 weeks was further decreased compared with 2 weeks ( P<0.05). Conclusions:Mfn2 may play an important role in the injury of tubular epithelial cells caused by cyclosporine.

OBJECTIVE:To optimize the formulation of Compound tripterygium hypoglaucum gel. METHODS:Using the comprehensive score(total score was 15.0)composed by forming property,glossiness,uniformity,viscosity,pH,spreadable prop-erty and stability as indexes,using the usage amount of carbomer 940,propylene glycol,triethanolamine and extracts in formula as study factors,orthogonal test was designed to optimized the formulation of Compound tripterygium hypoglaucum gel,and the verification test was conducted. RESULTS:The optimal matrix formulation was as follow as carbomer 9401.0 g,azone 2.0 g,so-dium bisulfite 0.4 g,extracts 50 mL,propylene glycol 10 g,triethanolamine 1.0 g,adding water to 100 g. The average comprehen-sive score of the gel in verification test was 14.8 (RSD=1.35%,n=3). CONCLUSIONS:The optimized formulation of Com-pound tripterygium hypoglaucum gel shows good forming property,the quality meets the requirements.

Objective To study the therapeutic effects and its possible mechanism ofBushen Paidu Mixture on renal interstitial fibrosis. Methods A total of 60 mice were randomly divided into a normal group,UUO group, Bushen Paidu Mixture group and Lotensin group. Mice models were induced by unilateral ureteral occlusion (UUO). Execute the mice at 7, 14, 21, and 28 days after UUO. The involved kidney were separated and had HE staining. Determine integrinβ1 in kidney tissue through immunohistochemical methods. Results Integrinβ1 tissues had a weak expression in normal kidney. Integrinβ1 expressed higher in UUO group than normal group. The expression of integrinβ1 in Bushen Paidu Mixture group and Lotensin group was lower than the UUO group at every timing point. There is no significant difference between the Bushen Mixture group and Lotensin group in terms of integrinβ1 expression. Conclusion Bushen Paidu Mixture can slow down the process of renal interstitial fibrosis through regulating integrinβ1 expression.

Objective: To investigate the trends in incidence of malignant tumors in Xiaoshan District, Hangzhou City from 2015 to 2020, so as to provide the evidence for improving the control strategy for malignant tumors. Methods: Data on incidence of malignant tumors in Xiaoshan District from 2015 to 2020 were collected through Hangzhou Municipal Chronic Disease Monitoring Management System. The crude incidence, Chinese population-standardized incidence, world population-standardized incidence, cumulative incidence for 0 to 74 years, and truncated age-standardized incidence for 35 to 64 years of malignant tumors were calculated, and the trends in incidence of malignant tumors were analyzed using average annual percent change (AAPC). Results: The crude incidence, Chinese population-standardized incidence, world population-standardized incidence, cumulative incidence for 0 to 74 years, and truncated age-standardized incidence for 35 to 64 years of malignant tumors were 476.95/105, 333.30/105, 257.01/105, 28.30% and 425.79/105 in Xiaoshan District from 2015 to 2020, which all appeared a tendency towards a rise (AAPC=4.36%, 3.82%, 3.99%, 3.79% and 5.20%, all P<0.05). The crude incidence, Chinese population-standardized incidence, world population-standardized incidence, cumulative incidence for 0 to 74 years, and truncated age-standardized incidence for 35 to 64 years of malignant tumors were 491.47/105, 313.31/105, 251.51/105, 28.78% and 338.82/105 among men, and both the crude incidence and truncated age-standardized incidence for 35 to 64 years appeared a tendency towards a rise (AAPC=3.00% and 1.73%, both P<0.05), while the crude incidence, Chinese population-standardized incidence, world population-standardized incidence, cumulative incidence for 0 to 74 years, and truncated age-standardized incidence for 35 to 64 years of malignant tumors were 462.98/105, 348.46/105, 262.13/105, 27.74% and 504.91/105 among women, which all appeared a tendency towards a rise (AAPC=5.77%, 5.72%, 5.79%, 5.65% and 7.48%, all P<0.05). The incidence of malignant tumors appeared a tendency towards a rise with age, and the crude incidence of malignant tumors showed a tendency towards a rise among people at ages of 15 to 44 years and 45 to 64 years (AAPC=9.85% and 4.88%, both P<0.05). Lung cancer, thyroid cancer, colorectal cancer, breast cancer and gastric cancer were the five most common cancers, accounting for 59.63% of all malignant tumors, and the incidence of lung cancer, thyroid cancer, colorectal cancer and breast cancer all showed a tendency towards a rise (AAPC=5.90%, 13.01%, 4.60% and 4.47%, all P<0.05). Conclusions The incidence of malignant tumors showed a tendency towards a rise in Xiaoshan District from 2015 to 2020. The rise in the incidence of malignant tumor was higher in females than in males, and malignant tumors tended to develop at a young age. Lung cancer, thyroid cancer, colorectal cancer, breast cancer and gastric cancer are major malignancies that threaten human health in Xiaoshan District.

Objective: To investigate the trend in mortality of malignant tumors in Xiaoshan District, Hangzhou City from 2017 to 2022, so as to provide insights into formulation of the malignant tumor control strategy. Methods: Data on mortality of malignant tumors in Xiaoshan District from 2017 to 2022 were collected through Hangzhou Municipal Chronic Disease Monitoring Management System, and the cause of death composition ratio and crude mortality were calculated. The mortality of malignant tumors was standardized by the population of the sixth National Population Census in China in 2010. The trend in mortality of malignant tumors were evaluated with average annual percent change (AAPC). Results: There were 13 301 malignant tumor deaths reported in Xiaoshan District from 2017 to 2022, accounting for 31.26% of the total cause of death and ranking the first among the causes of death. The crude mortality was 186.36/105 and standardized mortality was 106.63/105. There was no significant trend in the crude mortality of malignant tumors in Xiaoshan District from 2017 to 2022 (P>0.05), while the standardized mortality showed a tendency towards a decline (AAPC=-1.409%, P<0.05). The crude and standardized mortality of malignant tumors were higher in men than in women (241.40/105 vs. 133.37/105; 132.66/105 vs. 79.35/105; both P<0.05). There was no obvious trend in the crude mortality of malignant tumors in men (P>0.05), and the standardized mortality showed a tendency towards a decline (AAPC=-3.017%, P<0.05). While there was no obvious trend in the crude and standardized mortality of malignant tumors in women (P>0.05). The crude mortality of malignant tumors showed a tendency towards a decline among residents at ages of 15 to 44 years and 65 years and older (AAPC=-3.933% and -2.413%, both P<0.05). The crude mortality of malignant tumors was higher in men than in women among residents at ages of 0 to 14 years, 45 to 64 years and 65 years and older (all P<0.05). The five most common causes of death included lung cancer, colorectal cancer, liver cancer, gastric cancer and pancreatic cancer, accounting for 66.96% of all malignant tumors. The crude mortality of colorectal cancer from 2017 to 2022 showed a tendency towards a rise (AAPC=2.815%, P<0.05). Conclusions The standardized mortality of malignant tumors showed a tendency towards a decline in Xiaoshan District from 2017 to 2022. Management of malignant tumors should be given a high priority among men at ages of 45 years and older, and lung cancer, colorectal cancer, liver cancer, gastric cancer and pancreatic cancer were leading causes of death.

Objective: To investigate the mortality, probability of premature death and trends due to malignant tumors, cardio-cerebrovascular diseases, diabetes and chronic respiratory diseases in Xiaoshan District, Hangzhou City from 2015 to 2021, so as to provide the basis for the formulation of chronic diseases prevention and control strategies. Methods: The deaths of the four diseases in Xiaoshan District from 2015 to 2021 were collected from Zhejiang Provincial Chronic Diseases Surveillance Information Management System. The crude mortality, standardized mortality and probability of premature death were calculated. The trends in mortality and probability of premature death were analyzed using average annual percent change (AAPC), and the attainment of probability of premature death due to the four diseases was evaluated using the targets of probability of premature death control in 2025 and 2030. Results: Totally 36 130 deaths due to the four diseases were reported in Xiaoshan District from 2015 to 2021. The crude mortality and standardized mortality were 445.20/105 and 237.81/105, which appeared a tendency towards a decline (AAPC=-1.427% and -4.051%, both P<0.05), and the probability of premature death decreased from 9.99% to 7.82%, (AAPC=-4.123%, P<0.05). The standardized mortality of malignant tumors, cardio-cerebrovascular diseases and chronic respiratory diseases appeared a tendency towards a decline (AAPC=-3.017%, -4.999%, and -6.024%, all P<0.05), while there was no significant trend in the standardized mortality of diabetes (AAPC=-0.847%, P>0.05). The probability of premature death due to malignant tumors appeared a tendency towards a decline (AAPC=-4.167%, P<0.05), while there was no significant trends seen in the probability of premature death due to diabetes, cardio-cerebrovascular diseases and chronic respiratory diseases (AAPC=0.638%, -5.250% and -2.022%, all P>0.05). The average probability of premature death due to the four diseases decreased by 4.00% each year, and decreased by 6.64% in 2025 and 5.42% in 2030 as predicted, which were both lower than the target values of 7.99% and 6.99%. Conclusions The mortality and probability of premature death due to the four diseases appeared a tendency towards a decline in Xiaoshan District from 2015 to 2021, with the probability of premature death of malignant tumors decreased significantly. It is predicted that the probability of premature death of the four diseases can reach the target in 2025 and 2030.

Objective: To understand the survival status and influencing factors of first-ever stroke patients, so as to provide evidence for improving the quality of life and prognosis of stroke patients. Methods: Demographic information, medical history, smoking history, and alcohol consumption history of newly diagnosed stroke cases first reported in 2017 in Xiaoshan District were collected through the Hangzhou Chronic Disease Surveillance and Management System. Patients were followed up for 5 years, with stroke death as the outcome event. The survival rate was calculated using the Kaplan-Meier method, and factors affecting survival time of first-ever stroke patients were identified using a multivariable Cox proportional hazard regression model. Results: A total of 3 886 patients first-ever stroke patients were included, the cases of cerebral infarction, intracerebral hemorrhage, subarachnoid hemorrhage, and stroke unspecified as to whether it was hemorrhagic or ischemic (unspecified) accounted for 86.93%, 11.45%, 1.06% and 0.57%, respectively. There were 2 047 males (52.68%) and 1 839 females (47.32%), with a mean onset age of (72.01±11.61) years. By the end of the follow-up on December 31, 2022, 906 patients died from stroke, with a median follow-up time of 62.00 (interquartile range, 35.00) months. The 1-year survival rate was 87.35% (95%CI: 86.30%-88.41%), the 3-year survival rate was 82.11% (95%CI: 80.88%-83.34%), and the 5-year survival rate was 76.64% (95%CI: 75.26%-78.02%), respectively. Multivariable Cox proportional hazard regression analysis showed that onset age of ≥75 years (HR=5.543, 95%CI: 3.822-8.039), being treated at township-level hospitals (HR=5.934, 95%CI: 4.027-8.743), history of hypertension (HR=1.566, 95%CI: 1.317-1.863), history of chronic ischemic heart disease (HR=1.611, 95%CI: 1.362-1.906), smoking history (HR=1.455, 95%CI: 1.190-1.778), alcohol consumption history (HR=1.323, 95%CI: 1.067-1.641), stroke subtype of intracerebral hemorrhage (HR=3.442, 95%CI: 2.923-4.053) and unspecified (HR=6.843, 95%CI: 4.353-10.756) were associated with higher mortality risk among first-ever stroke patients. Conclusion The 5-year survival rate of first-ever stroke patients was 76.64%, which was influenced by age of onset, hospital level for diagnosis and treatment, stroke subtype, medical history, smoking and alcohol consumption.

Objective To investigate the infection rates of mycoplasma penetrans (Mpe),mycoplasma pneumoniae (Mp) and mycoplasma ferments (Mf) in patients with IgA nephropathy (IgAN),chronic kideny disease (CKD),and heathy people,to compare the difference of infection rate,and to analyze the association of mycoplasma infection and clinicopathological features in IgAN.Methods Blood samples were collected from 118 patients in IgAN group,90 patients in CKD group,and 89 cases in health control group.DNA of Mpe,Mp and Mf was detected in plasma by PCR.Positive cases were confirmed by Southern blot.According to mycoplasma infection,IgAN patients were divided into two groups,then analyzed the clinicopatholgical features.Results (1)Genus,Mpe,Mp,and Mf positive rates were 33.05％,16.1％,25.45 ％,and 8.47％ in IgAN group,respectively; 5.56％,2.22％,5.56％,and 2.22％ in CKD group,respectively; and 3.33 ％,1.11％,2.22％,and 0 in health group,respectively.Compared with CKD and health group,patients in IgAN group had a higher infection rate in Genus,Mpe,and Mp (P ＜ 0.05).In IgAN group,10 patients had three kinds of mycoplasmas infection at the same time,and positive rate was 8.47％ much higher than CKD group (positive rate was 2.22％) (P ＜ 0.05).(2) Based on mycoplasm detection results,IgAN patients were divided into two groups,overlapping infection group and mycoplasma negative group.In overlapping infection group,the mean age of onset was much younger than negative group.Compared with negative group,overlapping infection group had higher tonsillitis and urinary tract infection rate,more severe microscopic hematuria and tubulointerstitium lesion (P ＜ 0.05).Conclusions Patients with IgAN had higher infection rate of Genus,Mpe and Mp,compared with CKD patients and health people.Compared with mycoplasma negative group in IgAN patients,more severe microscopic hematuria and tubulointerstitium lesion in overlapping infection group,which suggested that infection of Mpe might have some possible connection with IgAN.

Objective To observe the changes of intraocular pressure(IOP)in surgical treatment of Arnold-Chiari malformation.Methods The IOP of 20 patients who underwent surgical treatment of ArnoldChiari malformation were detected by Tono-Pen tonometer at 5 min utes after general anesthesia(T0),5 minutes after prone position(T1),30 minutes after prone position(T2),60 minutes after prone position(T3),prone position before the end of operation(T4),5 minutes after recovery prostration position(Ts)and 30 minutes after prostration position(T6),mean aortic pressure(MAP),heart rate(HR)and partial pressure of carbon dioxide in end tidal(PETCO2)were recorded at the same time.With the prone position,head was fixed bead-holder with skull pin.Results There was no statistical difference in MAP,HR,PEtCO2 at each time point(P＞ 0.05).The IOP significantly increased at T1[(20.9 ±2.5)mm Hg(1 mm Hg =0.133 kPa)],T2[(17.7 ± 1.7)mm Hg],T3[(23.9 ±2.4)mm Hg],T4[(26.3 ± 1.0)mm Hg]compared with IOP at T0 [(9.5 ± 1.5)mm Hg](P ＜ 0.05),there were significant differences between T2 and T3,T3 and T4(P ＜ 0.05).Recovery prostration position,the IOP decreased gradually,IOP at T5[(18.6 ± 1.8)mm Hg]was significantly lower than that at T4(P ＜ 0.05),but T5 was still higher than T0(P ＜ 0.05).The IOP at T6[(10.3 ± 1.7)mm Hg]was no difference compared with T0.Inserting of skull pin might be increase IOP for a moment,the IOP at T; was significantly higher than that at T2(P ＜ 0.05).Conclusion IOP gradually increases as the patients prone position changes in surgical treatment of Arnold-Chiari malformation,and inserting of skull pin maybe increase IOP for a moment.

Silibinin, from milk thistle (Silybum marianum), is a flavonolignan with anti-oxidative and anti-inflammatory properties. It has been therapeutically used for the treatment of hepatic diseases in China, Germany and Japan. Recently, increasing evidences prove that silibinin is also a potent antitumor agent, and the major anti-tumor mechanism for silibinin is the prominent inhibition of the activities of receptor tyrosine kinases (RTKs) and their downstream signal molecules in a variety of tumor cell lines, such as epidermal growth factor receptor 1 (EGFR) and insulin-like growth factor 1 receptor (IGF-1R) signaling pathways. Meanwhile, the evidences that silibinin selectively scavenges hydroxyl free radical (*OH) and specifically inhibits the action of nuclear factor kappaB (NF-kappaB) provide more complicated explanations for its antioxidant and anti-inflammatory effects. Some new findings such as that silibinin attenuating the cognitive deficits induced by amyloid beta protein (Abeta) peptide through its antioxidative and anti-inflammatory properties is valuable to broad the medical prospect of silibinin. In this review, we discuss the molecular pharmacological mechanisms of silibinin, focusing on its inhibition of tyrosine kinases, actions of antioxidation, free radical scavenging, immunoregulation and anti-inflammation.