ObjectiveTo investigate the effect of Danggui Shaoyaosan on ferroptosis in the rat model of non-alcoholic fatty liver disease （NAFLD） and explore the underlying mechanism based on the nuclear factor E₂-related factor 2 （Nrf2）/solute carrier family 7 member 11 （SLC7A11）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodsThe sixty SD rats were randomly grouped as follows： control， model， Yishanfu （0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， and 9.76 g·kg^-1， respectively） Danggui Shaoyaosan. A high-fat diet was used to establish the rat model of NAFLD. After 12 weeks of modeling， rats were treated with corresponding agents for 4 weeks. Then， the body weight and liver weight were measured， and the liver index was calculated. At the same time， serum and liver samples were collected. The levels or activities of total cholesterol （TC）， triglycerides （TG）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and Fe²⁺ in the serum and TC， TG， free fatty acids （FFA）， malondialdehyde （MDA）， superoxide dismutase （SOD）， glutathione peroxidase （GPX）， and Fe²⁺ in the liver were measured. Hematoxylin-eosin staining and oil red O staining were employed to observe the pathological changes in the liver. Immunofluorescence was used to assess the reactive oxygen species （ROS） content in the liver. Mitochondrial morphology was observed by transmission electron microscopy. The protein levels of Nrf2， SLC7A11， GPX4， transferrin receptor 1 （TFR1）， and divalent metal transporter 1 （DMT1） in the liver were determined by Western blot. ResultsCompared with the control group， the model group showed increases in the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， and decreases in the activities of SOD， GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.05， P<0.01）. Meanwhile， the liver tissue in the model group presented steatosis， iron deposition， mitochondrial shrinkage， and blurred or swollen mitochondrial cristae. Compared with the model group， all doses of Danggui Shaoyaosan reduced the body weight， liver weight， liver index， levels or activities of TC， TG， ALT， AST， and Fe²⁺ in the serum， levels of TC， TG， FFA， MDA， Fe²⁺， and ROS in the liver， and protein levels of TFR1 and DMT1 in the liver （P<0.01）， while increasing the activities of SOD and GPX and the protein levels of Nrf2， SLC7A11， and GPX4 in the liver （P<0.01）. Furthermore， Danggui Shaoyaosan alleviated steatosis， iron deposition， and mitochondrial damage in the liver. ConclusionDanggui Shaoyaosan may inhibit lipid peroxidation and ferroptosis by activating the Nrf2/SLC7A11/GPX4 signaling pathway to treat NAFLD.

Objective:To evaluate postoperative biochemical and clinical remission rates in patients with unilateral primary aldosteronism and analyze related influencing factors.Methods:A total of 406 patients of primary aldosteronism with confirmed subtyping, who underwent adrenalectomy and completed follow-up in the Department of Endocrinology of the First Affiliated Hospital of Chongqing Medical University from November 2013 to March 2022 were retrospectively enrolled. Clinical and biochemical data were recorded. Postoperative clinical and biochemical outcomes were assessed according to Primary Aldosteronism Surgery Outcome(PASO) consensus.Results:Complete biochemical success was achieved in 391(96.31%) of 406 primary aldosteronism patients, while partial and absent biochemical success in only 4(0.99%) and 11(2.71%) primary aldosteronism patients; Complete clinical success was seen in 217(53.45%) patients, and partial clinical success in 189(46.55%) patients. Compared to the partial clinical success group, the complete clinical success group was younger, had a greater proportion of women, a smaller body mass index, a shorter duration of hypertension, a smaller daily defined dose value for antihypertensive medication, a higher estimated glomerular filtration rate(eGFR), and a lower proportion of family history of hypertension and diabetes mellitus. Multifactorial logistic regression analysis further showed that gender( OR=2.49, 95% CI 1.42-4.35, P=0.001), body mass index( OR=1.16, 95% CI 1.05-1.28, P=0.003), antihypertensive drug daily defined dose( OR=1.83, 95% CI 1.37-2.44, P<0.001), family history of hypertension( OR=2.16, 95% CI 1.22-3.83, P=0.008), history of diabetes( OR=2.47, 95% CI 1.15-5.29, P=0.021), and eGFR( OR=0.98, 95% CI 0.97-0.99, P=0.001) were independent factors influencing clinical prognosis of primary aldosteronism. Conclusion:The postoperative complete biochemical success is higher in patients with unilateral primary aldosteronism, but only about half of all patients achieve complete clinical success.

Objective:To investigate the appropriate cut-off for diagnosis of primary aldosteronism (PA) by seated saline suppression test (SSST) based on liquid chromatography with tandem mass spectrometry (LC-MS/MS).Methods:In this cross-sectional study, patients who underwent SSST for suspected PA in the First Affiliated Hospital of Chongqing Medical University from January 2018 to March 2022 were evaluated. Briefly, 300 patients with PA and 119 with essential hypertension (EH) were included. Plasma aldosterone concentration (PAC) after SSST was determined by LC-MS/MS. Primary aldosteronism confirmatory testing (PACT) score was used as the reference standard for diagnosis of PA, and receiver operating characteristic (ROC) curve was used to explore the cut-off value.Results:The average age of the PA group was (50.8±10.5) years, and males accounted for 53.00% ( n=159); the average age of the EH group was (49.4±11.2) years, and males accounted for 26.89% ( n=32). The area under the ROC curve of PAC post-SSST was 0.819 (95% CI 0.775-0.862). When 40 pg/ml (110.8 pmol/L) was selected as the appropriate cut-off for diagnosis of PA, the sensitivity was 83.67% (95% CI 78.88%-87.56%) and specificity was 60.50% (95% CI 51.10%-69.21%). Thus, 95.09% (155/163) of patients with unilateral PA could be identified. Conclusion:PAC after SSST determined by LC-MS/MS has high efficacy for diagnosis of PA, and 40 pg/ml is recommended as the appropriate cut-off value.

The incidence rate of cerebral small vessel disease(CSVD)is increasing year by year,and early screen-ing,diagnosis,and treatment of CSVD is of great significance.Cognitive impairment is one of the manifestations of CSVD that have a great impact on the quality of life of patients.Transcranial Doppler(TCD)can early judge the vascular reserve capacity of patients with CSVD,and the total MRI load of CSVD can calculate the degree of CSVD lesions more compre-hensively than that of independent lesions.This article reviews the research advances in the association of CSVD with total MRI load,vascular reserve,and cognitive impairment in CSVD patients and elaborates on the early screening,diagnosis,and treatment of CSVD.

With the popularity of sports, the number of anterior cruciate ligament (ACL) injuries in children is increasing year by year. Most ACL injuries in children are tibial avulsion fractures or ACL body tears, seriously affecting the health and sports level of the patients. Due to the special anatomical structure of the patients, unclosed epiphysis makes the diagnosis and treatment of ACL injuries more complex. It is necessary to choose the optimal treatment regimen according to the bone maturity and the type and degree of ACL injuries to reduce the damage to the epiphysis and avoid the impact on the growth and development of the patients. It was treated with non-surgical treatment and then ACL reconstruction when the bones were mature in the past, which could cause secondary meniscus and cartilage damage. In recent years, non-surgical treatment has mainly been indicated for children with low-degree ACL injuries and small demand for exercise. With the increased ratio of early surgical treatment, the patients′ levels of recovery and return to sports after injury have been improved. However, improper surgery may still lead to complications such as growth and development disorders and postoperative re-injuries. Different from traditional ACL reconstruction, personalized diagnosis and treatment regimen of ACL injuries are very important for the patients at different stages of growth and development. For a better understanding of the diagnosis and treatment of ACL injuries in children, the authors reviewed the research progress on the diagnosis and treatment of ACL injuries in children from the aspects of the characteristics, diagnosis and evaluation, treatment methods, etc., hoping to provide a reference for the personalized diagnosis and treatment.

Objective To investigate the therapeutic effect of isoorientin on ulcerative colitis(UC)mice induced by dextran sulfate sodium(DSS)and its mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into control group,model group,mesalazine group(600 mg·kg-1),isoorientin low dose group(25 mg·kg-1),isoorientin high dose group(50 mg·kg-1)and isoorientin control group(50 mg·kg-1),with eight mice in each group.Mice were free to drink 2%DSS solution to replicate UC model.After three weeks of experiment,each drug administration group was given corresponding drug by intragastric administration for four weeks.After the last administration,the body weight was weighed,blood was taken from eyeballs,and colon tissue was dissected.The pathological changes of colon were observed by hematoxylin-eosin(HE)and alcian blue-periodic acid-Schiff(AB-PAS)staining.The ultrastructure of colon tissue was observed by transmission electron microscope.Serum levels of interleukin(IL)-6,IL-8,IL-10,IL-1β,tumor necrosis factor α(TNF-α),lipopolysaccharide(LPS)and myeloperoxidase(MPO)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of galectin-3(Gal-3)protein in colon tissue of mice was detected by immunohistochemistry analysis.The expression of MUC2 and the co-localization of NOD-like receptor heat protein domain associated protein 3(NLRP3)and apoptosis-associated speck-like protein(ASC)were detected by immunofluorescence assay.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,IL-18,Occludin,and zonula occludens protein-1(ZO-1)in colon tissue of mice were detected by Western Blot.Results Compared with the control group,the body weight and colon length in the model group were shortened significantly,while the index of colonic weight of mice were increased significantly(P＜0.01).The intestinal mucosal structure of mice was disordered,the microvilli were sparse,the crypt structure was infiltrated by a large number of inflammatory cells,mitochondria were significantly swollen,and goblet cells were obviously decreased.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO were significantly increased,while IL-10 level was significantly decreased(P＜0.01).The positive expression of MUC2 protein in colon tissue was decreased and the co-localization of NLRP3 and ASC was enhanced.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in colon tissue were significantly increased,and the protein expression of Occludin and ZO-1 were significantly decreased(P＜0.01).Compared with the model group,the body weight and colon length of mice in isoorientin low-and high-dose groups were significantly increased,the index of colonic weight of mice was apparently decreased(P＜0.05,P＜0.01).The structure of intestinal mucosa,microvilli and mitochondria recovered obviously,inflammatory infiltration was alleviated,and goblet cells were increased obviously.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO were significantly decreased,while IL-10 level was significantly increased(P＜0.05,P＜0.01).The positive expression of MUC2 protein in colon tissue was increased and the co-localization of NLRP3 and ASC was reduced.The protein expression of Gal-3,NLRP3,ASC,Caspase-1,IL-1β,and IL-18 in colon tissue were significantly decreased,and the protein expression of Occludin and ZO-1 were significantly increased(P＜0.05,P＜0.01).Conclusion Isoorientin has a great therapeutic effect on DSS-induced UC mice.Its mechanism may be related to the protection of intestinal mucosal barrier by Gal-3/NLRP3/IL-1β signaling pathway.

Objective: To describe the sickness absenteeism among primary and secondary school students in Jiading District and to analyze its correlation with the incidence of infectious diseases and associated lead or lag times, so as,to provide a scientific basis for the health and education departments to take measures. Methods: The regularity and symptom composition of school sickness absenteeism among primary and secondary school students in Jiading District from the 2010-2017 were described. The Joinpoint model was applied to analyze the changing trend of absenteeism. And the rate of school sickness absenteeism and incidences of 7 acute infectious diseases were compared through visual analysis. The time lagged correlation coefficients and Granger causality tests were applied to quantitatively analyze the correlation and lead/lag patterns. Results: The average rate of school sickness absenteeism among primary and secondary school students in Jiading District, Shanghai was 0.27%. Since the 2012 academic year, the overall rate of sickness absenteeism has been on the rise. Fever was the most common symptom of absenteeism (47.49%). The trend of sickness absenteeism rate was mainly consistent with the incidence of influenza, and showed a one way Granger causality. The maximum time lagged correlation coefficient was obtained in the second semester of the 2017 academic year with a value of 0.43 (95% CI =0.25-0.58). The maximum time lagged correlation coefficient between the rate of sickness absenteeism with fever and other respiratory symptoms and the incidence of influenza was also obtained in the second semester of the 2017 academic year and the maximum correlation coefficient was 0.50(95% CI =0.33-0.65). Conclusion The sickness absenteeism rate in primary and secondary school students is correlated to influenza incidence, and it has potential application value in supplementing early warning of influenza activities in the community.

Objective To optimize the culture and fermentation conditions of the Penicillium aurantiocandidum Z12 strain, a fungal strain with molluscicidal actions against Oncomelania hupensis, so as to provide the basis for the research and development of molluscicidal active substances from the P. aurantiocandidum Z12 strain and its fermentation broth and large-scale fermentation. Methods The carbon source, nitrogen source and mineral salts were identified in the optimal culture medium for the P. aurantiocandidum Z12 strain with a single-factor experiment to determine the best fermentation condition for the P. aurantiocandidum Z12 strain. Factors that significantly affected the growth of the P. aurantiocandidum Z12 strain were identified using the Plackett-Burman design, and the best range of each factor was determined using the steepest climb test. Response surface analyses of temperature, pH value, seeding amount and liquid-filling quantity were performed using the Box-Behnken design to create a regression model for fermentation of the P. aurantiocandidum Z12 strain to identify the optimal culture medium. Results Single-factor experiment preliminarily identified the best culture medium and conditions for the P. aurantiocandidum Z12 strain as follows: sucrose as the carbon source at approximately 20 g/L, tryptone as the nitrogen source at approximately 5 g/L, K₂HPO₄ as the mineral salt at approximately 5 g/L, initial pH at approximately 8, temperature at approximately 28 °C, seeding amount at approximately 6%, and liquid-filling quantity at approximately 50 mL/100 mL. Plackett-Burman design showed that factors that significantly affected the growth of the P. aurantiocandidum Z12 strain included temperature (t = −5.28, P < 0.05), seeding amount (t = 5.22, P < 0.05), pH (t = −4.30, P < 0.05) and liquid-filling quantity (t = −4.39, P < 0.05). Steepest climb test showed the highest mycelial growth at pH of 7.5, seeding amount of 8%, and liquid-filling quantity of 40 mL/100 mL, and this condition was selected as the central point of response surface analysis for the subsequent optimization of fermentation conditions. Response surface analyses using the Box-Behnken design showed that the optimal conditions for fermentation of the P. aurantiocandidum Z12 strain included sucrose at 15 g/L, tryptone at 5 g/L, K₂HPO₄ at 5 g/L, temperature at 28.2 °C, pH at 7.5, seeding amount at 10%, and liquid-filling quantity at 35.8 mL/100.0 mL, resulting in 0.132 g yield of the P. aurantiocandidum Z12 strain. Conclusion The optimal culture condition for the P. aurantiocandidum Z12 strain has been identified, and the optimized culture medium and fermentation condition may effectively improve the fermentation yield of the P. aurantiocandidum Z12 strain.

Alcoholic liver disease (ALD) is a growing global health concern, and its early pathogenesis includes steatosis and steatohepatitis. Inhibiting lipid accumulation and inflammation is a crucial step in relieving ALD. Evidence shows that puerarin (Pue), an isoflavone isolated from Pueraria lobata, exerts cardio-protective, neuroprotective, anti-inflammatory, antioxidant activities. However, the therapeutic potential of Pue on ALD remains unknown. In the study, both the NIAAA model and ethanol (EtOH)-induced AML-12 cell were used to explore the protective effect of Pue on alcoholic liver injury in vivo and in vitro and related mechanism. The results showed that Pue (100 mg·kg^-1) attenuated EtOH-induced liver injury and inhibited the levels of SREBP-1c, TNF-α, IL-6 and IL-1β, compared with silymarin (Sil, 100 mg·kg^-1). In vitro results were consistent within vivo results. Mechanistically, Pue might suppress liver lipid accumulation and inflammation by regulating MMP8. In conclusion, Pue might be a promising clinical candidate for ALD treatment.

Objective:To explore the spatial and temporal distribution patterns of emerging snail-infested sites in different environmental types in Yunnan Province.Methods:The data of snail-infested sites in Yunnan Province from 1950 to 2014 (from Yunnan Institute for Endemic Diseases Control and Prevention), were collected and sorted out, a spatial and temporal database on the distribution of emerging snail-infested sites were established, and the changes in the spatial and temporal distribution of emerging snail-infested sites in different environments types (ditches, tangerines, paddy fields, dry land, beaches and other environments) were studied by using spatial autocorrelation analysis and scanning statistics analysis.Results:From 1950 to 2014, the annual number of emerging snail-infested sites in Yunnan Province reached a peak (1 730) in 1955 and then showed a fluctuating downward trend. From 1993 to 2014, the number of emerging snail-infested sites remained below 100, and increased to 160 and 131, respectively, in 2004 and 2013. The longest mean duration of 43.85 years was recorded for the beaches environment for emerging snail-infested sites, followed by the paddy fields environment with a mean duration of 37.01 years, and the shortest mean duration of 20.44 years for the tangerines environment. Spatial autocorrelation analysis showed that there was a positive spatial correlation between the duration of emerging snail-infested sites of different environmental types (global Moran's I ranged from 0.43 to 0.64, P < 0.05). Scanning statistics analysis showed that emerging snail-infested sites of different environmental types had spatial and temporal aggregation ( P < 0.001), with 3- 6 clusters of statistically significant aggregation detected respectively. Conclusion:The emerging snail-infested sites in different environments types in Yunnan Province have spatial and temporal aggregation, and it is necessary to strengthen monitoring and prevention and control of the aggregation areas of different environment types to prevent further spread of the snail.