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 explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

ObjectiveTo investigate the regulatory effect of Danggui Shaoyaosan on adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR）/Unc-51-like kinase-1 （ULK1） signaling pathway in the rat model of metabolism-associated fatty liver disease （MAFLD）. MethodSixty SD rats were randomized into control， model， western medicine （polyene phosphatidylcholine capsules，0.144 g·kg^-1）， and low-， medium-， and high-dose （2.44， 4.88， 9.76 g·kg^-1， respectively） Danggui Shaoyaosan groups. After being fed with a high-fat diet for 8 weeks， the rats in each group were administrated with corresponding drugs for 4 weeks. At the end of drug treatment， serum and liver tissue were collected for subsequent determination of related indicators. ResultCompared with the control group， the model group showed increased contents of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and activities of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum， increased contents of TC， TG， and free fatty acids （FFAs） in the liver （P<0.01）， and decreased content of high-density lipoprotein cholesterol （HDL-C） in the serum （P<0.01）. Furthermore， the model group showed down-regulated protein levels of p-AMPK， microtubule-associated protein 1 light chain 3B （LC3B） Ⅱ， Beclin1， and ULK1 （P<0.01） and up-regulated protein levels of p-mTOR and ubiquitin-binding protein p62 in the liver （P<0.01）. The hepatic steatosis was obvious and the NAFLD activity score （NAS） and oil red O staining area increased in the model group， （P<0.05， P<0.01）. Compared with the model group， Danggui Shaoyaosan reduced the contents of TC and TG and the activities of ALT and AST in the serum， lowered the levels of TC， TG， and FFA in the liver， down-regulated the protein levels of p-mTOR and p62 （P<0.01）， elevated the serum HDL-C level， and up-regulated the protein levels of p-AMPK， LCBⅡ， Beclin1， and ULK1 in the liver （P<0.05， P<0.01）. Moreover， it alleviated hepatic steatosis and decreased the NAS and oil red O staining area （P<0.05， P<0.01）. ConclusionDanggui Shaoyaosan has therapeutic effect on MAFLD rats by regulating AMPK/mTOR/ULK1 signaling pathway to enhance autophagy.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.

Objective To elucidate the effect of curcumol on hepatic stellate cell iron death and epithelial-mesenchymal transition(EMT),and to investigate the molecular mechanism of its anti-liver fibrosis effect.Methods A model of hepatic stellate cell activation was constructed using normal cultured hepatic stellate cells in vitro,and the cells were divided into blank group and experimental-L,-M,-H groups.The blank group was given DMEM complete culture solution for normal culture;the experimental-L,-M,-H groups were given DMEM complete culture solution containing 12.5,25.0 and 50.0 mg·L-1 curcumol for 48 h of intervention.The effects of curcumol on the proliferation of hepatic stellate cells was observed by CCK-8.The expression levels of glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blot.The expression levels of E-cadherin and N-cadherin were detected by immunofluorescence.Results The cell proliferation rates of the experimental-M,-H groups and blank group were(68.97±5.61)％,(61.91±4.40)％and(118.07±10.01)％;the relative expression levels of GPX4 were 0.37±0.04,0.28±0.03 and 0.58±0.05;the relative expression levels of SLC7A11 were 0.38±0.04,0.28±0.03 and 0.60±0.05;E-cadherin levels were 6.76±1.09,9.57±1.73 and 2.05±0.72;N-cadherin levels were 5.66±0.66,3.44±0.78 and 10.37±0.66.The differences of above indicators were statistically significant between the blank group and the experimental-M,-H groups(P＜0.05,P＜0.01).Conclusion Curcumol promotes iron death in hepatic stellate cells,thereby inhibiting hepatic stellate cell EMT,which may be its molecular mechanism to prevent and treat liver fibrosis.

Objective:To examine the clinical subtypes of patients with multisystem atrophy(MSA)that may indicate the prognosis of patients.Additionally, we aim to compare the ability to perform daily activities among patients of each subtype using cluster analysis.Methods:The retrospective analysis included demographic data, clinical symptoms and signs, scale scores, and ancillary examinations of 94 patients diagnosed with multisystem atrophy at Xuanwu Hospital of Capital Medical University.The study aimed to analyze the clinical characteristics of each subtype obtained through clustering.Additionally, a comparison was made between patients with traditional motor subtypes and those with new subtypes in terms of activities of daily living.The study consisted of 94 MSA patients, with an average age of 61 years and a female representation of 51.1%.Using the data collected on the continuum, a full linkage hierarchical cluster analysis was performed to classify MSA patients into four clinical subtypes: gait disorder(17 cases, 18.1%), malignant tonic hyperkinetic with premature haircut(25 cases, 26.6%), intermediate(43 cases, 45.7%), and autonomic benign type(9 cases, 9.6%).Each subtype exhibited various clinical motor and non-motor symptoms, including UPDRS-Ⅲ( χ2=27.90, P<0.001), gait disturbance( χ2=33.23, P<0.001), MoCA( χ2=10.98, P=0.012), HAMA( χ2=12.14, P=0.007), HAMD( χ2=13.62, P=0.003), smell score( χ2=10.16, P=0.017), postural hypotension( χ2=14.59, P=0.028), and a statistically significant difference in the ability to perform daily living score( χ2=25.35, P<0.001).No statistically significant differences in non-motor symptoms and activities of daily living abilities were observed between the cerebellar and Parkinsonian types of traditional motor typing( P>0.05). Conclusions:The hierarchical clustering analysis conducted in this study reveals that the clinical phenotype of MSA provides a more accurate reflection of patients' clinical characteristics and their impact on quality of life compared to the traditional motor phenotype.Additionally, it may help predict variations in the underlying pathological impairment and the rate of disease progression.These findings offer a foundation for precise diagnostic interventions in patients with MSA.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Osteoporotic proximal humeral fracture (OPHF) is one of the common osteoporotic fractures in the aged, with an incidence only lower than vertebral compression fracture, hip fracture, and distal radius fracture. OPHF, secondary to osteoporosis and characterized by poor bone quality, comminuted fracture pattern, slow healing, and severely impaired shoulder joint function, poses a big challenge to the current clinical diagnosis and treatment. In the field of diagnosis, treatment, and rehabilitation of OPHF, traditional Chinese and Western medicine have accumulated rich experience and evidence from evidence-based medicine and achieved favorable outcomes. However, there is still a lack of guidance from a relevant consensus as to how to integrate the advantages of the two medical systems and achieve the integrated diagnosis and treatment. To promote the diagnosis and treatment of OPHF with integrated traditional Chinese and Western medicine, relevant experts from Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine have been organized to formulate Expert consensus on the diagnosis and treatment of osteoporotic proximal humeral fracture with integrated traditional Chinese and Western medicine ( version 2024) by searching related literatures and based on the evidences from evidence-based medicine. This consensus consists of 13 recommendations about the diagnosis, treatment and rehabilitation of OPHF with integrated traditional Chinese medicine and Western medicine, aimed at standardizing, systematizing, and personalizing the diagnosis and treatment of OPHF with integrated traditional Chinse and Western medicine to improve the patients ′ function.

Objective:To investigate the efficacy of arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon in the treatment of irreparable massive rotator cuff tears (IMRCT).Methods:A retrospective case series study was performed on 11 IMRCT patients who were admitted to Affiliated Fuyang Hospital of Bengbu Medical University (Fuyang People′s Hospital) from May 2020 to June 2022, including 7 males and 4 females, aged 54-74 years [(62.6±7.3)years]. All the patients were treated with arthroscopic superior capsular reconstruction using composite patch graft combined with tenodesis of the long head of the biceps tendon. The Visual Analogue Scale (VAS), Acromiohumeral Distance (AHD), Constant-Murley score and University of California Los Angeles (UCLA) score and active range of motion of the shoulder joint before, at 6 months after surgery and at the last follow-up were compared. At the last follow-up, the integrity of reconstructed superior capsule and the long head of the biceps tendon was evaluated using MRI of the shoulder joint. Postoperative complications were observed.Results:All the patients were followed up for 13-39 months [16(13, 36)months]. The VAS score, AHD, Constant-Murley score, and UCLA score were 2(2, 3)points, (9.1±1.1)mm, (56.1±5.4)points, and (19.7±2.8)points respectively at 6 months after surgery, which were all significantly improved from those before surgery [6(5, 7)points, (5.1±1.2)mm, (37.9±2.2)points, and (11.8±1.2)points] ( P<0.05). The VAS score, AHD, Constant-Murley score, and UCLA score were 0(0, 1)points, (8.4±0.9)mm, (83.6±3.8)points, and (28.2±2.3)points respectively at the last follow-up, which were all significantly improved from those before surgery ( P<0.05). At the last follow-up, the VAS score or AHD were not significantly improved from those at 6 months after surgery ( P>0.05); Constant-Murley score and UCLA score were both significantly improved from those at 6 months after surgery ( P<0.05). At 6 months after surgery, shoulder active ranges of motion in forward flexion, abduction and external rotation were (134.6±13.5)°, (124.6±18.6)° and 45(40, 50)° respectively, which were all significantly improved compared with those before surgery [(63.2±36.1)°, (65.0±23.1)°, and [30(20, 40)°] ( P<0.05). At the last follow-up, shoulder active ranges of motion in forward flexion, abduction and external rotation were (144.1±12.6)°, (139.6±15.4)° and 60(45, 65)° respectively, which were all significantly improved compared with those before surgery ( P<0.05). There were no significant differences in active range of motion of the shoulder in forward flexion, abduction and external rotation between 6 months after surgery and the last follow-up ( P>0.05). At the last follow-up, MRI revealed integrity of the reconstructed superior joint capsule and the long head of the biceps tendon in 10 patients. One patient developed resorption of the greater tuberosity and 1 showed a partial tear of the supraspinatus tendon at 1 year after surgery. Conclusion:Arthroscopic superior capsular reconstruction using composite autologous patch graft combined with tenodesis of the long head of the biceps tendon can relieve shoulder pain, decrease upward displacement of the humerus head, improve the function and range of motion of the shoulder joint, and reduce complications in the treatment of IMRCT.

Objective:This study aimed to analyze the genomic characteristics of Varicella-Zoster Virus (VZV) strains circulating in Jilin province from 2010 to 2023.Methods:Vesicle fluid from 78 sporadic cases with VZV infection were collected in Jilin province from 2010 to 2023, after detecting by Real-time PCR, 26 specimens (CT<25) were detected by PCR. Open reading frame 22(ORF22), ORF38 and ORF62 were amplified and analyzed. Genotyping was confirmed by SNPs ORF22 (37902, 38019, 38055, 38081 and 38177) and ORF38 (69424). Vaccine strains were indentified from wild-type strains according to ORF38 (69349) and ORF62 (106262, 107252, and 108111). Sequences were analyzed by homologous comparison and phylogenetic analysis.Results:The comparison with Dumas sequence revealed that SNPs (37902, 38055, 38081 and 38177) in ORF22 and ORF38 (69424) have mutations similar to the pOka strain, which belong to clade 2. Compared to the Dumas and Baike strains, all 26 samples were wild-type strains. JL2016-4 strain changes from threonine to asparaginyl at position 38059, JL2021-4 strain changes from arginine to proline at position 37933, from aspartic acid to tyrosine at position 37935, and from aspartic acid at base 38031 to tyrosine. JL2023-1 strain changes from arginine to leucine at position 37933.Conclusions:VZV has been prevalent for 14 years in Jilin province. The main epidemic strains belong to the clade 2. We should strengthen the monitoring of VZV outbreaks and raise the coverage rate of VZV vaccination.