Vascular cognitive impairment (VCI), caused by cerebrovascular dysfunction, severely impacts the quality of life in the elderly population, yet effective therapeutic approaches remain limited. Mitophagy, a selective mitochondrial quality-control mechanism, has emerged as a critical focus in neurological disease research. Accumulating evidence indicates that mitophagy modulates oxidative stress, neuroinflammation, and neuronal apoptosis. Key signaling pathways associated with mitophagy—including PINK1/Parkin, BNIP3/Nix, FUNDC1, PI3K/Akt/mTOR, and AMPK—have been identified as potential therapeutic targets for VCI. This review summarizes the mechanistic roles of mitophagy in VCI pathogenesis and explores emerging therapeutic strategies targeting these pathways, aiming to provide novel insights for clinical intervention and advance the development of effective treatments for VCI.

Vascular dementia(VD)is a neurodegenerative disease caused by brain injury.Research on the processes leading to its occurrence is lacking depth.In recent years,it has been proposed that regulatory cell death(RCD)mechanisms,including apoptosis,pyroptosis,autophagy,ferroptosis,and cuproptosis,are related to the pathological mechanisms of VD.Therefore,studies aiming to explain the links between the mechanisms of regulatory death and the pathology of VD would be beneficial to our understanding of VD.This article provides a review of the roles of five mechanisms of RCD in VD and summarizes the recent progress made in researching the treatment of VD with traditional Chinese medicine,providing a resource for the development of new traditional Chinese medicine drugs.

Objective:To explore the effect of the isolated organ laparoscopic simulation training teaching mode in laparoscopic partial nephrectomy training.Methods:A 39-hour in vitro organ laparoscopic simulation training for 12 urologists who had previously participated in laparoscopic basic technique training but had not independently completed laparoscopic partial nephrectomy in Peking Union Medical College Hospital. The training was conducted twice a week for 3 months from April to June 2022. Five modules, namely ultrasonic knife separation training, ultrasonic knife cutting training, vascularization training, blunt separation training, and partial nephrectomy and wound closure training, were used to provide targeted training for the decomposition of laparoscopic partial nephrectomy, and each training item was assessed and scored according to the scoring rules. At the same time, a questionnaire was used to find out the level of confidence of the 12 physicians in completing the operation and each step in the procedure, so as to assess the changes in the operational skills and psychological quality of the physicians before and after training using paired t-tests or Wilcoxon paired rank sum tests. Results:After the training, the assessment scores of operations in all surgeons were significantly improved. The training scores of ultrasonic knife separation training, ultrasonic knife cutting training, blood vessel nudity training, blunt separation training, and partial nephrectomy and traumatic suture improved from (8.5±0.3), (6.9±0.3), (4.2±0.4), (6.6±0.4), and (5.6±0.7) to (9.8±0.2), (9.6±0.3), (9.3±0.2), (9.4±0.3), and (9.8±0.2), respectively( P<0.05). The average operation time for the partial renal excision and traumatic suture training improved from (47.5±5.8) minutes to (21.6±5.1) minutes( t=18.72, P<0.001). At the same time, self-confidence in completing the operation was also significantly improved from 2(1, 3) before the training to 4(4, 4) after the training ( Z=-3.002, P =0.003). Conclusions:After laparoscopic simulation training with isolated organs, physicians with no previous experience in partial nephrectomy can become proficient in all steps of the procedure, complete the resection of the renal tumor and suturing of the wound within 30 minutes, and gain confidence in the operation of all steps of partial nephrectomy.

OBJECTIVE To investigate the anti-pulmonary fibrosis effect of linarin in vivo and in vitro， and investigate its mechanism preliminarily. METHODS C57BL/6J mice were randomly divided into normal group （carboxymethylcellulose sodium）， model group （carboxymethylcellulose sodium）， positive control group （pirfenidone， 200 mg/kg）， linarin low-dose and high-dose groups （12.5， 25 mg/kg）， with 8 mice in each group. Except for normal group， pulmonary fibrosis model was induced in other groups. After modeling， they were given relevant medicine intragastrically， once a day， for consecutive 14 d. The general situation of mice was observed， and their lung indexes were measured； the levels of tumor necrosis factor-α （TNF-α） and transforming growth factor-β1（ TGF-β1） in serum and interleukin-6 （IL-6） in lung tissue were determined. Hematoxylin-eosin （HE） staining and Masson staining were used to observe the histopathological morphology of lung. The pulmonary fibrosis was scored according to Ashcroft score standard. The expressions of α-smooth muscle actin （α-SMA） and （type Ⅰ collagen， Collagen Ⅰ）， phosphorylated extracellular signal-regulated kinase （p-ERK1/2） and TGF-β1 in lung tissues were detected. HFL1 cells were stimulated by TGF- β1 to form pulmonary fibrosis model in vitro， which were divided into normal group， model group and linarin low-， medium- and high-concentration groups （3.7， 7.4， 14.8 mg/L）. After being cultured for 48 h， the protein expressions of α-SMA， Collagen Ⅰ and p-ERK1/2 in HFL1 cells were detected. RESULTS In vivo， compared with normal group， the lung index of model group and the levels of TNF- α， TGF- β1 and IL-6 were significantly increased （P＜0.01）. There were a large number of inflammatory infiltration and cellular fibrosis lesions in the alveoli， and a large number of collagen depositions. The scores of HE staining and Masson staining were significantly increased （P＜0.01）. The protein expressions of α-SMA， Collagen Ⅰ， p-ERK1/2 and TGF-β1 in lung tissue were up-regulated significantly （P＜0.01）. Compared with model group， above indexes of mice were improved significantly in linarin high-dose group （P＜0.05 or P＜0.01）， and most of indexes （except for lung index） were improved significantly in linarin low-dose group （P＜0.05 or P＜0.01）. In vitro， compared with blank group， the density of cells in the model group increased， and obvious proliferation and other changes occurred； protein expressions of α-SMA， Collagen Ⅰ and p-ERK1/2 were significantly up-regulated （P＜0.05 or P＜0.01）. Compared with model group， the cell density of each concentration group was decreased and the morphology gradually returned to normal； the expressions of above proteins in linarin high-concentration group and the protein expression of p-ERK1/2 in linarin medium-concentration group were down-regulated significantly（P＜0.05 or P＜0.01）. CONCLUSIONS Linarin may regulate ERK and inflammatory pathways to reduce the inflammatory response， thereby exerting anti-pulmonary fibrosis effect.

Objective: To investigate the specificity of endogenous metabolic profile in plasma of patients with occupational acute methyl acetate poisoning using non-targeted metabolomics. Methods: A total of six patients with occupational acute methyl acetate poisoning were selected as the poisoning group, while 10 healthy workers without occupational exposure history of chemical hazards in the same industry were selected as the control group using the judgment sampling method. Metabolites in patient plasma of the two groups were detected using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry, and non-targeted metabolomics analysis was performed. Principal component analysis and partial least squares discriminant analysis were used to identify differential metabolites and analyze their metabolic pathways. Results: There were significant differences in metabolite profiles in patient plasma between poisoning group and control group. A total of 195 differentially expressed metabolites were screened in plasma of patients in poisoning group, including 119 upregulated and 76 downregulated metabolites. Lipid substances (lipids and lipid-like molecules) accounted for the highest proportion (21.5%). The differential metabolites of poisoning group were related to folate biosynthesis, amino acid metabolism, pyrimidine metabolism, sphingolipid biosynthesis and other metabolic pathways in plasma compared with the control group (all P<0.05). Conclusion: Occupational acute methyl acetate poisoning affects metabolism of the body. The folic acid biosynthesis, amino acid and lipid metabolism and other pathways may be involved in the occurrence and development of poisoning.

{L-End}Objective To establish a method for the simultaneous determination of dimethyltin (DMT), trimethyltin (TMT), diethyltin (DET), and triethyltin (TET) in human whole blood using high performance liquid chromatography-inductively coupled plasma-mass spectrometry (ICP-MS). {L-End}Methods The 1.0 mL of blood was added with 4.0 mL 65% aqueous solution (containing 6% acetic acid), extracted and separated by C₄ column (150 mm×3 mm×3 μm) using a mobile phase of methanol and 4% acetic acid aqueous solution (containing 0.25 mmol/L tropolone) at a volume ratio of 35∶65, and detected by ICP-MS. {L-End}Results The linear range of DMT, TMT, DET, and TET was 30.60-550.80, 29.00-522.00, 46.10-829.80, and 34.05-612.90 μg/L, respectively. All correlation coefficients were 0.999. The detection limit of DMT, TMT, DET and TET was 21.40, 20.30, 32.27 and 23.80 μg/L, respectively. The recovery rate was 81.9%-104.9%. The within-run and between-run relative standard deviation was 1.6%-6.9% and 0.1%-10.0%, respectively. The samples can be stored at -20 ℃ and 4 ℃ for at least three days. {L-End}Conclusion This method can be used for trace analysis of DMT, TMT, DET, and TET in whole blood.

【Objective】 To analyze the clinical characteristics and prognostic differences between type Ⅰ and type Ⅱ papillary renal cell carcinoma (PRCC), and identify the prognosis-related independent predictors. 【Methods】 A total of 143 PRCC patients treated during Jan.2012 and Dec.2019 were involved, including 91 type Ⅰ patients and 52 type Ⅱ patients. The prognostic factors were analyzed with univariate and multivariate Cox regression analysis. The differences in cancer-specific survival (CSS) between the two groups were analyzed with Kaplan-Meier method and log-rank test. 【Results】 The patients’ age was 53.41±13.50 years. After a mean follow-up of 63.27±26.20 months, 14 patients died, and the overall CSS was 90.2%. The prognosis of type Ⅰ patients was better than type Ⅱ patients (94.5% vs. 82.7%, P=0.020). Cox regression suggested that PRCC subtype and stage were significantly associated with prognosis. There was no difference in prognosis between type Ⅰ and type Ⅱ patients in T1/T2 subgroup (P>0.05). However, in T3/T4 subgroup, type Ⅰ patients had a significant better prognosis than type Ⅱ patients (P=0.023), while the above trends were not observed in G1/G2 and G3/G4 subgroups (P>0.05). 【Conclusion】 PRCC subtype and stage are independent prognostic predictors. The impact of PRCC subtype on prognosis is mainly manifested in the subgroup of patients with T3 or higher stage.

Objective:To analyze the distribution of TCM syndrome elements and syndromes in patients with hypertension with insomnia (HWI) in the real world.Methods:A cross-sectional study and retrospectively enrolled. The positive symptoms and TCM syndrome type entries of 359 patients with HWI who were collected from Henan Integrated Medicine Hospital,Henan Provincial People's Hospital,the First Affiliated Hospital of Henan University of Chinese Medicine from December 2020 to August 2022 were retrospectively studied. Based on factor analysis dimension reduction and systematic cluster analysis, the TCM syndrome elements and potential syndrome types of patients were summarized. The Latern 5.0 software was used to establish a latent structure model and comprehensive clustering based on the mountain climbing method (LTM-EAST) algorithm, and analyze and judge the common syndrome types, providing a basis for proposing the clinical common syndrome types of this disease.Results:Factor analysis extracted 14 common factors, and the cumulative contribution rate was 63.254%. Among the 36 symptom variables with frequency ≥ 70, more than half of the patients with hypertension and insomnia were upset, irritable, less sleepy, dreamy, dizzy, palpitations, stuffy chest, dry mouth, easy to wake up, and tired. The tongue color was mainly light red tongue and red tongue. The tongue is mainly thin and greasy. The first three pulse conditions are string pulse, number pulse and slippery pulse. The disease location and syndrome elements of hypertension with insomnia were mainly liver (52.09%), heart (33.43%), spleen (26.46%) and kidney (23.68%); The disease syndrome elements are mainly phlegm dampness (34.54%), yin deficiency (29.25%), heat (fire) (25.35%), and qi stagnation (25.07%). Ten syndrome types are obtained by frequency statistics, nine syndrome types are obtained by factor clustering, and seven syndrome types are inferred by implicit structure clustering. Among the syndrome types inferred by the above three methods, there are seven syndrome types that recur at least twice, which can be identified as the common syndrome type of hypertension with insomnia.Conclusions:The common clinical symptoms of HWI are upset and irritable, less sleep, more dreams, dizziness, palpitations, stuffy chest, dry mouth, easy to wake up, mental fatigue and body tiredness. The disease location and syndrome elements are mainly in liver, heart, spleen and kidney. The disease mainly involves phlegm dampness, yin deficiency, heat and qi stagnation. The common clinical syndrome types are liver depression transforming fire type, yin deficiency and yang hyperactivity type, phlegm dampness intrinsic type, yin deficiency and internal heat type, heart and gallbladder qi deficiency type, heart and spleen deficiency type, and heart kidney disjunction type.

Objective To establish a method for the determination of thallium and its soluble compounds in workplace air using microporous filter membrane sampling and inductively coupled plasma mass spectrometry (ICP-MS). Methods Thallium and its soluble compounds in workplace air were collected using microporous filter membranes, digested with nitric acid, quantified using lutetium internal standard method, and detected by ICP-MS. Results The linear range of thallium was 0.00 to 600.00 μg/L, with the correlation coefficient of 1.000. The detection limit was 0.08 μg/L, and the lower limit of quantification was 0.26 μg/L. The minimum detection concentration and minimum quantitation concentration of thallium of 75.00 L workplace air were 1.0×10^-5 and 3.0×10^-5 mg/m³, respectively. The minimum detection concentration and minimum quantitation concentration of thallium of 480.00 L workplace air was 2.0×10^-6 and 5.0×10^-6 mg/m³, respectively. The recovery rate of spiking was 100.82%-103.44%, and the relative standard deviation within- and between-batches was 1.50%-3.32% and 1.32%-3.11%, respectively. The sample could be stored at room temperature for at least 14 days. Conclusion This method can be used for the detection of thallium and its soluble compounds in workplace air.

Objective:To compare the numerical rating scales (NRS) and Oswestry disability index (ODI) of denosumab in Chinese postmenopausal osteoporosis patients after 3 months, and analyze the early adverse reactions to provide reference for clinical diagnosis and treatment.Methods:Using a prospective study method, 260 patients with postmenopausal osteoporosis who were outpatients and inpatients in the Second Affiliated Hospital of Soochow University from September 2020 to October 2021 were selected, and general information, including age, height, weight, bone mineral density, history of fragility fractures, and use of anti-osteoporosis drugs. All subjects received denosumab 60 mg subcutaneously, and were given calcium and vitamin D at the same time. Pain was scored by NRS before treatment and 3 months after treatment, and functional improvement was assessed by ODI.Results:After 3 months of denosumab treatment in postmenopausal women with osteoporosis, among patients with different age groups, different degrees of osteoporosis, history of fragility fractures, and history of use of anti-osteoporosis drugs, NRS score and ODI score were lower than those before treatment, and the difference was statistically significant ( P<0.05). In addition, in patients with a history of fragility fractures (mainly vertebral fractures), the NRS scores and the ODI score decreased more significantly, and the difference was statistically significant ( P<0.05); the NRS score and ODI score decreased more significantly in patients with severe osteoporosis than in patients with osteoporosis, and the difference was statistically significant ( P<0.05); the BMD value of lumbar spine was negatively correlated with the reduction of NRS score before and after treatment ( P=0.042). In this study, 260 patients had musculoskeletal pain in 6 (2.3%), fatigue in 5 (1.9%), rash in 4 (1.5%), urinary tract infection in 2 (0.7%), and dizziness in 2 (0.7%), 2 case of fever (0.7%), 1 case of hypocalcemia (0.4%), a total of 22 cases of adverse reactions were reported, and the overall adverse reaction rate was 8.5%. Conclusion:Denosumab can improve pain symptoms and functional disability early in the clinical application of Chinese postmenopausal women with osteoporosis, and the incidence of adverse reactions is low. Especially for postmenopausal female osteoporosis patients with severe osteoporosis, low lumbar spine bone density, and a history of fragility fractures (mainly vertebral fractures), the application effect is more significant.