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.

Objective:To study the clinicopathological features of Sjogren′s syndrome (SS) with liver injury and to improve the understanding of this disease.Methods:Forty-nine patients with SS complicated with liver injury were collected from Beijing Ditan Hospital, Capital Medical University from October 2008 to January 2022. All patients underwent ultrasound-guided liver biopsy, and all specimens were stained with HE. The histopathologic characteristics were observed and the pathologic indexes were graded. Immunohistochemical stains for CK7, CK19, CD38, MUM1 and CD10 were performed by EnVision method; and special histochemical stains for reticulin, Masson′s trichrome, Rhodanine, Prussian blue, periodic acid Schiff (PAS) and D-PAS stains were conducted .Results:The age of patients ranged from 31 to 66 years, including 3 males and 46 females. SS combined with drug-induced liver injury was the most common (22 cases, 44.9%), followed by autoimmune liver disease (13 cases, 26.5%, including primary biliary cholangitis in eight cases, autoimmune hepatitis in 3 cases, and PBC-AIH overlap syndrome in 2 cases), non-alcoholic fatty liver disease (NAFLD, 9 cases, 18.4%) and other lesions (5 cases, 10.2%; including 3 cases of nonspecific liver inflammation, 1 case of liver amyloidosis, and 1 case of porto-sinusoidal vascular disease). Among them, 28 cases (57.1%) were associated with obvious interlobular bile duct injury, mainly in SS combined with PBC group and drug-induced liver injury group. Twenty-three cases (46.9%) were associated with hepatocyte steatosis of varying degrees. In SS with autoimmune liver disease group, ISHAK score, degree of fibrosis bile duct injury, bile duct remodeling, lymphocyte infiltration of portal area, and plasma cell infiltration, MUM1 and CD38 expression; serum ALP and GGT, IgM; elevated globulin; positive AMA, proportion of AMA-M2 positive and IgM positive were all significantly higher than those in other groups(all P<0.05). Serum ALT, direct bilirubin and SSA positive ratio in SS combined with drug liver group were significantly higher than those in other groups(all P<0.05). The serum total cholesterol level in SS combined with PBC group ( P=0.006) and NALFD group ( P=0.011) were significantly higher than those in other groups ( P<0.05). Conclusions:The pathologic manifestations of SS patients with liver injury are varied. The inflammatory lesions of SS patients with autoimmune liver disease are the most serious, and the inflammatory lesions of SS patients with non-alcoholic fatty liver disease and non-specific inflammation are mild. Comprehensive analysis of liver histopathologic changes and laboratory findings is helpful for the diagnosis of SS complicated with different types of liver injury.

Objective:To investigate the clinicopathological characteristics of rashes in monkeypox patients through a series of skin biopsies, and examine their pathological features and the most effective tests.Methods:Patients with monkeypox virus infection admitted to Beijing Ditan Hospital from June to August 2023 were identified. Among them, 24 patients underwent skin biopsies for clinical pathological study that were included in this study. Clinical information, rash pictures, and nucleic acid test results were analyzed using histopathology, immunohistochemistry, RNAscope ? hybridization and electron microscopy. Results:All 24 patients were male, including 14 patients with concurrent human immunodeficiency virus infection. Their average age was (32.3±5.4) years. The nucleic acid test confirmed monkeypox virus infection. The clinical feature of monkeypox rashes was solitary rather than clustered distribution, with rashes occurring in similar phase, distinguishing it from herpesvirus. The rashes in these patients were mostly scattered, with an average of (13.0±11.8) rashes, and most commonly present in the perineum, face, limbs, and trunk. The three main pathological features of these rashes were ballooning degeneration of the epidermal spinous cell layer, the characteristic intra-cytoplasmic Guarnieri′s bodies and significant infiltration of inflammatory cells in whole dermal layer. Immunohistochemistry, RNAscope ? hybridization, and electron microscopy can all effectively detect the monkeypox virus. Electron microscopy showed viral replication in various types of skin cells. Conclusions:The study describes the pathological features of monkeypox virus rashes. Pathological examination of skin biopsy samples is helpful to diagnose these rashes. The study suggests that the monkeypox virus has a unique epitheliotropic affinity and can infect various types of cells in the skin.

Objective:To investigate the clinical features of amoebic enteritis with acquired immunodeficiency syndrome (AIDS) patients.Methods:The clinical data of patients diagnosed of amoebic enteritis in Beijing Ditan Hospital, Capital Medical University from April 2011 to October 2019 were collected. They were divided into amoebic enteritis group and amoebic enteritis with AIDS group. The laboratory indexes, pathological examination and colonoscopic appearance of the two groups were analyzed retrospectively. The clinical characteristics of amoeba enteritis with AIDS patient were summarized. Pearson chi-square test, continuous calibration chi-square test, Fisher′s exact test, independent sample t test and Mann-Whitney U test were used for statistical analysis. Results:A total of 53 patients with amoebic enteritis were included, including 31 cases in amoebic enteritis group and 22 cases in amoebic enteritis with AIDS group. The detection rate of amoebic trophozoite in cases feces in amoebic enteritis with AIDS group was lower than that in amebic enteritis group (68.2%(15/22) vs 96.8%(30/31)) with statistical significance ( χ2=6.13, P=0.013). The detection rate of amoebic trophozoite by colonoscopy in amoebic enteritis with AIDS was higher than that in amebic enteritis group (7/15 vs 1/16) with statistical significance (Fisher′s exact test, P=0.015). Amoebic enteritis with AIDS cases had lower levels of red blood cell count ((3.48±0.80)×10 12/L vs (4.11±0.81)×10 12/L), hemoglobin ((102.40±25.74) g/L vs (121.52±22.73) g/L), albumin ((29.07±5.94) g/L vs (35.48±6.92) g/L), CD4 + T-lymphocyte counts (76.00 (26.25, 228.50)/μL vs 514.50 (444.00, 752.25)/μL) than patients with amoebic enteritis, which were all statistically significant ( t=2.80, 2.86, 3.52 and Z=-5.27, respectively, all P<0.050). And amoebic enteritis with AIDS cases had higher level of alanine aminotransferase (ALT) (21.00 (12.85, 41.33) U/L vs 13.40 (9.40, 22.40) U/L, Z=-2.32, P=0.020). The results of colonoscopy showed that amoebic enteritis with AIDS cases had higher rate of intestinal mucosa ulcer than amoebic enteritis cases ((11/15 vs 5/16) Fisher′s exact test, P=0.032). Conclusions:Amoebic enteritis with AIDS cases have lower levels of red blood cells, hemoglobin, albumin and CD4 + T-lymphocyte counts and higher levels of ALT. Amoebic enteritis with AIDS cases have higher rate of intestinal mucosa ulcer detected by colonoscopy. Colonoscopy combined with biopsy play an important role in the diagnosis of amoebic enteritis with AIDS patients.

Objective:To explore rational surgical treatment for childhood nail matrix nevi.Methods:A retrospective analysis was conducted on clinical data from 35 children with pathologically confirmed nail matrix nevi, who received surgical treatment in Children′s Hospital of Chongqing Medical University from September 2015 to March 2019. Different surgical approaches were adopted according to the site and width of lesions. For lesions with a width of ≤ 3 mm, the nail bed and nail matrix lesions were directly excised with 1-to-2-mm margins and sutured in 11 cases. For lesions with a width of > 3 mm, one of the following 3 surgical procedures was selected by the children′s parents: (1) shaving of nail bed and nail matrix lesions under a microscope at ×8 magnification (8 cases) ; (2) excision of lesions followed by full-thickness skin grafting on the periosteum of the phalanx (8 cases) ; (3) excision of lesions of the second to fifth fingers followed by transfer of skin flaps from the thenar muscle area and full-thickness skin grafting (5 cases) , or excision of lesions of the thumb followed by abdominal-wall flap transfer (3 cases) . The patients were followed up for 12 months, and clinical efficacy was evaluated.Results:During the follow-up, no recurrence occurred in the 11 cases receiving direct excision and suture, with good appearances and longitudinal linear scars on the nail. Among the 8 cases receiving shaving therapy under a microscope, 4 experienced relapse during the follow-up of 6 - 12 months, and the nail/toenail plates were rough and poor in lustrousness in the other 4 without recurrence. No recurrence was observed in the 8 cases receiving excision of the lesions and full-thickness skin grafting, of whom 1 experienced skin graft necrosis, and skin grafts survived with obvious pigmentation in the other 7 cases. Among cases receiving excision of the lesions combined with transfer of skin flaps from the thenar muscle area or abdominal-wall flap transfer, no recurrence was observed, and all transferred flaps survived; good appearances, nearly normal color and gloss of nails were obtained in the cases after transfer of skin flaps from the thenar muscle area, while the color and gloss of postoperative nails were markedly different from those of normal nails in the cases receiving abdominal-wall flap transfer.Conclusion:For nail matrix nevi with a width of ≤ 3 mm, direct excision and suture with 1-to-2-mm margins are recommended; for those with a width of > 3 mm, excision of lesions combined with full-thickness skin grafting, transfer of skin flaps from the thenar muscle area or abdominal-wall flap transfer is recommended; the shaving procedure under a microscope should be used with caution.

Objective:To investigate the long-term survival and safety in patients with muscle-invasive bladder cancer (MIBC) who experienced a noninvasive down-staging (≤pT 1)after transurethral resection of bladder tumor (TURBT) plus systemic chemotherapy and received bladder-sparing treatment. Methods:The records of patients with MIBC who underwent maximal TURBT plus systemic chemotherapy-guided bladder-sparing treatment were reviewed retrospectively from Dec 2013 to Dec 2020. Eventually, 22 patients who achieved noninvasive down-staging underwent conservative management. The total patient cohort contained 10 males and 12 females. A majority of patients had single lesion and stage T2 disease. The median age of the patients was 66 years and the median tumor size was 3.0 cm. All patients underwent maximal TURBT to resect all visible diseases and followed by 3-4 cycles platinum-based systemic chemotherapy. After achieving noninvasive down-staging, 14 patients received concurrent chemoradiotherapy, and the other 8 patients underwent surveillance. Overactive bladder symptom score (OABSS) was used to assess the bladder function after treatment.Results:Twelve patients achieved pT 0 and 10 patients were down-staged to cT a-T 1. At a median follow-up of 36.7 months, 90.9%(20/22) patients retained their bladder function successfully. Among the 14 patients who received concurrent chemoradiotherapy, 4 had grade 3 or 4 adverse events. Among the 8 patients who underwent surveillance, 3 had grade 3 or 4 adverse events after systemic chemotherapy.Nine patients experienced tumor recurrence in the bladder, and 2 patients died of bladder cancer. Seven (31.8%) patients experienced Ⅲ/Ⅳ grade complications. The 5-year recurrence-free survival (RFS) and overall survival (OS) in patients achieved pT0 were 66.7% and 100.0%, respectively. The 5-year RFS and OS in patients achieved cTa-T1 were 40% and 72%, respectively. The OABSS score of 20 patients who retained their bladder successfully was (1.00±1.03). Conclusions:MIBC patients who achieved noninvasive down-staging might be candidates for the bladder-sparing treatment with maximum TURBT followed by systemic chemotherapy.The patients who achieved pT 0 might have better prognosis with functional bladder.

Purpose: Reduced quality of life after cystectomy has made bladder preservation a popular research topic for muscle-invasive bladder cancer (MIBC). Previous research has indicated significant tumor downstaging after neoadjuvant chemotherapy (NAC). However, maximal transurethral resection of bladder tumor (TURBT) was performed before NAC to define the pathology, impacting the real evaluation of NAC. This research aimed to assess real NAC efficacy without interference from TURBT and apply combined modality therapies guided by NAC efficacy. Materials and Methods: Patients with cT2-4aN0M0 MIBC were confirmed by cystoscopic biopsy and imaging. NAC efficacy was assessed by imaging, urine cytology, and cystoscopy with multidisciplinary team discussion. Definite responders (≤ T1) underwent TURBT plus concurrent chemoradiotherapy. Incomplete responders underwent radical cystectomy or partial cystectomy if feasible. The primary endpoint was the bladder preservation rate. Results: Fifty-nine patients were enrolled, and the median age was 63 years. Patients with cT3-4 accounted for 75%. The median number of NAC cycles was three. Definite responders were 52.5%. The complete response (CR) was 10.2%, and 59.3% of patients received bladder-sparing treatments. With a median follow-up of 44.6 months, the 3-year overall survival (OS) was 72.8%. Three-year OS and relapse-free survival were 88.4% and 60.0% in the bladder-sparing group but only 74.3% and 37.5% in the cystectomy group. The evaluations of preserved bladder function were satisfactory. Conclusion After stratifying MIBC patients by NAC efficacy, definite responders achieved a satisfactory bladder-sparing rate, prognosis, and bladder function. The CR rate reflected the real NAC efficacy for MIBC. This therapy is worth verifying through multicenter research.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.

Objective:To preliminarily evaluate the effect of Fam114A1 on the biological function of melanocytes.Methods:A375 human melanoma cells was used to construct stably Fam114A1-overexpressing or -inhibited cell line by lentiviral transfection, namely overexpression group and expression inhibition group respectively, and A375 cells transfected with an empty lentivirus served as control group. Real-time fluorescence-based quantitative PCR was performed to evaluate effect of Fam114A1 on the mRNA expression of melanin synthesis-related genes tyrosinase (TYR) , tyrosinase-related protein 1 (TYRP1) , premelanosome protein (PMEL) , microphthalmia-associated transcription factor (MITF) and dopachrome isomerase (DCT) , Western blot analysis was conducted to determine the protein expression of TYR and MITF, methyl thiazol tetrazolium (MTT) assay, Transwell migration and adhesion assays were conducted to assess the effect of Fam114A1 on cellular proliferative activity, migratory and adhesive ability of A375 cells respectively. Statistical analysis was carried out by using one-way analysis of variance and Dunnett- t test. Results:Fluorescence microscopy showed that lentivirus-based transfection efficiency was about 90% in the 3 groups. Compared with the control group (0.850 ± 0.120) , the protein expression of Fam114A1 significantly increased in the overexpression group (1.507 ± 0.170, t = 5.888, P = 0.001) , but significantly decreased in the expression inhibition group (0.397 ± 0.120, t = 4.065, P = 0.007) , suggesting that the stably Fam114A1-overexpressing or -inhibited A375 cell line was successfully constructed. Real-time fluorescence-based quantitative PCR and Western blot analysis showed that the mRNA and protein expression of TYR and MITF were significantly lower in the expression inhibition group than in the control group (all P < 0.01) , but did not differ between the overexpression group and control group (all P > 0.05) . Compared with the control group, the expression inhibition group showed significantly increased cellular proliferative activity and adhesive ability ( P = 0.009, 0.001, respectively) , but significantly decreased migratory ability ( P = 0.005) , while the overexpression group only showed significantly increased migratory ability ( P = 0.021) . Conclusions:Fam114A1 can affect the proliferative activity, migratory and adhesive abilities of A375 cells, and the expression of melanin synthesis-related proteins TYR and MITF in A375 cells. Fam114A1 may be a functional protein involved in regulating the biological activity of melanocytes.

Objective To investigate the levels of 5-hydroxymethylcytosine (5-hmC) and teneleven-translocation proteins (TET1/2/3) in diagnosis and prognosis prediction of hepatocellular carcinoma (HCC).Methods The expression of 5-hmC in 130 cases of HCC tissues were detected by immunohistochemical staining.Kaplan-Meier test was used for survival analysis.TET family plays critical role in the conversion of 5-methylcytosine (5-mC) to 5-hmC.The TET levels were detected by using immunohistochemical staining and RT-PCR,the correlation between 5-hmC and TET was analyzed.Results The level of 5-hmC decreased in HCC tissues,as compared with non-tumor tissues,the expression of TET1 was downregulated in HCC.There was significant difference in the expression between low and high grades of HCC tissues (x2 =10.611,P =0.001).Kaplan-Meier survival analysis showed that there was significant difference between the 5-hmC expression level and the survival rate of HCC patients (x2 =4.412,P =0.036).Conclusions In HCC tissues the expression of 5-hmC was specifically downregulated.Low 5-hmC level is significantly correlated with poor differentiation of the tumor and worse overall survival.Decreased expression of TET1 is likely one of the mechanisms underlying 5-hmC loss in HCC.