ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

ObjectiveMitochondria are not only the central organelles responsible for cellular energy metabolism but also play essential roles in regulating cell cycle progression and cytoskeletal dynamics. In recent years, accumulating evidence has demonstrated that mitochondrial homeostasis is closely associated with mitotic progression and cytokinesis. Schizosaccharomyces pombe serves as a classical and well-established model organism. Because its cell cycle regulatory mechanisms are highly conserved throughout evolution, its genetic background is clearly defined, and experimental manipulation is efficient and convenient, it has been extensively applied in studies of cell growth, division, and reproductive mechanisms. The SPBC1604.04 gene encodes a previously uncharacterized mitochondrial carrier protein in Schizosaccharomyces pombe. This gene is located on chromosome II and spans 1 018 base pairs in length. It encodes a protein consisting of 238 amino acids with a predicted molecular mass of approximately 31.03 ku. Bioinformatic analysis predicts that this protein is responsible for the transport of thiamine pyrophosphate (TPP) into mitochondria. However, the effects of SPBC1604.04 gene deletion on mitotic cell dynamics under different temperature conditions have not been fully elucidated. MethodsThe SPBC1604.04 deletion strain of Schizosaccharomyces pombe was used as the experimental model. Fluorescent protein markers were constructed in the deletion background to label mitochondria, microtubules, actin, myosin, the nuclear envelope, and chromosomes. Live-cell imaging was performed using a TCS-SP8 laser scanning confocal microscope under normal temperature conditions (25℃) and heat stress conditions (37℃). Time-lapse microscopy was applied to dynamically monitor mitochondrial morphology and distribution, spindle assembly and elongation, chromosome segregation, as well as the formation and constriction of the actomyosin ring during cytokinesis. ImageJ software was used for quantitative measurements, including microtubule length during mitosis, spindle length at different mitotic stages, mitochondrial fluorescence intensity as an indicator of mitochondrial content, actomyosin ring length, nuclear envelope area, and chromosome segregation timing. Statistical analyses were conducted to compare phenotypic differences between the wild-type and SPBC1604.04 deletion strains at both temperature conditions. Through these analyses, we systematically investigated the impact of SPBC1604.04 deletion on mitotic cell dynamics in fission yeast under both normal physiological conditions and temperature stress. ResultsAt 25℃, compared with wild-type cells, the SPBC1604.04Δ strain exhibited a pronounced tendency toward mitochondrial fragmentation, accompanied by abnormal mitochondrial content and a significant reduction in mitochondrial fluorescence intensity. These observations suggest impaired mitochondrial homeostasis under normal growth conditions. In addition, the constriction time of actomyosin ring during cytokinesis was markedly prolonged, indicating that deletion of SPBC1604.04 affects the dynamics of the contractile machinery. However, no obvious defects were observed in spindle assembly, spindle elongation, or chromosome segregation. Under heat stress at 37℃, mitochondrial morphology in the SPBC1604.04Δ strain showed a tendency to recover toward a continuous tubular network structure. Mitochondrial content was restored, fluorescence intensity increased, and the constriction time of the actomyosin ring returned to levels comparable to those of wild-type cells. These results indicate that the mitotic defects observed at normal temperature are partially or fully alleviated under heat stress conditions. ConclusionThis study demonstrates that deletion of the SPBC1604.04 gene leads to abnormal mitochondrial content in Schizosaccharomyces pombe. The mitochondrial carrier protein SPBC1604.04 participates in regulating actomyosin ring constriction during mitosis but does not appear to be directly involved in the regulation of spindle dynamics or chromosome segregation. Our findings provide key experimental evidence for understanding the functional link between the SPBC1604.04 gene, mitochondrial homeostasis, and mitotic regulation.

This comprehensive review synthesizes the latest advancements in understanding inflammatory disorders affecting cerebral small vessels, a distinct yet understudied category within cerebral small vessel diseases (SVD). Unlike classical SVD, these inflammatory conditions exhibit unique clinical presentations, imaging patterns, and pathophysiological mechanisms, posing significant diagnostic and therapeutic challenges. Highlighting their heterogeneity, this review spans primary angiitis of the central nervous system, cerebral amyloid angiopathy-related inflammation, systemic vasculitis, secondary vasculitis, and vasculitis in autoinflammatory diseases. Key discussions focus on emerging insights into immune-mediated processes, neuroimaging characteristics, and histopathological distinctions. Furthermore, this review underscores the importance of standardized diagnostic frameworks, individualized immunomodulation approaches, and novel targeted therapies to address unmet clinical demands.
Humans ; Cerebral Small Vessel Diseases/pathology* ; Inflammation/pathology* ; Cerebral Amyloid Angiopathy/pathology* ; Vasculitis, Central Nervous System/pathology* ; Vasculitis/pathology*

The rapid screening of bioactive constituents within traditional Chinese medicine (TCM) presents a significant challenge to researchers. Prevailing strategies for the screening of active components in TCM often overlook trace components owing to their concealment by more abundant constituents. To address this limitation, a fishing strategy based on offline two-dimensional liquid chromatography (2D-LC) combined with surface plasmon resonance (SPR) was utilized to screen bioactive trace components targeting peroxiredoxin 3 (PRDX3), using Uncaria alkaloids (UAs) as a case study. Initially, an orthogonal preparative offline 2D-LC system combining a positively charged C₁₈ column and a conventional C₁₈ column under disparate mobile phase conditions was constructed. To fully reveal the trace alkaloids, 13 2D fractions of UAs were prepared, and their components were characterized using mass spectrometry (MS). Subsequently, employing PRDX3 as the targeting protein, a SPR-based screening approach was established and rigorously validated with geissoschizine methyl ether (GSM) serving as a positive control for binding. Employing this refined strategy, 29 candidate binding alkaloids were fished from the 13 2D fractions. Notably, combining offline 2D-LC with SPR increased the yield of candidate binding components from 10 to 29 when compared to SPR-based screening alone. Subsequent binding affinity assays confirmed that PRDX3 was a direct binding target for the 12 fished alkaloids, with isovallesiachotamine (IV), corynoxeine N-oxide (CO-N), and cadambine (CAD) demonstrating the highest affinity for PRDX3. Their interactions were further validated through molecular docking analysis. Subsequent intracellular H₂O₂ measurement assays and transfection experiments confirmed that these three trace alkaloids enhanced PRDX3-mediated H₂O₂ clearance. In conclusion, this study introduced an innovative strategy for the identification of active trace components in TCM. This approach holds promise for accelerating research on medicinal components within this field.

Objective:To investigate the ability to diagnose, treat and manage kidney disease in Shanghai community health service centers.Methods:This was a cross-sectional survey. An online questionnaire survey was conducted in November 2023 among 248 Shanghai community health service centers and 2 140 general practitioners in Shanghai. The main topics of the institutional research were the kidney disease-related inspection items that medical institutions could carry out, the kidney disease diagnosis and treatment drugs, the kidney disease grass-roots management training, the opening of kidney disease clinics and the establishment of kidney disease standard diagnosis and treatment records. The main topics of the survey of general practitioners were general information, standardized diagnosis and management measures of kidney disease, knowledge based on the diagnosis and treatment guidelines of chronic kidney disease, and difficulties in standardized management of kidney disease.Results:Among the laboratory examination items in Shanghai community health service centers, the rates of routine urine (99.60%, 247 centers), renal function (95.16%, 236 centers) and urinary microalbumin (89.11%, 229 centers) were high. Among the imaging examinations, B-ultrasound of urinary system had the highest rate (92.34%, 229 centers). The preparation rate of kidney disease drugs varied widely among the centers, and the preparation rate of Chinese drugs such as Jinshuibao, nephritis Kangfu tablet and Shenshuaining was more than 90%. Sixty-six (26.61%) community health service centers had established kidney disease clinics. The overall accuracy rate of community general practitioners was 63.81% (13 656/21 400), of which the accuracy rate for diagnosis and screening method, referral indication and emergency dialysis indication was more than 85%, but the accuracy rate for drug treatment and careful medication was low at 28.93% (1 238/4 280) and 33.22% (711/2 140), respectively. There was a willingness for Community general practitioners to provide all aspects of life guidance for patients with kidney disease, but for patients with end-stage renal disease replacement therapy, there was a preference for this to be provided by the appropriate specialist.Conclusions:The community health service centers in Shanghai has already had the basic conditions for the management of kidney disease in terms of basic examination and testing equipment, drugs, etc. The community general practitioners have a certain knowledge of kidney disease, and the drug treatment needs to be strengthened.

Objective"Red butterfly sore","yin-yang toxin"and"Bi disease"are different Chinese medicine diagnoses of systemic lupus erythematosus(SLE).It is not clear whether there are biological differences between these three types of Chinese medicine diagnoses.The aim of this study was to compare the different TCM diagnoses of SLE patients from the perspective of lymphocyte subsets and cytokines.Methods Patients diagnosed with SLE in our hospital from June 1,2021 to December 1,2023 were retrospectively collected,and the differences of T cell subsets,NK cells,B lymphocytes and Th1,Th2 and Th17 cytokines among different groups were compared by one-way ANOVA or nonparametric test.As well as differences in laboratory test indicators such as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),immunoglobulin,and complement,receiver operating characteristic curve(ROC curve)was used to analyze the value of these indexes in the differential diagnosis of different types of SLE.Results From June 1,2021 to December 1,2023,291 patients diagnosed with SLE in our hospital for the first time were collected,and 104 cases meeting the exclusion criteria of this study were included,including 31 cases of red butterfly sores,30 cases of yin-yang toxin and 43 cases of BI disease.The absolute number and percentage of CD8+T cells,interleukin-10(IL-10)content and tumor necrosis factor α(TNF-α)content were different among the three groups of SLE patients diagnosed by different Chinese medicine,and the absolute number of CD8+T cells in the red butterfly sore group was significantly higher than that in the yin-yang toxicities group(P=0.039)and the disease group(P=0.008).CD8+T cell percentage in red butterfly sore group was significantly higher than that in yin-yang toxin group(P=0.014)and disease group(P=0.004),IL-10 and TNF-α levels in red butterfly sore group were significantly lower than those in disease group(P=0.015,P=0.036),and ROC curve analysis showed that,the absolute number and percentage of CD8+T cells can effectively distinguish red butterfly sores from yin-yang toxins(AUC=0.65,AUC=0.61,P<0.05),and the absolute number and percentage of CD8+T cells,IL-10 and TNF-α can effectively distinguish red butterfly sores from diseases(AUC=0.68,AUC=0.66,P<0.01,AUC=0.67,AUC=0.64,P<0.05).Conclusion Immune lymphocyte subtypes,cytokines,especially the absolute number and percentage of CD8+T cells,IL-10 and TNF-α may play an important role in the identification of different TCM diagnosis of SLE.

Objective"Red butterfly sore","yin-yang toxin"and"Bi disease"are different Chinese medicine diagnoses of systemic lupus erythematosus(SLE).It is not clear whether there are biological differences between these three types of Chinese medicine diagnoses.The aim of this study was to compare the different TCM diagnoses of SLE patients from the perspective of lymphocyte subsets and cytokines.Methods Patients diagnosed with SLE in our hospital from June 1,2021 to December 1,2023 were retrospectively collected,and the differences of T cell subsets,NK cells,B lymphocytes and Th1,Th2 and Th17 cytokines among different groups were compared by one-way ANOVA or nonparametric test.As well as differences in laboratory test indicators such as erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),immunoglobulin,and complement,receiver operating characteristic curve(ROC curve)was used to analyze the value of these indexes in the differential diagnosis of different types of SLE.Results From June 1,2021 to December 1,2023,291 patients diagnosed with SLE in our hospital for the first time were collected,and 104 cases meeting the exclusion criteria of this study were included,including 31 cases of red butterfly sores,30 cases of yin-yang toxin and 43 cases of BI disease.The absolute number and percentage of CD8+T cells,interleukin-10(IL-10)content and tumor necrosis factor α(TNF-α)content were different among the three groups of SLE patients diagnosed by different Chinese medicine,and the absolute number of CD8+T cells in the red butterfly sore group was significantly higher than that in the yin-yang toxicities group(P=0.039)and the disease group(P=0.008).CD8+T cell percentage in red butterfly sore group was significantly higher than that in yin-yang toxin group(P=0.014)and disease group(P=0.004),IL-10 and TNF-α levels in red butterfly sore group were significantly lower than those in disease group(P=0.015,P=0.036),and ROC curve analysis showed that,the absolute number and percentage of CD8+T cells can effectively distinguish red butterfly sores from yin-yang toxins(AUC=0.65,AUC=0.61,P<0.05),and the absolute number and percentage of CD8+T cells,IL-10 and TNF-α can effectively distinguish red butterfly sores from diseases(AUC=0.68,AUC=0.66,P<0.01,AUC=0.67,AUC=0.64,P<0.05).Conclusion Immune lymphocyte subtypes,cytokines,especially the absolute number and percentage of CD8+T cells,IL-10 and TNF-α may play an important role in the identification of different TCM diagnosis of SLE.

Objective:To investigate the ability to diagnose, treat and manage kidney disease in Shanghai community health service centers.Methods:This was a cross-sectional survey. An online questionnaire survey was conducted in November 2023 among 248 Shanghai community health service centers and 2 140 general practitioners in Shanghai. The main topics of the institutional research were the kidney disease-related inspection items that medical institutions could carry out, the kidney disease diagnosis and treatment drugs, the kidney disease grass-roots management training, the opening of kidney disease clinics and the establishment of kidney disease standard diagnosis and treatment records. The main topics of the survey of general practitioners were general information, standardized diagnosis and management measures of kidney disease, knowledge based on the diagnosis and treatment guidelines of chronic kidney disease, and difficulties in standardized management of kidney disease.Results:Among the laboratory examination items in Shanghai community health service centers, the rates of routine urine (99.60%, 247 centers), renal function (95.16%, 236 centers) and urinary microalbumin (89.11%, 229 centers) were high. Among the imaging examinations, B-ultrasound of urinary system had the highest rate (92.34%, 229 centers). The preparation rate of kidney disease drugs varied widely among the centers, and the preparation rate of Chinese drugs such as Jinshuibao, nephritis Kangfu tablet and Shenshuaining was more than 90%. Sixty-six (26.61%) community health service centers had established kidney disease clinics. The overall accuracy rate of community general practitioners was 63.81% (13 656/21 400), of which the accuracy rate for diagnosis and screening method, referral indication and emergency dialysis indication was more than 85%, but the accuracy rate for drug treatment and careful medication was low at 28.93% (1 238/4 280) and 33.22% (711/2 140), respectively. There was a willingness for Community general practitioners to provide all aspects of life guidance for patients with kidney disease, but for patients with end-stage renal disease replacement therapy, there was a preference for this to be provided by the appropriate specialist.Conclusions:The community health service centers in Shanghai has already had the basic conditions for the management of kidney disease in terms of basic examination and testing equipment, drugs, etc. The community general practitioners have a certain knowledge of kidney disease, and the drug treatment needs to be strengthened.

[Objective]To investigate the relationship between the non-fasting triglyceride and glucose(TyG)index and hyperglycemia in pregnancy during the third trimester in high altitudes.[Methods]This study selected clinical and laboratory data of 774 Tibetan singleton pregnant women who delivered at Chaya People's Hospital of Qamdo city in Xizang autonomous region,from January 2023 to April 2025.The non-fasting TyG index was calculated from non-fasting triglyceride(TG)and random plasma glucose(PG).Based on the tertiles of the non-fasting TyG index values,the individuals were split into three groups(corresponding to non-fasting TyG index of 8.89 and 9.21,respectively).The baseline clinical characteristics,lipid levels and the occurrence of developing hyperglycemia in pregnancy were compared among the three groups.Statistical analyses were performed using ANOVA,Kruskal-Wallis H test,Chi-square test,or Fisher exact test and the relationship between the non-fasting TyG index and hyperglycemia in pregnancy were examined using multivariate logistic regression models and curve fitting.[Results]A total of 774 Tibetan singleton pregnant women were included,with a average age of 27.3±6.1 years,a pre-delivery body mass index(Pre-BMI)of(25.2±2.3)kg/m2,a proportion of 26.7%(207/774)primigravid women,the mean non-fasting TyG index was 9.1±0.4.Thirty pregnant women were diagnosed with hyperglycemia in pregnancy,with a detection rate of 3.9%(30/774).Statistically significant differences in serum total cholesterol(TC),TG,low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)levels were identified when comparing different non-fasting TyG groups(all P values<0.05).Subsequent trend test analysis indicated that the levels of TC,TG,LDL-C,and PG gradually increased with elevated the non-fasting TyG index(Ftrend TC=95.61,P<0.001;Ftrend TG=1 051.91,P<0.001;Ftrend LDL-C=97.20,P<0.001;Ftrend TG=195.20;P<0.001).After adjustment for maternal age,pre-delivery BMI,altitude,TC,LDL-C,and HDL-C,multivariate Logistic regression models revealed independent positive associations between non-fasting TyG index and hyperglycemia in pregnancy(Model 1:OR=2.72,95%CI:1.13-6.53,P=0.026;Model 2:OR=2.56,95%CI:1.01-6.50,P=0.048;Model 3:OR=2.72,95%CI:1.06-6.97,P=0.037;Model 4:OR=4.02,95%CI:1.42-11.40,P=0.009)and the incident of hyperglycemia in pregnancy showed an increasing tendency as increasing with the non-fasting TyG index,however,this association did not statistical significance(P trend>0.05).Curve fitting by restricted cubic splines(RCS)were used to assess linearity between non-fasting TyG and hyperglycemia in pregnancy,and there was a linear dose-response relationship between non-fasting TyG and hyperglycemia in pregnancy(P for non-linear=0.515).[Conclusion]Non-fasting TyG index in the third trimester is a risk factor for hyperglycemia in pregnancy among the Tibetan singleton pregnant women at high altitudes and there was a possible linear dose-response relationship between the non-fasting TyG index and hyperglycemia in pregnancy.

A high-throughput three-dimensional (3D) hepatocyte culture model is constructed in this study. It is capable of replicating the 3D in vivo environment and offers the advantages of high throughput, enhanced reproducibility, low cost, and simplified operation, rendering a valuable tool for hepatotoxicity screening of traditional Chinese medicine (TCM). First, we constructed the 3D high throughput liver chip model using collagen hydrogel. The precision and its difference with traditional cell culture plates were assessed using acetaminophen, Tripterygium hypoglaucum, and Qili San as the references. The feasibility of this model was also investigated by comparing the hepatotoxicity among four batches of T. hypoglaucum and Qili San. The methodology verification shows that the 3D hepatocyte model is better than traditional two-dimensional (2D) cell culture model in precision and feasibility. Subsequently, we compared the hepatotoxicity of different samples over a period of three or seven days and found that the hepatotoxicity of TCM extracts increased over time. Finally, we compared the hepatotoxicity of T. hypoglaucum and its compound formula Kunxian capsule under equivalent concentration. The results showed that the compound Kunxian capsule could significantly reduce hepatotoxicity of T. hypoglaucum. Generally, we constructed a high-throughput, robust 3D liver-on-a-chip model with the potential of rapid assessing TCM-induced liver toxicity.