Objective: To assess the dynamic changes of microcirculation at acupoints in patients with primary dysmenorrhea and cold congelation and blood stasis syndrome using laser speckle blood flow imaging. Methods: Patients with primary dysmenorrhea and cold coagulation and blood stasis syndrome (primary dysmenorrhea group, n=53) and healthy female college students(control group, n=57) who met the inclusion and exclusion criteria from October 2020 to July 2022 were enrolled at Hebei University of Chinese Medicine. On the premenstrual and first day of menstruation, a laser speckle blood flow imaging system was used to measure the microcirculation blood flow perfusion on the surface of acupoints related to the conception, thoroughfare, and governor vessels, and stomach, spleen, and bladder meridians in the abdomen and lumbosacral regions. The dynamic changes in microcirculation were calculated based on the difference in average blood flow perfusion at each acupoint before and after menstruation. Receiver operating curve (ROC) analysis was used to analyze the diagnostic efficacy of dynamic changes in microcirculation on the surface of each acupoint. The microcirculation sensitization rate of acupoints was calculated. Results: Compared with the control group, the dynamic changes in microcirculation at the following acupoints in the primary dysmenorrhea group were increased (P<0.05): conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]); left thoroughfare vessel (left Huangshu[KI16], left Zhongzhu[KI15], left Siman[KI14], left Qixue[KI13], left Dahe[KI12], left Henggu[KI11]); left stomach meridian (left Tianshu[ST25], left Wailing[ST26], left Qichong[ST30]); left spleen meridian (left Daheng[SP15], left Fujie[SP14]); right thoroughfare vessel (right Huangshu[KI16], right Zhongzhu[KI15], right Siman[KI14], right Qixue[KI13], right Dahe[KI12], right Henggu[KI11]); right stomach meridian (right Wailing[ST26], right Daju[ST27], right Shuidao[ST28], right Guilai[ST29], right Qichong[ST30]); and right spleen meridian (right Fujie[SP14]). The area under the ROC curve of conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]), thoroughfare vessel (right Siman[KI14], left Huangshu[KI16], right Qixue[KI13], right Zhongzhu[KI15], right Dahe[KI12], left Zhongzhu[KI15], left Siman[KI14], right Huangshu[KI16], left Qixue[KI13], right Henggu[KI11], left Henggu[KI11], left Dahe[KI12]); stomach meridian (left Tianshu[ST25], right Guilai[ST29], left Wailing[ST26], right Shuidao[ST28], right Daju[ST27], right Wailing[ST26], right Qichong[ST30], left Qichong[ST30]), and spleen meridian (left Daheng[SP15], left Fujie[SP14], right Fujie[SP14]) was 0.610-0.682 (P<0.05). Compared with the control group, the sensitization rate of some acupoints in the primary dysmenorrhea group increased (P<0.05). Conclusion With the onset of menstruation, the blood flow perfusion of some acupoints in the abdomen (thoroughfare, and conception vessels, and stomach and spleen meridians) of patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome increased, and the status of acupoints changed from a resting state to an active state. These acupoints are sensitive in patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome and have a certain diagnostic efficacy, providing a basis for further analyzing the efficacy and mechanism of acupuncture and moxibustion to treat primary dysmenorrhea with cold blood coagulation and blood stasis syndrome.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

ObjectiveRepetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in enhancing neurocognitive performance in Alzheimer’s disease (AD), but the neurobiological mechanisms linking synaptic pathology, neural oscillatory dynamics, and brain network reorganization remain unclear. This investigation seeks to systematically evaluate the therapeutic potential of rTMS as a non-invasive neuromodulatory intervention through a multimodal framework integrating clinical assessments, molecular profiling, and neurophysiological monitoring. MethodsIn this prospective double-blind trial, 12 AD patients underwent a 14-day protocol of 20 Hz rTMS, with comprehensive multimodal assessments performed pre- and post-intervention. Cognitive functioning was quantified using the mini-mental state examination (MMSE) and Montreal cognitive assessment (MOCA), while daily living capacities and neuropsychiatric profiles were respectively evaluated through the activities of daily living (ADL) scale and combined neuropsychiatric inventory (NPI)-Hamilton depression rating scale (HAMD). Peripheral blood biomarkers, specifically Aβ1-40 and phosphorylated tau (p-tau181), were analyzed to investigate the effects of rTMS on molecular metabolism. Spectral power analysis was employed to investigate rTMS-induced modulations of neural rhythms in AD patients, while brain network analyses incorporating topological properties were conducted to examine stimulus-driven network reorganization. Furthermore, systematic assessment of correlations between cognitive scale scores, blood biomarkers, and network characteristics was performed to elucidate cross-modal therapeutic associations. ResultsClinically, MMSE and MOCA scores improved significantly (P<0.05). Biomarker showed that Aβ1-40 level increased (P<0.05), contrasting with p-tau181 reduction. Moreover, the levels of Aβ1-40 were positively correlated with MMSE and MOCA scores. Post-intervention analyses revealed significant modulations in oscillatory power, characterized by pronounced reductions in delta (P<0.05) and theta bands (P<0.05), while concurrent enhancements were observed in alpha, beta, and gamma band activities (all P<0.05). Network analysis revealed frequency-specific reorganization: clustering coefficients were significantly decreased in delta, theta, and alpha bands (P<0.05), while global efficiency improvement was exclusively detected in the delta band (P<0.05). The alpha band demonstrated concurrent increases in average nodal degree (P<0.05) and characteristic path length reduction (P<0.05). Further research findings indicate that the changes in the clinical scale HAMD scores before and after rTMS stimulation are negatively correlated with the changes in the blood biomarkers Aβ1-40 and p-tau181. Additionally, the changes in the clinical scales MMSE and MoCA scores were negatively correlated with the changes in the node degree of the alpha frequency band and negatively correlated with the clustering coefficient of the delta frequency band. However, the changes in MMSE scores are positively correlated with the changes in global efficiency of both the delta and alpha frequency bands. Conclusion20 Hz rTMS targeting dorsolateral prefrontal cortex (DLPFC) significantly improves cognitive function and enhances the metabolic clearance of β-amyloid and tau proteins in AD patients. This neurotherapeutic effect is mechanistically associated with rTMS-mediated frequency-selective neuromodulation, which enhances the connectivity of oscillatory networks through improved neuronal synchronization and optimized topological organization of functional brain networks. These findings not only support the efficacy of rTMS as an adjunctive therapy for AD but also underscore the importance of employing multiple assessment methods—including clinical scales, blood biomarkers, and EEG——in understanding and monitoring the progression of AD. This research provides a significant theoretical foundation and empirical evidence for further exploration of rTMS applications in AD treatment.

BackgroundPrenatal depression has an important impact on maternal health and pregnancy outcomes. Previous studies have shown that maternal prenatal depression is associated with social support， and social support is related to fear of childbirth. However， there is limited research on the relationship among maternal prenatal depression， social support and fear of childbirth， and no studies have specifically explored the influence of social support and fear of childbirth on prenatal depression in primiparous women. ObjectiveTo investigate the current status of prenatal depression among primiparous women， and to analyze the correlation between social support and fear of childbirth， and to further explore the influence of social support and fear of childbirth on prenatal depression in this population， so as to provide references for improving their mental health. MethodsA total of 380 primiparous women admitted to the inpatient department of Chengdu Wenjiang District People's Hospital from December 2022 to September 2023 were enrolled as study subjects. A self-made questionnaire， Edinburgh Postnatal Depression Scale （EPDS）， Social Support Rating Scale （SSRS） and Childbirth Attitudes Questionnaire （CAQ） were used to conduct the survey. Pearson correlation analysis was employed to examine the relationships between scale scores. Multiple linear regression analysis was conducted to identify influencing factors of prenatal depression. ResultsA total of 380 questionnaires were distributed， with 372 （97.89%） valid responses collected. Among the participants， 222 cases （59.68%） were identified with prenatal depression. Pearson correlation analysis revealed that EPDS score was negatively correlated with SSRS score （r=-0.283， P<0.01） and positively correlated with CAQ score （r=0.341， P<0.01）. Multiple linear regression analysis indicated that social support （β=-0.166， P<0.01） and fear of childbirth （β=0.269， P<0.01） were influencing factors of prenatal depression in primiparous women. ConclusionThe prevalence of prenatal depression among primiparous women is concerning， with depression levels showing significant associations with both social support and fear of childbirth.

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice. The molecular mechanisms underlying this difference are largely unknown. Here, we found that bone morphogenic protein 7 (BMP7) is expressed by increasing the number of cortical radial glial cells during mammalian evolution (mouse, ferret, monkey, and human). BMP7 expression in cortical radial glial cells promotes neurogenesis, inhibits gliogenesis, and thereby increases the length of the neurogenic period, whereas Sonic Hedgehog (SHH) signaling promotes cortical gliogenesis. We demonstrate that BMP7 signaling and SHH signaling mutually inhibit each other through regulation of GLI3 repressor formation. We propose that BMP7 drives the evolutionary expansion of the mammalian cortex by increasing the length of the neurogenic period.
Animals ; Mice ; Humans ; Ependymoglial Cells/metabolism* ; Hedgehog Proteins/metabolism* ; Ferrets/metabolism* ; Cerebral Cortex ; Neurogenesis ; Mammals/metabolism* ; Neuroglia/metabolism* ; Bone Morphogenetic Protein 7/metabolism*

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.

BACKGROUND:Nanostructure modification of pure titanium surface is a hot research field of titanium implant surface treatment. OBJECTIVE:To evaluate the effect of nano-modified titanium surface treated with alkali heat treatment on early adhesion and growth of osteoblasts. METHODS:Four-grade pure titanium sheets with a diameter of 15 mm and a thickness of 1.5 mm were taken and processed in three groups:the smooth treatment group was polished step by step with 250 mesh,800 mesh,and 1 500 mesh silicon carbide sandpaper.In the sandblasting group,the smoothed titanium sheet was sandblasted with 100 μm Al2O3 particles at 0.45 MPa pressure,and then the acid etching was carried out.In the alkali heat treatment group,the smoothed titanium sheet was placed in the reactor,immersed in 10 mol/L NaOH solution,and heated in the oven at 100 ℃for 12 hours.The surface morphology,roughness,and hydrophilicity of three groups of titanium sheets were measured.MG63 osteoblasts were inoculated on the surface of three groups of titanium tablets,and the adhesion of the cells was observed by immunofluorescence staining. RESULTS AND CONCLUSION:(1)Scanning electron microscopy showed that the surface of titanium sheets in the smooth treatment group had uniform scratches;the surface of titanium sheets in the sandblasting group was uneven,and the surface of titanium sheets in the alkali heat treatment group had uniform nanoscale three-dimensional pore morphology.The roughness value of the titanium sheets in sandblasting and alkali heat treatment groups was higher than that in the smooth treatment group(P<0.05),and the water contact angle was lower than that in the smooth treatment group(P<0.05).(2)Immunofluorescence staining after 3 and 6 hours of inoculation of MG63 cells showed that the number of adhesion cells on the surface of the titanium sheet in the sandblasting group and alkali heat treatment group was higher than that in the smooth treatment group(P<0.05).Immunofluorescence staining 12 hours after inoculation showed that compared with the smooth treatment group,the actin skeleton of cells on the surface of titanium sheets in the sandblasting group and alkali heat treatment group was more extended,and most cells extended stronger pseudopodia,which was conducive to subsequent intercellular signal transduction and intercellular interaction.(3)The results showed that the nanostructures with certain biological activity could be prepared on the surface of a titanium sheet by alkali heat treatment,which was conducive to the early adhesion of osteoblasts.