Anti-inflammatory bicyclic polyprenylated acylphloroglucinols with diverse architectures including an unprecedented 6/6/6 tricyclic core from Garcinia yunnanensis.

Garciyunnanol A (1), an unprecedented 1,2-seco-bicyclic polyprenylated acylphloroglucinol (BPAP) possessing a unique 6/6/6 tricyclic core, was characterized from Garcinia yunnanensis together with 16 BPAPs, including eight new compounds (garciyunnanols B-I, 2-9). Biogenetically, the bicyclo[3.3.1]nonane-2,4,9-trione moiety of 12 reconstructed the bicyclic δ-lactone core of 2 through Norrish type Ⅰ cleavage and cyclization, followed by a cyclization of two side chains to form an intriguing 6/6/6 tricyclic core of 1. Their structures were elucidated through analysis of spectroscopic data, calculation and comparison of ECD spectra. Bioactivity evaluation manifested that compounds 1, 2, 5, 6 and 14 demonstrated superior inhibition of NO production compared to the positive control dexamethasone. Notably, compound 5 exhibited a dose-dependent inhibitory effect on NO production, with an IC50 value of 0.25 ± 0.87 µM. Furthermore, experiments involving ELISA, Western blotting, and immunofluorescence staining revealed that 5 effectively reduced the secretion of interleukin-1ß in LPS plus nigericin-stimulated THP-1 macrophages by inhibiting the activation of the NLRP3 inflammasome.

A chitosan-modified tea tree oil self-nanoemulsion improves antibacterial effects in vivo and in vitro and promotes wound healing by influencing metabolic processes against multidrug-resistant bacterial infections.

Infectious diseases, especially multidrug-resistant bacterial infections, have caused crises and majorly disrupted public health and economic stability worldwide. Many natural essential oils, especially tea tree oil, have potential to treat multidrug-resistant bacteria, such as H. pylori and P. aeruginosa. However, there are some problems need to be solved, such as poor stability upon light or oxygen exposure. Therefore, it is urgent to develop the ideal formation to tackle these difficulties. Herein, we reported the novel chitosan-modified self-nanoemulsion (TNE) encapsulating natural essential tea tree oil with strong antibacterial and stability characterize. In this study, we found that this self-nanoemulsion (size: 212 nm, PDI: 0.124, zeta potential: -20.5 mV, 6 % tea tree oil) not only had physical properties, good stability and tissue safety, but also had better antibacterial synergism (2-8 times) than that of water suspension against various multidrug-resistant bacterial (such as H. pylori, MRSA and P. aeruginosa). Additionally, TNE showed high antibacterial effectiveness in vivo, reduced inflammation, promoted ulcer healing after H. pylori infection and accelerated wound healing after P. aeruginosa infection. Importantly, this novel self-nanoemulsion can induce 274 protein down-regulated and 251 protein up-regulated, and disrupt H. pylori metabolic processes (glyoxylate, dicarboxylic acid, glutamate and tryptophan metabolism) and reduced its viability, leading to significant synergistic antibacterial effects. TNE is a potential treatment for skin wounds or ulcers caused by multidrug-resistant bacterial infections.

Influence of High-Altitude Residential History on Optimal HbA1c Cutoff for Detecting Abnormal Glucose Metabolism.

Aims: To explore the influence of recent high-altitude residential history on the optimal cutoff of glycosylated hemoglobin (HbA1c) for detecting abnormal glucose metabolism. Methods: The study included 505 self-reported healthy Han participants of age 18-65 years, recruited in Chengdu and categorized based on recent (within 3 months) high-altitude (>2,500 m) residential history. The 1999 WHO criteria was used as the gold standard for defining prediabetes and diabetes. HbA1c test performance was assessed using receiver operating characteristic curve, with the optimal cutoff determined by Maximum Youden index. Propensity score matching with 0.02 calipers and nearest neighbor method was used to balance confounding factors between groups. Results: Of the participants, 238 (47.13%) were populations with recent high-altitude residential history (HA group), and 267 (52.87%) were low-altitude dwellers (LA group). The HA group had slightly higher HbA1c levels (p > 0.05) and higher erythrocyte and hemoglobin levels (p < 0.05), compared to the LA group. Weak correlations between prediabetes and HbA1c levels were observed in the HA group (rs = 0.21, p < 0.05) and the LA group (rs = 0.07, p = 0.25). The optimal cutoff for the detection of diabetes was 6.5% (area under the curve [AUC] 0.94) in the HA group and 5.9% (AUC 0.97) in the LA group, which remained unchanged after adjustment for confounders. Conclusions: The optimal cutoff of HbA1c for the detection of diabetes in populations with recent history of living at high altitude was higher than that in general populations living at low altitude, and the diagnostic value of HbA1c for prediabetes was also inadequate.

Identification and Potential Clinical Utility of Common Genetic Variants in Gestational Diabetes among Chinese Pregnant Women.

Background: The genetic basis for hyperglycaemia in pregnancy remain unclear. This study aimed to uncover the genetic determinants of gestational diabetes mellitus (GDM) and investigate their applications. Methods: We performed a meta-analysis of genome-wide association studies (GWAS) for GDM in Chinese women (464 cases and 1,217 controls), followed by de novo replications in an independent Chinese cohort (564 cases and 572 controls) and in silico replication in European (12,332 cases and 131,109 controls) and multi-ethnic populations (5,485 cases and 347,856 controls). A polygenic risk score (PRS) was derived based on the identified variants. Results: Using the genome-wide scan and candidate gene approaches, we identified four susceptibility loci for GDM. These included three previously reported loci for GDM and type 2 diabetes mellitus (T2DM) at MTNR1B (rs7945617, odds ratio [OR], 1.64; 95% confidence interval [CI],1.38 to 1.96]), CDKAL1 (rs7754840, OR, 1.33; 95% CI, 1.13 to 1.58), and INS-IGF2-KCNQ1 (rs2237897, OR, 1.48; 95% CI, 1.23 to 1.79), as well as a novel genome-wide significant locus near TBR1-SLC4A10 (rs117781972, OR, 2.05; 95% CI, 1.61 to 2.62; Pmeta=7.6×10-9), which has not been previously reported in GWAS for T2DM or glycaemic traits. Moreover, we found that women with a high PRS (top quintile) had over threefold (95% CI, 2.30 to 4.09; Pmeta=3.1×10-14) and 71% (95% CI, 1.08 to 2.71; P=0.0220) higher risk for GDM and abnormal glucose tolerance post-pregnancy, respectively, compared to other individuals. Conclusion: Our results indicate that the genetic architecture of glucose metabolism exhibits both similarities and differences between the pregnant and non-pregnant states. Integrating genetic information can facilitate identification of pregnant women at a higher risk of developing GDM or later diabetes.

ZFP64 drives glycolysis-mediated stem cell-like properties and tumorigenesis in breast cancer.

BACKGROUND: Breast cancer (BC) is a great clinical challenge because of its aggressiveness and poor prognosis. Zinc Finger Protein 64 (ZFP64), as a transcriptional factor, is responsible for the development and progression of cancers. This study aims to investigate whether ZFP64 regulates stem cell-like properties and tumorigenesis in BC by the glycolytic pathway. RESULTS: It was demonstrated that ZFP64 was overexpressed in BC specimens compared to adjacent normal tissues, and patients with high ZFP64 expression had shorter overall survival and disease-free survival. The analysis of the association of ZFP64 expression with clinicopathological characteristics showed that high ZFP64 expression is closely associated with N stage, TNM stage, and progesterone receptor status. Knockdown of ZFP64 suppressed the viability and colony formation capacity of BC cells by CCK8 and colony formation assays. The subcutaneous xenograft models revealed that ZFP64 knockdown reduced the volume of formatted tumors, and decreased Ki67 expression in tumors. The opposite effects on cell proliferation and tumorigenesis were demonstrated by ZFP64 overexpression. Furthermore, we suggested that the stem cell-like properties of BC cells were inhibited by ZFP64 depletion, as evidenced by the decreased size and number of formatted mammospheres, the downregulated expressions of OCT4, Nanog, and SOX2 proteins, as well as the reduced proportion of CD44+/CD24- subpopulations. Mechanistically, glycolysis was revealed to mediate the effect of ZFP64 using mRNA-seq analysis. Results showed that ZFP64 knockdown blocked the glycolytic process, as indicated by decreasing glycolytic metabolites, inhibiting glucose consumption, and reducing lactate and ATP production. As a transcription factor, we identified that ZFP64 was directly bound to the promoters of glycolysis-related genes (ALDOC, ENO2, HK2, and SPAG4), and induced the transcription of these genes by ChIP and dual-luciferase reporter assays. Blocking the glycolytic pathway by the inhibition of glycolytic enzymes ENO2/HK2 suppressed the high proliferation and stem cell-like properties of BC cells induced by ZFP64 overexpression. CONCLUSIONS: These data support that ZFP64 promotes stem cell-like properties and tumorigenesis of BC by activating glycolysis in a transcriptional mechanism.

Neuromechanisms of simulation-based arthroscopic skills assessment: a fNIRS study.

BACKGROUND: The neural mechanisms underlying differences in the performance of simulated arthroscopic skills across various skill levels remain unclear. Our primary objective is to investigate the learning mechanisms of simulated arthroscopic skills using functional near-infrared spectroscopy (fNIRS). METHODS: We recruited 27 participants, divided into three groups: novices (n = 9), intermediates (n = 9), and experts (n = 9). Participants completed seven arthroscopic tasks on a simulator, including diagnostic navigation, triangulation, grasping stars, diagnostic exploration, meniscectomy, synovial membrane cleaning, and loose body removal. All tasks were videotaped and assessed via the simulator system and the Arthroscopic Surgical Skill Evaluation Tool (ASSET), while cortical activation data were collected using fNIRS. Simulator scores and ASSET scores were analyzed to identify different level of performance of all participants. Brain region activation and functional connectivity (FC) of different types of participants were analyzed from fNIRS data. RESULTS: Both the expert and intermediate groups scored significantly higher than the novice group (p < 0.001). There were significant differences in ASSET scores between experts and intermediates, experts and novices, and intermediates and novices (p = 0.0047, p < 0.0001, p < 0.0001), with the trend being experts > intermediates > novices. The intermediate group exhibited significantly greater activation in the left primary motor cortex (LPMC) and left prefrontal cortex (LPFC) compared to the novice group (p = 0.0152, p = 0.0021). Compared to experts, the intermediate group demonstrated significantly increased FC between the presupplementary motor area (preSMA) and the right prefrontal cortex (RPFC; p < 0.001). Additionally, the intermediate group showed significantly increased FC between the preSMA and LPFC, RPFC and LPFC, and LPMC and LPFC compared to novices (p = 0.0077, p = 0.0285, p = 0.0446). CONCLUSION: Cortical activation and functional connectivity reveal varying levels of activation intensity in the PFC, PMC, and preSMA among novices, intermediates, and experts. The intermediate group exhibited the highest activation intensity.

Increased Thyroid Hormone Action Alleviates Hippocampal Damage by Downregulating Neuronal Type I Interferon Signaling/Necroptosis in Diabetes-Associated Cognitive Dysfunction.

Background: Thyroid dysfunction plays an important role in the pathology of diabetes-associated cognitive dysfunction (DACD). However, thyroid hormone (TH) signaling and action changes in DACD brains remain unknown. This study evaluated the alternations in TH signaling and action in the brains of DACD mice and explored the beneficial effects of levothyroxine (L-T4) treatment. Methods: KK-Ay mice, serving as a spontaneous type 2 diabetes mellitus model, underwent intragastric administration of 10 ng/g and 20 ng/g of L-T4 solution or normal saline for 8 weeks. Age-matched C57BL/6J mice were used as normal controls. Cognitive and memory functions were examined through the open field and Morris water maze tests. Hippocampal TH signaling and pathogenic status were evaluated. The potential signaling pathways involved in the neuroprotective action of L-T4 were investigated through RNA sequencing and further verified through quantitative real-time PCR (qPCR), Western blotting (WB), immunofluorescence (IF), and fluorescent multiplex immunohistochemistry (mIHC) in vivo and vitro. Results: The expressions of hippocampal TH transporters (Mct8 and Oatp1c1), Dio2, and TH receptor were upregulated, whereas Dio3 as well as the TH-positive regulated genes MBP, Enpp2, and Klf9 were downregulated in DACD mice. Exogenous L-T4 partially alleviated cognitive and memory dysfunction and restored hippocampal neuronal activity by optimizing TH signaling. RNA sequencing provided insights into the role of type I interferon (IFN-I) signaling and necroptosis on the amelioration of hippocampal damage after L-T4 treatment. WB and qPCR further confirmed that the levels of key proteins for IFN-I signaling and necroptosis (p-STAT1, p-STAT2, IRF9, ZBP1, p-RIP3, and p-MLKL) were increased, but largely returned after L-T4 administration in vivo and T3 treatment in vitro. IF and mIHC revealed that IRF9 and p-MLKL colocalized in neurons, but not in astrocytes or microglia, of the hippocampus in DACD mice. The diabetes mellitus group had an increased number of IRF9+ p-MLKL+ NeuN+ cells, which decreased after L-T4 treatment. The elevated IFN-I signaling-mediated necroptosis in HT22 cells was also decreased by T3. Conclusion: We demonstrated abnormal hippocampal TH signaling and action in DACD. Promoting TH action with exogenous L-T4 ameliorated hippocampal impairment through inhibiting IFN-I signaling-induced necroptosis.

Prohibitin 2 confers NADPH oxidase 1-mediated cytosolic oxidative signaling to promote gastric cancer progression by ERK activation.

Oxidative signaling plays a dual role in tumor initiation and progression to malignancy; however, the regulatory mechanisms of oxidative stress in gastric cancer remain to be explored. In this study, we discovered that Prohibitin 2 (PHB2) specifically regulates cytosolic reactive oxygen species production in gastric cancer and facilitates its malignant progression. Previously, we found that PHB2 is upregulated in gastric cancer, correlating with increased tumorigenicity of gastric cancer cells and poor patient prognosis. Here, we discovered that PHB2 expression correlates with the activation of the ERK/MAPK cascade, positively regulating the top gene NADPH oxidase 1 (NOX1) within this pathway. Further mechanistic investigation reveals that PHB2 enhances NOX1 transcription by interacting with the transcription factor C/EBP-beta and promoting its translocation into the nucleus, resulting in elevated intracellular oxidative signaling driven by NOX1, which subsequently activates ERK. Therefore, we propose that targeting PHB2-C/EBP-beta-NOX1-mediated cytosolic oxidative stress could offer a promising therapeutic avenue for combating gastric cancer malignant progression.

Simple and low-cost microscopy setup for 3D particle field measurement using incoherent illumination and open-source hardware.

The quantification of 3D particle field is of interest for a vast range of fields. While in-line particle holography (PH) can provide high-resolution measurements of particles, it suffers from speckle noise. Plenoptic imaging (PI) is less susceptible to speckle noises, but it involves a trade-off between spatial and angular resolution, rendering images with low resolution. Here, we report a simple microscopy setup with the goals of getting the strengths of both techniques. It is built with off-the-shelf and cost-effective components including a photographic lens, a diaphragm, and a CCD camera. The cost of the microscopy setup is affordable to small labs and individual researchers. The pupil plane of the proposed setup can be mechanically accessible, allowing us to implement pupil plane modulation and increase the depth of field (DOF) without requiring any additional relay lenses. It also allows us to understand the working principle of pupil plane modulation clearly, benefiting microscopy education. It illuminates the sample (particles) using diffuse white light, and thus avoids the problem of speckle noise. It captures multiple perspective images via pupil plane modulation, without requiring trading off angular and spatial resolution. We validate the setup with 2D and 3D particle samples. RESEARCH HIGHLIGHTS: We report a simple and cost-effective microscopy setup with the goals of getting the strengths of plenoptic imaging and in-line particle holography. It is built with off-the-shelf and cost-effective components. The cost of the microscopy setup is affordable to small labs and individual researchers. The pupil plane of the proposed setup can be mechanically accessible, allowing us to implement pupil plane modulation and increase the DOF without requiring any additional relay lenses. It also allows us to understand the working principle of pupil plane modulation clearly, benefiting microscopy education. It illuminates the sample (particles) using diffuse white light, and thus avoids the problem of speckle noise. It captures multiple perspective images via pupil plane modulation, without requiring trading off angular and spatial resolution. We validate the setup with 2D and 3D particle samples.

The Impact of Kidney/Pancreas Transplantation on Peripheral Arterial Disease.

INTRODUCTION: It is unclear whether kidney/pancreas (KP) transplantation will prevent the progression of peripheral arterial disease (PAD) in patients with insulin dependent diabetes (IDDM) and end-stage renal disease. We sought to determine the pre- and posttransplant prevalence of symptomatic PAD and changes in carotid artery intima-media thickness (IMT) in KP recipients. METHODS: In this single center study, outcomes were compared between KP recipients with and without a history of PAD. A subset of recipients underwent pre- and posttransplant IMT measurements. RESULTS: Among the study group (N = 107), 18 (17%) recipients admitted to a pretransplant history of symptomatic PAD, comprised 11 foot infections and 7 amputations (5 minor and 2 major). Baseline characteristics of age, gender, race, years of diabetes, dialysis history, smoking history, years of hypertension, and history of coronary artery disease (CAD) were equivalent between PAD and non-PAD cohorts. At a median follow-up of 60 months (IQR: 28, 110), 16 (15%) KP recipients had suffered a PAD event. In multivariate analysis, a pretransplant history of PAD (hazard ratio [HR] 9.66, p < 0.001) and CAD (HR 3.33, p = 0.04) were independent predictors of posttransplant PAD events. Among a subset of 20 recipients (3 with PAD), mean IMT measurements pretransplant and at a median of 24 (range 18-24) months posttransplant, showed no evidence of disease progression. CONCLUSION: Based on IMT measurements and clinical results, KP transplantation stabilized PAD in most patients, but did not alter outcomes of symptomatic PAD recipients. A pretransplant history of PAD and CAD was an independent predictor of posttransplant PAD events.

Quantifying the effects of five rehabilitation training methods on the ability of elderly men to control bowel movements: a finite element analysis study.

Purpose: The study aims to develop a finite element model of the pelvic floor and thighs of elderly men to quantitatively assess the impact of different pelvic floor muscle trainings and the urinary and defecation control ability. Methods: A finite element model of the pelvic floor and thighs of elderly men was constructed based on MRI and CT. Material properties of pelvic floor tissues were assigned through literature review, and the relative changes in waistline, retrovesical angle (RVA) and anorectad angulation (ARA) to quantitatively verify the effectiveness of the model. By changing the material properties of muscles, the study analyzed the muscle strengthening or impairment effects of the five types of rehabilitation training for four types of urination and defecation dysfunction. The changes in four outcome indicators, including the retrovesical angle, anorectad angulation, stress, and strain, were compared. Results: This study indicates that ARA and RVA approached their normal ranges as material properties changed, indicating an enhancement in the urinary and defecation control ability, particularly through targeted exercises for the levator ani muscle, external anal sphincter, and pelvic floor muscles. This study also emphasizes the effectiveness of personalized rehabilitation programs including biofeedback, exercise training, electrical stimulation, magnetic stimulation, and vibration training and advocates for providing optimized rehabilitation training methods for elderly patients. Discussion: Based on the results of computational biomechanics, this study provides foundational scientific insights and practical recommendations for rehabilitation training of the elderly's urinary and defecation control ability, thereby improving their quality of life. In addition, this study also provides new perspectives and potential applications of finite element analysis in elderly men, particularly in evaluating and designing targeted rehabilitation training.

Accuracy of FreeStyle Libre flash glucose monitoring in patients with type 2 diabetes who migrated from highlands to plains.

BACKGROUND: The FreeStyle Libre flash glucose monitoring (FGM) system entered the Chinese market in 2017 to complement the self-monitoring of blood glucose. Due to its increased usage in clinics, the number of studies investigating its accuracy has increased. However, its accuracy has not been investigated in highland popu-lations in China. AIM: To evaluate measurements recorded using the FreeStyle Libre FGM system compared with capillary blood glucose measured using the enzyme electrode method in patients with type 2 diabetes (T2D) who had migrated within 3 mo from highlands to plains. METHODS: Overall, 68 patients with T2D, selected from those who had recently migrated from highlands to plains (within 3 mo), were hospitalized at the Department of Endocrinology from August to October 2017 and underwent continuous glucose monitoring (CGM) with the FreeStyle Libre FGM system for 14 d. Throughout the study period, fingertip capillary blood glucose was measured daily using the enzyme electrode method (Super GL, China), and blood glucose levels were read from the scanning probe during fasting and 2 h after all three meals. Moreover, the time interval between reading the data from the scanning probe and collecting fingertip capillary blood was controlled to < 5 min. The accuracy of the FGM system was evaluated according to the CGM guidelines. Subsequently, the factors influencing the mean absolute relative difference (MARD) of this system were analyzed by a multiple linear regression method. RESULTS: Pearson's correlation analysis showed that the fingertip and scanned glucose levels were positively correlated (R = 0.86, P = 0.00). The aggregated MARD of scanned glucose was 14.28 ± 13.40%. Parker's error analysis showed that 99.30% of the data pairs were located in areas A and B. According to the probe wear time of the FreeStyle Libre FGM system, MARD1 d and MARD2-14 d were 16.55% and 14.35%, respectively (t = 1.23, P = 0.22). Multiple stepwise regression analysis showed that MARD did not correlate with blood glucose when the largest amplitude of glycemic excursion (LAGE) was < 5.80 mmol/L but negatively correlated with blood glucose when the LAGE was ≥ 5.80 mmol/L. CONCLUSION: The FreeStyle Libre FGM system has good accuracy in patients with T2D who had recently migrated from highlands to plains. This system might be ideal for avoiding the effects of high hematocrit on blood glucose monitoring in populations that recently migrated to plains. MARD is mainly influenced by glucose levels and fluctuations, and the accuracy of the system is higher when the blood glucose fluctuation is small. In case of higher blood glucose level fluctuations, deviation in the scanned glucose levels is the highest at extremely low blood glucose levels.

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial.

OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.

Influence of cervical treatment methods on subsequent vaginal lesions: A study of HPV-related neoplasia.

The development of cervical and vaginal intraepithelial neoplasias (CIN and VaIN) is strongly associated with human papillomavirus (HPV) infections, representing key precancerous conditions in women. This study investigates the influence of different cervical treatment methods on the rate of subsequent vaginal neoplasia. It also considers age and menopausal status as risk factors for higher-grade VaIN and the role of persistent HPV infections in the development of new VaIN cases post-treatment. The cohort consisted of 275 female patients treated for CIN, with a follow-up period of six months including HPV and ThinPrep cytologic test (TCT) testing. The evaluated treatments included laser therapy, cervical conization, loop electrosurgical excision procedure (LEEP), and radical hysterectomy. Statistical analysis was performed using SPSS 26.0 to determine treatment efficacy, the impact of age and menopausal status, and the relationship between HPV clearance and VaIN outcomes. Radical hysterectomy was linked with a higher recurrence of VaIN. Additionally, patients over 50 years old and those who were postmenopausal were significantly more likely to develop more severe VaIN and persistent HPV infections. Persistence of HPV after treatment was linked to a higher incidence of new VaIN cases. High-risk HPV significantly increased the recurrence of VaIN, with no significant link found between TCT results and VaIN severity. Therefore, selecting appropriate cervical lesion treatment, considering the patient's age and menopausal status, and managing HPV infections are essential in preventing and managing the risk and progression of VaIN. Radical hysterectomy showed a distinct increase in VaIN incidence, emphasizing the need for individualized clinical assessments.

Efficacy and safety of bismuth quadruple regimens containing minocycline and vonoprazan for eradication of Helicobacter pylori: Real-world evidence.

Background and Aim: To evaluate the efficacy and safety of minocycline, vonoprazan, amoxicillin, and bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. Methods: From August 2022 to May 2023, clinical data were collected from patients who received H. pylori eradication treatment at West China Fourth Hospital, Sichuan University. One group received the MVAB regimen (amoxicillin, minocycline, vonoprazan, and colloidal bismuth pectin), while another group received the FOAB regimen (amoxicillin, furazolidone, omeprazole, and colloidal bismuth pectin), both administered for 14 days. Follow-up assessments of safety and compliance were conducted within 1 week after treatment completion. One and a half months after treatment, the success of eradication was evaluated using the urea breath test. Results: For the MVAB regimen as a first-line treatment, the eradication rate was 90.1% (127/141, 95% CI: 85.1-95.1%) in the ITT analysis and 93.4% (127/136, 95% CI: 89.2-97.6%) in the PP analysis as a first-line treatment. As a second-line treatment, the eradication rate was 91.3% (21/23, 95% CI: 78.8-103.8%) in both analyses. For the FOAB regimen as a first-line treatment, the eradication rate was 98.0% (50/51, 95% CI: 94.1-101.2%) in the ITT analysis and 100% (50/50, 95% CI: 100%) in the PP analysis. As a second-line treatment, the eradication rate was 100% (6/6, 95% CI: 100%) in both analyses. Moreover, there was no significant difference in the incidence of adverse events between the two groups (MVAB regimen: 5.5% and FOAB regimen: 8.8%; P > 0.05). Conclusions: The MVAB regimen could indeed be a viable alternative treatment option to conventional therapies.

Diagnosis of Canine Tumours and the Value of Combined Detection of VEGF, P53, SF and NLRP3 for the Early Diagnosis of Canine Mammary Carcinoma.

The average life of a dog is generally maintained at ten to fifteen years, and tumours are the predominant reason that leads to the death of dogs, especially canine mammary carcinoma. Therefore, early diagnosis of tumours is very important. In this study, tumor size, morphology, and texture could be seen through general clinical examination, tumor metastasis could be seen through imaging examination, inflammatory reactions could be seen through hematological examination, and abnormal cell morphology could be seen through cytological and histopathological examination. In the 269 malignant cases and 179 benign cases, we randomly selected 30 cases each, and an additional 30 healthy dogs were selected for the experiment (healthy dogs: dogs in good physical condition without any tumor or other diseases). We used RT-qPCR and ELISA to determine the relative expression of vascular endothelial growth factor (VEGF), tumor protein P53 (P53), serum ferritin (SF), and NOD-like receptor protein 3 (NLRP3) in 30 healthy dogs, 30 dogs with benign mammary tumours, and 30 dogs with malignant mammary tumours. In the results, the same expression trend was obtained both in serum and tissues, and the expression of the four markers was the highest in malignant mammary tumours, with highly significant differences compared with the benign and healthy/paracancerous groups. By plotting the ROC curves, it was found that the results of combined tests were better than a single test and the combination of the four markers was the best for the early diagnosis. In conclusion, this can assist the clinical early diagnosis to a certain extent, and also provides some references and assistance for the development of tumor detection kits in clinical practice.

Efficacy and safety of tetrandrine in treatment of rheumatoid arthritis: a meta-analysis. / æ±‰é˜²å·±ç”²ç´ æ²»ç–—ç±»é£Žæ¹¿å ³èŠ‚ç‚Žæœ‰æ•ˆæ€§å’Œå®‰å ¨æ€§çš„meta分析.

OBJECTIVES: To explore the efficacy and safety of tetrandrine in the treatment of rheumatoid arthritis. METHODS: Randomized controlled studies of tetrandrine in the treatment of rheumatoid arthritis were searched in CNKI, VIP, Wanfang database, SinoMed, PubMed, Springer, Web of Science and Cochrane Central Register of Controlled Trails databases. A meta-analysis was conducted using R 3.5.3 software to evaluate the clinical outcomes, including the total effective rate, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), visual analogue scale (VAS), disease activity score (DAS), tender joint count (TJC), swollen joint count (SJC), and morning stiffness duration, as well as adverse events of rheumatoid arthritis patients. RESULTS: A total of 10 articles were included in the study. The meta-analysis indicated that tetrandrine significantly improved the total effective rate (OR=3.27, 95%CI: 2.01-5.37, P<0.01), ESR (SMD=1.12, 95%CI: 0.06-2.19, P<0.05), CRP (SMD=0.75, 95%CI: 0.28-1.22, P<0.01), VAS (SMD=0.64, 95%CI: 0.29-1.00, P<0.01), TJC (SMD=1.16, 95%CI: 0.58-1.74, P<0.01), SJC (SMD=0.85, 95%CI: 0.40-1.31, P<0.01), and morning stiffness (SMD=1.09, 95%CI: 0.68-1.50, P<0.01). However, no statistical significance was found in RF (SMD=1.70, 95%CI: －1.10-4.51, P>0.05) and DAS (SMD=0.26, 95%CI: －0.59-1.11, P>0.05). The overall incidence of adverse events associated with tetrandrine treatment for rheumatoid arthritis was 20% (95%CI: 12%-27%, I2=60%, P<0.05), with mild severity and favorable outcomes. CONCLUSIONS: Tetrandrine is effective in the treatment of RA patients with a mild degree of adverse events.

PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α.

Pyruvate dehydrogenase kinase 1 (PDK1) phosphorylates the pyruvate dehydrogenase complex, which inhibits its activity. Inhibiting pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis, which plays an important role in tumor progression. This study aims to elucidate how PDK1 promotes breast cancer progression. We found that PDK1 was highly expressed in breast cancer tissues, and PDK1 knockdown reduced the proliferation, migration, and tumorigenicity of breast cancer cells and inhibited the HIF-1α (hypoxia-inducible factor 1α) pathway. Further investigation showed that PDK1 promoted the protein stability of HIF-1α by reducing the level of ubiquitination of HIF-1α. The HIF-1α protein levels were dependent on PDK1 kinase activity. Furthermore, HIF-1α phosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer cells. The phosphorylation of HIF-1α at Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1α with von Hippel-Lindau and prolyl hydroxylase domain. We also found that PDK1 enhanced HIF-1α transcriptional activity. In summary, PDK1 enhances HIF-1α protein stability by phosphorylating HIF-1α at Ser451 and promotes HIF-1α transcriptional activity by enhancing the binding of HIF-1α to P300. PDK1 and HIF-1α form a positive feedback loop to promote breast cancer progression.