Current advances in understanding endometrial epithelial cell biology and therapeutic applications for intrauterine adhesion.

The human endometrium is a highly regenerative tissue capable of undergoing scarless repair during the menstruation and postpartum phases. This process is mediated by endometrial adult stem/progenitor cells. During the healing of endometrial injuries, swift reepithelization results in the rapid covering of the wound surface and facilitates subsequent endometrial restoration. The involvement of endogenous endometrial epithelial stem cells, stromal cells, and bone marrow-derived cells in the regeneration of the endometrial epithelium has been a subject of prolonged debate. Increasing evidence suggests that the regeneration of the endometrial epithelium mainly relies on epithelial stem cells rather than stromal cells and bone marrow-derived cells. Currently, no consensus has been established on the identity of epithelial stem cells in the epithelial compartment. Several markers, including stage-specific embryonic antigen-1 (SSEA-1), sex-determining region Y-box 9 (SOX9), neural-cadherin (N-cadherin), leucine-rich-repeat-containing G-protein-coupled receptor 5 (LGR5), CD44, axis inhibition protein 2 (Axin2), and aldehyde dehydrogenase 1A1 (ALDH1A1), have been suggested as potential candidate markers for endometrial epithelial stem cells. The identification of endometrial epithelial stem cells contributes to our understanding of endometrial regeneration and offers new therapeutic insights into diseases characterized by regenerative defects in the endometrium, such as intrauterine adhesion. This review explores different perspectives on the origins of human and mouse endometrial epithelial cells. It summarizes the potential markers, locations, and hierarchies of epithelial stem cells in both human and mouse endometrium. It also discusses epithelial cell-based treatments for intrauterine adhesion, hoping to inspire further research and clinical application of endometrial epithelial stem cells.

Shorter Leukocyte Telomere Length Is Associated with Increased Major Adverse Cardiovascular Events or Mortality in Patients with Essential Hypertension.

The association between leukocyte telomere length (LTL) alteration and major adverse cardiovascular events (MACE) or mortality in patients with hypertension is still unclear. 20,034 patients with essential hypertension were enrolled from UK biobank. Multivariable COX regression models were performed to assess the association. LTL was shorter in hypertensive patients with MACE compared to those without MACE. Hypertensive patients in the lowest LTL quartile were at higher risk to develop MACE (adjusted HR 1.15 [95% CI 1.02-1.29], vs top LTL quartile, p-trend = 0.03). Similarly, shorter LTL was related with increased mortality (adjusted HR 1.18[95% CI 1.06-1.3], lowest vs top LTL quartile, p-trend < 0.001). This investigation demonstrated that shorter LTL is associated with increased risk of MACE or mortality in patients with essential hypertension, which indicates that LTL may be a potential predictor of prognosis or underlying therapeutic target for hypertension.

Effect of Shi-Style Steaming and Bathing Decoction in Patients with Knee Osteoarthritis: Study Protocol for a Randomized Placebo-Controlled Trial.

Purpose: To prove more accurately that Chinese herbal bath therapy may be a safe, effective, simple alternative treatment modality for knee OA, we designed a randomized, double-blind, placebo-controlled trial to explore the effectiveness of SSBD for the relief of pain, daily activities, and quality of life in patients with knee OA. Patients and Methods: A single-center, 52-week, randomized controlled trial of SSBD versus placebo is being performed. A total of 200 patients with symptomatic knee OA will be randomly allocated to the SSBD treatment or placebo intervention group for 4 weeks. The two groups of patients are allowed to steam and bathe their knees once every other day, using one packet of SSBD each time, for 30 minutes, 3 times a week, for a total of 4 weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale at 4 weeks is the primary outcome measure, and the secondary outcomes include WOMAC stiffness and function scores, the Lysholm knee scale score, quality of life, the Brief Pain Inventory score, the Patient's Global Impressions of Improvement Scale score and the Clinical Global Impressions of Severity scale score. The safety of the herbal medications will also be evaluated. Conclusion: We will discuss whether SSBD has greater advantages in terms of efficacy, safety, and patient overall perception than does placebo control in middle-aged and elderly patients with knee OA. The findings may provide new and valuable information about the efficacy and safety of Chinese herbal bath therapy in the treatment of knee osteoarthritis.

Specific growth velocity reference charts for monochorionic twin pregnancies.

OBJECTIVE: We aimed to create specific growth velocity reference charts for monochorionic (MC) twin pregnancies and provide additional information for assessing fetal growth in MC twins. STUDY DESIGN: This retrospective study collected data from uncomplicated MC twins with serial ultrasound parameters. The four ultrasound parameters, including biparietal diameter, femur length, head circumference, and abdominal circumference, were used to calculate the estimated fetal weight (EFW). Multilevel linear regression models were applied to fit growth velocity charts for each biometric parameter and EFW. Analysis of variance was used to examine differences in birthweight by whether EFW velocity and EFW values were <10th or ≥10th percentiles. RESULTS: The final analysis encompassed a total of 5956 ultrasound examinations conducted on 487 MC twins. The growth velocity of four biparietal diameters exhibited a gradual decrease in a nearly linear fashion progressing from 18 to 37 gestational weeks. The EFW velocity increased steadily from 18 to 36 gestational weeks, reaching a peak of 178.2 g/week, and then the velocity gradually decreased until delivery. At 32 weeks for illustration, the lightest birth weight was observed when both EFW and EFW velocity were <10th percentile (1899 g). The study also found that birth weight was higher when EFW velocity was ≥10th percentile compared with <10th percentile, regardless of EFW being below or above the 10th percentile (2263 and 1906 g, respectively; P < 0.001). CONCLUSION: We developed specific growth velocity reference charts for MC twins, which could provide a valuable reference point for a more precise evaluation of fetal growth in MC twins. Preliminary findings indicate that the inclusion of fetal growth velocity in monitoring fetal growth provides additional information beyond EFW alone.

A multicenter prospective study on the ESC algorithm for the early diagnosis of non-ST-elevation myocardial infarction.

This study aimed to determine the optimal high-sensitivity cardiac troponin I (hs-cTnI)-based algorithm for early diagnosis of non-ST-elevation myocardial infarction (NSTEMI) in Chinese patients. We prospectively enrolled 1,606 patients with suspected NSTEMI from three emergency departments across China, collecting blood samples at 0, 1, and 3 h post-admission. Patients were classified using the 0/1-h and 0/3-h algorithms. The 2015 and 2020 ESC 0/1-h algorithms rapidly triaged 70% of patients with high negative predictive value (NPV) (99.7%) and sensitivity (99.5%). The 0/3-h algorithm showed higher specificity (93.8%) but lower NPV (96.8%) and sensitivity (91.2%). An optimized 0/1-h algorithm improved specificity to 92.1% while maintaining high NPV (99.7%) and sensitivity (99.2%). Low 30-day and 180-day all-cause mortality and major adverse cardiac event (MACE) rates were observed in rule-out groups for all algorithms. The ESC 0/1-h algorithm is a safe and efficient triage method for patients with suspected NSTEMI, with optimization further enhancing specificity and efficiency for the Chinese population.

First isolation, identification, and pathogenicity evaluation of an EV-G6 strain in China.

Enterovirus G (EV-G) belongs to the Picornaviridae family and infects porcine populations worldwide. A total of 20 EV-G genotypes (EV-G1 to EV-G20) have been identified. In this study, we isolated and characterized an EV-G strain, named EV-G/YN29/2022, from the feces of diarrheic pigs. This was the first EV-G6 strain isolated in China. Comparison of the whole genome nucleotide and corresponding amino acid sequences showed that the isolate was more closely related to those of the EV-G6 genotype than other genotypes, with the complete genome sequence similarity ranging from 83.7% (Iba46442) to 84.4% (PEV-B-KOR), and corresponding amino acid homology ranged from 96% (Iba46442) to 96.8% (PEV-B-KOR). Similarly, the VP1 gene and corresponding amino acid sequences of EV-G/YN29/2022 were highly similar to those of the EV-G6 genotype (>82.9% and >94.3%, respectively). Thus, the isolated strain was classified as EV-G6 genotype. This was the first EV-G6 strain isolated in China. Pathogenicity analyses revealed that EV-G/YN29/2022 infection caused mild diarrhea, typical skin lesions, and weight reduction. The strain was mainly distributed to the intestinal tissue but was also found in the brain, mesenteric lymph nodes, spleen, and liver. Our results can be used as a reference to further elucidate the epidemiology, evolution, and pathogenicity of EV-G.

Axillary lymph node removal in de novo metastatic breast cancer.

Background: Several prospective studies have found that local surgical resection did not improve the survival of patients with de novo metastatic breast cancer (dnMBC). However, a significant portion of dnMBC patients still undergo local surgery, and the role of axillary lymph node dissection (ALND) in dnMBC patients remains unclear. This study aimed to investigate the effect of ALND in patients with dnMBC. Methods: We included patients diagnosed with dnMBC between 2010 and 2020 using the data from the Surveillance, Epidemiology, and End Results program. The Chi-square test, binomial logistic regression, propensity score matching (PSM), Kaplan-Meier method, and multivariate Cox proportional models were employed for statistical analysis. Results: A total of 6,838 patients were identified, with 5,562 (81.3%) in the ALND group and 1,276 (18.7%) in the non-ALND group. Being diagnosed in later years emerged as an independent predictive factor related to the receipt of ALND (P=0.003). Before PSM, the 5-year breast cancer-specific survival (BCSS) was 51.1% and 38.2% in those with and without ALND, respectively (P<0.001). The 5-year overall survival (OS) was 45.9% and 32.3% in those with and without ALND, respectively (P<0.001). ALND was identified as an independent prognostic factor related to better BCSS (P<0.001) and OS (P<0.001) compared to the non-ALND group. Similar findings were observed after PSM. The outcomes were significantly better in the ALND group than in the non-ALND group in most subgroups. However, the number of removed lymph nodes did not show a significant association with BCSS (P=0.27) and OS (P=0.29). Conclusions: Our study suggests that ALND is associated with improved survival outcomes in dnMBC patients. These findings advocate for a re-evaluation of the role of surgical interventions in dnMBC, emphasizing the need for personalized treatment strategies that consider the potential benefits of ALND.

Epigallocatechin Gallate Derivative Y6 Reverses Oxaliplatin Resistance in Hepatocellular Carcinoma via Targeting the MiR-338-3p/HIF-1α/TWIST Axis to Inhibit EMT.

BACKGROUND: The emergence of drug resistance to oxaliplatin (OXA) is one of the critical obstacles in the therapy of advanced Hepatocellular Carcinoma (HCC). As an ethyl derivative of the natural compound epigallocatechin gallate (epigallocatechin-3-gallate, EGCG), Y6 was found to be able to enhance the sensitivity of HCC cells to doxorubicin. This study aimed to investigate the effect of Y6 on oxaliplatin resistance in HCC. METHODS: MTT was used to determine the reversal effect of Y6 on OXA resistance. To further explore the reversal mechanism, we treated OXA alone or in combination with Y6 or EGCG in drugresistant cells and observed the morphological changes of the cells. At the same time, transwell assay was used to detect the invasion and migration ability of cells. Moreover, Real-time PCR and Western blot analysis were performed to determine the expression levels of the miR-338-3p gene, HIF-1α/Twist proteins, and EMT-related proteins. RESULTS: We found that Y6 could inhibit the proliferation of HCC cells and effectively reverse the drug resistance of oxaliplatin-resistant human liver cancer cells (SMMC-7721/OXA) to OXA, and the reversal effect was more significant than that of its lead drug EGCG. Most of the cells in the control group and OXA group showed typical mesenchymal-like cell morphology, while most of the cells in co-administration groups showed typical epithelioid cell morphology, and the ability of the cells to invade and migrate decreased dramatically, particularly in Y6 plus OXA group. At the same time, Y6 could up-regulate the EMT epithelial marker protein E-cadherin and down-regulate the interstitial marker protein Vimentin. In addition, in co-administration groups, the expression of miR-338-3p was up-regulated, while the expression of HIF-1α and Twist was down-regulated. CONCLUSION: Y6 significantly enhanced the susceptibility of drug-resistant cells to OXA, and the process may be related to the regulation of miR-338-3p/HIF-1α / TWIST pathway to inhibit EMT. Therefore, Y6 could be considered an effective medication resistance reversal agent, which could improve the therapeutic effect for hepatocellular cancer patients.

Curative Approaches for Metaplastic Breast Cancer: A Retrospective Cohort Outcome Review.

PURPOSE: Metaplastic breast cancer (MBC) is a rare and heterogeneous breast cancer subtype, and there are critical gaps in our understanding of its long-term outcomes. This retrospective cohort study aimed to address these gaps by scrutinizing the pathologic and clinical aspects of MBC to enhance clinical decision-making and refine patient care strategies. METHODS AND MATERIALS: This registry-based retrospective cohort study included women aged ≥21 years diagnosed with MBC or matrix-producing carcinoma. The data were obtained from January 2001 to August 2020 from the Joint Breast Cancer Registry of Singapore Health Services, which included 23,935 patients. Demographic and clinicopathologic characteristics, neoadjuvant chemotherapy responses, and survival outcomes were analyzed. Statistical assessments involved univariate and multivariate Cox proportional hazards models and Kaplan-Meier survival analyses. RESULTS: This study enrolled 170 patients; 87.1% had non-metastatic disease, and 12.9% had metastatic disease. The age of patients at diagnosis ranged from 46 to 65 years (median, 56 years). The cohort's predominant characteristics were triple negative breast cancer (64%), advanced clinical stage (77.6%), node negativity (67.6%), and grade 3 disease (74.1%). In patients receiving neoadjuvant chemotherapy with curative intent treatment (17.6%), neoadjuvant chemotherapy yielded a pathologic complete response of 19.2% and a disease progression rate of 46.2%. Multivariate analysis showed that adjuvant radiation therapy significantly improved overall survival and disease-free survival, with hazard ratios of 0.29 (95% CI, 0.13-0.62; P < .005) and 0.23 (95% CI, 0.10-0.50; P < .005), respectively. Clinical T3 and T4 stages and nodal involvement were associated with poor outcomes. Stable disease after neoadjuvant chemotherapy was associated with poor overall survival and disease-free survival. CONCLUSIONS: This study sheds light on the complex landscape of MBC and emphasizes the pivotal role of adjuvant radiation therapy in enhancing patient outcomes. Despite advancements, challenges persist that warrant continued research to refine neoadjuvant chemotherapy strategies and delve into the nuanced factors that influence treatment responses.

A retrospective analysis of transudative pleural effusion due to fibrosing mediastinitis.

BACKGROUND: Pleural effusion caused by fibrosing mediastinitis is rarely reported. This study aimed to summarize the clinical manifestations, diagnosis and treatment of transudative pleural effusion due to fibrosing mediastinitis. METHODS: Medical records and follow-up data of 7 patients with transudative pleural effusion due to fibrosing mediastinitis in Beijing Chaoyang Hospital between May 2014 and Feb 2018 were retrospectively analyzed. RESULTS: These patients included 4 males and 3 females, with an average age of (64 ± 9) years. There were 3 left-sided effusions, 2 right-sided effusions and 2 bilateral effusions. Previous or latent tuberculosis was found in 6 patients. Pulmonary hypertension was indicated by echocardiography in all the 7 patients. Computed tomography pulmonary angiography (CTPA) of all the 7 cases showed increased soft tissue images visible in the mediastinum and bilateral hilus, different degrees of stenosis or occlusion in the pulmonary artery and pulmonary vein. In addition, 4 cases were found of right middle lobe atelectasis with a mediastinal window setting. There was interstitial pulmonary edema on the side of pleural effusion with a lung window setting. All the 7 patients were treated with intermittent drainage of pleural effusion combined with diuretic therapy. Five patients were treated with antituberculosis therapy. Up to now, two patients died of right heart failure and respiratory failure after 2 and 16 months respectively; The remaining 5 patients were still in follow up. CONCLUSION: Fibrosing mediastinitis can lead to pulmonary vein stenosis or occlusion, and thus cause transudative pleural effusion, which can be detected by CTPA. Pulmonary hypertension, long time of cough, and a history of tuberculosis are common in these patients. The common therapy is intermittent drainage of pleural effusion combined with diuretic therapy.

An adult with hemorrhagic varicella co-infects with cytomegalovirus: a case report.

BACKGROUND: Hemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions. CASE PRESENTATION: We present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient's extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient's demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient's diagnosis should be classified as a rare case of hemorrhagic varicella. CONCLUSION: Swift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.

Umbilical cord blood T cells can be isolated and enriched by CD62L selection for use in 'off the shelf' chimeric antigen receptor T-cell therapies to widen transplant options.

Umbilical cord blood (UCB) T cells exhibit distinct naive ontogenetic profiles and may be an attractive source of starting cells for the production of chimeric antigen receptor (CAR) T cells. Pre-selection of UCB-T cells on the basis of CD62L expression was investigated as part of a machine-based manufacturing process, incorporating lentiviral transduction, CRISPR-Cas9 editing, T-cell expansion and depletion of residual TCReeeT cells. This provided stringent mitigation against the risk of graft versus host disease (GVHD), and was combined with simultaneous knockout of CD52 to enable persistence of edited T cells in combination with preparative lymphodepletion using Alemtuzumab. Under compliant manufacturing conditions, two cell banks were generated with high levels of CAR19 expression and minimal carriage of TCReeeT cells. Sufficient cells were cryopreserved in dose-banded aliquots at the end of each campaign to treat dozens of potential recipients. Molecular characterisation captured vector integration sites and CRISPR editing signatures and functional studies, including in vivo potency studies in humanised mice, confirmed antileukaemic activity comparable to peripheral blood-derived universal CAR19 T cells. Machine manufactured UCB derived T cells banks offer an alternative to autologous cell therapies and could help widen access to CAR T cells.

Positive-strand RNA virus genome replication organelles: structure, assembly, control.

Positive-strand RNA [(+)RNA] viruses include pandemic SARS-CoV-2, tumor-inducing hepatitis C virus, debilitating chikungunya virus (CHIKV), lethal encephalitis viruses, and many other major pathogens. (+)RNA viruses replicate their RNA genomes in virus-induced replication organelles (ROs) that also evolve new viral species and variants by recombination and mutation and are crucial virus control targets. Recent cryo-electron microscopy (cryo-EM) reveals that viral RNA replication proteins form striking ringed 'crowns' at RO vesicle junctions with the cytosol. These crowns direct RO vesicle formation, viral (-)RNA and (+)RNA synthesis and capping, innate immune escape, and transfer of progeny (+)RNA genomes into translation and encapsidation. Ongoing studies are illuminating crown assembly, sequential functions, host factor interactions, etc., with significant implications for control and beneficial uses of viruses.

Safety and efficacy of Yaobitong capsules for lumbar disc herniation: A multicenter, randomized, double-blinded, parallel, positive-controlled clinical trial.

BACKGROUND: Lumbar disc herniation (LDH) is one of the most common diseases and is a global medical and socioeconomic problem characterized by leg or back pain, weakness in the lower extremities and paresthesia. OBJECTIVES: A multicenter, randomized, double-blinded, parallel, positive-controlled clinical trial was conducted to evaluate the efficacy and safety of Yaobitong capsules (YBT) for LDH. MATERIAL AND METHODS: Patients (n = 479) were recruited and randomized into YBT and Jingyaokang capsule (JYK) groups (the positive control), and received YBT or JYK at a dose of 3 capsules 3 times per day after a meal for 30 days. The primary efficacy outcome was the Oswestry Disability Index (ODI), with the visual analogue scale (VAS) used as the secondary efficacy outcome. The adverse events and adverse reactions were also evaluated. RESULTS: There was no significant difference in baseline characteristics between YBT (n = 358) and JYK groups (n = 120), and no difference was observed between groups for mean ODI score at day 0 (p = 0.064) or day 7 (p = 0.196), but there were differences at days 14, 21 and 30 (p < 0.001). The YBT showed more decline from baseline, and the decreased ODI score was substantially different from JYK (p < 0.001). The differences in decreased VAS scores between YBT and JYK were also significant at each time point (days 7, 14, 21, and 30), with better scores in the YBT group than in the JYK group (p < 0.001). In terms of safety, there was no obvious disparity in adverse events or adverse reactions between the 2 groups (p > 0.05). CONCLUSIONS: Yaobitong was better than JYK for LDH treatment, with no significant difference in safety. The study suggests that YBT is a promising and effective treatment for LDH.

The discovery of an anti-Candida xanthone with selective inhibition of Candida albicans GAPDH.

OBJECTIVES: This study aimed to discover novel antifungals targeting Candida albicans glyceraldehyde-3-phosphate dehydrogenase (CaGAPDH), have an insight into inhibitory mode, and provide evidence supporting CaGAPDH as a target for new antifungals. METHODS: Virtual screening was utilized to discover inhibitors of CaGAPDH. The inhibitory effect on cellular GAPDH was evaluated by determining the levels of ATP, NAD, NADH, etc., as well as examining GAPDH mRNA and protein expression. The role of GAPDH inhibition in C. albicans was supported by drug affinity responsive target stability and overexpression experiments. The mechanism of CaGAPDH inhibition was elucidated by Michaelis-Menten enzyme kinetics and site-specific mutagenesis based on docking. Chemical synthesis was used to produce an improved candidate. Different sources of GAPDH were used to evaluate inhibitory selectivity across species. In vitro and in vivo antifungal tests, along with anti-biofilm activity, were carried out to evaluate antifungal potential of GAPDH inhibitors. RESULTS: A natural xanthone was identified as the first competitive inhibitor of CaGAPDH. It demonstrated in vitro anti-C. albicans potential but also caused hemolysis. XP-W, a synthetic side-chain-optimized xanthone, demonstrated a better safety profile, exhibiting a 50-fold selectivity for CaGAPDH over human GAPDH. XP-W also exhibited potent anti-biofilm activity and displayed broad-spectrum anti-Candida activities in vitro and in vivo, including multi-azole-resistant C. albicans. CONCLUSIONS: These results demonstrate for the first time that CaGAPDH is a valuable target for antifungal drug discovery, and XP-W provides a promising lead.

Effect of acupotomy combined with electroacupuncture on knee function of patients with knee osteoarthritis. / åˆƒé’ˆç»“åˆç”µé’ˆæ²»ç–—å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žæ‚£è€ è†å ³èŠ‚åŠŸèƒ½çš„å½±å“.

OBJECTIVES: To compare the clinical effect of combined therapy of acupotomy and electroacupuncture (EA) with the simple application of EA on knee osteoarthritis (KOA), and their influence on knee function. METHODS: Sixty-eight KOA patients were randomly divided into 2 groups, an acupotomy group and an EA group. In the acupotomy group, the combined therapy of acupotomy and EA was adopted. In the EA group, EA was simply used, delivered once every two days, 3 treatments a week；and the duration of treatment was 4 weeks. In the acupotomy group, besides the treatment as the EA group, acupotomy was combined once weekly, and the duration of treatment was 4 weeks. Separately, before and after treatment, and in 4 and 12 weeks after treatment completion (1-month and 3-month follow-up), the results of the timed up and go test (TUG), the 9-step stair climb test (9-SCT) and the knee function (Western Ontario and McMaster University osteoarthritis index visualization scale ［WOMAC］) were measured in the two groups. RESULTS: By the intention-to-treat analysis, the results of TUG, 9-SCT and WOMAC scores were reduced after treatment and in 1-month and 3-month follow-up when compared with those before treatment in the patients of the two groups (P<0.05). Compared with the EA group at the same time point, TUG results were decreased after treatment and in 1-month follow-up, and WOMAC score was reduced after treatment in the acupotomy group. WOMAC score in 1-month follow-up was reduced when compared with that before treatment within the acupotomy group (P<0.05). CONCLUSIONS: Either the simple application of EA or the combined therapy of acupotomy and EA can improve knee function, but the combined therapy obviously increases the walking speed and relieves the symptoms such as joint pain and morning stiffness. The treatment with acupotomy and EA is safe and effective on KOA and the long-term effect is satisfactory.

Characterizing the Efficacy and Safety of Chemotherapy Plus Everolimus in HER2-Negative Metastatic Breast Cancer Harboring Altered PI3K/AKT/mTOR.

BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.

Treatment of bilateral developmental dysplasia of the hip joint with an improved technique: A case report.

BACKGROUND: Developmental dysplasia of the hip (DDH) is a common osteoarticular deformity in pediatric orthopedics. A patient with bilateral DDH was diagnosed and treated using our improved technique "(powerful overturning acetabuloplasty)" combined with femoral rotational shortening osteotomy. CASE SUMMARY: A 4-year-old girl who was diagnosed with bilateral DDH could not stand normally, and sought surgical treatment to solve the problem of double hip extension and standing. As this child had high dislocation of the hip joint and the acetabular index was high, we changed the traditional acetabuloplasty to "powerful turnover acetabuloplasty" combined with femoral rotation shortening osteotomy. During the short-term postoperative follow-up (1, 3, 6, 9, 12, and 15 months), the child had no discomfort in her lower limbs. After the braces and internal fixation plates were removed, formal rehabilitation training was actively carried out. CONCLUSION: Our "powerful overturning acetabuloplasty" combined with femoral rotational shortening osteotomy is feasible in the treatment of DDH in children. This technology may be widely used in the clinic.

Suicide death, suicidal ideation and suicide attempt in patients with diabetes: A systematic review and meta-analysis.

AIMS: Diabetes has been indicated to be a risk factor for suicide. We aim to estimate the prevalence of suicide in patients with diabetes. DESIGN: A meta-analysis using PRISMA methodology was adopted to examine the incidence of suicide in diabetic patients. DATA SOURCES: From inception to October 2022, three online databases (PubMed, China National Knowledge Infrastructure and Web of Science) were used to search studies. REVIEW METHODS: We used random-effects model to analysis. And our primary outcome was the incidence of suicide death per 100 person-years, and other outcomes were prevalence of suicidal ideation and suicide attempt. To explore the sources of heterogeneity in our study, we performed subgroup and meta-regression analyses. RESULTS: The suicide death rate in diabetic patients was 0.027 per 100 person-years, with a higher rate for Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicidal ideation in diabetes patients was 0.175, with a higher prevalence in Type 1 Diabetes Mellitus compared to Type 2 Diabetes Mellitus. The prevalence of suicide attempts in diabetes patients was 0.033, indicating a higher rate for Type 2 Diabetes Mellitus compared to Type 1 Diabetes Mellitus. CONCLUSIONS: The results indicate a high rate of suicide among people with diabetes, and this study identifies populations and regions at high risk for suicide. Our review emphasizes interventions in mental health and the improvement of suicide prevention programmes. IMPACT: The study investigated suicide death, suicidal ideation and suicide attempt in diabetic individuals. Suicide rates are elevated among diabetic patients, and various patient groups face distinct suicide risks. It is important to prioritize the mental well-being of diabetic individuals and enhance interventions, including personalized approaches, to inform public health efforts aimed at preventing and addressing suicide among diabetic patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public involvement.