T2-weighted imaging-based radiomic-clinical machine learning model for predicting the differentiation of colorectal adenocarcinoma.

BACKGROUND: The study on predicting the differentiation grade of colorectal cancer (CRC) based on magnetic resonance imaging (MRI) has not been reported yet. Developing a non-invasive model to predict the differentiation grade of CRC is of great value. AIM: To develop and validate machine learning-based models for predicting the differentiation grade of CRC based on T2-weighted images (T2WI). METHODS: We retrospectively collected the preoperative imaging and clinical data of 315 patients with CRC who underwent surgery from March 2018 to July 2023. Patients were randomly assigned to a training cohort (n = 220) or a validation cohort (n = 95) at a 7:3 ratio. Lesions were delineated layer by layer on high-resolution T2WI. Least absolute shrinkage and selection operator regression was applied to screen for radiomic features. Radiomics and clinical models were constructed using the multilayer perceptron (MLP) algorithm. These radiomic features and clinically relevant variables (selected based on a significance level of P < 0.05 in the training set) were used to construct radiomics-clinical models. The performance of the three models (clinical, radiomic, and radiomic-clinical model) were evaluated using the area under the curve (AUC), calibration curve and decision curve analysis (DCA). RESULTS: After feature selection, eight radiomic features were retained from the initial 1781 features to construct the radiomic model. Eight different classifiers, including logistic regression, support vector machine, k-nearest neighbours, random forest, extreme trees, extreme gradient boosting, light gradient boosting machine, and MLP, were used to construct the model, with MLP demonstrating the best diagnostic performance. The AUC of the radiomic-clinical model was 0.862 (95%CI: 0.796-0.927) in the training cohort and 0.761 (95%CI: 0.635-0.887) in the validation cohort. The AUC for the radiomic model was 0.796 (95%CI: 0.723-0.869) in the training cohort and 0.735 (95%CI: 0.604-0.866) in the validation cohort. The clinical model achieved an AUC of 0.751 (95%CI: 0.661-0.842) in the training cohort and 0.676 (95%CI: 0.525-0.827) in the validation cohort. All three models demonstrated good accuracy. In the training cohort, the AUC of the radiomic-clinical model was significantly greater than that of the clinical model (P = 0.005) and the radiomic model (P = 0.016). DCA confirmed the clinical practicality of incorporating radiomic features into the diagnostic process. CONCLUSION: In this study, we successfully developed and validated a T2WI-based machine learning model as an auxiliary tool for the preoperative differentiation between well/moderately and poorly differentiated CRC. This novel approach may assist clinicians in personalizing treatment strategies for patients and improving treatment efficacy.

A nomogram for predicting lymph nodes metastasis at the inferior mesenteric artery in rectal cancer: a retrospective case-control study.

According to past and current literature, metastasis of the lymph nodes at the inferior mesenteric artery (IMA-LN), also known as 253LN of colorectal cancer has been seldom investigated. To date, there are still controversies on whether the 253LN need to be routinely cleaned. Using specific criteria, 347 patients who underwent radical resection for rectal cancer between April 2019 and July 2022 were selected for the study. Logistic regression was used to determine the likelihood that a patient may suffer 253LN metastasis, and a nomogram for 253LN metastasis subsequently developed. The c-index and calibration curve were used to evaluate precision and discrimination in the nomogram, and the appropriateness of the final nomogram for the clinical setting determined using decision curve analysis (DCA). 253LN metastases appeared in the pathological specimens of 29 (8.4%) of the selected patients. Logistic regression showed that preoperative parameters including serum carcinoembryonic antigen (CEA) value ( > 5 ng / ml, OR = 2.894, P = 0.023), distance from anal margin (> 9 cm, OR = 2.406, P = 0.045) and degree of differentiation (poor, OR = 9.712, P < 0.001) were significantly associated with 253LN metastasis. A nomogram to predict 253LN metastasis in rectal cancer was developed and showed considerable discrimination and good precision (c-index = 0.750). Furthermore, DCA confirmed that the nomogram has some feasibility for the clinical environment. Clinicopathological and radiological patient data can be pivotal for making surgical decisions relating to 253LN metastasis. A nomogram was developed using this data, providing an objective method that can significantly improve prognoses in colorectal cancer.

Latest advances in the study of non-coding RNA-mediated circadian rhythm disorders causing endometrial cancer.

Endometrial cancer (EC) is one of the most common gynecological cancers, and its risk factors include obesity and metabolic, genetic, and other factors. Recently, the circadian rhythm has also been shown to be associated with EC, as the severity of EC was found to be related to night work and rhythm disorders. Therefore, circadian rhythm disorders (CRDs) may be one of the metabolic diseases underlying EC. Changes in the circadian rhythm are regulated by clock genes (CGs), which in turn are regulated by non-coding RNAs (ncRNAs). More importantly, the mechanism of EC caused by ncRNA-mediated CRDs is gradually being unraveled. Here, we review existing studies and reports and explore the relationship between EC, CRDs, and ncRNAs.

Effects of treatment with stem cell-derived extracellular vesicles in preclinical rodent models of intrauterine adhesion: A meta-analysis.

Background: Intrauterine adhesion (IUA) results from serious complications of intrauterine surgery or infection and mostly remains incurable. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) have emerged as a potential new approach for the treatment of IUA; however, their impact is not fully understood. Here, we performed a meta-analysis summarizing the effects of sEVs on IUA in preclinical rodent models. Methods: This meta-analysis included searches of PubMed, EMBASE, Cochrane, and the Web of Science databases from January 1, 1997, to April 1, 2022, to identify studies reporting the therapeutic effect of sEVs on rodent preclinical animal models of IUA. We compared improvements in endometrial thickness, endometrial gland number, fibrosis area, embryo number, vascular endothelial growth factor (VEGF), transforming growth factor ß1 (TGFß1), and leukemia inhibitory factor (LIF) levels after treatment. Results: Our search included 100 citations, of which 7 met the inclusion criteria, representing 231 animals. Compared with that in the control group, the fibrosis area in the sEV-treated group was significantly reduced (standardized mean difference (SMD) = -6.87，95 % confidence interval (CI) = -9.67 to -4.07). The number of glands increased after the intervention (95 % CI, 3.72-7.68; P = 0.000). Endometrial thickness was significantly improved in the sEV-treated group (SMD = 2.57, 95 % CI, 1.62-3.52). Conclusions: This meta-analysis is highlighting that sEV treatment can improve the area of endometrial fibrosis, as well as VEGF, and LIF level, in a mouse IUA model. This knowledge of these findings will provide new insights into future preclinical research.

[Effects of Straw Returning with Lime on SOC and Carbon Pool Management in Acidic Paddy Soil].

Soil acidification and low SOC are the main limiting factors in acidic paddy soils. Straw returning with lime is an effective measure to alleviate soil acidification and improve soil fertility; however, its interaction effects on SOC and carbon pool management are still unclear. To investigate the impact of straw returning with lime on the organic carbon pool of acidic paddy soil, field experiments were conducted on acidic paddy soil in Baiyun District and Huiyang District of Guangdong Province. The changes in soil total organic carbon (TOC), water-soluble organic carbon (DOC), active organic carbon (LOC), particulate organic carbon (POC), microbial biomass carbon (MBC), carbon pool index (CPI), stable organic carbon (IOC), carbon pool activity (L), carbon pool activity index (CPAI), and carbon pool management index (CPMI) were analyzed under three treatments (CK, conventional fertilization; RS, straw returning+conventional fertilization; RS+L straw returning with lime+conventional fertilization). The results demonstrated that compared with that in CK, the TOC, LOC, POC, and MBC in the RS+L treatment were significantly increased by 10.24%-17.79%, 34.49%-44.37%, 19.27%-23.59%, and 33.36%-43.26%, respectively (P<0.05). Compared with that in CK, the RS+L treatment significantly increased the DOC content during the early growth stage (15-45 days after transplanting) of rice (P<0.05) but had no significant influence on the DOC content during the late growth stage of rice. Compared with that in RS, the TOC, LOC, POC, and MBC in the RS+L treatment were increased by 2.15%-6.95%, 1.17%-17.90%, 4.27%-8.65%, and 12.99%-14.53%, respectively. Compared with that in CK, the RS+L treatment significantly increased IOC and CPI by 8.32%-15.57% and 14.00%-20.00%, respectively (P<0.05). Compared with that in the CK treatment, the RS treatment significantly increased CPI by 14.00%-18.00% (P<0.05). No significant differences in L, CPAI, or CPMI were detected among the different treatments. The soil pH in the RS+L treatment was significantly higher than that in the CK treatment (P<0.05). No significant differences in rice yield were detected among the different treatments. Principal component analysis demonstrated that rice yield was primarily correlated with DOC, LOC, CPAI, and CPMI but its contribution to SOC and carbon pool management index was low. Principal component analysis also indicated that straw returning with lime could improve soil pH and nutrient contents of acidic paddy soil, driving the formation and accumulation of organic carbon fraction such as MBC and POC, thus boosting the increase in SOC. In conclusion, straw returning with lime is beneficial to the accumulation of MBC, POC, LOC, and IOC in acidic paddy soil to improve the content and stability of soil total organic carbon, which is an effective way to improve the carbon sequestration of acidic paddy soil.

Recent advances microRNAs and metabolic reprogramming in colorectal cancer research.

Colorectal cancer (CRC) is a cancer with the highest incidence and mortality. Alteration of gene expression is the main pathophysiological mechanism of CRC, which results in disturbed signaling pathways and cellular metabolic processes. MicroRNAs are involved in almost all pathophysiological processes and are correlative with colorectal cancer metabolism, proliferation, and chemotherapy resistance. Metabolic reprogramming, an important feature of cancer, is strongly correlative with the development and prognosis of cancers, including colorectal cancer. MicroRNAs can target enzymes involved in metabolic processes, thus playing a regulatory role in tumor metabolism. The disorder of the signaling pathway is another characteristic of tumor, which induces the occurrence and proliferation of tumors, and is closely correlative with the prognosis and chemotherapy resistance of tumor patients. MicroRNAs can target the components of the signaling pathways to regulate their transduction. Understanding the function of microRNAs in the occurrence and proliferation of CRC provides novel insights into the optimal treatment strategies, prognosis, and development of diagnosis in CRC. This article reviews the relationship between CRC and microRNA expression and hopes to provide new options for the diagnosis and treatment of CRC.

Traditional Chinese medicine for the treatment of Alzheimer's disease: A focus on the microbiota-gut-brain axis.

Alzheimer's disease (AD), the most frequent cause of dementia, is a neurodegenerative disorder characterised by a progressive decline in cognitive function that is associated with the formation of amyloid beta plaques and neurofibrillary tangles. Gut microbiota comprises of a complex community of microorganisms residing in the gastrointestinal ecosystem. These microorganisms can participate in gut-brain axis activities, thereby affecting cognitive function and associated behaviours. Increasing evidence has indicated that gut dysbiosis can jeopardise host immune responses and promote inflammation, which may be an initiating factor for the onset and evolution of AD. Traditional Chinese medicine (TCM) is a promising resource which encompasses immense chemical diversity and multiple-target characteristics for the treatment of AD. Many TCMs regulate the gut microbiota during treatment of diseases, indicating that gut microbiota may be an important target for TCM efficacy. In this review, we summarised the role of the microbiota-gut-brain axis in the development of AD and the effects of TCM in treating AD by regulating the gut microbiota. We anticipate that this review will provide novel perspectives and strategies for future AD research and treatments.

Potential for NPY receptor-related therapies for polycystic ovary syndrome: an updated review.

Polycystic ovary syndrome (PCOS) is a complex endocrine disease that can cause female infertility and bring economic burden to families and to society. The clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, and polycystic ovarian changes, often accompanied by insulin resistance and obesity. Although its pathogenesis is unclear, PCOS involves the abnormal regulation of the hypothalamic-pituitary-ovarian axis and the abnormal activation of GnRH neurons. Neuropeptide Y (NPY) is widely distributed in the arcuate nucleus of the hypothalamus and functions as the physiological integrator of two neuroendocrine systems, one governing feeding and the other controlling reproduction. In recent years, an increasing number of studies have focused on the improvement of the reproductive and metabolic status of PCOS through the therapeutic application of NPY and its receptors. In this review, we summarize the central and peripheral regulation of NPY and its receptors in the development of PCOS and discuss the potential for NPY receptor-related therapies for PCOS.

Focusing on scRNA-seq-Derived T Cell-Associated Genes to Identify Prognostic Signature and Immune Microenvironment Status in Low-Grade Glioma.

Background: The clinical outcomes of low-grade glioma (LGG) are associated with T cell infiltration, but the specific contribution of heterogeneous T cell types remains unclear. Method: To study the different functions of T cells in LGG, we mapped the single-cell RNA sequencing results of 10 LGG samples to obtain T cell marker genes. In addition, bulk RNA data of 975 LGG samples were collected for model construction. Algorithms such as TIMER, CIBERSORT, QUANTISEQ, MCPCOUTER, XCELL, and EPIC were used to depict the tumor microenvironment landscape. Subsequently, three immunotherapy cohorts, PRJEB23709, GSE78820, and IMvigor210, were used to explore the efficacy of immunotherapy. Results: The Human Primary Cell Atlas was used as a reference dataset to identify each cell cluster; a total of 15 cell clusters were defined and cells in cluster 12 were defined as T cells. According to the distribution of T cell subsets (CD4+ T cell, CD8+ T cell, Naïve T cell, and Treg cell), we selected the differentially expressed genes. Among the CD4+ T cell subsets, we screened 3 T cell-related genes, and the rest were 28, 4, and 13, respectively. Subsequently, according to the T cell marker genes, we screened six genes for constructing the model, namely, RTN1, HERPUD1, MX1, SEC61G, HOPX, and CHI3L1. The ROC curve showed that the predictive ability of the prognostic model for 1, 3, and 5 years was 0.881, 0.817, and 0.749 in the TCGA cohort, respectively. In addition, we found that risk scores were positively correlated with immune infiltration and immune checkpoints. To this end, we obtained three immunotherapy cohorts to verify their predictive ability of immunotherapy effects and found that high-risk patients had better clinical effects of immunotherapy. Conclusion: This single-cell RNA sequencing combined with bulk RNA sequencing may elucidate the composition of the tumor microenvironment and pave the way for the treatment of low-grade gliomas.

Comparison of Yizhiqingxin formula extraction methods and their pharmacodynamic differences.

Objectives: This study compared different extraction methods of Yizhiqingxin formula (YQF) and its neuroprotective effects based on pharmacodynamic indices such as learning and memory ability, brain tissue histopathology and morphology, and inflammatory factor expression in a mouse model of Alzheimer's disease (AD). Methods: The pharmaceutical components of YQF were extracted using three extraction processes, and the components were analyzed by high performance liquid chromatography. Donepezil hydrochloride was used as a positive control drug. Fifty 7-8-month-old 3 × Tg AD mice were randomly divided into three YQF groups (YQF-1, YQF-2, and YQF-3), a donepezil group, and a model group. Ten age-matched C57/BL6 mice were used as normal controls. YQF and Donepezil were administered by gavage at a clinically equivalent dose of 2.6 and 1.3 mg⋅kg-1⋅d-1, respectively, with a gavage volume of 0.1 ml/10 g. Control and model groups received equal volumes of distilled water by gavage. After 2 months, the efficacy was evaluated using behavioral experiments, histopathology, immunohistochemistry, and serum assays. Results: The main components in YQF are ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, epiberberine, coptisine chloride, palmatine, berberine, and ferulic acid. YQF-3 (alcohol extraction) has the highest content of active compounds, followed by YQF-2 (water extraction and alcohol precipitation method). Compared to the model group, the three YQF groups showed alleviated histopathological changes and improved spatial learning and memory, with the effect in YQF-2 being the most significant. YQF showed protection of hippocampal neurons, most significantly in the YQF-1 group. YQF significantly reduced Aß pathology and tau hyperphosphorylation, decreased expressions of serum pro-inflammatory factors interleukin-2 and interleukin-6 as well as serum chemokines MCP-1 and MIG. Conclusion: YQF prepared by three different processes showed differences in pharmacodynamics in an AD mouse model. YQF-2 was significantly better than the other extraction processes in improving memory.

Laparoscopic resection and endoscopic submucosal dissection for treating gastric ectopic pancreas.

BACKGROUND: Gastric ectopic pancreas (GEP) is a rare developmental abnormality that refers to the existence of pancreatic tissue in the stomach with no anatomical relationship with the main pancreas. It is usually difficult to diagnose through histological examination, and the choice of treatment method is crucial. AIM: To describe the endoscopic ultrasound characteristics of GEP and evaluate the value of laparoscopic resection (LR) and endoscopic submucosal dissection (ESD). METHODS: Forty-nine patients with GEP who underwent ESD and LR in the Second Affiliated Hospital of Fujian Medical University from May 2018 to July 2023 were retrospectively included. Data on clinical characteristics, endoscopic ultrasonography (EUS), ESD, and LR were collected and analyzed. The characteristics of EUS and the efficacy of the two treatments were analyzed. RESULTS: The average age of the patients was 43.31 ± 13.50 years, and the average maximum diameter of the lesions was 1.55 ± 0.70 cm. The lesion originated from the mucosa in one patient (2.04%), from the submucosa in 42 patients (85.71%), and from the muscularis propria in 6 patients (12.25%). Twenty-nine patients (59.20%) with GEP showed umbilical depression on endoscopy. The most common initial symptom of GEP was abdominal pain (40.82%). Tumor markers, including carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA-19-9), were generally within the normal range. One patient (2.04%) with GEP had increased CEA and CA-19-9 levels. However, no cancer tissue was found on postoperative pathological examination, and tumor markers returned to normal levels after resecting the lesion. There was no significant difference in surgery duration (72.42 ± 23.84 vs 74.17 ± 12.81 min) or hospital stay (3.70 ± 0.91 vs 3.83 ± 0.75 d) between the two methods. LR was more often used for patients with larger tumors and deeper origins. The amount of bleeding was significantly higher in LR than in ESD (11.28 ± 16.87 vs 16.67 ± 8.76 mL, P < 0.05). Surgery was associated with complete resection of the lesion without any serious complications; there were no cases of recurrence during the follow-up period. CONCLUSION: GEP has unique characteristics in EUS. LR and ESD seem to be good choices for treating GEP. LR is better for large GEP with a deep origin. However, due to the rarity of GEP, multicenter large-scale studies are needed to describe its characteristics and evaluate the safety of LR and ESD.

Therapeutic potential of exosomes/miRNAs in polycystic ovary syndrome induced by the alteration of circadian rhythms.

Polycystic ovary syndrome (PCOS) is a reproductive dysfunction associated with endocrine disorders and is most common in women of reproductive age. Clinical and/or biochemical manifestations include hyperandrogenism, persistent anovulation, polycystic ovary, insulin resistance, and obesity. Presently, the aetiology and pathogenesis of PCOS remain unclear. In recent years, the role of circadian rhythm changes in PCOS has garnered considerable attention. Changes in circadian rhythm can trigger PCOS through mechanisms such as oxidative stress and inflammation; however, the specific mechanisms are unclear. Exosomes are vesicles with sizes ranging from 30-120nm that mediate intercellular communication by transporting microRNAs (miRNAs), proteins, mRNAs, DNA, or lipids to target cells and are widely involved in the regulation of various physiological and pathological processes. Circadian rhythm can alter circulating exosomes, leading to a series of related changes and physiological dysfunctions. Therefore, we speculate that circadian rhythm-induced changes in circulating exosomes may be involved in PCOS pathogenesis. In this review, we summarize the possible roles of exosomes and their derived microRNAs in the occurrence and development of PCOS and discuss their possible mechanisms, providing insights into the potential role of exosomes for PCOS treatment.

[Effects of Early Rice Straw Returning with Reducing Potassium Fertilizer on Late Rice Yield and Soil Fertility].

Rice straw is an important organic fertilizer in the region for double-cropping rice in South China. To reveal the effects of early rice returning with reducing potassium fertilizer on the yield of late rice and soil fertility, field experiments were carried out in Baiyun and Huiyang district in Guangdong province. The biomass, K content, and yield of late rice and the soil fertility properties, such as soil available potassium, soil organic carbon, bacterial diversity, and bacterial community structure were analyzed under three treatments (CK, conventional fertilization; RS, straw returning with conventional fertilization; RS-K, straw returning with reducing 20% potassium fertilizer). The results showed no significant differences in the biomass and yield of late rice between the RS-K treatment and CK treatment. Compared with that in CK, the RS treatment significantly increased the K contents of rice by 3.97% (Baiyun) and 6.91% (Huiyang). The K contents of late rice under the RS-K treatment were significantly lower than that under the CK treatment during the early growth period in rice, but there was no significant difference between them during the late growth period. Compared with that in CK, the soil available K in the RS treatment increased by 13.90% (Baiyun) and 21.67% (Huiyang) (P<0.05), and the soil available K in the RS-K treatment also increased by 3.56% (Baiyun) and 4.23% (Huiyang). Compared with that in the CK treatment, the soil dissolved organic carbon increased significantly in the RS and RS-K treatments (P<0.05). Compared with that in CK, the straw returning treatments (RS and RS-K) significantly improved the Chao1 and Shannon indexes of soil bacteria (P<0.05). Straw returning treatments (RS and RS-K) increased the relative abundance of Proteobacteria, Actinobacteria, and Nitrospirae compared with that in CK, whereas they decreased the relative abundance of Acidobacteria, Bacteroidetes, and Firmicutes. Redundancy analysis showed that the soil bacterial community was mainly influenced by soil organic carbon, dissolved organic carbon, microbial biomass carbon, available P, and available K. In summary, early rice returning could increase soil available K and K content in late rice. Early rice straw returning with reducing potassium fertilizer had no negative impacts on the growth and yield of late rice and could also improve soil organic carbon and the diversity of soil bacteria. Therefore, early rice straw returning with reducing potassium fertilizer can guarantee the grain yield of late rice and improve soil fertility.

HSP70-Promoter-Driven CRISPR/Cas9 System Activated by Reactive Oxygen Species for Multifaceted Anticancer Immune Response and Potentiated Immunotherapy.

To address the low response rate to immune checkpoint blockade (ICB) therapy, we propose a specific promoter-driven CRISPR/Cas9 system, F-PC/pHCP, that achieves permanent genomic disruption of PD-L1 and elicits a multifaceted anticancer immune response to potentiate immunotherapy. This system consists of a chlorin e6-encapsulated fluorinated dendrimer and HSP70-promoter-driven CRISPR/Cas9. F-PC/pHCP under 660 nm laser activated the HSP70 promoter and enabled the specific expression of the Cas9 protein to disrupt the PD-L1 gene, preventing immune escape. Moreover, F-PC/pHCP also induced immunogenic cell death (ICD) of tumor cells and reprogrammed the immunosuppressive tumor microenvironment. Overall, this specific promoter-driven CRISPR/Cas9 system showed great anticancer efficacy and, more importantly, stimulated an immune memory response to inhibit distant tumor growth and lung metastasis. This CRISPR/Cas9 system represents an alternative strategy for ICB therapy as well as enhanced cancer immunotherapy.

Melatonin enhances autologous adipose-derived stem cells to improve mouse ovarian function in relation to the SIRT6/NF-κB pathway.

BACKGROUND: Premature ovarian insufficiency (POI) is the main cause of female infertility. Adipose-derived stem cells (ADSCs) are ideal candidates for the treatment of POI. However, some deficient biological characteristics of ADSCs limit their utility. This study investigated whether melatonin (MLT)-pretreated autologous ADSCs were superior to ADSCs alone in the treatment of the POI mouse model. METHODS: Autologous ADSCs were isolated and cultured in MLT-containing medium. Surface markers of ADSCs were detected by flow cytometry. To determine the effect of MLT on ADSCs, CCK-8 assay was used to detect ADSCs proliferation and enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokines. The POI model was established by intraperitoneal injection of cyclophosphamide and busulfan. Then, MLT-pretreated autologous ADSCs were transplanted into mice by intraovarian injection. After 7 days of treatment, ovarian morphology, follicle counts, and sex hormones levels were evaluated by hematoxylin and eosin (H&E) staining and ELISA, and the recovery of fertility was also observed. The expressions of SIRT6 and NF-κB were detected by immunohistochemical (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Flow cytometry showed that autologous ADSCs expressed CD90 (99.7%) and CD29 (97.5%). MLT can not only promote the proliferation of ADSCs but also boost their secretory function, especially when ADSCs were pretreated with 5 µM MLT for 3 days, improving the interference effect. After transplantation of autologous ADSCs pretreated with 5 µM MLT, the serum hormone levels and reproductive function were significantly recovered, and the mean counts of primordial follicle increased. At the same time, the expression of SIRT6 was remarkably increased and the expression of NF-κB was significantly decreased in this group. CONCLUSIONS: MLT enhances several effects of ADSCs in restoring hormone levels, mean primordial follicle counts, and reproductive capacity in POI mice. Meanwhile, our results suggest that the SIRT6/NF-κB signal pathway may be the potential therapeutic mechanism for ADSCs to treat POI.

Clinical Evaluation of Autologous and Allogeneic Stem Cell Therapy for Intrauterine Adhesions: A Systematic Review and Meta-Analysis.

Objective: Intrauterine adhesions (IUAs) are a major cause of female infertility. Stem cells can be used to restore endometrial function owing to their regenerative abilities. We compared the safety and efficacy of autologous and allogeneic stem cell treatments in patients with recurrent IUA after conventional therapy based on a systematic review of the related literature. Methods: The PubMed, Embase, and Cochrane databases were systematically searched. All analysis were performed using Review Manager 5.4. We compared improvements in endometrial thickness, pregnancy rates, menstruation, and side effects after autologous and allogeneic stem cell therapy. The study was registered with PROSPERO, CRD 42022322870. Results: Our search returned 154 reports, 10 of which met the inclusion criteria, representing 116 patients. Of these, 44 patients in two studies were treated with allogeneic stem cells and 72 patients in eight studies were treated with autologous stem cells. Improvements in endometrial thickness and pregnancy rates after intrauterine device treatment were compared between the autologous and allogeneic stem cell groups. Endometrial thickness increased more after autologous stem cell IUA treatment (mean difference, 1.68; 95% confidence interval [CI]: 1.30-2.07; P < 0.00001), and the pregnancy rate was also improved (relative risk, 1.55; 95% CI: 1.19-2.02, P < 0. 001). No obvious and serious adverse reactions were observed during stem cell therapy in either group. Conclusions: This meta-analysis and systematic review of the results of randomized trials of autologous and allogeneic stem cell treatments for IUA suggests that autologous stem cells have a better effect in improving the endometrium thickness and pregnancy rate. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022322870.

Staphylococcus aureus small-colony variants: Formation, infection, and treatment.

Staphylococcus aureus (Sau) plays an important role in human infections occurring in both the community and hospital settings. Sau-related chronic and relapsing infections are mainly attributed to small-colony variants (SCVs), a type of subpopulation that has a size one-tenth that of normal colonies and is accompanied by several unique characteristics, including a lack of or reduced pigmentation, decreased hemolytic activity, increased biofilm formation, enhanced resistance to antimicrobials, upregulated genes encoding adhesion molecules, and downregulated genes for virulence factors. This review summarizes the significance of genetic mutations involved in diverse biosynthesis pathways that contribute to Sau-SCV promotion. Sau-SCV-caused persistent infections and the prospects and challenges faced in the treatment of Sau-SCV infections are addressed. Progress in the management of Sau-SCVs may provide guidance for addressing the long-term and recurrent infections caused by other bacterial SCVs.

Therapeutic options for premature ovarian insufficiency: an updated review.

Primary ovarian insufficiency (POI) is a rare gynecological condition. This disease causes menstrual disturbances, infertility, and various health problems. Historically, hormone replacement therapy is the first-line treatment for this disorder. Women diagnosed with POI are left with limited therapeutic options. In order to remedy this situation, a new generation of therapeutic approaches, such as in vitro activation, mitochondrial activation technique, stem cell and exosomes therapy, biomaterials strategies, and platelet-rich plasma intra-ovarian infusion, is being developed. However, these emerging therapies are yet in the experimental stage and require precise design components to accelerate their conversion into clinical treatments. Thus, each medical practitioner bears responsibility for selecting suitable therapies for individual patients. In this article, we provide a timely analysis of the therapeutic strategies that are available for POI patients and discuss the prospects of POI therapy.

A network meta-analysis on the improvement of cognition in patients with vascular dementia by different acupuncture therapies.

Introduction: The second most prevalent cause of dementia is vascular dementia (VaD). Furthermore, acupuncture is a relatively safe and effective traditional therapy for individuals with VaD. We performed a network meta-analysis to assess the effectiveness and safety of various acupuncture therapies for VaD based on existing research. Methods: We searched six electronic databases to screen for randomized controlled trials (RCTs) comparing different acupuncture treatments in VaD patients. The Cochrne tool (Review Manager 5.3) was used to evaluate the risk of bias of the included RCTs. Based on the Grading of Recommendations Assessment, Development and Evaluation framework, we assessed the confidence in the evidence using the Confidence In the results from Network Meta-Analysis approach. We used the frequency approach to perform the network meta-analysis. Data were analyzed using R 4.1.1. Results: In total, we included 46 eligible studies. The results of the network analysis showed that the combined interventions of moxibustion (MB) with body acupuncture (BA) (MB + BA) and electroacupuncture (EA) with scalp acupuncture (SA) with BA (EA + SA + BA) were more effective in improving cognitive functions and activities of daily living compared with SA or BA alone. However, in the subgroup analysis, EA + SA + BA showed better efficacy in short- and mid-term acupuncture compared with other acupuncture therapies. Conclusion: Combined acupuncture therapy may be a safe and effective intervention for individuals with VaD, and MB + BA and EA + SA + BA appear to be the most effective interventions. However, because the analysis of this study was based on low-to-moderate evidence, there remains no strong supporting evidence. Thus, high-quality, large-scale, and long-term studies should be conducted in the future to assess the effectiveness and safety of acupuncture in VaD. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42022354573.