Inflammatory stimulus-responsive polymersomes reprogramming glucose metabolism mitigates rheumatoid arthritis.

Inflammation-resident cells within arthritic sites undergo a metabolic shift towards glycolysis, which greatly aggravates rheumatoid arthritis (RA). Reprogramming glucose metabolism can suppress abnormal proliferation and activation of inflammation-related cells without affecting normal cells, holding potential for RA therapy. Single 2-deoxy-d-glucose (2-DG, glycolysis inhibitor) treatment often cause elevated ROS, which is detrimental to RA remission. The rational combination of glycolysis inhibition with anti-inflammatory intervention might cooperatively achieve favorable RA therapy. To improve drug bioavailability and exert synergetic effect, stable co-encapsulation of drugs in long circulation and timely drug release in inflamed milieu is highly desirable. Herein, we designed a stimulus-responsive hyaluronic acid-triglycerol monostearate polymersomes (HTDD) co-delivering 2-DG and dexamethasone (Dex) to arthritic sites. After intravenous injection, HTDD polymersomes facilitated prolonged circulation and preferential distribution in inflamed sites, where overexpressed matrix metalloproteinases and acidic pH triggered drug release. Results indicated 2-DG can inhibit the excessive cell proliferation and activation, and improve Dex bioavailability by reducing Dex efflux. Dex can suppress inflammatory signaling and prevent 2-DG-induced oxidative stress. Thus, the combinational strategy ultimately mitigated RA by inhibiting glycolysis and hindering inflammatory signaling. Our study demonstrated the great potential in RA therapy by reprogramming glucose metabolism in arthritic sites.

Highly selective photocatalytic CO2 reduction into C2H4 enabled by metal-organic framework-derived catalysts with high Cu+ content.

The highly selective conversion of CO2 into valuable C2H4 is a highly important but particularly challenging reaction. Herein, the metal-organic frameworks MOF-74(Cu) with infinite Cu(II)-O chains and Cu-BTC (BTC=benzene-1,3,5-tricarboxylate) with paddle-wheel binuclear Cu(II) clusters are used as precursors. These MOFs are reduced by NaBH4 to obtain Cu0/Cuδ+-based photocatalysts denoted as R-MOF-74(Cu) and R-Cu-BTC, respectively. Significantly, R-MOF-74(Cu) achieves a high selectivity of 90.2 % for C2H4 with a yield rate of 6.5 µmol g-1 within 5 h due to its high Cu+ content. To the best of our knowledge, this C2H4 product selectivity is a record high among all the photocatalysts reported so far for photocatalytic CO2 reduction. In contrast, R-Cu-BTC only forms CO as a product with a cumulative yield of 0.7 µmol g-1 within 5 h. Photoelectrochemical characterization and electron paramagnetic resonance results show that R-MOF-74(Cu) has low interfacial transfer resistance, high photogenerated electron separation efficiency, and excellent CO2 activation and water oxidation performance. In addition, in situ Fourier transform infrared spectroscopy is used to determine the possible reaction pathway from CO2 to C2H4 over R-MOF-74(Cu). This work demonstrates the great potential of MOF-derived photocatalysts for the conversion of CO2 into C2H4 and provides guidance for future photocatalyst development.

Bioinformatics analysis of effective biomarkers and immune infiltration in type 2 diabetes with cognitive impairment and aging.

With the increasing prevalence of diabetes mellitus worldwide, type 2 diabetes mellitus (T2D) combined with cognitive impairment and aging has become one of the common and important complications of diabetes mellitus, which seriously affects the quality of life of the patients, and imposes a heavy burden on the patients' families and the society. Currently, there are no special measures for the treatment of cognitive impairment and aging in type 2 diabetes mellitus. Therefore, the search for potential biological markers of type 2 diabetes mellitus combined with cognitive impairment and aging is of great significance for future precisive treatment. We downloaded three gene expression datasets from the GEO database: GSE161355 (related to T2D with cognitive impairment and aging), GSE122063, and GSE5281 (related to Alzheimer's disease). Differentially expressed genes (DEGs) were identified, followed by gene set enrichment analysis (GSEA). A protein-protein interaction (PPI) network was constructed using the STRING database, and the top 15 hub genes were identified using the CytoHubba plugin in Cytoscape. Core genes were ultimately determined using three machine learning methods: LASSO regression, Support Vector Machine Recursive Feature Elimination (SVM-RFE), and Linear Discriminant Analysis (LDA). The diagnostic performance of these genes was assessed using ROC curve analysis and validated in an independent dataset (GSE5281). Regulatory genes related to ferroptosis were screened from the FerrDb database, and their biological functions were further explored through GO and KEGG enrichment analyses. Finally, the CIBERSORT algorithm was used to analyze immune cell infiltration, and the correlation between core genes and immune cell infiltration levels was calculated, leading to the construction of an mRNA-miRNA regulatory network. In the GSE161355 and GSE122063 datasets, 217 common DEGs were identified. GSEA analysis revealed their enrichment in the PI3K-PLC-TRK signaling pathway, TP53 regulation of metabolic genes pathway, Notch signaling pathway, among others. PPI network analysis identified 15 candidate core genes, and further selection using LASSO, LDA, and SVM-RFE machine learning algorithms resulted in 6 core genes: BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1. ROC curve analysis indicated that these genes had good diagnostic performance in the GSE161355 dataset, with TP53 and IL1B achieving an AUC of 0.9, indicating the highest predictive accuracy. BCL6, HSP90AA1, CRYAB, and DNAJB1 also had AUCs greater than 0.8, demonstrating moderate predictive accuracy. Validation in the independent dataset GSE5281 showed that these core genes also had good diagnostic performance in Alzheimer's disease samples (AUC > 0.6). Ferroptosis-related analysis revealed that IL1B and TP53 play significant roles in apoptosis and immune response. Immune cell infiltration analysis showed that IL1B is significantly positively correlated with infiltration levels of monocytes and NK cells, while TP53 is significantly negatively correlated with infiltration levels of follicular helper T cells. The construction of the miRNA-mRNA regulatory network suggested that miR-150a-5p might play a key role in the regulation of T2D-associated cognitive impairment and aging by TP53. This study, by integrating bioinformatics and machine learning methods, identified BCL6, TP53, HSP90AA1, CRYAB, IL1B, and DNAJB1 as potential diagnostic biomarkers for T2D with cognitive impairment and aging, with a particular emphasis on the significance of TP53 and IL1B in immune cell infiltration. These findings not only enhance our understanding of the molecular mechanisms linking type 2 diabetes to cognitive impairment and aging, providing new targets for early diagnosis and treatment, but also offer new directions and targets for basic research.

NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction.

BACKGROUND: N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional mechanism, plays a pivotal role in RNA modification and tumor progression. However, the molecular mechanism by which ac4C modification mediates tumor immunosuppression remains elusive in triple-negative breast cancer (TNBC). METHODS: NAT10 expression was analyzed in TNBC samples in the level of mRNA and protein, and compared with the corresponding normal tissues. ac4C modification levels also measured in the TNBC samples. The effects of NAT10 on immune microenvironment and tumor metabolism were investigated. NAT10-mediated ac4C and its downstream regulatory mechanisms were determined in vitro and in vivo. The combination therapy of targeting NAT10 in TNBC was further explored. RESULTS: The results revealed that the loss of NAT10 inhibited TNBC development and promoted T cell activation. Mechanistically, NAT10 upregulated JunB expression by increasing ac4C modification levels on its mRNA. Moreover, JunB further up-regulated LDHA expression and facilitated glycolysis. By deeply digging, remodelin, a NAT10 inhibitor, elevated the surface expression of CTLA-4 on T cells. The combination of remodelin and CTLA-4 mAb can further activate T cells and inhibite tumor progression. CONCLUSION: Taken together, our study demonstrated that the NAT10-ac4C-JunB-LDHA pathway increases glycolysis levels and creates an immunosuppressive tumor microenvironment (TME). Consequently, targeting this pathway may assist in the identification of novel therapeutic strategies to improve the efficacy of cancer immunotherapy.

Noninvasive Left Ventricular Pressure-Strain Loop for Quantitative Assessment of Early Left Ventricular Systolic Dysfunction in Patients With Chronic Kidney Disease.

BACKGROUND: Patients with chronic kidney disease (CKD) possess a pronounced risk for cardiovascular events. A noninvasive left ventricular pressure-strain loop (LV-PSL) has recently been introduced to detect subtler changes in cardiac function. This study aims to investigate the value of LV-PSL for quantitative assessment of myocardial work (MW) in patients with CKD. METHODS: Seventy-five patients with CKD were enrolled retrospectively (37 patients with CKD Stages 2-3, and 38 patients with CKD Stages 4-5), and 35 healthy volunteers were included as controls. All subjects underwent transthoracic echocardiography. LV-PSL analysis was performed to estimate LV MW and efficiency. Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were obtained by echocardiography, and the differences among the groups were compared. RESULTS: There was a significant increase in GWW and reduction in GWE in patients with CKD compared to normal controls (p < 0.05). No significant difference in GWI and GCW was observed among the three groups. Multiple linear regression revealed that increased GWW was significantly associated with age, serum creatinine, and systolic pressure, and decreased GWE was associated with age, serum creatinine, and GLS. CONCLUSION: LV-PSL can be used for noninvasive quantitative assessment of MW in patients with CKD, providing a new sensitive approach for the clinical assessment of myocardial function.

A random survival forest-based pathomics signature classifies immunotherapy prognosis and profiles TIME and genomics in ES-SCLC patients.

BACKGROUND: Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with high mortality, and only a limited subset of extensive-stage SCLC (ES-SCLC) patients demonstrate prolonged survival under chemoimmunotherapy, which warrants the exploration of reliable biomarkers. Herein, we built a machine learning-based model using pathomics features extracted from hematoxylin and eosin (H&E)-stained images to classify prognosis and explore its potential association with genomics and TIME. METHODS: We retrospectively recruited ES-SCLC patients receiving first-line chemoimmunotherapy at Nanjing Jinling Hospital between April 2020 and August 2023. Digital H&E-stained whole-slide images were acquired, and targeted next-generation sequencing, programmed death ligand-1 staining, and multiplex immunohistochemical staining for immune cells were performed on a subset of patients. A random survival forest (RSF) model encompassing clinical and pathomics features was established to predict overall survival. The function of putative genes was assessed via single-cell RNA sequencing. RESULTS AND CONCLUSION: During the median follow-up period of 12.12 months, 118 ES-SCLC patients receiving first-line immunotherapy were recruited. The RSF model utilizing three pathomics features and liver metastases, bone metastases, smoking status, and lactate dehydrogenase, could predict the survival of first-line chemoimmunotherapy in patients with ES-SCLC with favorable discrimination and calibration. Underlyingly, the higher RSF-Score potentially indicated more infiltration of CD8+ T cells in the stroma as well as a greater probability of MCL-1 amplification and EP300 mutation. At the single-cell level, MCL-1 was associated with TNFA-NFKB signaling and apoptosis-related processes. Hopefully, this noninvasive model could act as a biomarker for immunotherapy, potentially facilitating precision medicine in the management of ES-SCLC.

A Medicago truncatula HD-ZIP gene MtHB2 is involved in modulation of root development by regulating auxin response.

HD-Zip proteins are plant-specific transcription factors known for their diverse functions in regulating plant growth, development, and responses to environmental stresses. Among the Medicago truncatula HD-Zip II genes, MtHB2 has been previously linked to abiotic stress responses. In this study, we conducted a functional characterization of MtHB2 in the regulation of root growth and development. Upon auxin stimulation, expression of MtHB2 was promptly up-regulated. Overexpression of MtHB2 in Arabidopsis thaliana led to reduced primary root growth and inhibited lateral root formation. Interestingly, the transgenic plants expressing MtHB2 exhibited differential responses to three types of auxins (IAA, NAA, and 2,4-D) in terms of root growth and development compared to the wild-type plants. Specifically, primary root growth was less affected, and lateral root formation was enhanced in the transgenic plants when exposed to auxins. This differential response suggests a potential role for MtHB2 in modulating auxin transport and accumulation, as evidenced by the reduced sensitivity of the transgenic plants to the auxin transport inhibitor NPA and lower expression levels of auxin-related reporters such as PIN-FORMED (PIN1)::PIN1-GFP, PIN3::PIN3-GFP, PIN7::PIN7-GFP, and DR5::GFP compared to wild-type plants. Additionally, microarray analysis of the root tissues revealed down-regulation of several auxin-responsive genes in transgenic seedlings compared to wild-type plants. These findings collectively indicate that MtHB2 plays a critical regulatory role in root growth and development by modulating auxin accumulation and response in the roots.

Exploring the causes of variability in quality of oropharyngeal swab sampling for SARS-CoV-2 nucleic acid testing and proposed improvement measures: a multicenter, double-blind study.

Although coronavirus disease 2019 (COVID-19) has not been considered a public health emergency of international concern since last year, intermittent regional impacts still persist, and accurate testing remains crucial. Ribonuclease P protein subunit P30 (RPP30) RNA, known for its broad and stable expression in tissue cells, was used to evaluate samples from 10 hospitals with over 3,000 negative nucleic acid tests. The results revealed that the overall pass rate for the collected samples was consistently low and exhibited significant heterogeneity. After reassessing the evaluative effectiveness of RPP30 RNA Ct values from the samples of 132 positive individuals under quarantine observation, it was used to identify factors affecting sampling quality. These factors included different stages ranging from sample collection to PCR processing, various characteristics of both samplers and individuals being sampled, as well as sampling season and location. The results indicated that post-sampling handling had minimal impact, winter and fever clinic samples showed higher quality, whereas children's samples had lower quality. The key finding was that the characteristics of samplers were closely related to sampling quality, emphasizing the role of subjectivity. Quality control warnings led to substantial improvements, confirming this finding. Consequently, although there are various factors during the testing process, the most critical aspect is to improve, supervise, and maintain standardized practices among sampling staff.IMPORTANCEThis study further confirmed the reliability of internal references (IRs) in assessing sample quality, and utilized a large sample IR data to comprehensively and multidimensionally identify significant interference factors in nucleic acid test results. By further reminding and intervening in the subjective practices of specimen collectors, good results could be achieved.

Characterization of clinical infection and drug resistance of group B streptococcus in Chengdu, China.

OBJECTIVE: To investigate the clinical infection characteristics and antibiotic resistance of Group B Streptococcus (Streptococcus agalactiae, GBS) in Chengdu, China, from 2019 to 2021, as well as to provide data to support rational clinical drug use. METHODS: This was a retrospective study to collect 203 culture-positive GBS strains isolated from January 2019 to December 2021 in Chengdu, China, all of which were identified by the VITEK 2 Compact automated microbial Bacterial identification instrument. Data were derived using WHONET 5.6 software. The sample type and ward distribution were counted. Pregnant women and newborns were screened from the original data and their pregnancy outcomes were calculated respectively. RESULTS: GBS strains were mainly concentrated in obstetrics and neonatology departments, accounting for 40.9 % and 33.5 %. The types of specimens were mainly vaginal secretions, amniotic fluid and sputum, accounting for 25.6 %, 26.1 % and 18.7 %, respectively. Chorioamnionitis, premature rupture of membranes and preterm delivery occurred mainly in pregnant women after infection, accounting for 44.4 %, 31.5 % and 24.1 %. Neonates, on the other hand, were mainly diagnosed with neonatal pneumonia, neonatal sepsis, respiratory failure and septic meningitis, accounting for 91.8 %, 61.2 %, 44.9 % and 16.3 % of all positive neonates. 840 pregnant women were screened for GBS colonization from 2019 to 2021, and a total of 108 GBS positive pregnant women were identified, with a GBS colonization rate of 12.9 %. A total of 9 neonates from 108 GBS positive pregnant women developed early-onset disease. The morbidity in neonates was 8.3 %. No strains resistant to penicillin and ampicillin were found, while the resistance rates of tetracycline and clindamycin were higher than 50 %, respectively 60.1 % and 53.2 %. CONCLUSION: GBS infection mainly affected pregnant women and newborns in Chengdu, China, which can lead to adverse maternal and infant outcomes. Attention should be paid to strengthening general screening of GBS in perinatal urogenital secretions and the prevention strategy of IAP (intrapartum antibiotic prophylaxis). Antimicrobial therapy should be administered with appropriate antibiotics. Penicillin was still the first line drug for the treatment of GBS. These initiatives were important to reduce mother-to-child transmission and neonatal infections.

Novel mutation in XPNPEP3 in a patient with heart failure without nephronophthisis-like nephropathy (NPHPL1): case report and literature review.

BACKGROUND X-PROLYL AMINOPEPTIDASE 3: (XPNPEP3) mutations are known to cause nephronophthisis-like nephropathy-1 (NPHPL1), a rare autosomal-recessive kidney disease characterized by progressive kidney failure and cystic kidney disease in childhood. The full phenotypic spectrum associated with mutations in XPNPEP3 is not fully elucidated. CASE PRESENTATION: A 13-year-old Chinese female patient with intellectual disability presented with a 2-year history of convulsions and fatigue, with a recent episode of swelling, breathlessness, and nocturnal dyspnea lasting 10 days. The patient was diagnosed with heart failure and kidney failure. Whole exome sequencing revealed a homozygous c.970-2 A > G mutation in XPNPEP3 associated with severe cardiac dysfunction and neurological symptoms, including epilepsy and intellectual disability. Notably, kidney ultrasound did not reveal the typical changes of NPHPL1, and kidney failure was hypothesized to be secondary to cardiac dysfunction rather than primary kidney pathology. CONCLUSIONS: This case suggests the possible association of additional phenotypic features associated with XPNPEP3 mutations, emphasizing the need for further investigation into the heterogeneous clinical presentations associated with XPNPEP3 mutations. The findings highlight the importance of considering alternative phenotypes in patients with genetic mutations traditionally associated with specific diseases. Segregation and functional analyses are necessary to determine causality between the c.970-2 A > G XPNPEP3 mutation and disease.

NWD1 influences the extension of neuronal axons by regulating microtubule stability.

Proteins belonging to the STAND (signal transduction ATPases with numerous domains) family have been implicated in crucial functions across various signal transduction pathways, encompassing both apoptosis and innate immune responses. In this study, we have identified NWD1, a member of the STAND superfamily, as a gene that regulates neurite outgrowth. This was confirmed by siRNA knockdown assay in E18 neurons. A zebrafish model was utilized to create NWD1 knockdown using the NgAgo-gDNA system, revealing the significant role of NWD1 in neurogenesis. We further revealed that NWD1 siRNA reduced the acetylated tubulin protein, and changed the ratio of soluble and polymerized tubulin. Moreover, we investigated the mechanism underlying the regulation of NWD1-mediated microtubule dynamics, and MAP1B may be a target gene. This research unveiled, for the first time, the potential role of NWD1 in regulating axon outgrowth through modulating the ratio of acetylated tubulin.

Early vascular healing after neXt-generation drug-eluting stent implantation in Patients with non-ST elevation acute Coronary syndrome: a randomized optical coherence Tomography imaging study (EXPECT).

Early vascular healing after drug-eluting stent (DES) implantation is associated with better outcomes and lower incidence of in-stent thrombosis. To examine vascular healing response in patients with non-ST elevation acute coronary syndrome (NSTE-ACS) undergoing percutaneous coronary intervention (PCI) guided by optical coherence tomography (OCT) versus angiography alone. Sixty patients were randomized 1:1:1 to OCT-guided PCI with 3-month OCT follow-up (O3 group, n = 20), angiography-guided PCI with 3-month OCT follow-up (A3 group, n = 20), or angiography-guided PCI with 6-month OCT follow-up (A6 group, n = 20). The primary endpoint was the proportion of covered struts at 3- or 6-month follow-up. The proportion of covered struts in the O3 group was significantly higher than in the A3 group (95.2% vs. 92.3%, p < 0.001), but lower than in the A6 group (95.2% vs. 97.4%, p < 0.001). The O3 group had a lower proportion of incomplete strut apposition (ISA) than the A3 group (0.46% vs. 0.76%, p = 0.006), and higher than the A6 group (0.46% vs. 0.27%, p = 0.018) at follow-up. The optimal cut-off value of ISA after implantation of DES for predicting stent coverage at 3 and 6-month follow-up was 200 µm and 308 µm, respectively. Only one patient experienced target lesion revascularization in the A3 group during a 3-year clinical follow-up. In patients with NSTE-ACS undergoing PCI with DES, OCT guidance achieved higher strut coverage compared with angiography guidance at 3-month follow-up. However, the difference in the strut coverage between the OCT-guided group and the angiography-guided group at 6 months indicates that the degree of endothelialization may be more time-dependent instead of invasive device guidance.

[Diagnosis and treatment of gastrointestinal bleeding after kidney transplantation].

OBJECTIVE: To analyze the clinical characteristics of acute and chronic gastrointestinal bleeding in patients with end-stage renal disease (ESRD) after kidney transplantation, to improve the understanding of the causes, diagnosis, treatment and prevention of this complication, and to improve the management of patients with gastrointestinal bleeding after kidney transplantation. METHODS: The clinical, imaging and pathological data of patients with gastrointestinal bleeding after kidney transplantation in the Department of Urology of The First Affiliated Hospital of Anhui Medical University from August, 2015 to December, 2020 were collected. The etiology, early clinical manifestations, abnormal laboratory tests and examinations, treatment procedures, late prevention and treatment measures and outcomes of gastrointestinal bleeding were retrospectively studied, and the relevant literature was summarized and reviewed. RESULTS: A total of 17 patients were included in this study. Nine patients had chronic small amount of bleeding, hemoglobin gradually decreased, melena and fecal occult blood positive in the early stage, and the general condition was good, vital signs were stable, and were cured by drug treatment. Gastroscopy showed small ulcers with active bleeding foci in 2 cases, and the bleeding was stopped by titanium clips, and the prognosis was good. Gastroscopy showed that the anterior wall longitudinal ulcer at the junction of gastric antrum body was not effective in 1 case, and the small branch of right gastroepithelial artery was embolized, and the patient recovered and discharged after 2 weeks. Gastroscopy showed deep pit ulcer at the lesser curvature of gastric antrum in 1 patient, who underwent distal gastroduodenal artery embolization and had a good prognosis. Gastroscopy showed huge multiple ulcers in the stomach and duodenal bulb in 2 patients, who underwent subtotal gastrectomy and partial duodenectomy, duodenal stump exclusion and remnant gastrojejunostomy. One patient recovered and was discharged, and the other patient died of rebleeding on the 12th day after surgery. Two cases of diverticulum underwent surgical resection of diverticulum, and the prognosis was good. CONCLUSION: The onset of gastrointestinal hemorrhage in kidney transplant patients is insidious, and the condition is acute or slow, which can cause different degrees of damage to the patient and the transplanted kidney. Active prevention, early diagnosis, timely drug treatment, if the effect is not good, decisive endoscopic titanium clip hemostasis, transvascular interventional embolization, and even surgical treatment can minimize the harm of gastrointestinal bleeding.

HMGB1 promotes M1 polarization of macrophages and induces COPD inflammation.

Chronic obstructive pulmonary disease (COPD) is a pervasive and incapacitating respiratory condition, distinguished by airway inflammation and the remodeling of the lower respiratory tract. Central to its pathogenesis is an intricate inflammatory process, wherein macrophages exert significant regulatory functions, and High mobility group box 1 (HMGB1) emerges as a pivotal inflammatory mediator potentially driving COPD progression. This study explores the hypothesis that HMGB1, within macrophages, modulates COPD through inflammatory mechanisms, focusing on its influence on macrophage polarization. Our investigation uncovered that HMGB1 is upregulated in the context of COPD, associated with an enhanced proinflammatory M1 macrophage polarization induced by cigarette smoke. This polarization is linked to suppressed cell proliferation and induced apoptosis, indicative of HMGB1's role in the disease's inflammatory trajectory. The study further implicates HMGB1 in the activation of the Nuclear factor kappa-B (NF-κB) signaling pathway and chemokine signaling within macrophages, which are likely to amplify the inflammatory response characteristic of COPD. The findings underscore HMGB1's critical involvement in COPD pathogenesis, presenting it as a significant target for therapeutic intervention aimed at modulating macrophage polarization and inflammation.

[Clinical study of piriformis syndrome treated with trigger-point acupuncture]. / æ¿€ç—›ç‚¹é’ˆåˆºæ²»ç–—æ¢¨çŠ¶è‚Œç»¼åˆå¾çš„ä¸´åºŠç ”ç©¶.

OBJECTIVES: To compare the difference in the clinical efficacy on piriformis syndrome between trigger-point (TrP) acupuncture and glucocorticoid injection. METHODS: Sixty patients with piriformis syndrome were randomly allocated to an acupuncture group (30 cases, treated with TrP acupuncture) and a control group (30 cases, treated with glucocorticoid injection). In the two groups, the intervention was delivered once weekly and 2 treatments were required. Before treatment and 1 week, 1 month, 2 months and 3 months after treatment, the scores of the numerical rating scale (NRS) and Oswestry dysfunction index questionnaire (ODI), and the passive hip range of motion (PROM) were collected separately；the score of the 36-item short form of health survey (SF-36) was observed 3 months after treatment；and the administration of analgesic medication and the occurrence of adverse effects were recorded in the patients of 2 groups. RESULTS: The scores of NRS and ODI were decreased, and PROM was increased at each time point compared with the baseline (before treatment) in both groups (P<0.05). In comparison with the control group, the scores of NRS and ODI were decreased (P<0.01, P<0.05) and the range of hip internal rotation (HIR) was increased in the acupuncture group 2 and 3 months after treatment (P<0.01). Three months after treatment, the scores for physiological function, body pain, and vitality of SF-36 in the acupuncture group were higher than those of the control group (P<0.05). The number of patients with analgesic drugs was less (P<0.05) in the acupuncture group than that in the control group in 2 and 3 months after treatment. During treatment and in follow-up stage, no serious adverse reactions occurred in the patients of 2 groups. CONCLUSIONS: The clinical effect of TrP acupuncture is similar to that of glucocorticoid injection on piriformis syndrome in 1 month after treatment. In 2 months after treatment, TrP acupuncture is markedly effective for attenuating pain and the functional impairment of the lower limbs, improving the quality of life and reducing the use of analgesic drugs in comparison with glucocorticoid injection.

Giant ovarian yolk sac tumor during late pregnancy: a case report and literature review.

The manifestation of a giant ovarian yolk sac tumor during late pregnancy is relatively rare. A yolk sac tumor is a highly malignant germ cell tumor that originates from primitive germ cells. It is characterized by yolk sac differentiation in vitro. The frequency of prenatal examinations should be appropriately increased for ovarian tumors discovered during pregnancy. Furthermore, regular follow-up ultrasound should be performed, and tumor markers should be dynamically detected. If needed, imaging examinations such as computed tomography and magnetic resonance imaging should be combined to comprehensively investigate disease progression. If the tumor diameter and tumor marker levels rapidly increase during pregnancy, the possibility of malignancy increases. Therefore, exploratory laparotomy should be immediately performed to further improve subsequent treatment modalities, early diagnosis, early treatment, and prognosis. Herein, we report the case of a 28-year-old pregnant woman whose pregnancy was terminated at 29 weeks and 5 days. She complained of lower abdominal pain for 2 days. A pelvic mass was detected for 1 week, accompanied by increased levels of tumor markers such as serum alpha-fetoprotein, cancer antigen 125, carbohydrate antigen 724, and human epididymis protein 4. Imaging revealed the presence of a pelvic mass. At 32 weeks and 3 days of pregnancy, a cesarean section was performed, with a transverse incision in the lower uterine segment. Furthermore, pelvic adhesiolysis, omentectomy, right adnexectomy, right pelvic lymph node dissection, and pelvic metastasis peritonectomy were performed. The postoperative pathological diagnosis was yolk sac tumors of the ovary (stage IIB). Postoperatively, a five-cycle chemotherapy regimen comprising bleomycin, etoposide, and cisplatin was administered. During postoperative follow-up, the patient's general condition was noted to be good, with the newborn and pregnant women ultimately achieving good outcomes. We reviewed the relevant literature to increase clinical doctors' understanding of ovarian malignancy during pregnancy, guide treatment selection, and facilitate early intervention for associated diseases.

Identification and validation of a novel robust glioblastoma prognosis model based on bioinformatics.

Background: Glioblastoma (GBM) is a very common primary malignant tumor of the central nervous system (CNS). Aging, macrophage, autophagy, and methylation related genes are hypothesized to be crucial to its pathogenesis. In this study, we aimed to explore the role of these genes in the prognosis of GBM. Methods: The RNA sequence (RNA-seq) and clinical information were downloaded from The Cancer Genome Atlas database (TCGA) and the Chinese Glioma Genome Atlas database (CGGA). We performed univariate and least absolute shrinkage and selection operator (LASSO) multivariate Cox regression analysis to identify risk signatures related to overall survival (OS). We further developed a nomogram to predict individual outcomes. In addition, the immune microenvironment was analyzed by CIBERSORT. Results: 256 differentially expressed genes (DEGs) were obtained based on aging, macrophage, autophagy, and methylation related genes between GBM samples and normal tissues in TCGA-GBM cohort. We identified five optimal risk signatures with prognostic values in TCGA-GBM cohort and established a prognostic risk score model. The validity of the model was verified in the CGGA cohort and Huanhu cohort. Finally, we constructed a nomogram for clinical application by combining age, O(6)-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, and risk score. Activated NK cells and resting mast cells were highly expressed and memory B cells, plasma cells, resting NK cells, M1 macrophages, and neutrophils exhibited low expression in the high-risk score group. GBM patients with a low-risk score had a higher Tumor Immune Dysfunction and Exclusion (TIDE) score. The risk score of hot tumors was higher than that of the cold tumors. Additionally, 29 genes involved in glucose and lipid metabolism were highly expressed with a high-risk score. 31 metabolism-related pathways were significantly different between high-risk and low-risk groups. Conclusions: We constructed and validated a novel prognostic model for GBM. Aging, macrophage, autophagy, and methylation related genes may serve as prognostic and therapeutic biomarkers. The model developed may assist in guiding treatment for GBM patients. Our research had great significance in accurately predicting the prognosis of GBM and may offer reference for immunotherapy decision for GBM patients.

Mesenchymal stem cell-derived extracellular vesicles targeting irradiated intestine exert therapeutic effects.

Background: Radiation-induced intestinal injuries are common in patients with pelvic or abdominal cancer. However, these injuries are currently not managed effectively. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have been extensively used in regenerative medicine. However, the results of MSC-EVs in the repair of radiation-induced intestinal damage have been unsatisfactory. We here investigated the nanotherapeutic functions of MSC-EVs in radiation-induced intestinal injury. Methods: We visualized the biodistribution and trend of MSC-EVs through in vivo imaging. A radiation-induced intestinal injury model was constructed, and the therapeutic effect of MSC-EVs was explored through in vivo and in vitro experiments. Immunofluorescence and qRT-PCR assays were conducted to explore the underlying mechanisms. Results: MSC-EVs exhibited a dose-dependent tendency to target radiation-injured intestines while providing spatiotemporal information for the early diagnosis of the injury by quantifying the amount of MSC-EVs in the injured intestines through molecular imaging. Meanwhile, MSC-EVs displayed superior nanotherapeutic functions by alleviating apoptosis, improving angiogenesis, and ameliorating the intestinal inflammatory environment. Moreover, MSC-EVs-derived miRNA-455-5p negatively regulated SOCS3 expression, and the activated downstream Stat3 signaling pathway was involved in the therapeutic efficacy of MSC-EVs in radiation-induced intestinal injuries. Conclusion: MSC-EVs can dose-dependently target radiation-injured intestinal tissues, allow a spatiotemporal diagnosis in different degrees of damage to help guide personalized therapy, offer data for designing EV-based theranostic strategies for promoting recovery from radiation-induced intestinal injury, and provide cell-free treatment for radiation therapy.