Photosynthetic Bacteria-Hitchhiking 2D iMXene-mRNA Vaccine to Enable Photo-Immunogene Cancer Therapy.

Therapeutic mRNA vaccines have become powerful therapeutic tools for severe diseases, including infectious diseases and malignant neoplasms. mRNA vaccines encoding tumor-associated antigens provide unprecedented hope for many immunotherapies that have hit the bottleneck. However, the application of mRNA vaccines is limited because of biological instability, innate immunogenicity, and ineffective delivery in vivo. This study aims to construct a novel mRNA vaccine delivery nanosystem to successfully co-deliver a tumor-associated antigen (TAA) encoded by the Wilms' tumor 1 (WT1) mRNA. In this system, named PSB@Nb1.33C/mRNA, photosynthetic bacteria (PSB) efficiently delivers the iMXene-WT1 mRNA to the core tumor region using photo-driven and hypoxia-driven properties. The excellent photothermal therapeutic (PTT) properties of PSB and 2D iMxene (Nb1.33C) trigger tumor immunogenic cell death, which boosts the release of the WT1 mRNA. The released WT1 mRNA is translated, presenting the TAA and amplifying immune effect in vivo. The designed therapeutic strategy demonstrates an excellent ability to inhibit distant tumors and counteract postsurgical lung metastasis. Thus, this study provides an innovative and effective paradigm for tumor immunotherapy, i.e., photo-immunogene cancer therapy, and establishes an efficient delivery platform for mRNA vaccines, thereby opening a new path for the wide application of mRNA vaccines.

Predicting tall-cell subtype of papillary thyroid carcinomas independently with preoperative multimodal ultrasound.

OBJECTIVES: This study aimed to explore the differences between tall-cell subtype of papillary thyroid carcinoma (TCPTC) and classical papillary thyroid carcinoma (cPTC) using multimodal ultrasound, and identify independent risk factors for TCPTC to compensate the deficiency of preoperative cytological and molecular diagnosis on PTC subtypes. METHODS: 46 TCPTC patients and 92 cPTC patients were included. Each patient received grey-scale ultrasound, color Dopplor flow imaging (CDFI) and shear-wave elastography (SWE) preoperatively. Clinicopathologic information, grey-scale ultrasound features, CDFI features and SWE features of 98 lesion were compared using univariate analysis to find out predictors of TCPTC, based on which, a predictive model was built to differentiate TCPTC from cPTC and validated with 40 patients. RESULTS: Univariate and multivariate analysis identified that extrathyroidal extension (OR, 15.12; 95% CI, 2.26-115.44), aspect ratio (≥0.91) (OR, 29.34; 95% CI, 1.29-26.23), and maximum diameter ≥ 14.6 mm (OR, 20.79; 95% CI, 3.87-111.47) were the independent risk factors for TCPTC. Logistic regression equation: p = 1/1+ExpΣ[-5.099 + 3.004 × (if size ≥14.6 mm)+2.957 × (if aspect ratio≥0.91)+2.819 × (if extra-thyroidal extension)]. The prediction model had a good discrimination performance for TCPTC: the AUC, sensitivity and specificity were 0.928, 0.848 and 0.954 in cohort 1, and the corresponding values in cohort 2 were 0.943, 0.923 and 0.926. CONCLUSION: Ultrasound has potential for differential diagnosis of TCPTC from cPTC. A prediction model based on ultrasound characteristics (extrathyroidal extension, aspect ratio ≥0.91, and maximum diameter ≥14.6 mm) was useful to predict TCPTC. ADVANCES IN KNOWLEDGE: Multimodal ultrasound prediction of TCPTC were supplements to preoperative cytological diagnosis and molecular diagnosis on PTC subtypes.

Structurally diverse phthalides from fibrous roots of Ligusticum chuanxiong Hort. and their biological activities.

Falonolide A (1) and B (2), two novel polyyne hybrid phthalides resulting from unprecedented carbon skeleton polymerized by Z-ligustilide and falcarindiol, along with six new related phthalides (3-8), were isolated from Ligusticum chuanxiong Hort. Their structures were elucidated by spectroscopic analysis, computer-assisted structure elucidation (CASE) analysis, DP4+ probability analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1-8 was proposed, and the production mechanism of 2 was revealed by density functional theory (DFT) method. Compounds 4 and 6 exhibited significant vasodilatory activity with EC50 of 8.00 ± 0.86 and 6.92 ± 1.02 µM, respectively. Compound 4 also displayed significant inhibitory effect of NO production with EC50 value of 8.82 ± 0.30 µM. Based on the established compounds library, structure-activity relationship analysis of phthalides was explored to provide insights into the drug development of vasodilators and anti-flammatory.

Correlation between sarcopenia index and cognitive function in older adult women: A cross-sectional study using NHANES data.

OBJECTIVES: The Sarcopenia Index (SI) has the potential as a biomarker for sarcopenia, which is characterized by muscle loss. There is a clear association between sarcopenia and cognitive impairment. However, the relationship between SI and cognitive impairment is yet to be fully understood. METHODS: We employed data extracted from the U.S. National Health and Nutrition Examination Survey (NHANES) spanning the years 1999 to 2002. Our study encompassed individuals aged 65 to 80 who possessed accessible information regarding both SI and cognitive evaluations with a GFR ≥ 90. Cognitive function was assessed using the digit symbol substitution test (DSST). SI was calculated by serum creatinine (mg/dL)/cystatin C (mg/L)*100. Employing multivariate modeling, we estimated the connection between SI and cognitive performance. Furthermore, to enhance the reliability of our data analysis, we categorized SI using tertiles and subsequently calculated the P-value for trend. RESULTS: After adjustment for potential confounders, we found SI was significantly and positively correlated with cognitive function scores both in older female in the American population [ß = 0.160, 95 % confidence interval (CI) 0.050 to 0.271, P = 0.00461]. Similarly, when the total cognitive function score was treated as a categorical variable according to tertiles, higher SI was related to better total cognitive function scores in females [odds ratio (OR) = 3.968, 95 % CI 1.863 to 6.073, P = 0.00025] following adjustment for confounders. CONCLUSIONS: Higher SI was correlated with a lower prevalence of cognitive impairment among older adult women with normal kidney function.

Ganoderma lucidum-Derived Meroterpenoids Show Anti-Inflammatory Activity In Vitro.

Ganoderma lucidum, known as the "herb of spiritual potency", is used for the treatment and prevention of various diseases, but the responsible constituents for its therapeutic effects are largely unknown. For the purpose of obtaining insight into the chemical and biological profiling of meroterpenoids in G. lucidum, various chromatographic approaches were utilized for the title fungus. As a result, six undescribed meroterpenoids, chizhienes A-F (1-6), containing two pairs of enantiomers (4 and 5), were isolated. Their structures were identified using spectroscopic and computational methods. In addition, the anti-inflammatory activities of all the isolates were evaluated by Western blot analysis in LPS-induced macrophage cells (RAW264.7), showing that 1 and 3 could dose dependently inhibit iNOS but not COX-2 expression. Further, 1 and 3 were found to inhibit nitric oxide (NO) production using the Greiss reagent test. The current study will aid in enriching the structural and biological diversity of Ganoderma-derived meroterpenoids.

Minor ergosteroids and a 19-nor labdane-type diterpenoid with anti-inflammatory effects from Ganoderma lucidum.

A chemical investigation on the fruiting bodies of Ganoderma lucidum led to the isolation and identification of five undescribed ergosteroids including two des-D-steroids (3 and 4) and one rare 6/6/7/5-fused carbon skeletal ergosterol (5) along with one 19-nor labdane-type diterpenoid (6). Their structures including their absolute configurations, were assigned by spectroscopic methods, ECD calculations, and X-ray diffraction analysis. In addition, the anti-inflammatory activities of all the isolates were evaluated. The results indicated that compound 1 can significantly down-regulate the protein expression of iNOS and COX-2 at 20 µM in LPS- stimulated RAW264.7 cells.

Diagnostic accuracy of qualitative and quantitative magnetic resonance imaging-guided contrast-enhanced ultrasound (MRI-guided CEUS) for the detection of prostate cancer: a prospective and multicenter study.

PURPOSE: To evaluate the diagnostic value of MRI-guided contrast-enhanced ultrasound (CEUS) for prostate cancer (PCa) diagnosis, and characteristics of PCa in qualitative and quantitative CEUS. MATERIAL AND METHODS: This prospective and multicenter study included 250 patients (133 in the training cohort, 57 in the validation cohort and 60 in the test cohort) who underwent MRI, MRI-guided CEUS and prostate biopsy between March 2021 and February 2023. MRI interpretation, qualitative and quantitative CEUS analysis were conducted. Multitree extreme gradient boosting (XGBoost) machine learning-based models were applied to select the eight most important quantitative parameters. Univariate and multivariate logistic regression models were constructed to select independent predictors of PCa. Diagnostic value was determined for MRI, qualitative and quantitative CEUS using the area under receiver operating characteristic curve (AUC). RESULTS: The performance of quantitative CEUS was superior to that of the qualitative CEUS and MRI in predicting PCa. The AUC was 0.779 (95%CI 0.70-0.849), 0.756 (95%CI 0.638-0.874) and 0.759 (95%CI 0.638-0.879) of qualitative CEUS, and 0.885 (95%CI 0.831-0.940), 0.802 (95%CI 0.684-0.919) and 0.824 (95%CI 0.713-0.936) of quantitative CEUS in training, validation and test cohort, respectively. Compared with quantitative CEUS, MRI achieved less well performance for AUC 0.811 (95%CI 0.741-0.882, p = 0.099), 0.748 (95%CI 0.628-0.868, p = 0.539) and 0.737 (95%CI 0.602-0.873, p = 0.029), respectively. Moreover, the highest specificity of 80.6% was obtained by quantitative CEUS. CONCLUSION: We developed a reliable method of MRI-guided CEUS that demonstrated enhanced performance compared to MRI. The qualitative and quantitative CEUS characteristics will contribute to improved diagnosis of PCa.

A Novel Signature Based on m6A Regulator-Mediated Genes Along Glycolytic Pathway Predicts Prognosis and Immunotherapy Responses of Gastric Cancer Patients.

N6-methyladenosine (m6A) modification is involved in many aspects of gastric cancer (GC). Moreover, m6A and glycolysis-related genes (GRGs) play important roles in immunotherapeutic and prognostic implication of GC. However, GRGs involved in m6A regulation have never been analyzed comprehensively in GC. Herein, the study aims to identify and validate a novel signature based on m6A-related GRGs in GC patients. Therefore, a m6A-related GRGs signature is established, which can predict the survival of patients with GC and remain an independent prognostic factor in multivariate analyses. Clinical significance of the model is well validated in internal cohort and independent validation cohort. In addition, the expression levels of risk model-related GRGs in clinical samples are validated. Consistent with the database results, all model genes are up-regulated in expression except DCN. After regrouping the patients based on this risk model, the study can effectively distinguish between them in respect to immune-cell infiltration microenvironment and immunotherapeutic response. Additionally, candidate drugs targeting risk model-related GRGs are confirmed. Finally, a nomogram combining risk scores and clinical parameters is created, and calibration plots show that the nomogram can accurately predict survival. This risk model can serve as a reliable assessment tool for predicting prognosis and immunotherapeutic responses in GC patients.

Platycodin D2 enhances P21/CyclinA2-mediated senescence of HCC cells by regulating NIX-induced mitophagy.

BACKGROUND: Hepatocellular carcinoma (HCC) cells usually show strong resistance to chemotherapy, which not only reduces the efficacy of chemotherapy but also increases the side effects. Regulation of autophagy plays an important role in tumor treatment. Cell senescence is also an important anti-cancer mechanism, which has become an important target for tumor treatment. Therefore, it is of great clinical significance to find anti-HCC drugs that act through this new mechanism. Platycodin D2 (PD2) is a new saponin compound extracted from the traditional Chinese medicine Platycodon grandiflorum. PURPOSE: Our study aimed to explore the effects of PD2 on HCC and identify the underlying mechanisms. METHODS: First, the CCK8 assay was used to detect the inhibitory effect of PD2 on HCC cells. Then, different pathways of programmed cell death and cell cycle regulators were measured. In addition, we assessed the effects of PD2 on the autophagy and senescence of HCC cells by flow cytometry, immunofluorescence staining, and Western blotting. Finally, we studied the in vivo effect of PD2 on HCC cells by using a mouse tumor-bearing model. RESULTS: Studies have shown that PD2 has a good anti-tumor effect, but the specific molecular mechanism has not been clarified. In this study, we found that PD2 has no obvious toxic effect on normal hepatocytes, but it can significantly inhibit the proliferation of HCC cells, induce mitochondrial dysfunction, enhance autophagy and cell senescence, upregulate NIX and P21, and downregulate CyclinA2. Gene silencing and overexpression indicated that PD2 induced mitophagy in HCC cells through NIX, thereby activating the P21/CyclinA2 pathway and promoting cell senescence. CONCLUSIONS: These results indicate that PD2 induces HCC cell death through autophagy and aging. Our findings provide a new strategy for treating HCC.

Contributing Risk Factors to Self-Contamination During the Process of Donning and Doffing Personal Protective Equipment.

OBJECTIVE: The goal of this study is to explore the risk factors associated with self-contamination points during personal protective equipment (PPE) donning and doffing among health care workers (HCWs). METHODS: In total, 116 HCWs were randomly sampled and trained to don and doff the whole PPE set. We smeared the whole PPE set with the fluorescent powder. After each participant finished PPE doffing, the whole body was irradiated with ultraviolet light in order to detect contamination points and record the position and quantity. Sociodemographic characteristics and previous infection prevention control (IPC) training experience, among others, were collected by using electronic questionnaires. Poisson regression was used in identifying risk factors that are associated with the number of contamination points, and the relative risk (RR) and its 95% confidence interval (CI) were calculated. RESULTS: About 78.5% of participants were contaminated. Ever training experience (RR = 0.37; 0.26, 0.52), clinical departments (RR = 0.67; 0.49, 0.93), body mass index (BMI) (RR = 1.09; 1.01, 1.18), and shoulder width (RR = 1.07; 1.01, 1.13) were associated with the number of contamination points. CONCLUSIONS: Previous IPC training experience, department types, BMI, and shoulder width were associated with self-contamination points after the PPE was removed.

Identification of copy number variations among fetuses with isolated ultrasound soft markers in pregnant women not of advanced maternal age.

BACKGROUND: Pathogenic (P) copy number variants (CNVs) may be associated with second-trimester ultrasound soft markers (USMs), and noninvasive prenatal screening (NIPS) can enable interrogate the entire fetal genome to screening of fetal CNVs. This study evaluated the clinical application of NIPS for detecting CNVs among fetuses with USMs in pregnant women not of advanced maternal age (AMA). RESULTS: Fetal aneuploidies and CNVs were identified in 6647 pregnant women using the Berry Genomics NIPS algorithm.Those with positive NIPS results underwent amniocentesis for prenatal diagnosis. The NIPS and prenatal diagnosis results were analyzed and compared among different USMs. A total of 96 pregnancies were scored positive for fetal chromosome anomalies, comprising 37 aneuploidies and 59 CNVs. Positive predictive values (PPVs) for trisomy 21, trisomy 18, trisomy 13, and sex chromosome aneuploidies were 66.67%, 80.00%, 0%, and 30.43%, respectively. NIPS sensitivity for aneuploidies was 100%. For CNVs, the PPVs were calculated as 35.59% and false positive rate of 0.57%. There were six P CNVs, two successfully identified by NIPS and four missed, of which three were below the NIPS resolution limit and one false negative. The incidence of aneuploidies was significantly higher in fetuses with absent or hypoplastic nasal bone, while that of P CNVs was significantly higher in fetuses with aberrant right subclavian artery (ARSA), compared with other groups. CONCLUSIONS: NIPS yielded a moderate PPV for CNVs in non-AMA pregnant women with fetal USM. However, NIPS showed limited ability in identifying P CNVs. Positive NIPS results for CNVs emphasize the need for further prenatal diagnosis. We do not recommend the use of NIPS for CNVs screening in non-AMA pregnant women with fetal USM, especially in fetuses with ARSA.

Acupuncture therapies for relieving pain in pelvic inflammatory disease: A systematic review and meta-analysis.

BACKGROUND: Studies investigating the effectiveness of acupuncture therapies in alleviating pain in pelvic inflammatory disease (PID) have gained increasing attention. However, to date, there have been no systematic reviews and meta-analyses providing high-quality evidence regarding the efficacy and safety of acupuncture therapies in this context. OBJECTIVE: The objective of this review was to assess the efficacy and safety of acupuncture therapies as complementary or alternative treatments for pain relief in patients with PID. METHOD: A comprehensive search was conducted in eight databases from inception to February 20, 2023: PubMed, Embase, Web of Science, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and Chinese Biomedical Literature Database. Randomized controlled trials (RCTs) investigating acupuncture therapies as complementary or additional treatments to routine care were identified. Primary outcomes were pain intensity scores for abdominal or lumbosacral pain. The Cochrane risk of bias criteria was applied to assess the methodological quality of the included trials. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) system was used to evaluate the quality of evidence. Data processing was performed using RevMan 5.4. RESULT: This systematic review included twelve trials comprising a total of 1,165 patients. Among these, nine trials examined acupuncture therapies as adjunctive therapy, while the remaining three did not. Meta-analyses demonstrated that acupuncture therapies, whether used alone or in combination with routine treatment, exhibited greater efficacy in relieving abdominal pain compared to routine treatment alone immediately after the intervention (MD: -1.32; 95% CI: -1.60 to -1.05; P < 0.00001). The advantage of acupuncture therapies alone persisted for up to one month after the treatment (MD: -1.44; 95% CI: -2.15 to -0.72; P < 0.0001). Additionally, acupuncture therapies combined with routine treatment had a more pronounced effect in relieving lumbosacral pain after the intervention (MD: -1.14; 95% CI: -2.12 to -0.17; P < 0.00001) in patients with PID. The incidence of adverse events did not increase with the addition of acupuncture therapies (OR: 0.56; 95% CI: 0.21 to 1.51; P = 0.25). The findings also indicated that acupuncture therapies, as a complementary treatment, could induce anti-inflammatory cytokines, reduce pro-inflammatory cytokines, alleviate anxiety, and improve the quality of life in patients with PID. CONCLUSION: Our findings suggest that acupuncture therapies may effectively reduce pain intensity in the abdomen and lumbosacral region as complementary or alternative treatments, induce anti-inflammatory cytokines, decrease pro-inflammatory cytokines, alleviate anxiety, and enhance the quality of life in patients with PID, without increasing the occurrence of adverse events. However, due to the low quality of the included trials, the conclusion should be interpreted with caution, highlighting the need for further high-quality trials to establish more reliable conclusions.

Efficacy and safety of percutaneous ultrasound-guided thermal ablation in the treatment of cervical metastatic lymph nodes from papillary thyroid carcinoma.

OBJECTIVE: To evaluate the efficacy and safety of percutaneous ultrasound-guided thermal ablation in the treatment of cervical metastatic lymph nodes (LNs) from papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: A total of 77 patients with 79 LNs ablated by microwave ablation (MWA) or radiofrequency ablation (RFA) between September 2018 and October 2022 were enrolled in this study. After treatment, patients were followed up with measurement of diameters of LNs and serum thyroglobulin (s-Tg) at 1, 3, 6, and 12 months and annually thereafter. The paired t-test was used to compare the changes of s-Tg level, diameters of LNs before and after ablation. RESULTS: There were no serious complications related to ablation while one case of incomplete ablation in MWA was found during follow-up. The mean longest and shortest diameter of the ablated LNs reduced from 11.6 ± 4.3 mm to 5.0 ± 4.1 mm (p < 0.001), and from 6.1 ± 1.9 mm to 3.0 ± 2.5 mm (p < 0.001) at the last follow-up visit. Besides, the final volume reduction rate (VRR) was 61.8 ± 56.4% (range, -67.0 -100%). The complete disappearance rate was 46.8%, but there were 4 (5.1%) LNs becoming bigger than before. The average s-Tg level was 9.2 ± 26.6 ng/mL, a data significantly decreased to 3.7 ± 7.0 ng/mL at the last follow-up, but no statistical difference was shown. CONCLUSION: Thermal ablation is an effective and safe modality for the treatment of metastatic LNs from PTC.

Safety of fertility-sparing surgery in young women with stage I endometrioid epithelial and mucinous ovarian cancer: A population-based analysis.

INTRODUCTION: The aim of this study was to assess the safety of fertility-sparing surgery (FSS) in stage I endometrioid epithelial cancer (EEOC) and mucinous ovarian cancer (MOC). METHODS: A retrospective case‒controlled study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database, focusing on stage I EEOC and MOC between 2000 and 2016. The effects of FSS on overall survival (OS) were compared using log-rank tests. Univariate and multivariate Cox analyses were performed to control for confounders. RESULTS: The study identified 970 patients with FIGO stage I EEOC and 810 with stage I MOC. Of these patients, 116 (12.0%) EEOC and 268 (33.1%) MOC patients underwent fertility-sparing surgery. The results showed that patients with G3 EEOC had a worse 5-year OS than patients with G1 EEOC (96.1% vs. 90.1%, p = 0.020). IC stage MOC patients had a worse prognosis than IA and IB stage patients (94.9% vs. 88.7%, p = 0.001). FSS did not significantly affect the 5-year OS of patients with EEOC (94.8% vs. 95.4%, p = 0.687) or MOC (95.9% vs. 92.3%, p = 0.071). Further subgroup analysis according to tumor stage and histological grade did not show a worse OS with FSS in stage I EEOC or MOC patients, even with high-risk types such as G3 histology and IC phase. In a multivariable analysis, the application of FSS was not associated with inferior OS in EEOC or MOC. CONCLUSIONS: FSS for patients with stage I EEOC or MOC does not lead to worse outcomes than radical surgery, making it a viable option for young patients with early-stage disease wishing to preserve fertility.

Exploring the Diagnostic Potential of EPB41L3 Methylation in Cervical Cancer and Precancerous Lesions: A Systematic Review and Meta-Analysis.

OBJECTIVE: This meta-analysis aimed to comprehensively evaluate the diagnostic use of erythrocyte membrane protein band 4.1like3 (EPB41L3) methylation detection in cervical cancer (CC) and its precancerous lesions. METHODS: CNKI, Wanfang, Cochrane Library, PubMed, and Ovid databases were searched using a combination of subject headings and free words. Pertinent data were retrieved after screening for inclusion and exclusion criteria, and the quality of the included studies was evaluated using QUADAS-2 criteria. The appropriate software was used for heterogeneity analysis and combined effect size calculation. Additionally, sensitivity analysis was used to evaluate the robustness of the combined results, and meta-regression and subgroup analysis were conducted to investigate the origins of heterogeneity. RESULTS: This meta-analysis included six studies, including 525 healthy individuals, 182 cervical intraepithelial neoplasia 1 (CIN1) samples, 182 CIN2 samples, 281 CIN3 samples, and 226 CC samples. EPB41L3 methylation detection for CIN2 and above lesions demonstrated combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio (DOR), and the area under the curve of the comprehensive receiver operating characteristic curve of 0.67, 0.76, 3.19, 0.41, 7.60, and 0.80, respectively; CIN3 and above lesions demonstrated these evaluations at 0.73, 0.84, 4.35, 0.33, 23.94, and 0.90, respectively. Meta-regression analysis revealed that the population, time, sample type, detection method, literature quality, and sample size were not significant sources of heterogeneity affecting the combined diagnostic efficacy of CIN2 and above lesions (p > 0.05). Subgroup analysis revealed higher combined diagnostic values of CIN2 and above lesions in retrospective studies, tissue samples, and Chinese populations, with DORs of 41.03, 14.59, and 13.70, respectively. CONCLUSION: EPB41L3 methylation demonstrated a relatively low diagnostic performance in CC and precancerous lesions. However, it merits further investigation as a potential biomarker. Integrating it with multiple gene detection, human papillomavirus testing, and ThinPrep liquid-based cytology test examination is recommended to explore improved diagnostic strategies for CC and its precancerous lesions.

Unlock the C-N Bond Amidation of Enaminones: Metal-Free Synthesis of Enamides by Water-Assisted Transamidation.

The C-N bond transamidation of primary amides with N,N-dimethyl enaminones has been efficiently realized by heating in the presence of trifluoromethanesulfonic acid (TfOH). The method enables the practical synthesis of valuable enamides without the use of any metal reagent. In addition, this transamidation protocol can also be expanded to the reactions of sulfonamides, and the late-stage functionalization on sulfonamide drugs such as Celecoxib and Valdecoxib has been verified. Moreover, the participation of water in assisting the transamidation process has been identified by the isotope labeling experiments using D2O, disclosing a new possibility in designing catalytic tactic to other transamidation reactions.

Annulative Nonaromatic Newman-Kwart-Type Rearrangement for the Synthesis of Sulfur Heteroaryls.

By employing enaminones and thiuram disulfides as starting materials, the frontiers of Newman-Kwart rearrangement have been expanded to the alkenyl system for the first time. In addition, instead of leading to the formation of simple carbamothioates, the rearrangement has led to the unprecedented construction of S-heteroaryls. Depending on the differences in the enaminone structure, the efficient synthesis of functionalized isothiazoles and thiophenes has been achieved.

Observation of the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on recurrent implantation failure of kidney deficiency and blood stasis. / "é€šå ƒé’ˆæ³•"联合精玉药灸治疗肾虚血瘀型反复种植失败疗效观察.

OBJECTIVES: To observe the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on the patients with recurrent implantation failure (RIF) of kidney deficiency and blood stasis undergoing frozen embryo transfer of the conventional hormone replacement therapy cycle. METHODS: Sixty RIF of kidney deficiency and blood stasis patients who planned for frozen embryo transfer were randomly divided into a combined treatment group (30 cases) and a western medication group (30 cases). In the western medication group, the conventional hormone replacement therapy was performed for endometrial preparation during transfer cycle. On the basis of treatment as the western medication group, in the combined treatment group, Tongyuan needling combined with jingyu herb-separated moxibustion was adopted. Regarding tongyuan needling, the acupoint prescription for Tongdu Tiaoshen (promoting the governor vessel and regulating the spirit, e.g. Dazhui [GV 14], Ganshu [BL 18], Shenshu [BL 23] and back-shu points) and that for Yinqi Guiguan (conducting qi back to the primary, e.g. Zhongwan [CV 12], Qihai [CV 6], Guanyuan [CV 4] and front-mu points) were selected. Acupuncture was delivered at these two prescriptions alternatively each time. After acupuncture, the herb-separated moxibustion (in which, the herbal powder was prepared with the modified Yangjing Zhongyu decoction for cultivating the kidney essence and promoting pregnancy) was operated at Shenque (CV 8). This combined therapy was delivered once every two days, 3 sessions a week till the day of embryo transfer. The pregnancy outcomes (positive rate of human chorionic gonadotropin [ß-HCG] and clinical pregnancy rate) were compared between the two groups, as well as the TCM syndrome score, serum estradiol (E2) and progesterone (P) levels, endometrial thickness and type, endometrial blood flow index (pulsatility index [PI], resistance index [RI]) before and after treatment. RESULTS: After treatment, the clinical pregnancy rate of the combined treatment group was 40.0% (12/30), higher than that of the western medication group (16.7%, 5/30, P<0.05); and the difference in the positive rate of ß-HCG was not significant statistically between the two groups (P>0.05). After treatment, the serum levels of E2 and P were elevated (P<0.05), the endometrial thickness was thickened (P<0.05); the scores of TCM syndrome, and the levels of PI and RI were reduced (P<0.05) when compared with those before treatment in the two groups. The proportion of type A endometrium increased compared with that before treatment in the combined treatment group (P<0.05). Except the levels of E2 and P, the above indexes in the combined treatment group were superior to the western medication group (P<0.05). CONCLUSIONS: On the basis of frozen embryo transfer of conventional hormone replacement cycle, the intervention of Tongyuan needling combined with jingyu herb-separated moxibustion can effectively relieve the clinical symptoms, increase the endometrial blood flow and its thickness, and improve the endometrial receptivity, thereby ameliorate pregnancy outcomes in RIF patients of kidney deficiency and blood stasis.

Patient-derived organoids as personalized avatars and a potential immunotherapy model in cervical cancer.

Cervical cancer remains a significant health issue in developing countries. However, finding a preclinical model that accurately reproduces tumor characteristics is challenging. Therefore, we established a patient-derived organoids (PDOs) biobank containing 67 cases of heterogeneous cervical cancer that mimic the histopathological and genomic characteristics of parental tumors. The in vitro response of the organoids indicated their ability to capture the radiological heterogeneity of the patients. To model individual responses to adoptive T cell therapy (ACT), we expanded tumor-infiltrating lymphocytes (TILs) ex vivo and co-cultured them with paired organoids. The PDOs-TILs co-culture system demonstrates clear responses that correspond to established immunotherapy efficiency markers like the proportion of CTLs. This study supports the potential of the PDOs platform to guide treatment in prospective interventional trials in cervical cancer.

"Alkene-to-Alkene" Difunctionalization of Enaminones for the Synthesis of Polyfunctionalized Alkenes by Transition-Metal-Free C-H and C-N Bond Transformation.

The three-component reactions of enaminones, disulfides, and alcohols for the synthesis of polyfunctionalized alkenes have been realized via the C-H and C-N bond transformation on enaminones. The reactions proceed in a novel "alkene-to-alkene" difunctionalization mode without using any transition metal. The application of the alkene products in the synthesis of divergent sulfenyl heteroaryls, including sulfenylated pyrazoles, pyrimidines, and isoxazoles, via simple annulation has also been verified.