Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study.

BACKGROUND: Due to the complexity and numerous comorbidities associated with Crohn's disease (CD), the incidence of postoperative complications is high, significantly impacting the recovery and prognosis of patients. Consequently, additional studies are required to precisely predict short-term major complications following intestinal resection (IR), aiding surgical decision-making and optimizing patient care. AIM: To construct novel models based on machine learning (ML) to predict short-term major postoperative complications in patients with CD following IR. METHODS: A retrospective analysis was performed on clinical data derived from a patient cohort that underwent IR for CD from January 2017 to December 2022. The study participants were randomly allocated to either a training cohort or a validation cohort. The logistic regression and random forest (RF) were applied to construct models in the training cohort, with model discrimination evaluated using the area under the curves (AUC). The validation cohort assessed the performance of the constructed models. RESULTS: Out of the 259 patients encompassed in the study, 5.0% encountered major postoperative complications (Clavien-Dindo ≥ III) within 30 d following IR for CD. The AUC for the logistic model was 0.916, significantly lower than the AUC of 0.965 for the RF model. The logistic model incorporated a preoperative CD activity index (CDAI) of ≥ 220, a diminished preoperative serum albumin level, conversion to laparotomy surgery, and an extended operation time. A nomogram for the logistic model was plotted. Except for the surgical approach, the other three variables ranked among the top four important variables in the novel ML model. CONCLUSION: Both the nomogram and RF exhibited good performance in predicting short-term major postoperative complications in patients with CD, with the RF model showing more superiority. A preoperative CDAI of ≥ 220, a diminished preoperative serum albumin level, and an extended operation time might be the most crucial variables. The findings of this study can assist clinicians in identifying patients at a higher risk for complications and offering personalized perioperative management to enhance patient outcomes.

Perineural invasion in cervical cancer: A multicenter retrospective study.

OBJECTIVE: The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. METHODS: A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. RESULTS: This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. CONCLUSION: The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

Impact of intraoperative hypothermia on the recovery period of anesthesia in elderly patients undergoing abdominal surgery.

BACKGROUND: This study aimed to investigate the impact of intraoperative hypothermia on the recovery period of anesthesia in elderly patients undergoing abdominal surgery. METHODS: A prospective observational study was conducted based on inclusion and exclusion criteria. A total of 384 elderly patients undergoing abdominal surgery under general anesthesia were enrolled in a grade A tertiary hospital in Chengdu, Sichuan Province from October 2021 and October 2022. After anesthesia induction, inflatable warming blankets were routinely used for active heat preservation, and nasopharyngeal temperature was monitored to observe the occurrence of intraoperative hypothermia. Patients were divided into hypothermia group and nonhypothermia group according to whether hypothermia occurred during the operation. Anesthesia recovery time and the incidence of adverse events or unwanted events during anesthesia recovery between the two groups were compared. RESULTS: The numbers (percentage) of 384 patients who underwent abdominal surgery developed intraoperative hypothermia occurred in 240 (62.5%) patients, all of whom had mild hypothermia. There were statistically significant differences between mild hypothermia after active warming and nonhypothermia in the occurrence of shivering (χ2 = 5.197, P = 0.023) and anesthesia recovery time (Z = -2.269, P = 0.02) in elderly patients undergoing abdominal surgery during anesthesia recovery, and there were no statistically significant differences in hypoxemia, nausea or vomiting, hypertension, hypokalemia, hypocalcemia, analgesic drug use,postoperative wound infection or postoperative hospitalization days. CONCLUSIONS: The incidence of intraoperative mild hypothermia after active warming was high in elderly patients who underwent abdominal surgery. Mild hypothermia increased the incidence of shivering and prolonged anesthesia recovery time in elderly patients undergoing abdominal surgery.

mTOR inhibitor reduces nontumour-related death in liver transplantation for hepatocellular carcinoma.

Sirolimus is a regularly applied immunosuppressant for patients undergoing liver transplantation (LT) for hepatocellular carcinoma (HCC). Sirolimus not only significantly inhibits HCC recurrence but also protects renal function. However, the improvement effect of sirolimus on nontumour-related death in patients is still unknown. The aim of our study was to investigate the therapeutic effect of sirolimus on nontumour-related deaths. In this study, we retrospectively enrolled 403 LT patients with HCC from January 1, 2015, to December 31, 2018. The median follow-up time was 47.1 months. The patients were divided into the sirolimus group (N = 184) and the sirolimus-free group (N = 219). There were no significant differences between the sirolimus group and the sirolimus-free group in survival (P = 0.054). In transplant patients who exceeded the Milan or Hangzhou criteria, the sirolimus group achieved higher survival than the sirolimus-free group (P = 0.005; P = 0.02). Moreover, multivariate analysis showed that sirolimus strongly reduced the hazard ratio (HR) for nontumour-related death in LT patients who exceeded the Milan (HR: 0.42; 95% CI: 0.18-1; P = 0.05) or Hangzhou criteria (HR: 0.26; 95% CI: 0.08-0.89; P = 0.032). HCC recurrence increased the risk of nontumour-related death. In conclusion, sirolimus-based immunosuppression can significantly reduce nontumour-related death in LT patients who exceed the criteria for transplantation. In addition, this finding will further promote the application of sirolimus after liver transplantation for hepatocellular carcinoma.

Integrative analysis identifies cancer cell-intrinsic RARRES1 as a predictor of prognosis and immune response in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor prognosis and limited treatment options. Although immune checkpoint inhibitors (ICIs) have been proven to improve outcomes in TNBC patients, the potential mechanisms and markers that determine the therapeutic response to ICIs remains uncertain. Revealing the relationship and interaction between cancer cells and tumor microenvironment (TME) could be helpful in predicting treatment efficacy and developing novel therapeutic agents. By analyzing single-cell RNA sequencing dataset, we comprehensively profiled cell types and subpopulations as well as identified their signatures in the TME of TNBC. We also proposed a method for quantitatively assessment of the TME immune profile and provided a framework for identifying cancer cell-intrinsic features associated with TME through integrated analysis. Using integrative analyses, RARRES1 was identified as a TME-associated gene, whose expression was positively correlated with prognosis and response to ICIs in TNBC. In conclusion, this study characterized the heterogeneity of cellular components in TME of TNBC patients, and brought new insights into the relationship between cancer cells and TME. In addition, RARRES1 was identified as a potential predictor of prognosis and response to ICIs in TNBC.

Metabolic syndromes increase significantly with the accumulation of bad dietary habits.

BACKGROUND: The association between dietary habits and metabolic syndrome (MetS) has not been well documented, due to the complexity and individualization of dietary culture in the Chinese population. OBJECTIVE: To construct a composite score from various bad dietary habits and to evaluate their comprehensive association with the prevalence of MetS and its components among Chinese men and women across various age groups. SETTING: Serial cross-sectional studies. METHODS: Twenty-three dietary habits were assessed through face-to-face interviews with 98,838 males and 83,099 females in health check-up programs from 2015 to 2021, among which eighteen bad dietary habits were observed to be associated independently with total MetS. The total score of bad dietary habits was composed of four categories via variable clustering analysis, including irregular dietary habits, unhealthy dietary flavors, unbalanced dietary structure, and high-fat diet. The 2016 Chinese guideline for the management of dyslipidemia in adults was used to define MetS. RESULTS: Men had a higher score of bad dietary habits than women (9.63 ± 3.11 vs. 8.37 ± 3.23), which decreased significantly with increasing age in both males and females (Pinteraction<0.01). The prevalence of total MetS increased significantly with the cumulative score of bad dietary habits in both males (highest quintile vs. lowest quintile: OR, 1.90; 95% confidence interval [CI], 1.80-2.00; Plinear<0.01) and females (OR, 2.23; 95% CI, 2.02-2.46; Plinear<0.01) after adjusted for age, education, smoking status, alcohol consumption, and physical activities. These linear trends were also observed for each MetS component (all Plinear<0.01). The role of irregular dietary habits and high-fat diet on MetS prevalence are much higher in males than in females, while unhealthy dietary flavors and unbalanced dietary structure had a greater influence on females. CONCLUSIONS: The accumulation of bad dietary habits contributes to the MetS developments. Thus, individualized lifestyle interventions are needed to correct bad dietary habits with regard to gender differences.

Targeting DNA Damage and Repair Machinery via Delivering WEE1 Inhibitor and Platinum (IV) Prodrugs to Stimulate STING Pathway for Maximizing Chemo-Immunotherapy in Bladder Cancer.

Both cisplatin-based chemotherapy and immune checkpoint blockers (ICBs)-based immunotherapy are the first-line treatments for patients with advanced bladder cancer. Cancer cells can develop resistance to cisplatin through extensive DNA repair, while a low response rate to ICBs is mostly due to the presence of an immunosuppressive microenvironment and low PD-L1 expression. Herein, a glutathione (GSH)-responsive nanoparticle (NP2) loaded with cisplatin prodrug (Pt (IV)) and WEE1 inhibitor (MK1775) is designed. NP2 can be triggered by GSH in cancer cells, and the released MK1775 can inhibit the activity of WEE1 protein, which ultimately increases DNA damage by cisplatin. Genome-wide RNA sequencing first reveals that NP2 can inhibit DNA repair machinery by interfering with the cell cycle and significantly activate the stimulator of interferon genes pathway. Tumor growth is significantly inhibited by NP2 in vivo. As innate and adaptive immune responses are stimulated, the immunosuppressive microenvironment is modified, and the "immune cold tumor" is transformed into an "immune hot tumor". In addition, NP2 can upregulate PD-L1 expression in tumor cells, thereby increasing the response rate of PD-L1 monoclonal antibody (αPD-L1) and eliciting long-term immune responses in both primary and metastatic tumors.

Radiomics in cone-beam breast CT for the prediction of axillary lymph node metastasis in breast cancer: a multi-center multi-device study.

OBJECTIVES: To develop a radiomics model in contrast-enhanced cone-beam breast CT (CE-CBBCT) for preoperative prediction of axillary lymph node (ALN) status and metastatic burden of breast cancer. METHODS: Two hundred and seventy-four patients who underwent CE-CBBCT examination with two scanners between 2012 and 2021 from two institutions were enrolled. The primary tumor was annotated in each patient image, from which 1781 radiomics features were extracted with PyRadiomics. After feature selection, support vector machine models were developed to predict ALN status and metastatic burden. To avoid overfitting on a specific patient subset, 100 randomly stratified splits were made to assign the patients to either training/fine-tuning or test set. Area under the receiver operating characteristic curve (AUC) of these radiomics models was compared to those obtained when training the models only with clinical features and combined clinical-radiomics descriptors. Ground truth was established by histopathology. RESULTS: One hundred and eighteen patients had ALN metastasis (N + (≥ 1)). Of these, 74 had low burden (N + (1~2)) and 44 high burden (N + (≥ 3)). The remaining 156 patients had none (N0). AUC values across the 100 test repeats in predicting ALN status (N0/N + (≥ 1)) were 0.75 ± 0.05 (0.67~0.93, radiomics model), 0.68 ± 0.07 (0.53~0.85, clinical model), and 0.74 ± 0.05 (0.67~0.88, combined model). For metastatic burden prediction (N + (1~2)/N + (≥ 3)), AUC values were 0.65 ± 0.10 (0.50~0.88, radiomics model), 0.55 ± 0.10 (0.40~0.80, clinical model), and 0.64 ± 0.09 (0.50~0.90, combined model), with all the ranges spanning 0.5. In both cases, the radiomics model was significantly better than the clinical model (both p < 0.01) and comparable with the combined model (p = 0.56 and 0.64). CONCLUSIONS: Radiomics features of primary tumors could have potential in predicting ALN metastasis in CE-CBBCT imaging. CLINICAL RELEVANCE STATEMENT: The findings support potential clinical use of radiomics for predicting axillary lymph node metastasis in breast cancer patients and addressing the limited axilla coverage of cone-beam breast CT. KEY POINTS: • Contrast-enhanced cone-beam breast CT-based radiomics could have potential to predict N0 vs. N + (≥ 1) and, to a limited extent, N + (1~2) vs. N + (≥ 3) from primary tumor, and this could help address the limited axilla coverage, pending future verifications on larger cohorts. • The average AUC of radiomics and combined models was significantly higher than that of clinical models but showed no significant difference between themselves. • Radiomics features descriptive of tumor texture were found informative on axillary lymph node status, highlighting a higher heterogeneity for tumor with positive axillary lymph node.

A new membrane anatomy-oriented classification of radical surgery for rectal cancer.

For patients with different clinical stages of rectal cancer, tailored surgery is urgently needed. Over the past 10 years, our team has conducted numerous anatomical studies and proposed the "four fasciae and three spaces" theory to guide rectal cancer surgery. Enlightened by the anatomical basis of the radical hysterectomy classification system of Querleu and Morrow, we proposed a new classification system of radical surgery for rectal cancer based on membrane anatomy. This system categorizes the surgery into four types (A-D) and incorporates corresponding subtypes based on the preservation of the autonomic nerve. Our surgical classification unifies the pelvic membrane anatomical terminology, validates the feasibility of classifying rectal cancer surgery using the theory of "four fasciae and three spaces," and lays the theoretical groundwork for the future development of unified and standardized classification of radical pelvic tumor surgery.

TP53/mTORC1-mediated bidirectional regulation of PD-L1 modulates immune evasion in hepatocellular carcinoma.

BACKGROUND: Immunotherapy has facilitated great breakthroughs in the treatment of hepatocellular carcinoma (HCC). However, the efficacy and response rate of immunotherapy are limited and vary among different patients with HCC. TP53 mutation substantially affects the expression of immune checkpoint molecules in multiple cancers. However, the regulatory relationship between programmed death ligand 1 (PD-L1) and TP53 is poorly studied in HCC. We aimed to elucidate the regulatory mechanism of PD-L1 in HCC with different TP53 statuses and to assess its role in modulating immune evasion in HCC. METHODS: HCC mouse models and cell lines with different TP53 statuses were constructed. PD-L1 levels were detected by PCR, western blotting and flow cytometry. RNA-seqencing, immunoprecipitation, chromatin immunoprecipitation and transmission electron microscopy were used to elucidate the regulatory mechanism in HCC with different TP53 status. HCC mouse models and patient with HCC samples were analyzed to demonstrate the preclinical and clinical significance of the findings. RESULTS: We report that loss of p53 promoted PD-L1 expression and reduced CD8+ T-cell infiltration in patient with HCC samples and mouse models. Mammalian target of rapamycin (mTOR) pathway was activated in p53-loss-of-function HCC or after knocking down TP53. The transcription factor E2F1 was found to bind to the p53 protein in TP53 wild-type HCC cells, and inhibiting mammalian target of rapamycin complex 1 (mTORC1) disrupted this binding and enhanced E2F1 translocation to the nucleus, where it bound to the PD-L1 promoter and transcriptionally upregulated PD-L1. In p53-loss-of-function HCC cells, autophagosomes were activated after mTORC1 suppression, promoting the degradation of PD-L1 protein. The combination of mTOR inhibitor and anti-PD-L1 antibody enhanced CD8+ T-cell infiltration and tumor suppression in TP53 wild-type HCC mouse models, but no benefit was observed in p53-loss-of-function HCC mouse models. In patients with TP53 wild-type HCC, PD-L1 levels were significantly higher in the high E2F1 group than in the low E2F1 group, and the low E2F1 level group had significantly superior survival. CONCLUSION: We revealed the bidirectional regulatory mechanism of PD-L1 mediated by TP53/mTORC1 in HCC. The combination of mTOR inhibitor and anti-PD-L1 antibody could be a novel precise immunotherapy scheme for TP53 wild-type HCC.

Cuproptosis in ccRCC: key player in therapeutic and prognostic targets.

Background: Classical biomarkers have been used to classify clear cell renal cell carcinoma (ccRCC) patients in a variety of ways, and emerging evidences have indicated that cuproptosis is closely related to mitochondrial metabolism, thereby accelerating the development and progression of ccRCC. Nevertheless, the specific relationship between cuproptosis and the prognosis and treatment of ccRCC remains unclear. Methods: We comprehensively integrated several ccRCC patient datasets into a large cohort. Following that, we systematically analyzed multi-omics data to demonstrate the differences between two cuproptosis clusters. Results: We identified two cuproptosis clusters in ccRCC patients. Among the two clusters, cluster 1 patients showed favorable prognosis. We then confirmed the significant differences between the two clusters, including more typical cancer hallmarks were enriched in cluster 2 patients; cluster 2 patients were more susceptible to develop mutations and had a lower level of gistic score and mRNAsi. Importantly, both Tumor Immune Dysfunction and Exclusion analysis and subclass mapping algorithm showed that cuproptosis 1 patients were more susceptible to be responded to immunotherapy. In addition, a prognostic signature was successfully developed and also showed prominent predictive power in response to immunotherapy. Conclusion: As a result of our findings, we were able to classify ccRCC patients according to cuproptosis in a novel way. By constructing the cuproptosis clusters and developing the signature, patients with ccRCC could have a more accurate prognosis prediction and better immunotherapy options.

Transformation of colitis and colorectal cancer: a tale of gut microbiota.

Intestinal inflammation modifies host physiology to promote the occurrence of colorectal cancer (CRC), as seen in colitis-associated CRC. Gut microbiota is crucial in cancer progression, primarily by inducing intestinal chronic inflammatory microenvironment, leading to DNA damage, chromosomal mutation, and alterations in specific metabolite production. Therefore, there is an increasing interest in microbiota-based prevention and treatment strategies, such as probiotics, prebiotics, microbiota-derived metabolites, and fecal microbiota transplantation. This review aims to provide valuable insights into the potential correlations between gut microbiota and colitis-associated CRC, as well as the promising microbiota-based strategies for colitis-associated CRC.

Salidroside suppresses proliferation and migration in prostate cancer via the PI3K/AKT pathway.

BACKGROUND: Prostate cancer (PCa) is one of the most common malignancies in men. PCa is difficult to detect in its early stages, and most patients are diagnosed in the middle to late stages. At present, drug therapy for advanced PCa is still insufficient. Some patients develop drug resistance in the later stage of therapy, which leads to tumor recurrence, metastasis and even treatment failure. Therefore, it is crucial to find new and effective drugs to treat prostate cancer. OBJECTIVE: The aim of this study was to investigate the anti-cancer effect of salidroside, an active ingredient in a traditional Chinese herbal medicine, on PCa. METHODS: Two human PCa cell lines, PC3 and DU145, were cultured and treated with salidroside. Cell viability and proliferation ability were analyzed through CCK-8 and colony assays, and cell migration ability was detected by Transwell and Scratch assays. RT-PCR and WB were used to detected the expression levels of moleculars related to cell proliferation, apoptosis, migration, and AKT signaling pathway. Forthmore, we performed rescue experiments with agonist to verify the affected signaling pathway. RESULTS: Salidroside inhibited the proliferation, colony formation, and migration of PCa cells. Meanwhile, apoptosis of PCa cells was enhanced. Moreover, salidroside inhibited PI3K/AKT pathway in PCa cells. The treatment of AKT agonist 740Y-P abrogated the inhibitory effect of salidroside on the PI3K/AKT signaling pathway. CONCLUSIONS: Our study demonstrated that in PCa cells, salidroside inhibites proliferation and migration and promots apoptosis via inhibiting PI3K/AKT pathway.

Evaluation of 60Co Irradiation on Volatile Components of Turmeric (Curcumae Longae Rhizoma) Volatile Oil with GC-IMS.

60Co irradiation is an efficient and rapid sterilization method. The aim of this work is to determine the changes in essential-oil composition under different irradiation intensities of 60Co and to select an appropriate irradiation dose with GC-IMS. Dosages of 0, 5, and 10 kGy of 60Co were used to analyze turmeric (Curcumae Longae Rhizoma) volatile oil after 60Co irradiation (named JH-1, JH-2, and JH-3). The odor fingerprints of volatile organic compounds in different turmeric volatile oil samples were constructed by headspace solid-phase microextraction and gas chromatography-ion mobility spectrometry (GC-IMS) after irradiation. The differences in odor fingerprints of volatile organic compounds (VOCs) were compared by principal component analysis (PCA). The results showed that 97 volatile components were detected in the volatile oil of Curcuma longa, and 64 components were identified by database retrieval. With the change in irradiation intensity, the volatile compounds in the three turmeric volatile oil samples were similar, but the peak intensity was significantly different, which was attributed to the change in compound composition and content caused by different irradiation doses. In addition, the principal component analysis showed that JH-2 and JH-3 were relatively correlated, while JH-1 and JH-3 were far from each other. In general, different doses of 60Co irradiation can affect the content of volatile substances in turmeric volatile oil. With the increase in irradiation dose, the peak area decreased, and so the irradiation dose of 5 kGy/min was better. It is shown that irradiation technology has good application prospects in the sterilization of foods with volatile components. However, we must pay attention to the changes in radiation dose and chemical composition.

[Effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the expression of Fas/FADD/Caspase-8 of death receptor pathway in rats with primary ovarian insufficiency].

OBJECTIVE: To explore the effect of "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion on the ovarian function in the rats with primary ovarian insufficiency (POI) and the potential effect mechanism based on the Fas/FADD/Caspase-8 of death receptor pathway. METHODS: Forty-eight female SD rats were randomly divided into a blank group, a model group, a medication group and an acupuncture group, with 12 rats in each group. Except in the blank group, the rats in the other groups were intraperitoneally injected with cyclophosphamide to establish the POI model. In the acupuncture group, after successful modeling, the intervention was given with "Zhibian" (BL 54)-to- "Shuidao" (ST 28) needle insertion, once daily, 30 min in each intervention; and the duration of intervention was 4 weeks. In the medication group, estradiol valerate tablets were administered intragastrically, 0.09 mg•kg-1•d-1, for 4 weeks. The general situation and the estrous cycle of the rats were compared among groups. Using ELISA, the levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) in the serum were detected. HE staining was adopted to observe the morphological changes of ovarian tissue of rats. The protein expression of Fas, FADD and Caspase-8 in ovarian tissue was detected with immunohistochemistry and Western blot. RESULTS: After modeling, except the rats of the blank group, the rats of the other groups had dry fur, lost hair, low spirits, reduced food intake, increased urination and loose stool. After intervention, the stool became regular gradually in the acupuncture group and the medication group. The percentage of estrous cycle disturbance was increased in the rats of the model group when compared with the blank group (P<0.01); in comparison with the model group, the percentages of estrous cycle disturbance were reduced in the acupuncture group and the medication group after intervention (P<0.01). When compared with the blank group, the body mass and E2 content in the serum were lower (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were increased (P<0.01) in the model group. Compared with the model group, the body mass and E2 contents in the serum were higher (P<0.01), the levels of FSH and LH in the serum and the protein expression levels of Fas, FADD and Caspase-8 were reduced (P<0.01) in the acupuncture group and the medication group. CONCLUSION: "Zhibian" (BL 54)-to-"Shuidao" (ST 28) needle insertion can effectively improve the ovarian function of POI rats, and its effect mechanism may be related to regulating the serum sex hormone levels, reducing the expression of Fas, FADD and Caspase-8 in ovarian tissue and retarding apoptosis of ovarian cells.

Muscle size and density are independently associated with death after hip fracture: A prospective cohort study.

BACKGROUND: Mortality following hip fracture is high and incompletely understood. We hypothesize that hip musculature size and quality are related to mortality following hip fracture. This study aims to investigate the associations of hip muscle area and density from hip CT with death following hip fracture as well as assess the dependence of this association on time after hip fracture. METHODS: In this secondary analysis of the prospectively collected CT images and data from the Chinese Second Hip Fracture Evaluation, 459 patients were enrolled between May 2015 and June 2016 and followed up for a median of 4.5 years. Muscle cross-sectional area and density were measured of the gluteus maximus (G.MaxM) and gluteus medius and minimus (G.Med/MinM) and aBMD of the proximal femur. The Goutallier classification (GC) was used for qualitatively assessing muscle fat infiltration. Separate Cox models were used to predict mortality risk adjusted for covariates. RESULTS: At the end of the follow-up, 85 patients were lost, 81 patients (64% women) had died, and 293 (71% women) survived. The mean age of non-surviving patients at death (82.0 ± 8.1 years) was higher than that of the surviving patients (74.4 ± 9.9 years). The Parker Mobility Score and the American Society of Anesthesiologists scores of the patients that died were respectively lower and higher compared to the surviving patients. Hip fracture patients received different surgical procedures, and no significant difference in the percentage of hip arthroplasty was observed between the dead and the surviving patients (P = 0.11). The cumulative survival was significantly lower for patients with low G.MaxM area and density and low G.Med/MinM density, independent of age and clinical risk scores. The GC grades were not associated with the mortality after hip fracture. Muscle density of both G.MaxM (adj. HR 1.83; 95% CI, 1.06-3.17) and G.Med/MinM (adj. HR 1.98; 95% CI, 1.14-3.46) was associated with mortality in the 1st year after hip fracture. G.MaxM area (adj. HR 2.11; 95% CI, 1.08-4.14) was associated with mortality in the 2nd and later years after hip fracture. CONCLUSION: Our results for the first time show that hip muscle size and density are associated with mortality in older hip fracture patients, independent of age and clinical risk scores. This is an important finding to better understand the factors contributing to the high mortality in older hip fracture patients and to develop better future risk prediction scores that include muscle parameters.

Intraoperative Fluorescein Angiography Can Efficiently Identify Biomarkers and Guide Surgical Decision-Making.

PURPOSE: We sought to develop an efficient method for fluorescein angiography (FA) during digitally assisted vitreoretinal surgery (DAVS). METHODS: A 485-nm bandpass filter was placed into the filter holder of the accessory light sources of the Constellation Vision System with steel modified washers to produce an exciter source. A barrier filter was placed into the blank slot of a switchable laser filter with a 535-nm bandpass filter and another washer or created digitally with a specific color channel using NGENUITY software version 1.4. Fluorescein, 250 to 500 mg, was then injected intravenously during retinal surgery. RESULTS: These fluorescence patterns accurately detect many fluorescein angiography biomarkers, such as determination of vascular filling times, ischemia, neovascularization, shunt vessels, microaneurysms, and leakage into the vitreous. This enhanced surgical visualization permitted intervention in real time such as laser or diathermy to residual microvascular abnormalities after delamination of retinal neovascularization as well as heavier panretinal laser placement in areas of retinal capillary dropout to relatively preserve areas of more intact retinal microcirculation. CONCLUSION: The authors of this study are the first to report an efficient method that permits high-resolution detection of many classic FA biomarkers such as during DAVS to enhance surgical visualization and intervention in real time.

[Effect of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on the expression of apoptosis-related factors in rats with premature ovarian insufficiency based on oxidative stress].

OBJECTIVE: To explore the possible mechanism of acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) on premature ovarian insufficiency (POI) from the perspective of oxidative stress. METHODS: Sixty female SD rats were randomly divided into a blank group, a model group, a sham acupuncture group, a medication group, and an acupuncture group, 12 rats in each group. Except the blank group, the rats in the remaining groups were intraperitoneally injected with cyclophosphamide to establish the POI model. After the model was successfully established, the rats in the acupuncture group were treated with acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28), with a depth of about 12 mm, and the needle was retained for 30 min; the acupuncture was given once a day, for a total of 4 weeks. The rats in the sham acupuncture group were treated with blunt-head needle to tap the skin surface of "Zhibian" (BL 54), without penetrating the skin, once a day for 4 weeks. The rats in the medication group were treated with estradiol valerate by gastric gavage for 4 weeks. After the intervention, the level of reactive oxygen species (ROS) in the ovarian tissue was detected by fluorescence probe; the expression of c-Jun N-terminal kinase (JNK), forkhead box O1 (FoxO1), tumor suppressor gene protein 53 (p53) and p53 up-regulated modulator of apoptosis (Puma) mRNA and protein in ovarian tissue were detected by real-time fluorescence quantitative PCR and Western blot. RESULTS: Compared with the blank group, the level of ROS and the expression of JNK mRNA, p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the model group were increased (P<0.01). Compared with the model group, the level of ROS and the expression of p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the sham acupuncture group were slightly reduced, but the difference was not statistically significant (P>0.05). The level of ROS and the expression of JNK mRNA, p-JNK protein, FoxO1, p53, Puma mRNA and protein in the ovarian tissue in the acupuncture group and the medication group were reduced (P<0.01). CONCLUSION: Acupuncture at "Zhibian" (BL 54) through "Shuidao" (ST 28) could improve the level of oxidative stress, down-regulate the expression of apoptosis-related factors JNK, FoxO1, p53 and Puma induced by oxidative stress, and inhibit the premature failure of ovarian reserve function caused by apoptosis of ovarian granulosa cells in POI rats.

Bortezomib, Melphalan, and Prednisone With or Without Daratumumab in Transplant-ineligible Asian Patients With Newly Diagnosed Multiple Myeloma: The Phase 3 OCTANS Study.

INTRODUCTION: In the global phase 3 ALCYONE trial, daratumumab plus bortezomib/melphalan/prednisone (D-VMP) improved outcomes versus VMP in transplant-ineligible newly diagnosed multiple myeloma (NDMM) patients. Here, we report the primary analysis of the phase 3 OCTANS trial of D-VMP versus VMP in transplant-ineligible Asian NDMM patients. PATIENTS AND METHODS: In total, 220 patients were randomized (2:1) to receive 9 cycles of VMP (bortezomib 1.3 mg/m2 subcutaneously twice weekly in Cycle 1 and weekly in Cycles 2 to 9; melphalan 9 mg/m2 orally; and prednisone 60 mg/m2 orally on Days 1 to 4 of each cycle) ± daratumumab 16 mg/kg intravenously weekly in Cycle 1, every 3 weeks in Cycles 2 to 9, and every 4 weeks thereafter until disease progression. RESULTS: After a median follow-up of 12.3 months, very good partial response or better rates (primary endpoint) were 74.0% versus 43.2% with D-VMP versus VMP (odds ratio, 3.57; 95% confidence interval [CI], 1.99-6.43; P < .0001). Median progression-free survival (PFS) with D-VMP versus VMP was not reached versus 18.2 months (hazard ratio, .43; 95% CI, .24-.77; P = .0033); 12-month PFS rates were 84.2% versus 64.6%. The most frequent grade 3/4 treatment-emergent adverse events with D-VMP/VMP were thrombocytopenia (46.5%/45.1%), neutropenia (39.6%/50.7%), and leukopenia (31.3%/36.6%). CONCLUSION: D-VMP demonstrated a favorable benefit/risk profile in transplant-ineligible Asian NDMM patients. This trial was registered at www. CLINICALTRIALS: gov as #NCT03217812.