Potent inhibition of human and rat 17ß-hydroxysteroid dehydrogenase 1 by curcuminoids and the metabolites: 3D QSAR and in silico docking analysis.

Curcumin, an extensively utilized natural pigment in the food industry, has attracted considerable attention due to its potential therapeutic effects, such as anti-tumorigenic and anti-inflammatory activities. The enzyme 17ß-Hydroxysteroid dehydrogenase 1 (17ß-HSD1) holds a crucial position in oestradiol production and exhibits significant involvement in oestrogen-responsive breast cancers and endometriosis. This study investigated the inhibitory effects of curcuminoids, metabolites, and analogues on 17ß-HSD1, a key enzyme in oestradiol synthesis. Screening 10 compounds, including demethoxycurcumin (IC50, 3.97 µM) and dihydrocurcumin (IC50, 5.84 µM), against human and rat 17ß-HSD1 revealed varying inhibitory potencies. These compounds suppressed oestradiol secretion in human BeWo cells at ≥ 5-10 µM. 3D-Quantitative structure-activity relationship (3D-QSAR) and molecular docking analyses elucidated the interaction mechanisms. Docking studies and Gromacs simulations suggested competitive or mixed binding to the steroid or NADPH/steroid binding sites of 17ß-HSD1. Predictive 3D-QSAR models highlighted the importance of hydrophobic regions and hydrogen bonding in inhibiting 17ß-HSD1 activity. In conclusion, this study provides valuable insights into the inhibitory effects and mode of action of curcuminoids, metabolites, and analogues on 17ß-HSD1, which may have implications in the field of hormone-related disorders.

The factors influencing the occurrence of post-ischemic stroke depression and its relationship with the burden score of cerebral small vessel disease.

OBJECTIVE: This study explored the determinants of post-stroke depression (PSD) in ischemic stroke (AIS) patients and its association with the burden score of cerebral small vessel disease (CSVD). PATIENTS AND METHODS: We analyzed 374 AIS patients treated between January 2020 and January 2022. Patients were categorized into 90 with PSD and 284 without PSD, enabling an investigation into PSD risk factors and the CSVD-PSD relationship. RESULTS: There was no significant difference in health factors between PSD and non-PSD patients (p>0.05). However, significant disparities were noted in age, gender, initial Barthel Index (BI), Mini-Mental State Examination (MMSE) score, plasma fibrinogen, homocysteine, red cell distribution width, National Institutes of Health Stroke Scale (NIHSS) score, and CSVD burden score (p<0.05). Regression analysis indicated that these variables were pivotal PSD predictors (OR>1, p<0.05). Surprisingly, a positive correlation with PSD occurrence was found for age, NIHSS score, plasma fibrinogen, homocysteine levels, red cell distribution width, CSVD burden score (r=0.565, 0.615, 0.482, 0.514, 0.572, 0.608, respectively; p<0.05). Meanwhile, the MMSE score and BI index were inversely related to PSD onset (r=-0.604, -0.590; p<0.05). The ROC curve analysis of the combination model based on MMSE, NIHSS and CSVD score revealed an AUC of 0.926 and Youden's index of 0.744. CONCLUSIONS: Age, MMSE score, BI index, NIHSS score, plasma fibrinogen concentration, homocysteine level, red blood cell distribution width, and CSVD burden score are all major influencing factors in the occurrence of PSD. The combination model based on MMSE, NIHSS, and CSVD scores presented a valuable approach to predicting PSD.

[Transperineal targeted prostate puncture combined with rapid pathological examination in the diagnosis of prostate cancer].

Exploring the clinical value of multiparametric magnetic resonance (Mp-MRI)-cognitive fusion method of targeted transperineal prostate puncture combined with rapid pathological diagnosis. Patients with suspected prostate cancer admitted to our hospital from 2022.01 to 2023.05 were selected as the study subjects, and Mp-MRI was performed and the suspected lesions were scored by the Prostate Imaging Reporting and Data System (PI-RADS). The enrolled patients were randomly divided into the transperineal prostate targeted puncture plus rapid pathology group (experimental group) and the transperineal prostate systematic combined targeted puncture plus conventional pathology group (control group), and the positive puncture rate, pathological findings, and complications were analyzed to compare the differences between the two groups. A total of 100 patients were enrolled, 53 in the experimental group [age 55-89 years, (73.17±7.79) years; tPSA 7.01-100 µg/L, mean 21.34 (12.38, 44.42) µg/L]and 47 in the control group [age 60-87 years, (71.96±7.07) years; tPSA 6.11-98.82 µg/L, mean 18.77 (9.04, 38.09) µg/L], and there was no significant difference between the two groups in the diagnostic positivity rate of overall PCa and clinically significant PCa (P>0.05); there was no significant difference in the highest Gleason score of pathological tissues between the two groups (P>0.05); the number of cases of medically induced sarcoid hematuria in the experimental group were significantly reduced compared with the control group (P<0.05). In terms of biopsy pain score (VAS), patients in the experimental group experienced less pain than those in the control group (P<0.05). The Mp-MRI-cognitive fusion method of transperineal targeted prostate puncture combined with rapid frozen section pathological examination can provide rapid and accurate pathological results, reduce the chance of post-puncture complications, and alleviate the pain caused by puncture sampling, which has high clinical value.

The causal association between body fat distribution and risk of abdominal wall hernia: a two-sample Mendelian randomization study.

PURPOSE: Obesity and a high body mass index (BMI) are considered as risk factors for abdominal wall hernia (AWH). However, anthropometric measures of body fat distribution (BFD) seem to be better indicators in the hernia field. This Mendelian randomization analysis aimed to generate more robust evidence for the impact of waist circumstance (WC), body, trunk, arm, and leg fat percentages (BFP, TFP, AFP, LFP) on AWH. METHODS: A univariable MR design was employed and the summary statistics allowing for assessment were obtained from the genome-wide association studies (GWASs). An inverse variance weighted (IVW) method was applied as the primary analysis, and the odds ratio value was used to evaluate the causal relationship between BFD and AWH. RESULTS: None of the MR-Egger regression intercepts deviated from null, indicating no evidence of horizontal pleiotropy (p > 0.05). The Cochran Q test showed heterogeneity between the genetic IVs for WC (p = 0.005; p = 0.005), TFP (p < 0.001; p < 0.001), AFP-L (p = 0.016; p = 0.015), LFP-R (p = 0.012; p = 0.009), and LFP-L (p < 0.001; p < 0.001). Taking the IVW random-effects model as gold standard, each standard deviation increment in genetically determined WC, BFP, TFP, AFP-R, AFP-L, LFP-R, and LFP-L raised the risk of AWH by 70.9%, 70.7%, 56.5%, 69.7%, 78.3%, 87.7%, and 72.5%, respectively. CONCLUSIONS: This study proves the causal relationship between AWH and BFD, attracting more attention from BMI to BFD. It provides evidence-based medical evidence that healthy figure management can prevent AWH.

The top 100 most-cited papers in incisional hernia: a bibliometric analysis from 2003 to 2023.

PURPOSE: Incisional hernia (IH) is one of the most common complications after abdominal surgeries and may bring great suffering to patients. This study aims to evaluate the global trends in IH research from 2003 to 2023 and visualize the frontiers using bibliometric analysis. METHODS: The literature search was conducted on the Web of Science for IH studies published from 2003 to 2023 and sorted by citation frequency. The top 100 most-cited articles were analyzed by the annual publication number, prolific countries and institutions, influential author and journal, and the number of citations through descriptive statistics and visualization. RESULTS: The top paper was cited 1075 times and the median number of citations was 146. All studies were published between 2003 and 2019 and the most prolific year was 2003 with 14 articles. Jeekel J and Rosen M were regarded as the most productive authors with ten articles each and acquired 2738 and 2391 citations, respectively. The top three institutions with the most productive articles were Erasmus Mc, Carolinas Med Ctr, and Univ Utah, while the top three countries were the United States, Netherlands and Germany. The most frequent keyword was "incisional hernia" with 55 occurrences, followed by "mesh repair", "randomized controlled trial", and "polypropylene". CONCLUSION: The 100 most-cited papers related to IH were published predominantly by USA and European countries, with randomized controlled trial (RCT) and observational study designs, addressing topics related to risk factors, complications, mesh repair, and mesh components.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Risk factors for incisional hernia after gastrointestinal surgeries in non-tumor patients.

PURPOSE: Incisional hernia (IH) is a common secondary ventral hernia after abdominal incisions and there is still little reliable evidence to predict and prevent IH. This study aimed to estimate risk factors of its incidence, especially concentrating on blood results. METHODS: 96 patients received midline laparotomy for gastrointestinal benign diseases and suffered from IH were enrolled in the IH group. A control group of 192 patients were randomly selected from patients underwent midline laparotomy for gastrointestinal benign diseases without IH. RESULTS: Patients in the IH group exhibited higher age (P < 0.001), BMI (P < 0.001), hernia history (P = 0.001) and laparotomy history (P < 0.001). Rate of coronary heart disease (P = 0.046), hypertension (P < 0.001), diabetes (P = 0.008), incisional infection (P = 0.004) and emergency surgery (P = 0.041) were also higher in the IH group. Patients with IH had lower levels of Hb (P = 0.002), TP (P = 0.013), ALB (P < 0.001), A/G (P = 0.019), PA (P < 0.001), HDL-C (P = 0.008) and ApoA1 (P = 0.005). Meanwhile, patients in the control group bore lower levels of LDH (P = 0.008), GLU (P = 0.007), BUN (P = 0.048), UA (P = 0.021), TG (P = 0.011), TG/HDL-C (P = 0.002), TC/HDL-C (P = 0.013), ApoB/ApoA1 (P = 0.001) and Lp(a) (P = 0.001). A multivariate logistic regression revealed that high BMI, laparotomy history, incisional infection, decreased PA, elevated levels of UA, Lp(a) and ApoB/ApoA1 were independent risk factors of IH. CONCLUSION: This is the first study to reveal the relationship between IH and serum biochemical levels, and give a prediction through the nomograph model. These results will help surgeons identify high-risk patients, and take measures to prevent IH during the perioperative period.

[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

[Diagnostic value of contrast-enhanced ultrasound in hepatic epithelioid hemangioendothelioma].

Objective: To investigate the features of contrast-enhanced ultrasound (CEUS) in hepatic epithelioid hemangioendothelioma (HEHE) in order to improve the preoperative diagnosis rate. Methods: CEUS images of 32 pathologically-proven cases of hepatic epithelioid hemangioendothelioma from January 2004 to August 2021 were collected. Lesions were analyzed to observe the features of enhancement mode, enhancement intensity, and distinct enhancement phases. Results: Among the 32 cases, one had a solitary lesion, 29 had multiple lesions, and two had diffuse-type lesions. Contrast-enhanced ultrasound revealed a total of 42 lesions in 32 cases. In terms of arterial phase enhancement, 18 lesions had overall enhancement, six lesions had uneven dendritic enhancement, 16 lesions had rim-like enhancement, and two lesions had just slight peripheral spot enhancement around the lesions. Among the three cases, there were multiple lesions that had overall enhancement and ring enhancement. In terms of the enhancement phase, 20 lesions showed "fast progression", 20 lesions showed "same progression", and two lesions showed "slow progression". During the late arterial or early portal venous phases with rapid washout, all lesions manifested as hypoechoic. With peaked enhanced intensity, 11 lesions had a lower enhancement intensity than the surrounding normal liver parenchyma; 11 lesions had the same enhancement degree as the surrounding normal liver parenchyma; and 20 lesions had a higher enhancement degree than the surrounding normal liver parenchyma. All 16 ring-enhancing lesions had marked hyperenhancement. In the typical enhancing lesions, four showed hyperenhancement, five showed low enhancement, and nine showed isoenhancement. In the dendrite-enhancing lesions, there were two isoenhancing and four hypoenhancing. Contrast-enhanced ultrasound delineated the boundaries of all lesions more clearly than two-dimensional ultrasound. Conclusion: Contrast-enhanced ultrasound has certain value in the diagnosis of hepatic epithelioid hemangioendothelioma.

[Clinical efficacy and safety analysis of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer].

Objective: To investigate the clinical efficacy and safety of 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer. Methods: Clinical data of 36 patients who underwent CT-guided 125I seed implantation for mediastinal lymph node metastasis of lung cancer from August 2013 to April 2020 in three hospitals of the Northern radioactive particle implantation treatment collaboration group were retrospectively collected, including 24 males and 12 females, aged 46 to 84 years. Cox regression model was used to analyze the relationship between local control rate, survival rate and tumor stage, pathological type, postoperative D90, postoperative D100 and other variables, and to analyze the occurrence of complications. Results: The objective response rate of CT-guided 125I seed implantation in the treatment of mediastinal lymph node metastasis of lung cancer was 75% (27/36), the median control time was 12 months, the 1-year local control rate was 47.2% (17/36), and the median survival time was 17 months. The 1-year and 2-year survival rates were 61.1% (22/36) and 22.2% (8/36) respectively. Univariate analysis showed that in the treatment of mediastinal lymph node metastasis with CT-guided 125I implantation, factors related to local control included tumor stage (HR=5.246, 95%CI: 2.243-12.268, P<0.001), postoperative D90 (HR=0.191, 95%CI: 0.085-0.431, P<0.001), postoperative D100 (HR=0.240, 95%CI: 0.108-0.533, P<0.001); The factors affecting survival were tumor stage (HR=2.712, 95%CI: 1.356-5.425, P=0.005), postoperative D90 (HR=0.110, 95%CI: 0.041-0.294, P<0.001), postoperative D100 (HR=0.212, 95%CI: 0.092-0.489, P<0.001). Multivariate analysis showed that tumor stage (HR=5.305, 95%CI: 2.187-12.872, P<0.001) and postoperative D100 (HR=0.237, 95%CI: 0.099-0.568, P<0.001) were correlated with local control rate. Tumor stage (HR=2.347, 95%CI: 1.095-5.032, P=0.028) and postoperative D90 (HR=0.144, 95%CI: 0.051-0.410, P<0.001) were correlated with survival. In terms of complications, 9 of the 36 patients had pneumothorax, and 1 of them was cured by closed thoracic drainage for severe pneumothorax; 5 cases developed pulmonary hemorrhage and 5 cases developed hemoptysis, which recovered after hemostasis treatment. One case developed pulmonary infection and recovered after anti-inflammatory treatment. No radiation esophagitis and radiation pneumonia occurred; No grade 3 or higher complications occurred. Conclusion: 125I seed implantation in the treatment of lung cancer mediastinal lymph node metastasis has a high local control rate and controllable adverse effects.

Effects of coated sodium butyrate on growth performance, intestinal morphology, and caecal short-chain fatty acids of growing Pekin ducks.

1. A dose‒response experiment with six supplemental levels of coated sodium butyrate (CSB) (0, 250, 500, 750, 1,000, and 1,250 mg/kg) was conducted to investigate its effects on growth performance, intestinal morphology, and caecal short-chain fatty acids of growing Pekin ducks aged 14 to 35 d. A total of 288 male 14-d-old Pekin ducks were randomly allocated to six dietary treatments. Each treatment had eight replicate pens of six ducks per pen.2. The daily weight gain, daily feed intake, and feed/gain of ducks from 14 to 35 d of age were not influenced by increasing CSB levels. The relative weight and length of the duodenum, jejunum, and caecum increased linearly or quadratically as supplemental CSB increased (P < 0.05).3. For the ileum and caecum, the villus height and height/crypt depth increased linearly or quadratically, and the villus crypt depth decreased linearly as the supplemental CSB increased (P < 0.05). As supplemental CSB increased, the goblet cell numbers of the ileum increased and decreased and changed quadratically (P < 0.05), but caecal goblet cell number increased quadratically (P < 0.05). Increasing the CSB level linearly or quadratically elevated the concentrations of propionic acid and butyric acid in the caecum (P < 0.05).4. It was concluded that CSB can be used as a safe and effective feed additive to promote the intestinal integrity of growing ducks by improving intestinal morphology and increasing the concentration of caecal short-chain fatty acids.

Parents of preschoolers use multiple strategies to feed their children: Findings from an observational video pilot study.

The current study leveraged observational data collection methods to fill gaps in our understanding of parent approach to feeding as well as child responses to various parental approaches. Specifically, the study aimed to: 1) characterize the broad range of food parenting practices used by parents of preschoolers during shared mealtimes at home, including differences by child gender, and 2) describe child responses to specific parent feeding practices. Forty parent-child dyads participated by recording two in-home shared meals. Meals were coded using a behavioral coding scheme that coded the occurrence of 11 distinct food parenting practices (e.g. indirect and direct commands, praise, bribes) and eight child responses (e.g., eat, refuse, cry/whine) to food parenting practices. Results revealed that parents engaged in a broad range of food parenting practices at meals. On average, parents in our sample used 10.51 (SD 7.83; Range 0-30) total food parenting practices per mealtime with a mean use of 3.38 (SD 1.67; Range 0-8) unique food parenting practices per mealtime. Use of indirect and direct commands to eat were most common; direct and indirect commands were used by 97.5% (n = 39) and 87.5% (n = 35) of parents at meals, respectively. No statistically significant differences were observed by child gender. No one specific feeding practice consistently yielded compliance or refusal to eat from the child, instead child responses were often mixed (e.g., compliance followed by refusal and/or refusal followed by compliance). However, use of praise to prompt eating was the practice that most often resulted in child compliance; 80.8% of children complied following parent's use of praise as a prompt to eat. Findings deepen our understanding of the types and frequency of food parenting practices used by parents of preschoolers during meals eaten at home and illuminate child responses to specific food parenting practices.

[On the difficulties and pains in managing peritoneal metastasis from gastrointestinal cancer in China].

Modern clinical oncology has made great achievements over the last century. However, peritoneal metastasis from gastrointestinal cancer, as one of three most common metastasis modalities, was not re-recognized until the end of the last century, and a normative diagnosis and treatment system has been gradually beginning to be formed until today. This comment is to review the development history, reflect on the lessons and experiences in clinical practice, analyze the difficulties on redefinition, deep understanding and clinical management, and pain points on theory construction, technique practice and discipline construction, in the field of gastrointestinal cancer peritoneal metastasis. We suggested a solution to the difficulties and pain points by realizing the fact of burden of peritoneal metastasis, reinforcing technical training, and promoting collaborative researches, aiming to provide reference for the steady development of peritoneal surface oncology.