Endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) in small bowel subepithelial lesions: experience in treating fifteen cases.

AIM: The study objective was to evaluate the primary feasibility of endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) to treat small bowel subepithelial lesions (SELs). METHOD: A retrospective case series study was performed. The first fifteen consecutive patients who underwent ESD (n = 10) and EFTR (n = 5) via BAE to remove small bowel SELs from November 2016 to December 2023 were included. The main outcome measures were the technique success rate, operative time and complication rate. RESULTS: This research focused on 15 cases of jejunoileal SELs, four cases of lipomyoma, three cases of ectopic pancreas, two cases of NETs, three cases of benign fibrous tumours and three cases of angioma. The overall technique success rate was 86.7%, with 100% (10/10) and 60% (3/5) for BAE-ESD and BAE-EFTR, respectively, in removing small bowel SELs. Two cases of EFTR failed, as the BAE operation was unsuitable for tumour resection and suture repair of a perforated wound. No serious bleeding or any postoperative complications occurred. The median time of endoscopic resection via BAE for SELs was 44 min (range 22-68 min). CONCLUSION: ESD and EFTR via BAE might be alternative choices for treating small SELs in the small bowel, with the advantages of clear and accurate positioning and minimal invasiveness. However, its superiority over surgery still needs to be further investigated.

Intelligent medicine in focus: the 5 stages of evolution in robot-assisted surgery for prostate cancer in the past 20 years and future implications.

Robot-assisted surgery has evolved into a crucial treatment for prostate cancer (PCa). However, from its appearance to today, brain-computer interface, virtual reality, and metaverse have revolutionized the field of robot-assisted surgery for PCa, presenting both opportunities and challenges. Especially in the context of contemporary big data and precision medicine, facing the heterogeneity of PCa and the complexity of clinical problems, it still needs to be continuously upgraded and improved. Keeping this in mind, this article summarized the 5 stages of the historical development of robot-assisted surgery for PCa, encompassing the stages of emergence, promotion, development, maturity, and intelligence. Initially, safety concerns were paramount, but subsequent research and engineering advancements have focused on enhancing device efficacy, surgical technology, and achieving precise multi modal treatment. The dominance of da Vinci robot-assisted surgical system has seen this evolution intimately tied to its successive versions. In the future, robot-assisted surgery for PCa will move towards intelligence, promising improved patient outcomes and personalized therapy, alongside formidable challenges. To guide future development, we propose 10 significant prospects spanning clinical, research, engineering, materials, social, and economic domains, envisioning a future era of artificial intelligence in the surgical treatment of PCa.

Metformin use correlated with lower risk of cardiometabolic diseases and related mortality among US cancer survivors: evidence from a nationally representative cohort study.

BACKGROUND: In the USA, the prolonged effective survival of cancer population has brought significant attention to the rising risk of cardiometabolic morbidity and mortality in this population. This heightened risk underscores the urgent need for research into effective pharmacological interventions for cancer survivors. Notably, metformin, a well-known metabolic regulator with pleiotropic effects, has shown protective effects against cardiometabolic disorders in diabetic individuals. Despite these promising indications, evidence supporting its efficacy in improving cardiometabolic outcomes in cancer survivors remains scarce. METHODS: A prospective cohort was established using a nationally representative sample of cancer survivors enrolled in the US National Health and Nutrition Examination Survey (NHANES), spanning 2003 to 2018. Outcomes were derived from patient interviews, physical examinations, and public-access linked mortality archives up to 2019. The Oxidative Balance Score was utilized to assess participants' levels of oxidative stress. To evaluate the correlations between metformin use and the risk of cardiometabolic diseases and related mortality, survival analysis of cardiometabolic mortality was performed by Cox proportional hazards model, and cross-sectional analysis of cardiometabolic diseases outcomes was performed using logistic regression models. Interaction analyses were conducted to explore the specific pharmacological mechanism of metformin. RESULTS: Among 3995 cancer survivors (weighted population, 21,671,061, weighted mean [SE] age, 62.62 [0.33] years; 2119 [53.04%] females; 2727 [68.26%] Non-Hispanic White individuals), 448 reported metformin usage. During the follow-up period of up to 17 years (median, 6.42 years), there were 1233 recorded deaths, including 481 deaths from cardiometabolic causes. Multivariable models indicated that metformin use was associated with a lower risk of all-cause (hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.47-0.81) and cardiometabolic (HR, 0.65; 95% CI, 0.44-0.97) mortality compared with metformin nonusers. Metformin use was also correlated with a lower risk of total cardiovascular disease (odds ratio [OR], 0.41; 95% CI, 0.28-0.59), stroke (OR, 0.44; 95% CI, 0.26-0.74), hypertension (OR, 0.27; 95% CI, 0.14-0.52), and coronary heart disease (OR, 0.41; 95% CI, 0.21-0.78). The observed inverse associations were consistent across subgroup analyses in four specific cancer populations identified as cardiometabolic high-risk groups. Interaction analyses suggested that metformin use as compared to non-use may counter-balance oxidative stress. CONCLUSIONS: In this cohort study involving a nationally representative population of US cancer survivors, metformin use was significantly correlated with a lower risk of cardiometabolic diseases, all-cause mortality, and cardiometabolic mortality.

The role of EUS-guided iodine-125 seed implantation in patients with unresectable ampullary cancer after relief of obstructive jaundice.

Purpose: Few studies have focused on the management of inoperable ampullary carcinoma (AC), and patients with jaundice suffer from biliary stents replacement frequently. Iodine-125 (125I) brachytherapy has been used in the treatment of malignant tumors owing to its curative effect, minimal surgical trauma, and tolerable complications. The aim of the study was to investigate the role of 125I seed implantation in patients with unresectable ampullary carcinoma after relief of obstructive jaundice. Material and methods: A total of 44 patients with obstructive jaundice resulting from unresectable ampullary carcinoma from January 1, 2010 to October 31, 2020 were enrolled in the study. Eleven patients underwent implantation of 125I seeds under endoscopic ultrasound (EUS) after receiving biliary stent placement via endoscopic retrograde cholangiopancreatography (ERCP) (treatment group), and 33 patients received a stent alone via ERCP (control group). Cox regression model was applied in this single-center retrospective comparison study. Results: The median maximum intervention interval for biliary obstruction was 381 days (interquartile range [IQR]: 204-419 days) in the treatment group and 175 days (IQR: 126-274 days) in the control group (p < 0.05). Stent occlusion rates at 90 and 180 days in the control group were 12.9% and 51.6%, respectively. No stent occlusion occurred in the treatment group. Patients in the treatment group obtained longer survival time (median, 26 vs. 13 months; p < 0.01) and prolonged duodenal obstruction (median, 20.5 vs. 11 months; p < 0.05). No brachytherapy-related grade 3 or 4 adverse events were observed. Conclusions: Longer intervention interval for biliary obstruction and survival as well as better stent patency and prolonged time to duodenal obstruction could be achieved by implanting 125I seeds combined with biliary stent in patients with unresectable ampullary cancer.

[Network Meta-analysis of Chinese patent medicine in treatment of heart failure with preserved ejection fraction].

This study systematically evaluated the efficacy and safety of different Chinese patent medicines combined with conventional western medicine in the treatment of heart failure with preserved ejection fraction(HFpEF) and ranked for the drug selection. Randomized controlled trial(RCT) on Chinese patent medicines in treatment of HFpEF were obtained from the CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, Web of Science, and other databases from the inception to October 9, 2022. The included RCT was quantitatively analyzed using gemtc and rjags packages of R software for the network Meta-analysis. 74 RCTs were included, with a total of 7 192 patients enrolled, involving 11 different Chinese patent medicines(Shenfu Injection, Shenmai Injection, Qili Qiangxin Capsules, Shexiang Baoxin Pills, Xuezhikang Capsules, Salvia Miltiorrhiza Polyphenols Injection, Tanshinone Ⅱ_A Sulfonate Injection, Xinmailong Injection, Yangxinshi Tablets, Qishen Yiqi Dripping Pills, and Yixinshu Capsules). The results of network Meta-analysis are shown as followed.(1)In terms of improving clinical effective rate, for injection preparations, Xinmailong Injection + conventional western medicine was recommended. while for oral preparations, Shexiang Baoxin Pills + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine, and Qili Qiangxin Capsules + conventional western medicine were preferred.(2)In terms of improving the mitral ratio of peak early to late diastolic filling velocity(E/A), for injection preparations, Shenmai Injection + Salvia Miltiorrhiza Polyphenols Injection + conventional western medicine, Shenmai Injection + conventional western medicine, Shenfu Injection + conventional western medicine were preferred. While for oral preparations, Yixinshu Capsules + conventional western medicine was preferred.(3)In terms of reducing the ratio of early diastolic mitral inflow to early diastolic mitral annular velocity(E/e'), Shenfu Injection + conventional western medicine could be used as injection preparation, and Qili Qiangxin Capsules + conventional western medicine, Qishen Yiqi Dripping Pills + conventional western medicine for oral preparations.(4)In terms of improving 6-minute walking trail(6MWT), the injection preparations such as Shenmai Injection + conventional western medicine, Xinmailong Injection + conventional western medicine were suitable, while oral preparations like Qishen Yiqi Dripping Pills + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine were recommended.(5)In terms of reducing N-terminal pro B-type natriuretic peptide(NT-proBNP), Qili Qiangxin Capsules + conventional western medicine were preferred.(6)In terms of reducing B-type natriuretic peptide(BNP), Xinmailong Injection + conventional western medicine could be used for injection preparation and Qili Qiangxin Capsules + conventional western medicine can be used for oral preparation. In terms of adverse drug reactions, there was no significant difference between Chinese patent medicine combined with conventional western conventional and traditional western medicine alone. The results showe that Chinese patent medicine combined with conventional western medicine in treating HFpEF is superior to conventional western medicine alone in reducing clinical symptoms, improving cardiac function, and improving exercise tolerance, which also has good drug safety. However, the existing evidence is still limited by the quality and quantity of included studies, so the above conclusion requires further validation through more prospective RCT.

Deubiquitinating enzyme OTUD4 stabilizes RBM47 to induce ATF3 transcription: a novel mechanism underlying the restrained malignant properties of ccRCC cells.

Dysregulation of deubiquitination contributes to various diseases, including cancer, and aberrant expression of deubiquitinating enzymes is involved in carcinoma progression. As a member of the ovarian tumor (OTU) deubiquitinases, OTUD4 is considered a tumor suppressor in many kinds of malignancies. The biological characteristics and mechanisms of OTUD4 in clear cell renal cell carcinoma (ccRCC) remain unclear. The downregulation of OTUD4 in ccRCC was confirmed based on the TCGA database and a validation cohort of 30-paired ccRCC and para-carcinoma samples. Moreover, OTUD4 expression was detected by immunohistochemistry in 50 cases of ccRCC tissues, and patients with lower levels of OTUD4 showed larger tumor size (p = 0.015). TCGA data revealed that patients with high expression of OTUD4 had a longer overall survival rate. In vitro and in vivo studies revealed that downregulation of OTUD4 was essential for tumor cell growth and metastasis in ccRCC, and OTUD4 overexpression inhibited these malignant phenotypes. We further found that OTUD4 sensitized ccRCC cells to Erastin-induced ferroptosis, and ferrostain-1 inhibited OTUD4-induced ferroptotic cell death. Mechanistic studies indicated that OTUD4 functioned as an anti-proliferative and anti-metastasic factor through the regulation of RNA-binding protein 47 (RBM47)-mediated activating transcription factor 3 (ATF3). OTUD4 directly interacted with RBM47 and promoted its stability via deubiquitination events. RBM47 was critical in ccRCC progression by regulating ATF3 mRNA stability, thereby promoting ATF3-mediated ferroptosis. RBM47 interference abolished the suppressive role of OTUD4 overexpression in ccRCC. Our findings provide mechanistic insight into OTUD4 of ccRCC progression and indicate a novel critical pathway OTUD4/RBM47/ATF3 may serve as a potential therapeutic pathway for ccRCC.

Initial clinical experience of atrial fibrillation ablation guided by a cryoballoon-compatible, magnetic-based circular catheter.

INTRODUCTION: The circular catheter compatible with current cryoballoon system for atrial fibrillation (AF) ablation is exclusively sensed by impedance-based electro-anatomical mapping (EAM) system, limiting the accuracy of maps. We aim to investigate the feasibility and safety of a magnetic-based circular mapping catheter for AF ablation with cryoballoon. METHODS: Nineteen consecutive patients who underwent pulmonary vein isolation (PVI) with cryoballoon for paroxysmal or persistent AF were included. EAMs of left atrium (LA) created by the LASSOSTAR™NAV catheter (Lassostar map) before and after PVI were compared to that generated by a high-density mapping catheter (Pentaray map) from different aspects including structural similarity, PV angle, LA posterior wall (LAPW) and low voltage areas (LVAs), and the amplitude of far field electrograms (FFEs) recorded by catheters. RESULTS: All patients had successful PVI without major complications. With similar mapping time and density, the LA volume calculated from the Pentaray map and Lassostar map were comparable. There were no significant differences in PV angle of all PVs and PW area (16.8 ± 3.2 vs. 17.1 ± 2.8, p = .516) between Pentaray map and Lassostar map. High structural similarity score was observed between two maps (0.783 in RAO/LAO view and 0.791 in PA view). Lassostar map detected lesser but not statistically significant extension of LVA (13.9% vs. 18.3%, p = .07). Amplitude of FFE was larger at the right superior PV on Lassostar map (0.21 ± 0.16 vs. 0.14 ± 0.11 mV, p = .041) compared to that on the Pentaray map. CONCLUSION: In our initial experience, PVI with cryoballoon and magnetic-based circular LASSOSTAR™NAV catheter was safe and effective based on the accurate LA geometry it created.

Incidence of cryoballoon expansion dislodgement during pulmonary vein isolation-An underappreciated frequent cause of incomplete isolation.

BACKGROUND: Cryoballoon ablation for atrial fibrillation (AF) requires adequate contact between the pulmonary vein (PV) antrum and cryoballoon. The surge of intraballoon pressure during the initial phase of ablation may change the balloon's shape and compliance, resulting in balloon dislodgement and loss of PV occlusion. Without continuous monitoring, this phenomenon is often undetected but can be associated with incomplete PV isolation (PVI). METHODS: Primary cryoablation of AF was performed in 15 patients. PV occlusion status pre- and post-freezing were analyzed with intracardiac echocardiography (ICE) and dielectric imaging-based occlusion tool (DIOT) to calculate the incidence of expansion dislodgement of cryoballoon. RESULTS: A total of 105 cryoablation applications were performed on 57 veins, including three common ostiums of left pulmonary veins. In the evaluation of PV occlusion, both modalities reported consistent results in 86.7% of the assessments. Despite complete PV occlusion before ablation, peri-balloon leak after initiation of freezing was detected by ICE in 5/22 (22.7%) applications and by DIOT in 8/25 (32%) applications. CONCLUSION: Incidence of expansion dislodgement of the cryoballoon was detected in one-fourth to one-third of cryoablation applications depending on the imaging modality used, which was clinically frequent and significant.

[Meta-analysis of obesity on the outcome of rotator cuff repair].

OBJECTIVE: To systematically evaluate obesity on the outcome of rotator cuff repair. METHODS: Literatures on the relationship between obesity and outcomes after rotator cuff repair were searched from PubMed, Embase, Cochrane Library, Web of Science, China biology medicine(CBM), CNKI, Wanfang and VIP databases from building database to August 1, 2022, and were screened independently by two authors according to inclusion and exclusion criteria. Endnote X9 and Excel 2019 were used for literature extraction, management and data entry, and Newcastle-Ottawa Scale (NOS) was used to evaluate quality of the included literatures. STATA 16.0 and RevMan 5.4 softwares were used to evaluate postoperative retear rate, reoperation rate, complication rate, American Shoulder and Elbow Surgeons (ASES) score, visual analogue scale (VAS), operative time and external rotation angle of shoulder joint pain were analyzed. RESULTS: Totally 13 literatures were included, including 6 retrospective studies, 5 case-control studies, 1 prospective cohort study, and 1 abstract of a study for which the full text was not available, with 85 503 patients (31 973 in obese group and 53 530 in non-obese group). Meta-analysis showed there were statistical differences between two groups in retear rate [OR=2.58, 95%CI(1.23, 5.41), P=0.01], reoperation rate[OR=1.31, 95%CI(1.21, 1.42), P<0.00], complication rate [OR=1.57, 95%CI(1.31, 1.87), P=0.00], ASES score[MD=-3.59, 95%CI(-5.45, -1.74), P=0.00], and VAS[MD=0.24, 95%CI(0.00, 0.49), P=0.05]. While there were no differences between two groups in operative time[MD=6.03, 95%CI(-7.63, 19.69), P=0.39], external rotation angle of shoulder joint[MD=-1.79, 95%CI(-5.30, 1.71), P=0.32]. CONCLUSION: Obesity is associated with higher rates of retear, resurgery, complications, poorer shoulder function and pain after rotator cuff repair.

Expression of m6A Regulator Genes can Facilitate the Diagnosis of Chronic Heart Failure.

BACKGROUND: RNA N6-methyladenosine (m6A) is the most common type of modification in eukaryotic mRNA. The relationship between m6A modification and disease has been studied extensively, but there have been few studies on chronic heart failure (CHF). This study investigated a possible role for m6A in the diagnosis of CHF. METHODS: Seven candidate m6A regulators (writers: WTAP and ZC3H13; readers: YTHDF3, FMR1, IGFBP1, and ELAVL1; eraser: FTO) were identified using a random forest (RF) model and the GSE5406 dataset from the Gene Expression Omnibus database. A nomogram model was developed to predict the risk of CHF, while consensus clustering methodology assigned CHF samples into two m6A patterns (cluster A and cluster B) according to the 7 candidate m6A regulators. Principal component analysis was used to calculate an m6A score for each sample and to quantify m6A patterns. RESULTS: Decision curve analysis and the nomogram model were used to obtain predictions that may be of clinical use. Patients in cluster B had higher m6A scores than patients in cluster A. Cluster B patients also had higher expression levels (ELs) of IL-4, IL-5, IL-10 and IL-13 than patients in cluster A, whereas cluster A patients had a higher EL for IL-33. The m6A cluster B pattern likely represents the ischemic heart failure (HF) disease group. CONCLUSION: m6A regulators are important in the pathogenesis of CHF associated with ischemic and idiopathic dilated cardiomyopathy, and may prove useful for the diagnosis and treatment of CHF.

The PAPSS1 gene is a modulator of response to cisplatin by regulating estrogen receptor alpha signaling activity in ovarian cancer cells.

BACKGROUND: Cancer cells may develop resistance to cisplatin by various mechanisms. Yet, the exact mechanism of cisplatin in ovarian cancer remains unclear. Recent studies have shown that 3'-phospoadenosine 5'-phosphosulfate synthase 1 (PAPSS1) inhibition combined with low-dose cisplatin increases DNA damage. The aim of this study was to determine the value of targeting PAPSS1 as a cisplatin modulator in epithelial ovarian cancer (EOC). RESULTS: Increased expression of PAPSS1 was observed in both EOC cells and tissues. Also, its higher nuclear expression was distinctly associated with FIGO (The International Federation of Gynecology and Obstetrics) stage, histological subtype, metastasis, and recurrence. Down-regulation of the PAPSS1 gene increased the cisplatin sensitivity of EOC in vitro and in vivo. Expression of PAPSS1 was negatively correlated with estrogen receptor α (ERα) in EOC. Also, low nuclear PAPSS1 and high nuclear ERα expression in EOC were associated with longer overall survival and progression-free survival in all ovarian cancer and ovarian cancer patients who received platinum-based chemotherapy. PAPSS1 silencing increased the activity of ERα-signaling in EOC cells, thus sensitizing tumors to cisplatin. CONCLUSIONS: These findings characterize a novel interplay between PAPSS1-mediated sulfation and ERα-signaling in EOC cisplatin resistance. PAPSS1 may be exploited as a cisplatin-sensitizing therapeutic target.

The effectiveness and safety of eyelid defect reconstruction after sebaceous carcinoma of the eyelid surgery: A protocol for systematic review and meta-analysis.

INTRODUCTION: Sebaceous carcinoma of the eyelid is the third most common eyelid malignancy, after basal cell carcinoma and squamous cell carcinoma. It is highly malignant and potentially aggressive. Surgical excision is currently the best treatment option for this condition. Patients often require reconstruction surgery to repair eyelid defects to achieve normal eyelid function and appearance. However, no comprehensive systematic review has assessed the efficacy and safety of eyelid defect reconstruction. This protocol was developed to conduct a systematic review and meta-analysis to evaluate evidence related to the efficacy and safety of reconstruction. METHODS: We will systematically search the Cochrane Library, PubMed, Web of Science, China National Knowledge Infrastructure, WanFang Database, and Chinese Biomedical Literature Database from their inception to February 2023 for studies on eyelid defect reconstruction. We will identify other potential studies using multiple methods such as manual searching. The outcomes were eyelid function, eyelid morphology, patient satisfaction, recurrence rate, metastasis rate, tumor-related mortality, and adverse events. Two researchers will independently screen titles and abstracts, identify full-text studies for inclusion, extract data, and appraise the risk of bias in the included studies. A meta-analysis will be conducted using Review Manager 5.4 and R software. The certainty of evidence will be appraised by grading of recommendations, assessment, development, and evaluation system. RESULTS: This full-text will adhere to the preferred reporting items for systematic reviews and meta-analyses statement to ensure clarity and completeness of reporting in all phases of the systematic review. DISCUSSION: This study provides evidence of the efficacy and safety of reconstruction methods for sebaceous carcinoma of the eyelid.

Association of shift work and dietary inflammatory potential with all-cause death among us hypertensive population: national health and nutrition examination study, 2005-2010.

BACKGROUND & AIMS: The individual effect of working schedule on survival in the hypertensive population has not been adequately studied. Shiftworkers are also prone to unhealthy lifestyles like pro-inflammatory diet. Therefore, we assessed the effect of shift work and its joint association with dietary inflammatory potential on mortality risk among the large US nationally representative sample of adult hypertensive population. METHODS: Data were from a nationally representative prospective cohort among US hypertensive population (n = 3680; weighted population, 54,192,988). The participants were linked to the 2019 public-access linked mortality archives. The working schedule were self-reported using the Occupation Questionnaire Section. Dietary inflammatory index (DII) scores were equally calculated using the 24-hour dietary recall (24 h) interviews. Multivariable Cox proportional hazards regression models were used to estimate hazard ratio and 95% confidence intervals (95%CI) for survival of hypertension individuals by work schedule and dietary inflammatory potential. The joint effect of work schedule and dietary inflammatory potential was then examined. RESULTS: Among the 3680 hypertension individuals (39.89% female [n = 1479] and 71.42% white [n = 1707]; weighted mean [SE] age, 47.35 [0.32] years), 592 individuals reported shift work status. 474 (10.76%) reported shift work status with pro-inflammatory dietary pattern (DII scores > 0). 118 (3.06%) reported shift work status with anti-inflammatory dietary pattern (DII scores < 0). 646 (19.64%) reported a non-shift working schedule with anti-inflammatory dietary pattern, while 2442 (66.54%) reported non-shift working schedule with pro-inflammatory dietary pattern. After a median follow-up of 11.67 years (140 months), 317 deaths (cardiovascular diseases (CVD), 65; cancer, 104) were registered. Cox regression analysis showed that shift work was associated with higher risk of all-cause mortality (hazard ratio [HR], 1.48; 95% CI, 1.07-2.06) compared with non-shift workers. In the joint analysis, shift work status combined with pro-inflammatory dietary pattern was associated with the highest all-cause mortality risk. Moreover, adopting the anti-inflammatory diet significantly attenuates the deleterious effect of shift work on mortality risk. CONCLUSIONS: In this large representative sample of adults with hypertension in the U.S., the combination of shift work status with pro-inflammatory dietary pattern was highly prevalent and was associated with the highest risks of death from all causes.

Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer.

Currently, for ovarian cancer, which has the highest mortality rate among all gynecological cancers, the standard treatment protocol is initial tumor cytoreductive surgery followed by platinum-based combination chemotherapy. Although the survival rate after standard treatment has improved, the therapeutic effect of traditional chemotherapy is very limited due to problems such as resistance to platinum-based drugs and recurrence. With the advent of the precision medicine era, molecular targeted therapy has gradually entered clinicians' view, and individualized precision therapy has been realized, surpassing the limitations of traditional therapy. The detection of genetic mutations affecting treatment, especially breast cancer susceptibility gene (BRCA) mutations and mutations of other homologous recombination repair defect (HRD) genes, can guide the targeted drug treatment of patients, effectively improve the treatment effect and achieve a better patient prognosis. This article reviews different sites and pathways of targeted therapy, including angiogenesis, cell cycle and DNA repair, and immune and metabolic pathways, and the latest research progress from preclinical and clinical trials related to ovarian cancer therapy.

Gallbladder disease is associated with the risk of cardiovascular disease among Uyghurs in Xinjiang: a prospective cohort study.

BACKGROUND: Gallbladder disease (GBD) can increase the risk of cardiovascular disease (CVD). However, GBD has rarely been reported in the less developed, rural areas of Xinjiang. This study aimed to determine the prevalence of GBD and incidence of CVD in a prospective cohort study in rural Xinjiang. Moreover, the study aimed to explore the association between GBD and CVD within this cohort. METHODS: The study cohort included 11,444 Uyghur adults in Xinjiang, 3rd division, from the 51st Mission. Study groups were classified according to whether GBD was present or absent at baseline. The occurrence of CVD was the end event. Demographic, anthropometric, and biochemical data were recorded, and the incidence of CVD in the GBD and non-GBD groups analysed. Cox proportional hazards regression models were used to assess the association between GBD and CVD and factors associated with their incidence. Several subgroup analyses were performed to assess CVD incidence in different subgroups. The interaction between GBD and cardiometabolic risk factors, and subsequent risk of developing CVD, was evaluated. RESULTS: Prevalence of GBD in the study cohort was 10.29%. After a median follow-up of 4.92 years, the cumulative incidence of CVD in the study cohort was 10.49%, 8.43% in males and 12.65% in females. CVD incidence was higher in the GBD group (34.04% vs. 7.78%, HR = 4.96, 95% CI: 4.40-5.59). After multivariate adjustment, the risk of CVD remained higher in the GBD group (HR = 2.89, 95% CI: 2.54-3.29). Subgroup analyses showed male sex, smoking, alcohol consumption, lack of exercise, and abnormal renal function were all associated with increased risk of CVD. Moreover, the risk of CVD was markedly higher in GBD combined with cardiometabolic risk factors (hypertension, T2DM, dyslipidaemia, overweight, and abdominal obesity), than in cardiometabolic risk factors alone and this was higher in the GBD group than in the non-GBD group regardless of whether cardiometabolic risk factors were combined. CONCLUSION: GBD is an important independent risk factor for CVD development. Awareness of these associations will raise concerns among clinicians about the risk of cardiovascular disease in patients with GBD.

Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report.

The present study reports a patient case with a 17α-hydroxylase deficiency accompanied by triple X syndrome. A 17α-hydroxylase deficiency leads to a very low 17α-hydroxylated steroid synthesis as well as a non-feedback increase in the adrenocorticotropic hormone level. Meanwhile, the progesterone level increases the 17α-hydroxyprogesterone level and decreases the dehydroepiandrosterone sulfate level. The patient is characterized by intractable hypokalemia, high urinary potassium, hyperaldosteronemia, hyporeninemia, hypocortisolemia, hypertension, gonadal and secondary sexual dysplasia, a decreased estrogen level, primary amenorrhea, and infertility. The imaging findings indicate a presence of multiple bilateral adrenal gland adenomas, and the sequencing indicates a missense CYP17A1-E7 gene pathogenic variant. The karyotype is a 47, XXX [3]/46, XX [47] low-level chimeric karyotype. The patient's parents are cousins. To our knowledge, this patient is the first case diagnosed with congenital adrenal hyperplasia caused by hydroxylase deficiency and triple X syndrome. The uniqueness of this case is that this patient has two very rare genetic diseases, probably due to the marriage of close relatives.

Analysis of Risk Factors Related to the Efficacy of Foramen Ovale Closure as a Therapy for Migraine.

This study aimed to monitor the incidence of migraine non-remission after percutaneous patent foramen ovale (PFO) closure and to discuss relevant risk factors. Recently, evidence of a relationship between the presence of PFO and migraines has been found, and PFO closure has been pointed out as a possible treatment for migraineurs.A retrospective analysis was conducted, which involved 139 patients diagnosed with PFO and associated migraine who underwent percutaneous PFO closure in The First Affiliated Hospital of Zhengzhou University from October 2019 to April 2021. All the considered patients were evaluated using the Headache Impact Test (HIT-6™) and classified with a score higher than 55 points before closure. The HIT-6™ score was re-evaluated 1-6 months after the intervention. HIT-6™ ≤ 55 was defined as headache remission (n = 93) and > 55 as headache non-remission (n = 46). A logistic regression model was developed to identify the risk factors of headache non-remission after PFO closure.The incidence of headache non-remission after PFO closure was 33.09%. Statistically significant differences were observed between the two groups as regards age and serum phosphorus level (P < 0.05). History of smoking, atrial fibrillation, absolute lymphocyte count, platelet-to-lymphocyte ratio, and interventricular septal thickness were identified as independent risk factors for headache non-remission following PFO closure, which were statistically significant (P < 0.05).

Randomized prospective evaluation of same-day discharge after cryoballoon ablation of atrial fibrillation: results of the EASY PVI study.

BACKGROUND: With advancements in technology and ablation techniques, catheter ablation for the treatment of atrial fibrillation (AF) has become safer with time. In the past, standard-of-care recommended overnight stay for outpatient procedures. As safety has improved and procedure times have shortened, some centers have allowed for same-day discharge. We report the results of a multi-center, randomized clinical trial investigating the safety of same-day discharge post-cryoballoon ablation. METHODS: Patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation (PVI) with the Medtronic Arctic Advance cryoballoon at 3 US centers. Six hours after the procedure, patients were randomized to either stay overnight or be discharged same day. RESULTS: A total of 49 patients were enrolled. Two patients were withdrawn prior to randomization. One patient chose to withdraw after randomization. Of the 22 patients randomized to same-day discharge and the 23 patients randomized the overnight stay, no significant adverse outcomes were reported in either group. Occurrence of adverse events did not differ significantly between the two groups. Procedure time and fluoroscopy time did not significantly differ between groups. CONCLUSIONS: This is the first randomized trial examining the safety of same-day discharge post-cryoballoon ablation. Based on our results, same-day discharge following cryoballoon ablation for paroxysmal AF is a safe option following uncomplicated ablation for PVI. Operators should use their discretion in selecting patients for same-day discharge.