Histone deacetylase 6 as a novel promising target to treat cardiovascular disease.

Histone deacetylase 6 (HDAC6) belongs to a class of epigenetic targets that have been found to be a key protein in the association between tumors and cardiovascular disease. Recent studies have focused on the crucial role of HDAC6 in regulating cardiovascular diseases such as atherosclerosis, myocardial infarction, myocardial hypertrophy, myocardial fibrosis, hypertension, pulmonary hypertension, and arrhythmia. Here, we review the association between HDAC6 and cardiovascular disease, the research progress of HDAC6 inhibitors in the treatment of cardiovascular disease, and discuss the feasibility of combining HDAC6 inhibitors with other therapeutic agents to treat cardiovascular disease.

Association between Hepatitis B virus infection and liver metastasis in colorectal cancer.

The association between Hepatitis B virus (HBV) infection and colorectal liver metastases (CRLM) remains ambiguous in current population-based evidence. To clarify this, we present a retrospective analysis of 5871 colorectal cancer (CRC) patients. Propensity score matching (PSM) was applied to harmonize age and sex disparities within HBV+ (n = 1696) and HBV- (n = 4175) groups and further within HBV+ subgroups of chronic (CHB, n = 474) and occult (OHB, n = 1222) infections. Our initial results indicated a significant association between HBV infection and synchronous colorectal liver metastasis (SYN-CRLM); however, this association dissipated after PSM was employed to adjust for confounding variables. No significant association was observed between HBV infection and metachronous colorectal liver metastases (MET-CRLM) both before and after PSM. Further analysis revealed that HBV replication status did not influence the incidence of CRLM. However, HBV+ participants demonstrated an increased incidence of metachronous extrahepatic metastases, particularly to the lungs. Our findings imply that neither past nor present HBV infection is significantly correlated with the occurrence of SYN-CRLM or MET-CRLM. The absence of an association between HBV replication status and CRLM incidence highlights the importance of incorporating a broader range of factors in the clinical management of CRLM beyond the status of HBV infection.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Associations of Long-term Sleep Duration Trajectories with Overall and Cause-Specific Mortality Among Middle-to-older Aged Black and White Adults.

Background: Both short and long sleep durations are adversely associated with numerous chronic conditions, including cardiovascular disease (CVD), diabetes, hypertension, and mortality. The American Academy of Sleep Medicine recommends adults in the United States sleep at least 7 hours and less than 9 hours per night to maintain optimal health. It remains unclear how sleep duration trajectories over time are associated with mortality. Methods: This observational cohort study includes 46,928 Black and White adults (mean age: 53 ± 9 years) who enrolled in the Southern Community Cohort Study between 2002-2009 and completed a follow-up survey in 2008-2013. Participants were categorized into nine sleep duration trajectory categories based on the reported average sleep duration between study enrollment and at follow-up. Participant vital status and date and cause of death were ascertained via linkage to the National Death Index through 2022. Cox regression analysis was performed to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between sleep duration trajectory and all-cause and cause-specific mortality (CVD, cancer, and neurodegenerative disease) after adjustment for sociodemographic characteristics, health behaviors, and clinical factors. Results: During a median 12.6 years of follow-up, we documented 13,579 deaths, including 4,135 from CVD, 3,067 from cancer, and 544 from neurodegenerative diseases. Compared to the optimal sleep duration trajectory (maintaining 7-9 hours), all sub-optimal trajectories were associated with significant 6 to 33% greater risk of all-cause mortality in fully adjusted models. Compared to the optimal sleep trajectory, three of the sub-optimal trajectories were associated with increased CVD mortality, with HRs ranging from 1.20 to 1.34. The short-long trajectory was associated with the greatest risk of all-cause mortality (HR:1.33; 95%CI: 1.21, 1.46) and the long-short trajectory was associated with the greatest CVD mortality risk (HR:1.34; 95%CI: 1.10, 1.65). The healthy-long trajectory was associated with the greatest risk of cancer mortality (HR: 1.19; 95%CI:1.00, 1.41). None of the sub-optimal trajectories was associated with neurodegenerative disease mortality. Conclusions: Suboptimal sleep duration trajectories were associated with increased risk of all-cause mortality as well as CVD mortality. Findings highlight the importance of maintaining healthy sleep duration throughout midlife to reduce mortality risk.

[Study on mechanism of regulation of sex hormones in treatment of hyperprolactinemia-induced ovulatory disorder infertility with Bushen Culuan Formula].

Transcriptomics was used to investigate the mechanism of action of Bushen Culuan Formula in the treatment of infertility caused by hyperprolactinemia(HPRL), and animal experiments were carried out to verify the results. After establishing an animal model of HPRL-induced infertility, the mice were divided into normal group, model group, Bushen Culuan Formula groups with high-, medium-, and low-doses, and bromocriptine group, and they were observed in terms of the estrous cycle, gonadal index, serum sex hormones, morphology of ovary and mammary gland, follicle count, and fertility. The results showed that the Bushen Culuan Formula could effectively restore the estrous cycle, down-regulate the levels of prolactin(PRL), follicle-stimulating hormone(FSH), and luteinizing hormone(LH), up-regulate the level of estradiol(E_2), increase the number of primordial follicles and sinus follicles, and improve the ovulation rate and fertility of mice. Through RNA sequencing combined with biosignature analysis, Bushen Culuan Formula may regulate the metabolism of lipids, antioxidant enzymes, and other substances in the cells of the ovary and pituitary gland through the signaling pathways of cAMP-PKA, Kiss-1/GPR54, and Hippo and exert therapeutic effects. The results of animal experiments showed that Bushen Culuan Formula could up-regulate serum dopamine(DA) level and pituitary DRD2 expression, down-regulate hypothalamus and ovary cAMP levels, as well as protein expressions of the pituitary gland and ovary PKA, CREB, and p-CREB, and treat HPRL-induced infertility by regulating the cAMP-PKA signaling pathway.

Preparation of Medical 228Th-224Ra Radionuclide Generator Based on SiO2@TiO2 Microspheres.

224Ra (T1/2 = 3.63 d), an α-emitting radionuclide, holds significant promise in cancer endoradiotherapy. Current 224Ra-related therapy is still scarce because of the lack of reliable radionuclide supply. The 228Th-224Ra radionuclide generator can undoubtedly introduce continuous and sustainable availability of 224Ra for advanced nuclear medicine. However, conventional metal oxides for such radionuclide generators manifest suboptimal adsorption capacities for the parent nuclide, primarily attributable to their limited surface area. In this work, core-shell SiO2@TiO2 microspheres were proposed to develop as column materials for the construction of a 228Th-224Ra generator. SiO2@TiO2 microspheres were well prepared and systematically characterized, which has also been demonstrated to have good adsorption capacity to 228Th and very weak binding affinity toward 224Ra via simulated chemical separation. Upon introducing 228Th-containing solution onto the SiO2@TiO2 functional column, a 228Th-224Ra generator with excellent retention of the parent radionuclide and ideal elution efficiency of daughter radionuclide was obtained. The prepared 228Th-224Ra generator can produce 224Ra with high purity and medical usability in good elution efficiency (98.72%) even over five cycles. To the best of our knowledge, this is the first time that the core-shell mesoporous materials have been applied in a radionuclide generator, which can offer valuable insights for materials chemistry, radiochemical separation, and biological medicine.

Laparoscopic ileocecal-sparing vs traditional right hemicolectomy for cancer of the hepatic flexure or proximal transverse colon: a dual-center propensity score-matched study.

Background: Traditional right hemicolectomy (TRH) is the standard treatment for patients with nonmetastatic right colon cancer. However, the ileocecum, a vital organ with mechanical and immune functions, is removed in these patients regardless of the tumor location. This study aimed to evaluate the technical and oncological safety of laparoscopic ileocecal-sparing right hemicolectomy (LISH). Method: Patients who underwent LISH at two tertiary medical centers were matched 1:2 with patients who underwent TRH by propensity score matching based on sex, age, body mass index, tumor location, and disease stage. Data on surgical and perioperative outcomes were collected. Oncological safety was evaluated in a specimen-oriented manner. Lymph nodes (LNs) near the ileocolic artery (ICA) were examined independently in the LISH group. Disease outcomes were recorded for patients who completed one year of follow-up. Results: In all, 34 patients in the LISH group and 68 patients in the TRH group were matched. LISH added 8 minutes to the dissection of LNs around the ileocolic vessels (groups 201/201d, 202, and 203 LNs), without affecting the total operation time, blood loss, or perioperative adverse event rate. Compared with TRH, LISH had a comparable lymphadenectomy quality, specimen quality, and safety margin while preserving a more functional bowel. The LISH group had no cases of LN metastasis near the ICA. No difference was detected in the recurrence rate at the 1-year follow-up time point between the two groups. Conclusion: In this dual-center study, LISH presented comparable surgical and oncological safety for patients with hepatic flexure or proximal transverse colon cancer.

Deficiency of P2RY11 causes narcolepsy and attenuates the recruitment of neutrophils and macrophages in the inflammatory response in zebrafish.

Purinergic receptor P2Y11, a G protein-coupled receptor that is stimulated by extracellular ATP, has been demonstrated to be related to the chemotaxis of granulocytes, apoptosis of neutrophils, and secretion of cytokines in vitro. P2Y11 mutations were associated with narcolepsy. However, little is known about the roles of P2RY11 in the occurrence of narcolepsy and inflammatory response in vivo. In this study, we generated a zebrafish P2Y11 mutant using CRISPR/Cas9 genome editing and demonstrated that the P2Y11 mutant replicated the narcolepsy-like features including reduced HCRT expression and excessive daytime sleepiness, suggesting that P2Y11 is essential for HCRT expression. Furthermore, we accessed the cytokine expression in the mutant and revealed that the P2RY11 mutation disrupted the systemic inflammatory balance by reducing il4, il10 and tgfb, and increasing il6, tnfa, and il1b. In addition, the P2RY11-deficient larvae with caudal fin injuries exhibited significantly slower migration and less recruitment of neutrophils and macrophages at damaged site, and lower expression of anti-inflammatory cytokines during tissue damage. All these findings highlight the vital roles of P2RY11 in maintaining HCRT production and secreting anti-inflammatory cytokines in the native environment, and suggested that P2RY11-deficient zebrafish can serve as a reliable and unique model to further explore narcolepsy and inflammatory-related diseases with impaired neutrophil and macrophage responses.

Efficacy of Shenglin decoction in preventing acute severe lymphocytopenia in patients with non-small cell lung cancer undergoing concurrent chemoradiotherapy: a study protocol for a randomized controlled trial.

Background: Definitive concurrent chemoradiotherapy (CCRT) followed by maintenance therapy with immune checkpoint inhibitors offers the best chance of cure for patients with stage III non-small cell lung cancer (NSCLC). A significant challenge in this regimen is the occurrence of acute severe lymphopenia (ASL), which can compromise treatment efficacy. Currently, there are no effective strategies for preventing and treating ASL. Shenglin decoction (SLD), a traditional Chinese herbal medicine formulation, has demonstrated preliminary efficacy in mitigating ASL. However, robust evidence from clinical trials and a clear understanding of its mechanism of action are still needed. This study aims to comprehensively assess the efficacy, safety, and underlying mechanisms of SLD in the prevention of ASL. Methods: This prospective, dual-center, open-label, randomized controlled trial will enroll 140 stage III NSCLC patients. Participants will be randomly allocated in a 1:1 ratio to a control group or an experimental group. Both groups will undergo definitive CCRT. Alongside the commencement of CCRT, the experimental group will receive an additional oral SLD intervention for a duration of three months. The primary outcome is the incidence rate of ASL, defined as the proportion of patients who experience at least one instance of a total lymphocyte count falling below 0.5 × 10^9 cells/L within 3 months of initiating CCRT treatment. Additionally, 16S rRNA gene sequencing analysis of fecal samples to assess gut microbiota, as well as metabolomic analysis of fecal/blood samples, will be conducted to explore potential mechanisms. Discussion: This study protocol aims to rigorously evaluate the efficacy and safety of SLD, as well as elucidate its mechanism of action in preventing ASL. Successful outcomes could establish SLD as an evidence-based intervention for ASL prevention in NSCLC patients undergoing CCRT. Trial Registration: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR2300071788, https://www.chictr.org.cn/).

Properties and application of antioxidant and antibacterial composite films based on methylcellulose and spine grape pomace fabricated by thermos-compression molding.

Methylcellulose (MC)/grape pomace (GP) films, plasticized with either glycerol (GLY) or cinnamon essential oil (CEO), were prepared by thermo-compression molding and characterized. Compared to the GLY-plasticized MC50/GP50 films, a considerable increase in TS and YM values of CEO-plasticized films was observed, rising from 9.66 to 30.05 MPa, 762 to 1631 MPa, respectively. Moreover, the water vapor barrier, surface hydrophobic properties, and antioxidant/antibacterial activities of CEO-plasticized films remarkedly improved with increasing CEO content from 5 to 15% w/w. From scanning electron microscopy, phase separation between GP and the MC/GLY mixture were evident for GLY-plasticized MC/GP films. On the other hand, the CEO-plasticized films showed compact morphologies, attributable to the formation of hydrogen bonding and π-π stacking interaction. Preliminary shelf-life study on showed that fresh chicken wrapped with the CEO-plasticized MC/GP films exhibited lower TVB-N, TBARS, and TVC values than the unwrapped control samples, during 7 d storage at 4 °C.

Design and construction of chemical-biological module clusters for degradation and assimilation of poly(ethylene terephthalate) waste.

The rising accumulation of poly(ethylene terephthalate) (PET) waste presents an urgent ecological challenge, necessitating an efficient and economical treatment technology. Here, we developed chemical-biological module clusters that perform chemical pretreatment, enzymatic degradation, and microbial assimilation for the large-scale treatment of PET waste. This module cluster included (i) a chemical pretreatment that involves incorporating polycaprolactone (PCL) at a weight ratio of 2% (PET:PCL = 98:2) into PET via mechanical blending, which effectively reduces the crystallinity and enhances degradation; (ii) enzymatic degradation using Thermobifida fusca cutinase variant (4Mz), that achieves complete degradation of pretreated PET at 300 g/L PET, with an enzymatic loading of 1 mg protein per gram of PET; and (iii) microbial assimilation, where Rhodococcus jostii RHA1 metabolizes the degradation products, assimilating each monomer at a rate above 90%. A comparative life cycle assessment demonstrated that the carbon emissions from our module clusters (0.25 kg CO2-eq/kg PET) are lower than those from other established approaches. This study pioneers a closed-loop system that seamlessly incorporates pretreatment, degradation, and assimilation processes, thus mitigating the environmental impacts of PET waste and propelling the development of a circular PET economy.

Nicotine improves DSS-induced colitis by inhibiting NLRP3 and altering gut microbiota.

Ulcerative colitis (UC) is a chronic recurrent inflammatory disease affecting the rectum and colon. Numerous epidemiological studies have identified smoking as a protective factor for UC. Dysbiosis of intestinal microbiota and release of inflammatory factors are well-established characteristics associated with UC. Therefore, we have observed that nicotine exhibits the potential to ameliorate colitis symptoms in UC mice. Additionally, it exerts a regulatory effect on colonic microbiota dysbiosis by promoting the growth of beneficial bacteria while suppressing harmful bacteria. Combined in vivo and in vitro investigations demonstrate that nicotine primarily impedes the assembly of NLRP3, subsequently inhibiting downstream IL-1ß secretion.

Rational Design of Coordination Polymers Composited Hollow Multishelled Structures for Drug Delivery.

Multifunctional drug delivery systems (DDS) are in high demand for effectively targeting specific cells, necessitating excellent biocompatibility, precise release mechanisms, and sustained release capabilities. The hollow multishelled structure (HoMS) presents a promising solution, integrating structural and compositional design for efficient DDS development amidst complex cellular environments. Herein, starting from a Fe-based metal-organic framework (MOF), amorphous coordination polymers (CP) composited HoMS with controlled shell numbers are fabricated by balancing the rate of MOF decomposition and shell formation. Fe-CP HoMS loaded with DOX is utilized for synergistic chemotherapy and chemodynamic therapy, offering excellent responsive drug release capability (excellent pH-triggered drug release 82% within 72 h at pH 5.0 solution with doxorubicin (DOX) loading capacity of 284 mg g-1). In addition to its potent chemotherapy attributes, Fe-CP-HoMS possesses chemodynamic therapy potential by continuously catalyzing H2O2 to generate ·OH species within cancer cells, thus effectively inhibiting cancer cell proliferation. DOX@3S-Fe-CP-HoMS, at a concentration of 12.5 µg mL-1, demonstrates significant inhibitory effects on cancer cells while maintaining minimal cytotoxicity toward normal cells. It is envisioned that CP-HoMS could serve as an effective and biocompatible platform for the advancement of intelligent drug delivery systems in the realm of cancer therapy.

Targeted inhibition of the PI3K/AKT/mTOR pathway by (+)-anthrabenzoxocinone induces cell cycle arrest, apoptosis, and autophagy in non-small cell lung cancer.

Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells. Additionally, the augmentation of intracellular ROS levels by (+)-ABX is revealed, further contributing to the inhibition of the signaling pathway and exerting inhibitory effects on tumor growth. The findings presented in this study suggest that (+)-ABX possesses the potential to serve as a lead compound for the treatment of NSCLC.

[Effect of Intelligent Health Education Based on Health Belief Model on Patients With Kinesophobia After Surgical Treatment of Cervical Spondylosis]. / åŸºäºŽå¥åº·ä¿¡å¿µæ¨¡å¼çš„æ™ºèƒ½å¥åº·æ•™è‚²åœ¨é¢ˆæ¤Žç— æœ¯åŽæåŠ¨ç—‡æ‚£è€ ä¸­çš„æ•ˆæžœç ”ç©¶.

Objective: To explore the application effect of intelligent health education based on the health belief model on patients with postoperative kinesophobia after surgical treatment of cervical spondylosis. Methods: A prospective cohort study was conducted with patients who underwent anterior cervical discectomy, decompression, and fusion surgery with a single central nerve and spine center, and who had postoperative kinesophobia, ie, fear of movement. The patients made voluntary decisions concerning whether they would receive the intervention of intelligent health education. The patients were divided into a control group and an intelligent education group and the intervention started on the second day after the surgery. The intelligent education group received intelligent education starting from the second day after surgery through a WeChat widget that used the health belief model as the theoretical framework. The intelligent health education program was designed according to the concept of patient problems, needs, guidance, practice, and feedbacks. It incorporated four modules, including knowledge, intelligent exercise, overcoming obstacles, and sharing and interaction. It had such functions as reminders, fun exercise, shadowing exercise, monitoring, and documentation. Health education for the control group also started on the second day after surgery and was conducted by a method of brochures of pictures and text and WeChat group reminder messages. The participants were surveyed before discharge and 3 months after their surgery. The primary outcome measure compared between the two groups was the degree of kinesophobia. Secondary outcome measures included differences in adherence to functional exercise (Functional Exercise Adherence Scale), pain level (Visual Analogue Scale score), degree of cervical functional impairment (Cervical Disability Index), and quality of life (primarily assessed by the Quality of Life Short Form 12 [SF-12] scale for psychological and physiological health scores). Results: A total of 112 patients were enrolled and 108 patients completed follow-up. Eventually, there were 53 cases in the intelligent education group and 55 cases in the control group. None of the patients experienced any sports-related injuries. There was no statistically significant difference in the primary and secondary outcome measures between the two groups at the time of discharge. At the 3-month follow-up after the surgery, the level of kinesophobia in the intelligent education group (25.72±3.90) was lower than that in the control group (29.67±6.16), and the difference between the two groups was statistically significant (P<0.05). In the intelligent education group, the degree of pain (expressed in the median [25th percentile, 75th percentile]) was lower than that of the control group (0 [0, 0] vs. 1 [1, 2], P<0.05), the functional exercise adherence was better than that of the control group (63.87±7.26 vs. 57.73±8.07, P<0.05), the psychological health was better than that of the control group (40.78±3.98 vs. 47.78±1.84, P<0.05), and the physical health was better than that of the control group (43.16±4.41 vs. 46.30±3.80, P<0.05), with all the differences being statistically significant. There was no statistically significant difference in the degree of cervical functional impairment between the two groups (1 [1, 2] vs. 3 [2, 7], P>0.05). Conclusion: Intelligent health education based on the health belief model can help reduce the degree of kinesophobia in patients with postoperative kinesophobia after surgical treatment of cervical spondylosis and improve patient prognosis.

Correlational analysis of sarcopenia and multimorbidity among older inpatients.

BACKGROUND: Sarcopenia and multimorbidity are common in older adults, and most of the available clinical studies have focused on the relationship between specialist disorders and sarcopenia, whereas fewer studies have been conducted on the relationship between sarcopenia and multimorbidity. We therefore wished to explore the relationship between the two. METHODS: The study subjects were older patients (aged ≥ 65 years) who were hospitalized at the Department of Geriatrics of the First Affiliated Hospital of Chongqing Medical University between March 2016 and September 2021. Their medical records were collected. Based on the diagnostic criteria of the Asian Sarcopenia Working Group in 2019, the relationship between sarcopenia and multimorbidity was elucidated. RESULTS: 1.A total of 651 older patients aged 65 years and above with 2 or more chronic diseases were investigated in this study, 46.4% were suffering from sarcopenia. 2. Analysis of the relationship between the number of chronic diseases and sarcopenia yielded that the risk of sarcopenia with 4-5 chronic diseases was 1.80 times higher than the risk of 2-3 chronic diseases (OR 1.80, 95%CI 0.29-2.50), and the risk of sarcopenia with ≥ 6 chronic diseases was 5.11 times higher than the risk of 2-3 chronic diseases (OR 5.11, 95% CI 2.97-9.08), which remained statistically significant, after adjusting for relevant factors. 3. The Charlson comorbidity index was associated with skeletal muscle mass index, handgrip strength, and 6-meter walking speed, with scores reaching 5 and above suggesting the possibility of sarcopenia. 4. After adjusting for some covariates among 14 common chronic diseases in older adults, diabetes (OR 3.20, 95% CI 2.01-5.09), cerebrovascular diseases (OR 2.07, 95% CI 1.33-3.22), bone and joint diseases (OR 2.04, 95% CI 1.32-3.14), and malignant tumors (OR 2.65, 95% CI 1.17-6.55) were among those that still a risk factor for the development of sarcopenia. CONCLUSION: In the hospitalized older adults, the more chronic diseases they have, the higher the prevalence of sarcopenia. When the CCI is 5, attention needs to be paid to the occurrence of sarcopenia in hospitalized older adults.

Role of artificial intelligence in digital pathology for gynecological cancers.

The diagnosis of cancer is typically based on histopathological sections or biopsies on glass slides. Artificial intelligence (AI) approaches have greatly enhanced our ability to extract quantitative information from digital histopathology images as a rapid growth in oncology data. Gynecological cancers are major diseases affecting women's health worldwide. They are characterized by high mortality and poor prognosis, underscoring the critical importance of early detection, treatment, and identification of prognostic factors. This review highlights the various clinical applications of AI in gynecological cancers using digitized histopathology slides. Particularly, deep learning models have shown promise in accurately diagnosing, classifying histopathological subtypes, and predicting treatment response and prognosis. Furthermore, the integration with transcriptomics, proteomics, and other multi-omics techniques can provide valuable insights into the molecular features of diseases. Despite the considerable potential of AI, substantial challenges remain. Further improvements in data acquisition and model optimization are required, and the exploration of broader clinical applications, such as the biomarker discovery, need to be explored.

Effects of positive end-expiratory pressure on regional cerebral oxygen saturation in elderly patients undergoing thoracic surgery during one-lung ventilation: a randomized crossover-controlled trial.

BACKGROUND: A significant reduction in regional cerebral oxygen saturation (rSO2) is commonly observed during one-lung ventilation (OLV), while positive end-expiratory pressure (PEEP) can improve oxygenation. We compared the effects of three different PEEP levels on rSO2, pulmonary oxygenation, and hemodynamics during OLV. METHODS: Forty-three elderly patients who underwent thoracoscopic lobectomy were randomly assigned to one of six PEEP combinations which used a crossover design of 3 levels of PEEP-0 cmH2O, 5 cmH2O, and 10 cmH2O. The primary endpoint was rSO2 in patients receiving OLV 20 min after adjusting the PEEP. The secondary outcomes included hemodynamic and respiratory variables. RESULTS: After exclusion, thirty-six patients (36.11% female; age range: 60-76 year) were assigned to six groups (n = 6 in each group). The rSO2 was highest at OLV(0) than at OLV(10) (difference, 2.889%; [95% CI, 0.573 to 5.204%]; p = 0.008). Arterial oxygen partial pressure (PaO2) was lowest at OLV(0) compared with OLV(5) (difference, -62.639 mmHg; [95% CI, -106.170 to -19.108 mmHg]; p = 0.005) or OLV(10) (difference, -73.389 mmHg; [95% CI, -117.852 to -28.925 mmHg]; p = 0.001), while peak airway pressure (Ppeak) was lower at OLV(0) (difference, -4.222 mmHg; [95% CI, -5.140 to -3.304 mmHg]; p < 0.001) and OLV(5) (difference, -3.139 mmHg; [95% CI, -4.110 to -2.167 mmHg]; p < 0.001) than at OLV(10). CONCLUSIONS: PEEP with 10 cmH2O makes rSO2 decrease compared with 0 cmH2O. Applying PEEP with 5 cmH2O during OLV in elderly patients can improve oxygenation and maintain high rSO2 levels, without significantly increasing peak airway pressure compared to not using PEEP. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200060112 on 19 May 2022.

rs2736098, a synonymous polymorphism, is associated with carcinogenesis and cell count in multiple tissue types by regulating TERT expression.

rs2736098 is a synonymous polymorphism in TERT (telomerase reverse transcriptase), an enzyme involved in tumor onset of multiple tissues, and should play no roles in carcinogenesis. However, a search in cancer somatic mutation database indicated that the mutation frequency at rs2736098 is much higher than the average one for TERT. Moreover, there are significant H3K4me1 and H3K27Ac signals, two universal histone modifications for active enhancers, surrounding rs2736098. Therefore, we hypothesized that rs2736098 might be within an enhancer region, regulate TERT expression and influence cancer risk. Through luciferase assay, it was verified that the enhancer activity of rs2736098C allele is significantly higher than that of T in multiple tissues. Transfection of plasmids containing TERT coding region with two different alleles indicated that rs2736098C allele can induce a significantly higher TERT expression than T. By chromatin immunoprecipitation, it was observed that the fragment spanning rs2736098 can interact with USF1 (upstream transcription factor 1). The two alleles of rs2736098 present evidently different binding affinity with nuclear proteins. Database and literature search indicated that rs2736098 is significantly associated with carcinogenesis in multiple tissues and count of multiple cell types. All these facts indicated that rs2736098 is also an oncogenic polymorphism and plays important role in cell proliferation.

Intratumoral injection of interferon gamma promotes the efficacy of anti-PD1 treatment in colorectal cancer.

Immune checkpoint inhibitors (ICIs) offer new options for the treatment of patients with solid cancers worldwide. The majority of colorectal cancers (CRC) are proficient in mismatch-repair (pMMR) genes, harboring fewer tumor antigens and are insensitive to ICIs. These tumors are often found to be immune-deserted. We hypothesized that forcing immune cell infiltration into the tumor microenvironment followed by immune ignition by PD1 blockade may initiate a positive immune cycle that can boost antitumor immunity. Bioinformatics using a public database suggested that IFNγ was a key indicator of immune status and prognosis in CRC. Intratumoral administration of IFNγ increased immune cells infiltration into the tumor, but induced PD-L1 expression. A combined treatment strategy using IFNγ and anti-PD-1 antibody significantly increased T cell killing of tumor cells in vitro and showed synergistic inhibition of tumor growth in a mouse model of CRC. CyTOF found drastic changes in the immune microenvironment upon combined immunotherapy. Treatment with IFNγ and anti-PD1 antibody in CT26 tumors significantly increased infiltration of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs). IFNγ had a more pronounced effect in decreasing intratumoral M2-like macrophages, while PD1 blockade increased the population of CD8+Ly6C + T cells in the tumor microenvironment, creating a more pro-inflammatory microenvironment. Additionally, PD1 induced increased expression of lymphocyte activating 3 (LAG3) in a significant fraction of CD8+ T cells and Treg cells, indicating potential drug resistance and feedback mechanisms. In conclusion, our work provides preclinical data for the Combined immunotherapy of CRC using intratumoral delivery of IFNγ and systemic anti-PD1 monoclonoal antibody.