Long-term outcomes of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection (IOCCRC): a randomized, multicenter, prospective, phase III trial.

BACKGROUND: We aimed to compare combined intraoperative chemotherapy and surgical resection with curative surgical resection alone in colorectal cancer patients. METHODS: We performed a multicenter, open-label, randomized, phase III trial. All eligible patients were randomized and assigned to intraoperative chemotherapy and curative surgical resection or curative surgical resection alone (1:1). Survival actualization after long-term follow-up was performed in patients analyzed on an intention-to-treat basis. RESULTS: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled and randomly assigned to intraoperative chemotherapy and radical surgical resection (n=341) or curative surgical resection alone (n=344). Intraoperative chemotherapy with surgical resection showed no significant survival benefit over surgical resection alone in colorectal cancer patients (3-year DFS: 91.1% vs. 90.0%, P=0.328; 3-year OS: 94.4% vs. 95.9%, P=0.756). However, colon cancer patients benefitted from intraoperative chemotherapy, with a relative 4% reduction in liver and peritoneal metastasis (HR=0.336, 95% CI: 0.148-0.759, P=0.015) and a 6.5% improvement in 3-year DFS (HR=0.579, 95% CI: 0.353-0.949, P=0.032). Meanwhile, patients with colon cancer and abnormal pretreatment CEA levels achieved significant survival benefits from intraoperative chemotherapy (DFS: HR=0.464, 95% CI: 0.233-0.921, P=0.029 and OS: (HR=0.476, 95% CI: 0.223-1.017, P=0.049). CONCLUSIONS: Intraoperative chemotherapy showed no significant extra prognostic benefit in total colorectal cancer patients who underwent radical surgical resection; however, in colon cancer patients with abnormal pretreatment serum CEA levels (> 5 ng/ml), intraoperative chemotherapy could improve long-term survival.

A chimeric adenovirus-vectored vaccine based on Beta spike and Delta RBD confers a broad-spectrum neutralization against Omicron-included SARS-CoV-2 variants.

Urgent research into innovative severe acute respiratory coronavirus-2 (SARS-CoV-2) vaccines that may successfully prevent various emerging emerged variants, particularly the Omicron variant and its subvariants, is necessary. Here, we designed a chimeric adenovirus-vectored vaccine named Ad5-Beta/Delta. This vaccine was created by incorporating the receptor-binding domain from the Delta variant, which has the L452R and T478K mutations, into the complete spike protein of the Beta variant. Both intramuscular (IM) and intranasal (IN) vaccination with Ad5-Beta/Deta vaccine induced robust broad-spectrum neutralization against Omicron BA.5-included variants. IN immunization with Ad5-Beta/Delta vaccine exhibited superior mucosal immunity, manifested by higher secretory IgA antibodies and more tissue-resident memory T cells (TRM) in respiratory tract. The combination of IM and IN delivery of the Ad5-Beta/Delta vaccine was capable of synergically eliciting stronger systemic and mucosal immune responses. Furthermore, the Ad5-Beta/Delta vaccination demonstrated more effective boosting implications after two dosages of mRNA or subunit recombinant protein vaccine, indicating its capacity for utilization as a booster shot in the heterologous vaccination. These outcomes quantified Ad5-Beta/Delta vaccine as a favorable vaccine can provide protective immunity versus SARS-CoV-2 pre-Omicron variants of concern and BA.5-included Omicron subvariants.

Coordination environment dependence of anticancer activity in cyclometalated bismuth(III) complexes with C,O-chelating ligands.

In this paper, a series of cyclometalated bismuth(III) complexes bearing C,O-bidentate ligands were synthesized and characterized by techniques such as UV-vis, NMR, HRMS, and single crystal X-ray diffraction. Meanwhile, their cytotoxicities against various human cell lines, including colon cancer cells (HCT-116), breast cancer cells (MDA-MB-231), lung cancer cells (A549), gastric cancer cells (SGC-7901), and normal embryonic kidney cells (HEK-293) were assessed in vitro. Compared with the clinical cisplatin, most of the synthesized complexes possessed significantly higher degrees of anticancer activity and selectivity, giving a selectivity index of up to 71.3. The structure-activity relationship study revealed that the anticancer performance of these bismuth(III) species depends on the factors of coordination environment surrounding the metal center, such as coordination number, coordination bonding strength, lone 6s2 electron pair stereoactivity. The Annexin V-FITC/PI double staining assay results suggested that the coordination environment-dependent cytotoxicity is ascribable to apoptosis. Western blot analysis confirmed the proposal, as evidenced by the down-regulating level of Bcl-2 and the activation of caspase-3. Furthermore, the representative complexes Bi1, Bi4, Bi6, and Bi8 exhibited relatively lower inhibitory efficiency on human ovarian cancer cells (A2780) than on its cisplatin-resistant daughter cells (A2780/cis), thus demonstrating that such compounds are capable of circumventing the cisplatin-induced resistance. This investigation elucidated the excellent anticancer performance of C,O-coordinated bismuth(III) complexes and established the correlation between cytotoxic activity and coordination chemistry, which provides a practical basis for in-depth designing and developing bismuth-based chemotherapeutics.

[Levels and Clinical Significances of sPD-1 and sPD-L1 in Peripheral Blood of Lymphoma Patients].

OBJECTIVE: To observe the levels of soluble programmed cell death protein 1 (sPD-1) and soluble programmed cell death ligand 1 (sPD-L1) in peripheral blood of lymphoma patients, and reveal their clinical significances. METHODS: The peripheral blood specimens and clinical data of 64 newly diagnosed lymphoma patients and 30 healthy volunteers were collected. The levels of sPD-1 and sPD-L1 were detected by enzyme-linked immunosorbent assay (ELISA), and their correlations with clinical characteristics of the patients including pathological type, stage, lactate dehydrogenase (LDH) level, T cell subsets were analyzed. RESULTS: The levels of both sPD-1 and sPD-L1 in peripheral blood of lymphoma patients were higher than those of normal controls (P <0.05). There were no significant differences in sPD-1 and sPD-L1 levels in peripheral blood between Hodgkin lymphoma and non-Hodgkin lymphoma patients. Different pathological subtypes of lymphoma had different levels of sPD-1. The level of sPD-1 in patients with T-cell lymphoma was higher than that in patients with B-cell lymphoma (P =0.001). The levels of both sPD-1 and sPD-L1 in patients with Ann Arbor stage III and IV were higher than those in patients with stage I and II (P <0.05). The level of sPD-L1 in patients with abnormally increased LDH was higher than that in patients with normal LDH (P =0.001), but there was no significant difference in sPD-1 level. T cell subset analysis showed that the level of sPD-L1 was negatively correlated to CD4+ T cell content (r =-0.265). CONCLUSION: The levels of sPD-1 and sPD-L1 in peripheral blood of lymphoma patients are related to the pathological type, Ann Arbor stage, LDH content and T cell subsets, and will be potential biomarkers in predicting the prognosis of lymphoma.

Physiological, Photosynthetic, and Transcriptomics Insights into the Influence of Shading on Leafy Sweet Potato.

Leafy sweet potato is a new type of sweet potato, whose leaves and stems are used as green vegetables. However, sweet potato tips can be affected by pre-harvest factors, especially the intensity of light. At present, intercropping, greenhouse planting, and photovoltaic agriculture have become common planting modes for sweet potato. Likewise, they can also cause insufficient light conditions or even low light stress. This research aimed to evaluate the influence of four different shading levels (no shading, 30%, 50%, and 70% shading degree) on the growth profile of sweet potato leaves. The net photosynthetic rate, chlorophyll pigments, carbohydrates, and polyphenol components were determined. Our findings displayed that shading reduced the content of the soluble sugar, starch, and sucrose of leaves, as well as the yield and Pn. The concentrations of Chl a, Chl b, and total Chl were increased and the Chl a/b ratio was decreased for the more efficient interception and absorption of light under shading conditions. In addition, 30% and 50% shading increased the total phenolic, total flavonoids, and chlorogenic acid. Transcriptome analysis indicated that genes related to the antioxidant, secondary metabolism of phenols and flavonoids, photosynthesis, and MAPK signaling pathway were altered in response to shading stresses. We concluded that 30% shading induced a high expression of antioxidant genes, while genes related to the secondary metabolism of phenols and flavonoids were upregulated by 50% shading. And the MAPK signaling pathway was modulated under 70% shading, and most stress-related genes were downregulated. Moreover, the genes involved in photosynthesis, such as chloroplast development, introns splicing, and Chlorophyll synthesis, were upregulated as shading levels increased. This research provides a new theoretical basis for understanding the tolerance and adaptation mechanism of leafy sweet potato in low light environments.

Plasticity of the binding pocket in peptide transporters underpins promiscuous substrate recognition.

Proton-dependent oligopeptide transporters (POTs) are promiscuous transporters of the major facilitator superfamily that constitute the main route of entry for a wide range of dietary peptides and orally administrated peptidomimetic drugs. Given their clinical and pathophysiological relevance, several POT homologs have been studied extensively at the structural and molecular level. However, the molecular basis of recognition and transport of diverse peptide substrates has remained elusive. We present 14 X-ray structures of the bacterial POT DtpB in complex with chemically diverse di- and tripeptides, providing novel insights into the plasticity of the conserved central binding cavity. We analyzed binding affinities for more than 80 peptides and monitored uptake by a fluorescence-based transport assay. To probe whether all 8400 natural di- and tripeptides can bind to DtpB, we employed state-of-the-art molecular docking and machine learning and conclude that peptides with compact hydrophobic residues are the best DtpB binders.

MOB kinase activator 1A acts as an oncogene by targeting PI3K/AKT/mTOR in ovarian cancer.

BACKGROUND: To illuminate the precise roles of MOB Kinase Activator 1 A (MOB1A) in the development of ovarian cancer (OC). METHODS: MOB1A expression and clinical data of OC were obtained from the public database on gene expression and proteomics. Meanwhile, verification of expression was carried out in Gene Expression Omnibus, the Human Protein Atlas, and OC cell lines. The prognosis of MOB1A was explored in the Kaplan-Meier plotter. RNA interference and lentivirus vectors were applied to construct knockdown and overexpressed cell models. Changes in the malignant behaviors of OC cells were detected by cholecystokinin octopeptide cell counting kit, wound healing, colony formation assay, transwell, flow cytometry assays, and in vivo experiments. Changes in proteins in the PI3K and autophagy-related makers were detected by western blot analysis. RESULTS: The expression of MOB1A was significantly upregulated and accompanied by an inferior survival rate in OC. Knockdown of MOB1A inhibited the proliferation, invasion, migration, and cell cycle of OC cells, whereas induced cell autophagy. MOB1A upregulation had the opposite effects. In addition, bioinformatics analysis and western blot experiments showed that MOB1A plays an important role in the PI3K/AKT/mTOR pathway. CONCLUSIONS: Our findings indicated that MOB1A is highly expressed and related to poor prognosis in OC. MOB1A plays a role in promoting the malignant biological behavior of tumor cells through PI3K/AKT/mTOR signaling pathway.

Pharmacological inhibition of LSD1 suppresses growth of hepatocellular carcinoma by inducing GADD45B.

Lysine-specific histone demethylase 1 (LSD1) is an attractive target for malignancies therapy. Nevertheless, its role in hepatocellular carcinoma (HCC) progression and the potential of its inhibitor in HCC therapy remains unclear. Here, we show that LSD1 overexpression in human HCC tissues is associated with HCC progression and poor patient survival. ZY0511, a highly selective and potent inhibitor of LSD1, suppressed human HCC cell proliferation in vitro and tumor growth in cell-derived and patient-derived HCC xenograft models in vivo. Mechanistically, ZY0511 induced mRNA expression of growth arrest and DNA damage-inducible gene 45beta (GADD45B) by inducing histone H3 at lysine 4 (H3K4) methylation at the promoter of GADD45B, a novel target gene of LSD1. In human HCC tissues, LSD1 level was correlated with a decreased level of GADD45B, which was associated with HCC progression and predicted poor patient survival. Moreover, co-administration of ZY0511 and DTP3, which specifically enhanced the pro-apoptotic effect of GADD45B, effectively inhibited HCC cell proliferation both in vitro and in vivo. Collectively, our study revealed the potential value of LSD1 as a promising target of HCC therapy. ZY0511 is a promising candidate for HCC therapy through upregulating GADD45B, thereby providing a novel combinatorial strategy for treating HCC.

LncRNA CASC11 upregulation promotes HDAC4 to alleviate oxidized low-density lipoprotein-induced injury of cardiac microvascular endothelial cells.

Long noncoding RNAs (LncRNAs) are essential to regulate the pathogenesis of coronary artery disease (CAD). This study was conducted to analyze the functionality of long noncoding RNA cancer susceptibility candidate 11 (lncRNA CASC11) in oxidized low-density lipoprotein (ox-LDL)-induced injury of cardiac microvascular endothelial cells (CMECs). CMECs were treated with ox-LDL to induce the CAD cell model. The cellular expression levels of CASC11 and histone deacetylase 4 (HDAC4) were determined by real-time quantitative polymerase chain reaction or Western blot assay. Cell absorbance, apoptosis, angiogenesis, and inflammation were evaluated by cell counting kit-8, flow cytometry, tube formation, and enzyme-linked immunosorbent assays. The subcellular localization of CASC11 was examined by the nuclear/cytoplasmic fractionation assay. The binding of human antigen R (HuR) to CASC11 and HDAC4 was analyzed by RNA immunoprecipitation. HDAC4 stability was determined after actinomycin D treatment. CASC11 was found to be decreased in the CAD cell model. CASC11 upregulation increased cell viability and angiogenesis and reduced apoptosis and inflammation. CASC11 bound to HuR and improved HDAC4 expression. HDAC4 downregulation counteracted the protective role of CASC11 overexpression in CMECs. In summary, CASC11 alleviated ox-LDL-induced injury of CMECs by binding to HuR and stabilizing HDAC4.

Clinical characteristics, treatment patterns and survival outcomes of early-onset pancreatic adenocarcinoma: a population-based study.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a rare and refractory malignancy. Early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed before the age of 50 years, is very rare. Clinical presentation and oncological outcomes of EOPC are confusing according to previous studies. METHODS: We performed a retrospective, population-based study by querying the SEER database to analyze patients with PDAC from 2004 to 2018. Data on demographics, pathological characteristics, treatment patterns, and survival outcomes were compared between EOPC and pancreatic cancer in older patients. Propensity score matching (PSM) was used to minimize the potential bias of baseline characteristics between the two groups. The effect of age on changes in treatment modalities was evaluated using the Cochran-Armitage trend test. RESULTS: The entire study enrolled 42,414 patients, including 2,916 (6.9%) patients with EOPC. Patients with EOPC were more likely to be male (56.6% vs. 51.0%, P < 0.001) and more frequently to present with a larger tumor size (40 mm vs. 37 mm, P < 0.001), vascular invasion (28.6% vs. 25.9%, P = 0.022) and distant metastasis (56.2% vs. 50.8%, P < 0.001) compared with older group. However, surgical resection rates (29.3% vs. 28.3%, P = 0.284) were fairly comparable, and most clinicopathologic characteristics were similar in the patients underwent resection. Younger patients had longer 5-year overall survival (6.9% vs. 5.5%, P < 0.001) and 5-year cancer-specific survival (8.4% vs. 7.3%, P < 0.001) among the overall cohort but had comparable prognosis among patients received surgery (both P > 0.05). Similar survival outcomes were obtained after PSM. In addition, operated patients tended to receive fewer systemic treatments at an increasing age (Ptrend < 0.001). The survival analysis, which was stratified by age groups, suggested that younger patients only had a better prognosis than those over 70. CONCLUSIONS: Patients with EOPC exhibited an advanced stage and a male predilection at diagnosis in the overall cohort but broadly similar clinicopathologic characteristics in the operated patients. In the surgical cohort, although younger patients were more likely to receive systemic treatment, patients with EOPC presented comparable outcomes compared with elderly patients. We suggest that more research should be conducted to uncover the unique characteristics of EOPC for better clinical management.

Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial.

OBJECTIVE: To compare neoadjuvant chemotherapy (nCT) with CAPOX alone versus neoadjuvant chemoradiotherapy (nCRT) with capecitabine in locally advanced rectal cancer (LARC) with uninvolved mesorectal fascia (MRF). BACKGROUND DATA: nCRT is associated with higher surgical complications, worse long-term functional outcomes, and questionable survival benefits. Comparatively, nCT alone seems a promising alternative treatment in lower-risk LARC patients with uninvolved MRF. METHODS: Patients between June 2014 and October 2020 with LARC within 12 cm from the anal verge and uninvolved MRF were randomly assigned to nCT group with 4 cycles of CAPOX (Oxaliplatin 130 mg/m2 IV day 1 and Capecitabine 1000 mg/m2 twice daily for 14 d. Repeat every 3 wk) or nCRT group with Capecitabine 825 mg/m² twice daily administered orally and concurrently with radiation therapy (50 Gy/25 fractions) for 5 days per week. The primary end point is local-regional recurrence-free survival. Here we reported the results of secondary end points: histopathologic response, surgical events, and toxicity. RESULTS: Of the 663 initially enrolled patients, 589 received the allocated treatment (nCT, n=300; nCRT, n=289). Pathologic complete response rate was 11.0% (95% CI, 7.8-15.3%) in the nCT arm and 13.8% (95% CI, 10.1-18.5%) in the nCRT arm ( P =0.33). The downstaging (ypStage 0 to 1) rate was 40.8% (95% CI, 35.1-46.7%) in the nCT arm and 45.6% (95% CI, 39.7-51.7%) in the nCRT arm ( P =0.27). nCT was associated with lower perioperative distant metastases rate (0.7% vs. 3.1%, P =0.03) and preventive ileostomy rate (52.2% vs. 63.6%, P =0.008) compared with nCRT. Four patients in the nCT arm received salvage nCRT because of local disease progression after nCT. Two patients in the nCT arm and 5 in the nCRT arm achieved complete clinical response and were treated with a nonsurgical approach. Similar results were observed in subgroup analysis. CONCLUSIONS: nCT achieved similar pCR and downstaging rates with lower incidence of perioperative distant metastasis and preventive ileostomy compared with nCRT. CAPOX could be an effective alternative to neoadjuvant therapy in LARC with uninvolved MRF. Long-term follow-up is needed to confirm these results.

Cytotoxic nortriterpenoids from the barks of Juglans cathayensis.

A chemical study of 90% ethanol extract of the barks of Juglans cathayensis resulted in the isolation of three new nortriterpenoids, jugcathenoids A-C (1-3). The structures of the new compounds were elucidated by spectroscopic analysis (NMR, IR, UV, and MS). The isolated nortriterpenoids were tested in vitro for cytotoxic activities against 6 pancreatic cell lines. As a result, compounds 1-3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 50 µM.

Validation of E1L3N antibody for PD-L1 detection and prediction of pembrolizumab response in non-small-cell lung cancer.

BACKGROUND: The programmed death-ligand 1 (PD-L1) 22C3 assay is one of the approved companion diagnostic assays for receiving anti-programmed cell death ligand 1 (PD-L1) therapy. Our study evaluated the performance of E1L3N and 22C3 antibodies in estimating PD-L1 expression in non-small cell lung cancer (NSCLC). METHODS: Our retrospective study included 46 patients diagnosed with unresectable EGFR/ALK/ROS1-negative NSCLC who received first-line pembrolizumab therapy between 2018 and 2021. PD-L1 immunohistochemistry of baseline tissue biopsy samples was performed using PDL1-E1L3N and PDL1-22C3 antibodies. The concordance between the PD-L1 assays and the treatment outcomes was assessed. RESULTS: Using a tumor proportion score (TPS) cutoff of ≥1%, 67.4% of patients are evaluated to be positive using PDL1-E1L3N and 73.9% using PDL1-22C3. Using a TPS of ≥50% as the cutoff, 26.1% of patients are positive using PDL1-E1L3N and 30.4% using PDL1-22C3. The PDL1-22C3 and PDL1-E1L3N assays are highly concordant and reveal a correlation coefficient of 0.925 (p < 0.0001). Patients with PDL1-E1L3N TPS > 50% have a significantly higher objective response rate than patients with PDL1-E1L3N TPS < 1% (p = 0.047), with a similar trend observed for PDL1-22C3 (p = 0.051). Consistent with PDL1-22C3, patients with higher PDL1-E1L3N expression (≥50%, 1-49%) have longer progression-free survival than those with PDL1-E1L3N TPS < 1%. CONCLUSION: Our study provides clinical evidence on the concordance of PD-L1 TPS scores between clones E1L3N and 22C3. Moreover, the treatment responses to pembrolizumab are also comparable between the PDL1-E1L3N and PDL1-22C3. These findings indicate that E1L3N is a reliable and cost-effective assay and may serve as an alternative to 22C3.

To determine which patients might be suitable to receive immunotherapy, a type of cancer treatment that triggers the immune system to target the patient's tumor, a PD-L1 test is sometimes used. This test looks at the levels of PD-L1, which indicate whether immunotherapy might work in the patient. One of the tests commonly used can be expensive and a reliable and cost-effective alternative is needed. Here, we compare the results of PD-L1 testing with that test with an alternative that is more cost-effective. We show that the two tests are highly concordant, and also demonstrate that the results using the alternative test are able to predict response to immunotherapy in patients with advanced non-small cell lung cancer. Our findings provide evidence that the alternative, more cost-effective test might be useful and reliable in the clinic.

In vitro corrosion and in vivo behavior of high strength Mg-6Zn-1Mn alloy wire for gastrointestinal anastomosis nail application.

Ti and its alloy staples can be retained in the human body for a long period because of their excellent corrosion resistance and thus requires revision surgery for removal. In this study, biodegradable Mg-6Zn-1Mn alloy staples were fabricated using ∼99.8 % area reduction cold drawing, whose service performance was evaluated by in vitro corrosion and in vivo tests. The high strength (∼340 MPa) of staples is mainly attributed to the formation of fine grains, nanoparticles, and additional dislocations. Moreover, owing to the effect of fine grains, as well as the high Schmid factor of prismatic ⟨a⟩ slip and pyramidal ⟨c+a⟩ slip, the staples also exhibit acceptable ductility (∼10 %). The in vitro corrosion results indicate that staple fractures occurred after immersion for 21 h in a single PBS solution. With the addition of ∼0.5 g/L bovine serum albumin (BSA), the time required to maintain the mechanical integrity of staples can expand to 90 h. This is mainly related to the adsorption and chelating effects between BSA and Mg matrix. After the implantation surgery, all rabbits fully recovered with normal oral intake, and Mg ions generated by degradation effectively promoted the absorption of the alimentary system. Therefore, the Mg-6Zn-1Mn alloy staples fabricated in this study exhibit desired effect, and excellent clinical application prospects.

IbMYB308, a Sweet Potato R2R3-MYB Gene, Improves Salt Stress Tolerance in Transgenic Tobacco.

The MYB (v-myb avian myeloblastosis viral oncogene homolog) transcription factor family plays an important role in plant growth, development, and response to biotic and abiotic stresses. However, the gene functions of MYB transcription factors in sweet potato (Ipomoea batatas (L.) Lam) have not been elucidated. In this study, an MYB transcription factor gene, IbMYB308, was identified and isolated from sweet potato. Multiple sequence alignment showed that IbMYB308 is a typical R2R3-MYB transcription factor. Further, quantitative real-time PCR (qRT-PCR) analysis revealed that IbMYB308 was expressed in root, stem, and, especially, leaf tissues. Moreover, it showed that IbMYB308 had a tissue-specific profile. The experiment also showed that the expression of IbMYB308 was induced by different abiotic stresses (20% PEG-6000, 200 mM NaCl, and 20% H2O2). After a 200 mM NaCl treatment, the expression of several stress-related genes (SOD, POD, APX, and P5CS) was upregulation in transgenic plants, and the CAT activity, POD activity, proline content, and protein content in transgenic tobacco had increased, while MDA content had decreased. In conclusion, this study demonstrated that IbMYB308 could improve salt stress tolerance in transgenic tobacco. These findings lay a foundation for future studies on the R2R3-MYB gene family of sweet potato and suggest that IbMYB308 could potentially be used as an important positive factor in transgenic plant breeding to improve salt stress tolerance in sweet potato plants.

Tumor-Suppressor Gene Transmembrane Protein 98 Promotes Proliferation and Inhibits Apoptosis in Ovarian Cancer.

BACKGROUND: Ovarian cancer (OC) is the most deadly tumor in gynecology and there is no effective biomarker for diagnosis and treatment. The role of Transmembrane Protein 98 (TMEM98) in ovarian cancer is still unclear. METHODS: The expression and prognostic effect of TMEM98 in OC were analyzed using the public database. Cell Counting Kit-8 proliferation experiment, scratch experiment, Transwell invasion experiment, flow cytometry, TUNEL staining, and in vivo and vitro experiment were used. RESULTS: TMEM98 was significantly downregulated in OC tissues and cell lines compared to the normal ovarian tissue and cells lines. In addition, patients with lower TMEM98 levels exhibited inferior survival. Low expression of the TMEM98 promoted proliferation, migration, invasion, vasculogenic mimicry, and inhibited apoptosis in OC cells. The expression of Caspase-3 was significantly downregulated and the expression of Bcl-2 was significantly increased in the silencing-TMEM98 group. Moreover, low expression of TMEM98 promotes OC development in vivo. Bioinformatics analysis showed that TMEM98 expression was negatively correlated with poly ADP-ribose polymerase expression. CONCLUSIONS: This study demonstrates that TMEM98 is low expressed in OC and impacts the prognosis of OC patients. TMEM98 inhibits proliferation and promotes apoptosis and finally exerts a certain tumor-suppressor effect on OC.

Non-optimum ambient temperature may decrease pulmonary function: A longitudinal study with intensively repeated measurements among asthmatic adult patients in 25 Chinese cities.

BACKGROUND: Non-optimum ambient temperature has not been widely perceived as an important environmental risk factor for asthma, and the association between ambient temperature and pulmonary function is rarely explored. Our study aimed to investigate the associations between non-optimum ambient temperature and pulmonary function among asthmatic adult patients. METHODS: We performed a longitudinal study among 4,992 eligible adult asthmatic patients in 25 cities of China from 2017 to 2020. The patients were required to complete pulmonary function test every day in the morning and evening. Linear mixed-effects models and distributed lag non-linear models were used to evaluate the associations between ambient temperature and pulmonary function. RESULTS: We evaluated 298,396 records of pulmonary function tests. We found inversely J-shaped exposure-response relationship curves for ambient temperature and pulmonary function. The effects of extreme low temperature occurred at lag 0 h and vanished at lag 72 h (almost 3 days). Compared with referent temperature (29.5 °C), extreme low temperature (-9.4 °C) was associated with decreases of 60.4 mL in FEV1, 299.7 mL/s in PEF, and 101.5 mL in FVC. Extreme high temperature (34.2 °C) was associated with decreases of 26.0 mL in FEV1, 35.8 mL/s in PEF, and 23.4 mL in FVC. Patients of male, overweight, and elder ages were vulnerable populations, and cold effects were more prominent in the south and in areas without central heating. CONCLUSIONS: Both extreme low and high ambient temperatures were associated with decreased pulmonary function in adult asthmatic patients. The effect could last for almost 3 days and low temperature was more harmful.

Local treatment improves survival in patients with stage IVB cervical cancer.

OBJECTIVE: To evaluate the value of local treatment in stage IVB cervical cancer (CC). METHODS: Patients diagnosed with stage IVB CC between 2010 and 2015 were included using the data from the Surveillance, Epidemiology, and End Results program. Propensity score matching (PSM) was used to balance the clinicopathological variables of patients. Multivariate Cox regression analyses were performed to analyze the risk factors associated with cause-specific survival (CSS). RESULTS: We identified 960 patients in this study, all patients had received chemotherapy. Of these patients, 818 patients were treated with local treatment (85.2%), including 724 (88.5%) and 94 (11.5%) patients receiving radiotherapy (RT) alone and surgery ± RT, respectively. Local treatment was the independent prognostic factor associated with better CSS. Before PSM, patients who received RT (hazard ratio [HR] 0.633, 95% confidence interval [CI] 0.517-0.775, P < 0.001) or surgery (HR 0.391, 95% CI 0.277-0.552, P < 0.001) were independently associated with a better CSS compared to those with no local treatment. The 3-years CSS rate was 14.4%, 32.4%, and 54.8% in no local treatment, RT alone, and surgery groups, respectively (P < 0.001). Similar results were found after PSM. Patients receiving RT (HR 0.643, 95% CI 0.436-0.947, P = 0.025) and surgery (HR 0.146, 95% CI 0.052-0.410, P < 0.001) had better CSS compared to patients with no local treatment after PSM. While similar CSS was shown between RT alone cohort and the surgery cohort (HR 0.756, 95% CI 0.454-1.260, P = 0.284). CONCLUSIONS: The addition of local surgery or RT to chemotherapy appears to confer improved survival outcomes in patients with stage IVB CC.