Predicting the prognosis of hepatic arterial infusion chemotherapy in hepatocellular carcinoma.

Hepatic artery infusion chemotherapy (HAIC) has good clinical efficacy in the treatment of advanced hepatocellular carcinoma (HCC); however, its efficacy varies. This review summarized the ability of various markers to predict the efficacy of HAIC and provided a reference for clinical applications. As of October 25, 2023, 51 articles have been retrieved based on keyword predictions and HAIC. Sixteen eligible articles were selected for inclusion in this study. Comprehensive literature analysis found that methods used to predict the efficacy of HAIC include serological testing, gene testing, and imaging testing. The above indicators and their combined forms showed excellent predictive effects in retrospective studies. This review summarized the strategies currently used to predict the efficacy of HAIC in middle and advanced HCC, analyzed each marker's ability to predict HAIC efficacy, and provided a reference for the clinical application of the prediction system.

CISD2 downregulation participates in the ferroptosis process of human ovarian SKOV-3 cells through modulating the wild type p53-mediated GLS2/SAT1/SLC7A11 and Gpx4/TRF signaling pathway.

CISD2 and ferroptosis participate in cancer development, but are rarely reported in ovarian cancer. This study aimed to clarify interaction between CISD2 and ferroptosis and evaluate related mechanisms. si-CISD2, wt-p53 and mut-p53 lentiviruses were transfected into SKOV-3 cells. CISD2 and p53 (wild/mutant p53) gene transcriptions were evaluated by RT-PCR. Cell viability, invasion ability, and migration capacity were determined. Expressions of ferroptosis-associated CISD2, p53, elastin, ß-catenin and levels of Gpx4 and TRF were examined. CISD2 downregulation (si-CISD2) has a significant inhibitory effect on cell activity and exerts a synergistic effect with p53. si-CISD2 and Wt-p53 markedly inhibited SKOV-3 invasion and migration capacity, compared to the downregulation control (si-NC) and overexpression control (ov-NC) group (p < 0.001). p53 expression was increased significantly in si-CISD2 treated SKOV-3, compared to si-NC treated cells (p < 0.05). si-CISD2 markedly decreased elastin and ß-catenin expression compared to the si-NC and ov-NC group (p < 0.001). si-CISD2 modulated ferroptosis-associated molecules (CDKN1A, GLS2, SAT1, SLC7A11), decreased Gpx4 and increased TRF levels in SKOV-3. si-CISD2 and Wt-p53 played an obvious synergistic role in regulating ferroptosis-associated molecules and Gpx4/TRF pathway molecules. In conclusion, CISD2 downregulation was involved in ferroptosis process of SKOV-3 cells. This effect of CISD2 was mediated by wild-type p53-associated GLS2/SAT1/SLC7A11 and Gpx4/TRF pathway.

The impact of diet, exercise, and sleep on Helicobacter pylori infection with different occupations: a cross-sectional study.

BACKGROUND: Associations between Helicobacter pylori infection and lifestyle factors vary greatly by geographic location. This study aims to evaluate the prevalence of Helicobacter pylori infection in the Hunan cohort of central China and analyze the associations between Helicobacter pylori infection and lifestyle factors in different occupations. METHODS: This was a cross-sectional study. Participants who received an annual physical examination were invited. Helicobacter pylori infection was detected by the 13 C-urea breath test. Self-reported physical examination questionnaires were used to analyze participants' demographic information, diet, exercise status, and sleep situations. RESULTS: 23254 participants finished this study. The Helicobacter pylori infection rate in the Hunan area was 25.8%, with the lowest prevalence in students (8.5%) and the highest prevalence in business managers (29.9%). The risk factors for Helicobacter pylori infection were marital status (divorced or married) (OR:1.16, 95%CI:1.090-1.234), overeating (OR:1.105, 95%CI: 1.001-1.220), and consumption of eggs (OR:1.047, 95%CI:1.004-1.092), animal viscera (OR: 1.077, 95%CI:1.014-1.144) and coffee (OR:1.074, 95%CI:1.019-1.132). Participants' education level (OR:0.911, 95%CI:0.881-0942), consumption of midnight snack (OR:0.926, 95%CI:0.877-0.977), and vegetable (OR:0.927, 95%CI: 0.884-0.972) were protective factors against Helicobacter pylori infection. Whether participants exercised regularly or had sleep problems had no significant effect on Helicobacter pylori infection. Different professionals showed significant differences in the rates of overeating, eating three meals on time, midnight snack, and consuming coffee, eggs, animal viscera, and vegetables > 3 times/week (P values < 0.05). CONCLUSIONS: Helicobacter pylori infection showed a significant relationship with dietary factors, but not significantly with sleep and exercise factors. Different occupations showed different dietary tendencies related to Helicobacter pylori infection. The design of an occupation-based Helicobacter pylori screening and prevention program is supported.

Modeling microbial impact on macrophyte debris decomposition in macrophyte-dominated eutrophic lakes.

The decomposition of macrophytes plays a crucial role in the nutrient cycles of macrophyte-dominated eutrophication lakes. While research on plant decomposition mechanisms and microbial influences has rapid developed, it is curious that plant decomposition models have remained stagnant at the single-stage model from 50 years ago, without endeavor to consider any important factors. Our research conducted in-situ experiments and identified the optimal metrics for decomposition-related microbes, thereby establishing models for microbial impacts on decomposition rates (k_RDR). Using backward elimination in stepwise regression, we found that the optimal subset of independent variables-specifically Gammaproteobacteria-Q-L, Actinobacteriota-Q-L, and Ascomycota-Q-L-increased the adjusted R-squared (Ra2) to 0.93, providing the best modeling for decomposition rate (p = 0.002). Additionally, k_RDR can be modeled by synergic parameters of ACHB-Q-L, LDB-Q-L, and AB-Q-L for bacteria, and SFQ for fungi, albeit with a slightly lower Ra2 of 0.7-0.9 (p < 0.01). The primary contribution of our research lies in two key aspects. Firstly, we introduced optimal metrics for modeling microbes, opting for debris surface microbes over sediment microbes, and prioritizing absolute abundance over relative abundance. Secondly, our model represents a noteworthy advancement in debris modeling. Alongside elucidating the focus and innovative aspects of our work, we also addressed existing limitations and proposed directions for future research. SYNOPSIS: This study explores optimum metrics for decomposition-related microbes, offering precise microbial models for enhanced lake nutrient cycle simulation.

A Case Report of Pathologically Complete Response of a Huge Lymph Node Metastasis of Colorectal Cancer After Treatment with Intratumoral Oncolytic Virus H101 and Capecitabine.

Unresectable recurrent lymph node metastasis of colorectal cancer (CRC) is considered as an incurable disease clinically and has a very poor prognosis. Here, we report a male KRAS wild-type CRC case with a huge abdominal lymph node metastasis (12 cm in diameter) after CRC surgery. After three intratumoral injections of oncolytic virus (H101) combined with four cycles of low-dose oral capecitabine, the size of the metastatic lymph node shrank remarkably in response to the anticancer drug and a complete response (CR) was achieved with progression-free survival (PFS) of 19 months. The main adverse reaction was mild fever, which was relieved after physical cooling. The patient is in a general good condition now without any relapse of abdominal lymph node for over a year. On this basis, we propose that the combination therapy of oncolytic virus and capecitabine could be a promising clinical therapeutic strategy for unresectable recurrent lymph node metastasis in CRC patients.

DEVELOPING THERAPIES FOR C3G: REPORT OF THE KIDNEY HEALTH INITIATIVE C3G TRIAL ENDPOINTS WORK GROUP.

Randomized clinical trials are underway to evaluate the efficacy of novel agents targeting the alternative complement pathway in patients with C3G, a rare glomerular disease. The Kidney Health Initiative (KHI) convened a panel of experts in C3G to: (1) assess the data supporting the use of the prespecified trial endpoints as measures of clinical benefit; and (2) opine on efficacy findings they would consider compelling as treatment(s) for C3G in native kidneys. Two subpanels of the C3G Trial Endpoints Work group reviewed the available evidence and uncertainties for the association between the three prespecified endpoints -- (1) proteinuria; (2) estimated glomerular filtration rate (eGFR); and (3) histopathology -- and anticipated outcomes. The full work group provided feedback on the summaries provided by the subpanels and on what potential treatment effects on the proposed endpoints they would consider compelling to support evidence of an investigational product's effectiveness for treating C3G. Members of the full work group agreed with the characterization of the data, the evidence, and uncertainties, supporting the endpoints. Given the limitations of the available data, the workgroup was unable to define a minimum threshold for change in any of the endpoints that might be considered clinically meaningful. The workgroup concluded that a favorable treatment effect on all three endpoints would provide convincing evidence of efficacy in the setting of a therapy that targeted the complement pathway. A therapy might be considered effective in the absence of complete alignment in all three endpoints if there was meaningful lowering of proteinuria and stabilization or improvement in eGFR. The panel unanimously supported efforts to foster data sharing between academic and industry partners to address the gaps in the current knowledge identified by the review of the endpoints in the aforementioned trials.

Obesity enhances the response to neoadjuvant anti-PD1 therapy in oral tongue squamous cell carcinoma.

OBJECTIVES: Previous studies have demonstrated that obesity may impact the efficacy of anti-PD1 therapy, but the underlying mechanism remains unclear. In this study, our objective was to determine the prognostic value of obesity in patients with oral tongue squamous cell carcinoma (OTSCC) treated with pembrolizumab and establish a subtype based on fatty acid metabolism-related genes (FAMRGs) for immunotherapy. MATERIALS AND METHODS: We enrolled a total of 56 patients with OTSCC who underwent neoadjuvant anti-PD1 therapy. Univariate and multivariate Cox regression analyses, Kaplan-Meier survival analysis, and immunohistochemistry staining were performed. Additionally, we acquired the gene expression profiles of pan-cancer samples and conducted GSEA and KEGG pathway analysis. Moreover, data from TCGA, MSigDB, UALCAN, GEPIA and TIMER were utilized to construct the FAMRGs subtype. RESULTS: Our findings indicate that high Body Mass Index (BMI) was significantly associated with improved PFS (HR = 0.015; 95% CI, 0.001 to 0.477; p = 0.015), potentially attributed to increased infiltration of PD1 + T cells. A total of 91 differentially expressed FAMRGs were identified between the response and non-response groups in pan-cancer patients treated with immunotherapy. Of these, 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) were found to affect PD-1 expression and T cell infiltration in HNSCC, which may impact the efficacy of anti-PD1 therapy. CONCLUSION: This study demonstrates that obesity serves as a robust prognostic predictor for patients with OTSCC undergoing neoadjuvant anti-PD1 therapy. Furthermore, the expression of 6 hub FAMRGs (ACSL5, PLA2G2D, PROCA1, IL4I1, UBE2L6 and PSME1) plays a pivotal role in the context of anti-PD1 therapy and deserves further investigation.

Induction-concurrent chemoradiotherapy with or without sintilimab in patients with locoregionally advanced nasopharyngeal carcinoma in China (CONTINUUM): a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial.

BACKGROUND: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population. METHODS: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing. FINDINGS: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group. INTERPRETATION: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma. FUNDING: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Clinical Effect Analysis of Fire-needle Acupuncture at Neiyingxiang Treating Persistent Allergic Rhinitis.

OBJECTIVES: We conducted the first trial to evaluate the effect that fire-needle acupuncture at Neiyingxiang (ExHN 9) in patients with moderate to severe persistent AR. METHODS: This was a randomized, single-center, sham, and placebo-controlled rial. Patients were kept blinded to their group assignment. All participants were equally assigned to the fire-needle acupuncture (FA) treatment group, sham fire-needle acupuncture (SFA) group, or loratadine group. The trial was designed with an acupuncture intervention once a week for 4 weeks and follow-up 4 weeks. The Total Nasal Symptom Scores (TNSS), Total Non-Nasal Symptom Scores (TNNSS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Allergic Rhinitis Control Test (ARCT), and total nasal resistance of 150 Pa were evaluated as outcome measures. RESULTS: A total of 180 participants were enrolled, and 175 participants completed the trials. At 2 and 4 weeks, the TNSS, TNNSS, and RQLQ scores of the FA and loratadine groups were significantly lower than those of the SFA group. At 8 weeks, the scores of loratadine group increased compared with the FA group (Cohen's d >0.80, p < 0.01). The ACRT score of the FA treatment group rose gradually. After treatment, the total nasal resistance of the FA group was significantly decreased and was lower than that of the other two groups (Cohen's d >0.80, p < 0.01). CONCLUSION: Fire-needle acupuncture at Neiyingxiang (ExHN 9) is effective for improving nasal allergy symptoms and quality of life in patients with moderate and severe persistent AR, and the duration of its effects is long. LEVEL OF EVIDENCE: 2 Laryngoscope, 2024.

Feasibility, safety and efficacy of high intensity focused ultrasound ablation as a preoperative treatment for challenging hysteroscopic myomectomy.

PURPOSE: To investigate the feasibility, safety and efficacy of high intensity focused ultrasound ablation (HIFU) as a preoperative treatment for challenging hysteroscopic myomectomies. MATERIALS AND METHODS: A total of 75 patients diagnosed with types 0-III of uterine fibroids were enrolled. Based on the Size, Topography, Extension of the base, Penetration and lateral Wall position (STEPW) classification scoring system, 25 cases with a score ≥ 5 points were treated with HIFU followed by hysteroscopic myomectomy (HIFU + HM group), whereas 50 cases with a score < 5 points were treated with hysteroscopic myomectomy (HM group). RESULTS: The median preoperative STEPW score was 7 in the HIFU + HM group and 2 in the HM group. The average non-perfused volume (NPV) ratio achieved in fibroids after HIFU was 86.87%. Patients in the HIFU + HM group underwent hysteroscopic myomectomy one to four days after HIFU, and downgrading was observed in 81.81% of fibroids. The operation time for patients in the HIFU + HM group was 73 min and the success rate of myomectomy in a single attempt was 60%. The volume of distention medium used during the operation was greater in the HIFU + HM group than in the HM group (15,500 ml vs. 7500 ml). No significant difference was observed between the two groups in terms of intraoperative blood loss, the incidence of intraoperative and postoperative complications, menstrual volume score, or uterine fibroid quality of life score. CONCLUSION: HIFU can be utilized as a preoperative treatment for large submucosal fibroids prior to hysteroscopic myomectomy. HIFU offers a novel approach in the management of this subset of patients.

Electronic symptom monitoring after lung cancer surgery: establishing a core set of patient-reported outcomes for surgical oncology care in a longitudinal cohort study.

BACKGROUND: Electronic symptom monitoring via patient-reported outcome in surgical oncology is limited owing to lengthy instruments and non-specific items in common patient-reported outcome instruments. To establish electronic symptom monitoring through a clinically relevant and fit-for-purpose core set of patient-reported outcome in patients undergoing lung cancer surgery. MATERIALS AND METHODS: One qualitative (Cohort 1) and two prospective studies (Cohorts 2 and 3) were conducted between 2018 and 2023. Patients undergoing lung cancer surgery were recruited. Items of symptoms and daily functioning were generated through extensive interviews in Cohort 1 and incorporated into a smartphone-based platform to establish the electronic Perioperative Symptom Assessment for Lung surgery (ePSA-Lung). This tool was finalized and validated in Cohort 2. Patients in Cohort 3 were longitudinally monitored for the first year post-surgery using the validated ePSA-Lung. RESULTS: In total, 1,037 patients scheduled for lung cancer surgery were recruited. The 11-item draft PSA-Lung was generated based on qualitative interview with 39 patients and input from a Delphi study involving 42 experts. A 9-item ePSA-Lung was finalized by assessing 223 patients in the validation cohort; the results supported the instrument's understandability, reliability, sensitivity, and surgical specificity. In Cohort 3 (n=775), compliance ranged from 63.21% to 84.76% during the one-year follow-up after discharge. Coughing, shortness of breath, and disturbed sleep were the most severe symptoms after discharge. Longitudinally, patients who underwent single-port video-assisted thoracic surgery had a lower symptom burden than those who underwent multi-port video-assisted thoracic surgery or thoracotomy (all symptoms, P<0.001). CONCLUSION: The ePSA-Lung is valid, concise, and clinically applicable as it supports electronic symptom monitoring in surgical oncology care. The need for long-term extensive care was identified for patients after discharge, even in early-stage cancer with potential curative treatment.

USP22 is required for human endometrial stromal cell proliferation and decidualization by deubiquitinating FoxM1.

Despite significant advances in assisted reproductive technology (ART), recurrent implantation failure (RIF) still occurs in some patients. Poor endometrial receptivity and abnormal human endometrial stromal cell (HESC) proliferation and decidualization have been identified as the major causes. Ubiquitin-specific protease 22 (USP22) has been reported to participate in the decidualization of endometrial stromal cells in mice. However, the role of USP22 in HESC function and RIF development remains unknown. In this study, clinical endometrial tissue samples were gathered to investigate the involvement of USP22 in RIF, and HESCs were utilized to examine the molecular mechanisms of USP22 and Forkhead box M1 (FoxM1). The findings indicated a high expression of USP22 in the secretory phase of the endometrium. Knockdown of USP22 led to a notable reduction in the proliferation and decidualization of HESCs, along with a decrease in FoxM1 expression, while overexpression of USP22 yielded opposite results. Furthermore, USP22 was found to deubiquitinate FoxM1 in HESCs. Moreover, both USP22 and FoxM1 were downregulated in the endometria of patients with RIF. In conclusion, these results suggest that USP22 may have a significant impact on HESCs proliferation and decidualization through its interaction with FoxM1, potentially contributing to the underlying mechanisms of RIF pathogenesis.

A Targeted Deep Sequencing Method to Quantify Endogenous Retrovirus Gag Sequence Variants and Open Reading Frames Expressed in Nonobese Diabetic Mice.

Endogenous retroviruses (ERVs) are involved in autoimmune diseases such as type 1 diabetes (T1D). ERV gene products homologous to murine leukemia retroviruses are expressed in the pancreatic islets of NOD mice, a model of T1D. One ERV gene, Gag, with partial or complete open reading frames (ORFs), is detected in the islets, and it contains many sequence variants. An amplicon deep sequencing analysis was established by targeting a conserved region within the Gag gene to compare NOD with T1D-resistant mice or different ages of prediabetic NOD mice. We observed that the numbers of different Gag variants and ORFs are linked to T1D susceptibility. More importantly, these numbers change during the course of diabetes development and can be quantified to calculate the levels of disease progression. Sequence alignment analysis led to identification of additional markers, including nucleotide mismatching and amino acid consensus at specific positions that can distinguish the early and late stages, before diabetes onset. Therefore, the expression of sequence variants and ORFs of ERV genes, particularly Gag, can be quantified as biomarkers to estimate T1D susceptibility and disease progression.

Phosphorus accumulation during the ice-on season in macrophyte-dominated eutrophic lakes and its implications.

Macrophyte overgrowth in eutrophic lakes can hasten the decline of shallow water bodies, yet the impact of macrophyte deposition on sediment phosphorus (P) accumulation in the ice-on season remains unclear. Comparative analyses of P variations among 13 semi-connected sub-lakes in Wuliangsu Lake in China, a typical MDE lake, considered external flow and macrophyte decomposition as driving forces. Sediment P fractions and water total phosphorus (TP) were analyzed at 35 sampling points across three ice-on season stages, along with macrophyte TP content to assess debris contributions. Our findings reveal that phosphorus accumulation occurs during the ice-on season in the MDE lake, with an average TP content increase of 16 mg/kg. However, we observed a surprisingly small sediment nutrient accumulation ratio (ΔTP/ΔTN=0.006) compared to macrophyte nutrient levels before decomposition. Further analysis of the dominant species, Potamogeton pectinatus, indicates that a significant portion (55%) of macrophyte phosphorus is released before the ice-on season. This highlights the critical importance of timing macrophyte harvesting to precede the phosphorus leaching process, which has implications for lake management and ecosystem restoration efforts. Additionally, our research demonstrates similar transformations among different sediment fractions as previously reported. Macrophyte debris decomposition likely serves as the primary source of Residual P (Res-P) or TP accumulation. In addition, Ca-bound P (Ca-P) generally showed a decrease, which mainly caused by its transformation to Fe/Al-bound P (Fe/Al-P), Exchange-P (Ex-P), and sometimes to Res-P. However, we emphasize the significant impacts of flow dynamics on Ca-P transport and transformations. Its hydrodynamic action increases water dissolved oxygen, which accelerates the transformation of Ca-P to more easily released Fe/Al-P and Ex-P. Furthermore, hydrodynamic transport also leads to upstream Ca-P transport to downstream. This underscores the necessity of considering flow dynamics when estimating phosphorus variations and formulating phosphorus restoration strategies.

Effect of food on the pharmacokinetics and safety profiles of a new PARP inhibitor fuzuloparib capsules in healthy volunteers.

PURPOSE: This study assessed effect of food on pharmacokinetics (PK) and safety of fuzuloparib capsules. METHODS: A randomized, open-label, two-cycle, two-sequence, crossover clinical trial was conducted. 20 subjects were randomly assigned to 2 groups at a 1:1 ratio. The first group subjects were orally administered 150 mg fuzuloparib capsules under fasting condition in first dosing cycle. The same dose of fuzuloparib capsules were taken under postprandial state after a 7-day washout period. The second group was reversed. 3 ml whole blood was collected at each blood collection point until 72 h post dose. PK parameters were calculated. Furthermore, safety assessment was performed. RESULTS: The time to maximum concentration (Tmax) was prolonged to 3 h and maximum concentration (Cmax) decreased by 18.6% on high-fat diets. 90% confidence intervals (CIs) of geometric mean ratios (GMRs) for Cmax, area under the concentration-time curve from time zero to time t (AUC0-t), and area under the concentration-time curve extrapolated to infinity (AUC0-∞) after high-fat meal were 71.6-92.6%, 81.7-102.7% and 81.6-102.5%, respectively. All treatment-emergent adverse events (TEAEs) were grade 1; No serious adverse events (SAEs), serious unexpected suspected adverse reaction (SUSAR) or deaths were reported. CONCLUSION: Food decreased the absorption rate and slowed time to peak exposure of fuzuloparib capsules, without impact on absorption extent. Dosing with food was found to be safe for fuzuloparib capsules in this study. CLINICAL TRIAL REGISTRATION: This study was registered with chinadrugtrials.org.cn (identifier: CTR20221498).

Density functional theory study on the formation mechanism and electrical properties of two-dimensional electron gas in biaxial-strained LaGaO 3 /BaSnO 3 heterostructure.

The two-dimensional electron gas (2DEG) in BaSnO 3 -based heterostructure (HS) has received tremendous attention in the electronic applications because of its excellent electron migration characteristic. We modeled the n-type (LaO) + /(SnO 2 ) 0 interface by depositing LaGaO 3 film on the BaSnO 3 substrate and explored strain effects on the critical thickness for forming 2DEG and electrical properties of LaGaO 3 /BaSnO 3 HS system using first-principles electronic structure calculations. The results indicate that to form 2DEG in the unstrained LaGaO 3 /BaSnO 3 HS system, a minimum thickness of approximately 4 unit cells of LaGaO 3 film is necessary. An increased film thickness of LaGaO 3 is required to form the 2DEG for -3%-biaxially-strained HS system and the critical thickness is 3 unit cells for 3%-baxially-strained HS system, which is caused by the strain-induced change of the electrostatic potential in LaGaO 3 film. In addition, the biaxial strain plays an important role in tailoring the electrical properties of 2DEG in LaGaO 3 /BaSnO 3 HS syestem. The interfacial charge carrier density, electron mobility and electrical conductivity can be optimized when a moderate tensile strain is applied on the BaSnO 3 substrate in the ab-plane.

Circular RNA circIL21R promotes cervical cancer cells proliferation and migration by sponging the miR-1205/PTBP1 axis.

Increasing research has shown that the abnormal expression of circRNAs is closely related to tumorigenesis, apoptosis, and patient prognosis in cervical cancer. This study aimed to reveal the procancer role of circIL21R in cervical cancer and investigate its related molecular mechanisms. Bioinformatics analysis revealed that circIL21R promotes the progression of cervical cancer via the miR-1205/PTBP1 axis. CircIL21R expression was significantly greater in tumor tissue than in adjacent normal tissue, and higher circIL21R expression indicated shorter survival. We applied MTS assays, EdU assays, and Transwell assays to show that the overexpression of circIL21R promoted cervical cancer cell proliferation and invasion. Mechanistically, circIL21R promoted the expression of PTBP1 by sponging miR-1205. Moreover, rescue assays confirmed that regulating the expression of miR-1205 or PTBP1 could reverse the tumorigenic effect caused by circIL21R overexpression. In addition, circIL21R promoted the tumorigenesis of cervical cancer in vivo. In summary, our study demonstrated that circIL21R was highly expressed in cervical cancer and upregulated PTBP1 expression by acting as a ceRNA for miR-1205, making outstanding contributions to several malignant biological processes in cervical cancers, such as growth, proliferation, and invasion. CircIL21R is a potential biomarker for the diagnosis and treatment of cervical cancer.

Correction: Zhao et al. Hypermethylation of UCHL1 Promotes Metastasis of Nasopharyngeal Carcinoma by Suppressing Degradation of Cortactin (CTTN). Cells 2020, 9, 559.

In the original publication [...].

Metabolomics signature of blood pressure salt sensitivity and its link to cardiovascular disease: A dietary salt-intervention trial.

Individuals with a high degree of salt sensitivity (SS) have a greater risk of cardiovascular disease (CVD), but whether SS fosters CVD by influencing metabolomics homeostasis remains unclear. This study aimed to reveal the role of the SS-related metabolomics signature in the development of CVDs, based on the MetaSalt study, which was a dietary salt-intervention trial conducted at four centers in China in 2019. A total of 528 participants were recruited and underwent 3 days of baseline observations, a 10-day low-salt intervention, and a 10-day high-salt intervention. Plasma untargeted metabolomics, lipidomics, and BP measurements were scheduled at each stage. Participants were grouped into extreme SS, moderate SS, and salt-resistant (SR) individuals according to their BP responses to salt. Linear mixed models were used to identify SS-related metabolites and determine the relationship between the SS-related metabolomics signature and arterial stiffness. Mendelian randomization (MR) analyses were applied to establish the causal pathways among the SS-related metabolites, BP, and CVDs. Among the 713 metabolites, 467 were significantly changed after the high-salt intervention. Among them, the changes in 30 metabolites from the low-salt to the high-salt intervention differed among the SS groups. Of the remaining nonsalt-related metabolites, the baseline levels of 11 metabolites were related to SS. These 41 metabolites explained 23% of the variance in SS. Moreover, SS and its metabolomics signature were positively correlated with arterial stiffness. MR analyses demonstrated that the SS-related metabolites may affect CVD risk by altering BP, indicating that the increase in BP was the consequence of the changes in SS-related metabolites rather than the cause. Our study revealed that the metabolomics signature of SS individuals differs from that of SR individuals and that the changes in SS-related metabolites may increase arterial stiffness and foster CVDs. This study provides insight into understanding the biology and targets of SS and its role in CVDs.

Immunogenicity and safety of a recombinant Omicron BA.4/5-Delta COVID-19 vaccine ZF2202-A in Chinese adults.

BACKGROUND: The Recombinant Omicron BA.4/5-Delta COVID-19 Vaccine (ZF2202-A) is primarily designed for the Delta and Omicron BA.4/5 variants. Our objective was to assess the safety and immunogenicity of ZF2202-A in Chinese adults. METHODS: A total of 450 participants aged ≥ 18 years, who had completed primary or booster vaccination with a COVID-19 vaccine more than 6 months prior, were enrolled in this randomized, double-blind, active-controlled trial. Participants in the study and control groups were administered one dose of ZF2202-A and ZF2001, respectively. Immunogenicity subgroups were established in each group. RESULTS: At 14 days after vaccination, the seroconversion rates of Omicron BA.4/5, BF.7, and XBB.1 in the ZF2022-A group were 67.7 %, 58.6 %, and 62.6 %, with geometric mean titers (GMTs) of neutralizing antibodies at 350.2, 491.8, and 49.5, respectively. The main adverse reactions (ARs) were vaccination site pain, pruritus, fatigue, and asthenia in both the ZF2022-A group and ZF2001 group. CONCLUSIONS: The novel bivalent vaccine ZF2202-A demonstrated satisfactory immunogenicity and safety against Omicron variants as booster dose in adults with prior vaccination of COVID-19 vaccines.