Perioperative toripalimab plus neoadjuvant chemotherapy might improve outcomes in resectable esophageal cancer: an interim analysis of a phase III randomized clinical trial.

BACKGROUND: In the era of immunotherapy, neoadjuvant immunochemotherapy (NAIC) for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC) is used clinically but lacks of high-level clinical evidence. This study aimed to compare the safety and long-term efficacy of NAIC followed by minimally invasive esophagectomy (MIE) with those of neoadjuvant chemotherapy (NAC) followed by MIE. METHODS: A prospective, single-center, open-label, randomized phase III clinical trial was conducted at Henan Cancer Hospital, Zhengzhou, China. Patients were randomly assigned to receive either neoadjuvant toripalimab (240 mg) plus paclitaxel (175 mg/m2) + cisplatin (75 mg/m2) (toripalimab group) or paclitaxel + cisplatin alone (chemotherapy group) every 3 weeks for 2 cycles. After surgery, the toripalimab group received toripalimab (240 mg every 3 weeks for up to 6 months). The primary endpoint was event-free survival (EFS). The pathological complete response (pCR) and overall survival (OS) were key secondary endpoints. Adverse events (AEs) and quality of life were also assessed. RESULTS: Between May 15, 2020 and August 13, 2021, 252 ESCC patients ranging from T1N1-3M0 to T2-3N0-3M0 were enrolled for interim analysis, with 127 in the toripalimab group and 125 in the chemotherapy group. The 1-year EFS rate was 77.9% in the toripalimab group compared to 64.3% in the chemotherapy group (hazard ratio [HR] = 0.62; 95% confidence interval [CI] = 0.39 to 1.00; P = 0.05). The 1-year OS rates were 94.1% and 83.0% in the toripalimab and chemotherapy groups, respectively (HR = 0.48; 95% CI = 0.24 to 0.97; P = 0.037). The patients in the toripalimab group had a higher pCR rate (18.6% vs. 4.6%; P = 0.001). The rates of postoperative Clavien-Dindo grade IIIb or higher morbidity were 9.8% in the toripalimab group and 6.8% in the chemotherapy group, with no significant difference observed (P = 0.460). The rates of grade 3 or 4 treatment-related AEs did not differ between the two groups (12.5% versus 12.4%). CONCLUSIONS: The interim results of this ongoing trial showed that in resectable ESCC, the addition of perioperative toripalimab to NAC is safe, may improve OS and might change the standard treatment in the future.

Effect of sternocleidomastoid flap repair and endoscopic injection of emulsified adipose tissue stromal vascular fraction in the treatment of refractory cervical anastomotic leak contaminating mediastinum.

Mediastinal infection caused by anastomotic leak is hard to cure, mainly because the poor drainage at the site of mediastinal infection leads to persistent cavity infection, which in turn becomes a refractory mediastinal abscess cavity after minimally invasive esophagectomy (MIE)-McKeown. Herein, we explored sternocleidomastoid (SCM) muscle flaps and emulsified adipose tissue stromal vascular fraction containing adipose-derived stem-cells to address this issue. We studied 10 patients with esophageal cancer who underwent MIE-McKeown + 2-field lymphadenectomy and developed anastomotic and mediastinal leak and received new technology treatment in the Affiliated Cancer Hospital of Zhengzhou University from June 2018 to March 2022. The clinical data and prognosis of the patients were collected and analyzed. A total of 5 patients received this surgery, and no other complications occurred during the perioperative period. Among the 5 patients, 1 patient was partially cured, and 4 patients were completely cured. During the follow-up 3 months postoperatively, all these 5 patients could eat regular food smoothly, and no relapse of leak and mediastinal infection occurred. The new surgical method has achieved good results in the treatment of anastomotic leak. Compared with the traditional thoracotomy, it is a less invasive and feasible surgical approach, which can be used as a supplement to the effective surgical treatment of cervical anastomotic leak contaminating the mediastinum.

Mendelian randomization supports genetic liability to hospitalization for COVID-19 as a risk factor of pre-eclampsia.

Background: Pre-eclampsia and eclampsia are among the major threats to pregnant women and fetuses, but they can be mitigated by prevention and early screening. Existing observational research presents conflicting evidence regarding the causal effects of coronavirus disease 2019 (COVID-19) on pre-eclampsia risk. Through Mendelian randomization (MR), this study aims to investigate the causal effect of three COVID-19 severity phenotypes on the risk of pre-eclampsia and eclampsia to provide more rigorous evidence. Methods: Two-sample MR was utilized to examine causal effects. Summary-level data from genome-wide association studies (GWAS) of individuals of European ancestry were acquired from the GWAS catalog and FinnGen databases. Single-nucleotide polymorphisms associated with COVID-19 traits at p < 5 × -8 were obtained and pruned for linkage disequilibrium to generate instrumental variables for COVID-19. Inverse variance weighted estimates were used as the primary MR results, with weighted median and MR-Egger as auxiliary analyses. The robustness of the MR findings was also evaluated through sensitivity analyses. Bonferroni correction was applied to primary results, with a p < 0.0083 considered significant evidence and a p within 0.083-0.05 considered suggestive evidence. Results: Critical ill COVID-19 [defined as hospitalization for COVID-19 with either a death outcome or respiratory support, OR (95% CI): 1.17 (1.03-1.33), p = 0.020] and hospitalized COVID-19 [defined as hospitalization for COVID-19, OR (95% CI): 1.10 (1.01-1.19), p = 0.026] demonstrated suggestive causal effects on pre-eclampsia, while general severe acute respiratory syndrome coronavirus 2 infection did not exhibit a significant causal effect on pre-eclampsia. None of the three COVID-19 severity phenotypes exhibited a significant causal effect on eclampsia. Conclusions: Our investigation demonstrates a suggestive causal effect of genetic susceptibility to critical ill COVID-19 and hospitalized COVID-19 on pre-eclampsia. The COVID-19 severity exhibited a suggestive positive dose-response relationship with the risk of pre-eclampsia. Augmented attention should be paid to pregnant women hospitalized for COVID-19, especially those needing respiratory support.

A new, potential and safe neoadjuvant therapy strategy in epidermal growth factor receptor mutation-positive resectable non-small-cell lung cancer-targeted therapy: a retrospective study.

Background: Studies of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resectable non-small-cell lung cancer (NSCLC) have been conducted. The purpose of our study was to evaluate the benefits of osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC. Method: This retrospective study evaluated patients with EGFR mutations in exon 19 or 21 who received targeted therapy with osimertinib (80 mg per day) before surgery between January 2019 and October 2023 in Henan Cancer Hospital. Results: Twenty patients were evaluated, all of whom underwent surgery. The rate of R0 resection was 100% (20/20). The objective response rate was 80% (16/20), and the disease control rate was 95% (19/20). Postoperative pathological analysis showed a 25% (5/20) major pathological response rate and 15% (3/20) pathological complete response rate. In total, 25% (5/20) developed adverse events (AEs), and the rate of grades 3-4 AEs was 10% (2/20). One patient experienced a grade 3 skin rash, and 1 patient experienced grade 3 diarrhea. Conclusion: Osimertinib as neoadjuvant therapy for resectable EGFR-mutated NSCLC is safe and well tolerated. Osimertinib has the potential to improve the radical resection rate and prognosis.

Effects of obesity-related anthropometric indices and body composition on erectile dysfunction mediated by coronary artery disease: A Mendelian randomization study.

BACKGROUND: The causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction has not been established in previous observational studies. METHOD: We screened single nucleotide polymorphisms significantly associated with exposure from genome-wide association studies as instrumental variables (p < 5.0 × 10-8 ). The summary statistics for erectile dysfunction were collected from a genome-wide association study with a sample size of 223,805. Exposure and outcome populations included are of European ancestry. We used univariate and multivariate Mendelian randomization (i) to investigate the causal relationship between genetically predicted obesity-related anthropometric indicators/body composition and erectile dysfunction and (ii) to examine the mediating role of coronary artery disease. Mendelian randomization analysis was conducted using an inverse variance weighted method. A series of sensitivity analyses validated the results of the Mendelian randomization analysis. Causal estimates are expressed as odds ratios with 95% confidence intervals. RESULTS: Obesity-related anthropometric indicators/body composition were associated with an increased risk of erectile dysfunction in univariate Mendelian randomization analyses. For the 1-SD increase in body mass index, the odds ratio was 1.841 (95% confidence interval: 1.049-1.355, p = 0.006). For the 1-SD increase in waist circumference and hip circumference, the odds ratios were 1.275 (95% confidence interval: 1.101-1.478, p = 0.001) and 1.156 (95% confidence interval: 1.015-1.317, p = 0.009), respectively. The odds ratio for the 1-SD increase in whole body fat mass was 1.221 (95% confidence interval: 1.047-1.388, p = 0.002). For the 1-SD increase in leg fat percentage (left and right), the odds ratios were 1.256 (95% confidence interval: 1.006-1.567, p = 0.044) and 1.285 (95% confidence interval: 1.027-1.608, p = 0.028), respectively. For the 1-SD increase in leg fat mass (left and right), the odds ratios were 1.308 (95% confidence interval: 1.108-1.544, p = 0.001) and 1.290 (95% confidence interval: 1.091-1.524, p = 0.003), respectively. For the 1-SD increase in arm fat mass (left and right), the odds ratios were 1.269 (95% confidence interval: 1.113-1.447, p < 0.001) and 1.254, respectively. Multivariate Mendelian randomization analysis showed that after adjusting for coronary artery disease, some genetic predispositions to obesity-related anthropometric indicators and body composition were still associated with an increased risk of erectile dysfunction. Significant associations were found for waist circumference-erectile dysfunction (odds ratio: 1.218, 95% confidence interval: 1.036-1.432), leg fat percentage (left)-erectile dysfunction (odds ratio: 1.245, 95% confidence interval: 1.035-1.497), leg fat mass (left)-erectile dysfunction (odds ratio: 1.264, 95% confidence interval: 1.051-1.521), arm fat mass (right)-erectile dysfunction (odds ratio: 1.186, 95% confidence interval: 1.024-1.373), and arm fat mass (left)-erectile dysfunction (odds ratio: 1.17, 95% confidence interval: 1.018-1.360). Meanwhile, coronary artery disease mediated the effects of fat on erectile dysfunction, and the proportion of coronary artery disease-mediated cases ranged from 10% to 22%. CONCLUSION: There is a potential causal relationship between obesity-related anthropometric indicators/body composition and erectile dysfunction. Higher waist circumference, leg fat percentage, and arm fat mass may increase the risk of erectile dysfunction, and coronary artery disease partly mediates this overall effect. Understanding the causal relationship between obesity and erectile dysfunction and the mediating role of coronary artery disease may provide more information for erectile dysfunction intervention and prevention strategies.

The association between lipid parameters and erectile dysfunction: a two-sample Mendelian randomization and case-control study.

PURPOSE: Lipid parameters have been shown to have significant predictive value for cardiovascular disease, but few studies have evaluated their correlation with erectile dysfunction (ED) in young men. METHODS: The case-control study encompassed 186 young ED patients (ages 20-40) and 186 healthy controls. Lipid parameters, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), TC/HDL ratio, TG/HDL ratio, and LDL-C/HDL-C ratio, were assessed in all participants. The International Index of Erectile Function (IIEF-5) scores were collected for all participants to evaluate erectile status. Multivariate logistic regression analysis was utilized to appraise the association of lipid-related parameters with ED. Single-nucleotide polymorphisms (SNPs) significantly correlated with lipid parameters (TC, TG, LDL-C, HDL-C) were selected from genome-wide association studies (GWAS) as instrumental variables (IV) (P < 5.0 × 10-8). Summary data for ED was gathered from a GWAS with a sample size of (n = 17,353 cases/28,210 controls). The inverse variance weighted (IVW) method was employed as the primary mendelian randomization (MR) analysis method to assess causal effects. Causal estimates were represented as odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Results from the case-control study revealed that, when compared with the control group, levels of LDL-C, TG, UA, LDL-C/HDL-C, TG/HDL-C, and TC/HDL-C in the ED group were significantly elevated (P < 0.01), while HDL-C was significantly decreased (P < 0.01) in the ED group. Multivariate logistic regression analysis indicated LDL-C/HDL-C as a risk factor for both the incidence and severity of ED (P < 0.001). Two-sample MR analysis demonstrated no significant causal correlation between lipid parameters-LDL-C (OR, 0.98, 95% CI, 0.88-1.08, P = 0.616), HDL-C (OR, 1.07, 95% CI: 0.96-1.19, P = 0.249), TC (OR, 1.07, 95% CI, 0.96-1.18, P = 0.208), TG (OR, 0.98, 95% CI, 0.80-1.13, P = 0.579) -and an increased risk of ED (all P > 0.05). CONCLUSIONS: The case-control analysis ascertained a significant association between LDL-C, HDL-C, LDL-C/HDL-C, and ED and its severity. However, results from the MR study do not support a causal role of lipid parameters in ED.

Current status and prospects of diabetes mellitus induced erectile dysfunction: A bibliometric and visualization study.

Background: The prevalence of diabetes mellitus-induced erectile dysfunction (DMED) has recently increased, which has prompted numerous DMED studies. Here, we conduct a bibliometric analysis of relevant literature in the field of DMED and to discuss the research hotspots and future development directions. Methods: The Web of Science Core Collection database was searched for literature on DMED, and literature characterization including the number of articles, journals, countries/regions, institutions, authors, keywords, and other information was performed using VOS viewer and CiteSpace software. In addition, Pajek software was used for visual map adjustment, and GraphPad Prism was used to generate line graphs. Results: A total of 804 articles concerning DMED were included in this study. The Journal of Sexual Medicine issued the most documents(92 articles). The United States and China were in the leading position in the field of DMED research, and cross-institutional collaboration on DMED research worldwide needs to be further strengthened. Ryu JK were the authors with the highest number of documents issued (22 articles) while Bivalacqua TJ was the author with the most co-citated(249 co-citated). The keywords analysis shows that the main research hotspots in the field of DMED were mechanism discussions and disease treatment and management. Conclusions: Global research on DMED is expected to increase further. The investigation of the mechanism of DMED and the exploration of new therapeutic means and targets are the focus of future research.

CircSCN8A suppresses malignant progression and induces ferroptosis in non-small cell lung cancer by regulating miR-1290/ACSL4 axis.

Circular RNAs (CircRNAs) are reported to exert vital regulatory roles in the occurrence and development of various human malignancies, including non-small cell lung cancer (NSCLC). Bioinformatics methods identified the down-regulation of circSCN8A (circBase ID: hsa_circ_0026337) in NSCLC tissues. However, its biological functions and molecular mechanisms in NSCLC remain unknown. In this study, we found that circSCN8A expression was down-regulated in NSCLC tissues and cells. Low circSCN8A expression was positively associated with aggressive clinicopathological characteristics and poor prognosis in NSCLC patients. CircSCN8A suppressed cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) in vitro and blocked tumor growth in vivo. Moreover, circSCN8A promoted cell ferroptosis in NSCLC. Mechanistically, circSCN8A acted as a competing endogenous RNA (ceRNA) by sponging miR-1290 to enhance the expression of long-chain acyl-CoA synthetase-4 (ACSL4). Furthermore, the knockdown of ACSL4 or overexpression of miR-1290 reversed the effect of circSCN8A on facilitating ferroptosis and inhibiting cell proliferation and metastasis. In summary, circSCN8A represses cell proliferation and metastasis in NSCLC by regulating the miR-1290/ACSL4 axis to induce ferroptosis. Thus, circSCN8A may represent a promising therapeutic target against NSCLC.

[Short-term impact of COVID-19 on semen parameters: A retrospective study].

OBJECTIVE: To observe the changes in semen parameters after COVID-19 infection and clarify its impact on male fertility. METHODS: We collected semen samples from 82 male patients infected with COVID-19 in the past 2 months (the infection group) and 14 normal healthy men (the control group), obtained their semen parameters and compared them between the two groups before and after COVID-19 infection. RESULTS: There were no statistically significant differences in the baseline semen parameters between the infection and control groups (P > 0.05), nor in the semen volume within the infection group before and after infection (P > 0.05). Compared with the normal controls, the patients showed significantly decreased sperm concentration, total sperm count, percentage of progressively motile sperm, sperm motility and percentage of morphologically normal sperm after COVID-19 infection (P < 0.05), which were reduced even more significantly in those with than in those without fever during infection (P < 0.05). No statistically significant difference was observed in the semen quality of the patients with normal body temperature before and after COVID-19 infection (P > 0.05). Spearman correlation analysis showed no significant correlation between semen parameters and the severity of fever during infection (P > 0.05). CONCLUSION: COVID-19 infection decreases the semen quality of the patient, and fever during infection is a significant influencing factor. The severity of fever, however, is not related to the reduction of semen quality.

[Elaboration of male infertility from the theory of classical prescription theory].

Male infertility is a common condition in urology with complex etiology. This article explores the understanding of male infertility through the theories of traditional Classic prescriptions based on the text "Jin Gui Yao Lue". The aim is to provide references for clinical diagnosis and treatment of male infertility.

[The application of acupuncture in varicocele infertility based on " Visceral Collateral " theory].

The occurrence of varicocele infertility can be attributed to the small and flexural spermatic plexus which constitutes the main structure of spermatic cord.Obstruction of blood circulation, stagnation of qi and blood, ultimately leading to infertility. The spermatic plexus ' physiological and pathological symptoms are consistent with the theory of visceral collateral. Based on the theory of visceral collaterals, the varicocele infertility caused by stagnation of liver collateral and deficiency of kidney collateral. And the acupuncture is used to directly act on the relevant points on the meridians, so as to dredge the meridians, strengthen the healthy and expel the evil, and harmonize the yin and yang of visceral, which is more in line with the therapeutic principle of " unblocking the meridians " for collateral diseases. For varicocele infertility caused by liver meridian stasis, it can regulate the liver meridian Chong Ren, eliminate blood stasis and promote stagnation, and be combined with LR3, LI4, GB34, SP6, CV3. For varicocele infertility caused by kidney deficiency and meridian syndrome, it can tonify the kidney meridian Du Yang, warm and disperse the essence, and mainly focus on GV4, CV4, KI3, BL23 and BL43.

Arbuscular Mycorrhizal Fungi Alleviate Low Phosphorus Stress in Maize Genotypes with Contrasting Root Systems.

Soil available phosphorus (P) is one of the main factors limiting plant growth and yield. This study aimed to determine the role of arbuscular mycorrhizal fungi (AMF) in P-use efficiency in two maize genotypes with contrasting root systems in response to low P stress. Maize genotypes small-rooted Shengrui 999 and large-rooted Zhongke 11 were grown in rhizoboxes that were inoculated with or without AMF (Funneliformis mosseae) under low P (no added P) or optimal P (200 mg kg-1) for 53 days. Low P stress significantly inhibited shoot and root growth, photosynthesis, tissue P content, and root P concentration in both genotypes. Shengrui 999 was more tolerant to P stress with less reduction of these traits compared to Zhongke 11. Shengrui 999 had a higher AMF infection rate than Zhongke 11 at both P levels. Under P deficit, inoculation with AMF significantly promoted plant growth and P uptake in both genotypes with more profound effects seen in Zhongke 11, whilst Shengrui 999 was more dependent on AMF under optimal P. Low P stress inhibited the growth and physiological attributes of both genotypes. The small-rooted Shengrui 999 was more tolerant to low P than Zhongke 11. Inoculation with AMF alleviates low P stress in both genotypes with a more profound effect on Zhongke 11 at low P and on Shengrui 999 at high P conditions.

Interface Engineering with Quaternary Ammonium-Based Ionic Liquids toward Efficient Blue Perovskite Light-Emitting Diodes.

Perovskite light-emitting diodes (PeLEDs) have become a hot research topic in recent years and can now achieve an external quantum efficiency (EQE) of over 22% for green and red devices. However, the efficiency of blue PeLEDs, which are essential for display applications, lags far behind their green and red counterparts. The interface of the PeLEDs has a critical influence on the carrier transport and exciton recombination dynamics, and interface engineering is considered to be an effective strategy to improve the device performance. Herein, quaternary ammonium-based ionic liquids serve as an interfacial modification layer to significantly improve the device efficiency and stability. The interaction of quaternary ammonium cations with Pb(Br/Cl)6 octahedra promotes nucleation sites, which significantly improves the morphology of perovskite films and reduces the formation of defects in films. In addition, ion migration is also effectively suppressed in the device. As a result, with tributylmethylammonium bromide (TMAB) used as the interface layer, the EQE of the device is successfully increased from 3.5 to 6.7%, and the operational stability with a half-lifetime (T50) is increased by over 12 times. Our work provides a new class of interface modification materials toward high-performance blue PeLEDs.

Lattice strain modulation toward efficient blue perovskite light-emitting diodes.

The successful implementation of perovskite light-emitting diodes (PeLEDs) in advanced displays and lighting has proven to be challenging because of the inferior performance of blue devices. Here, we point out that a strained system would lead to the quasi-degenerate energy state to enhance the excited-state transition due to the formation of double-polarized transition channel. The tensile strained structure also brings about a synergetic control of the carrier dynamics in virtue of lattice structure deformation and reduced dimensional phase regulation to promote carrier population in large bandgap domains and to realize near-unit energy transfer from the large bandgap phases to the emitter phases. Accordingly, high external quantum efficiencies of 14.71 and 10.11% are achieved for the 488- and 483-nanometer PeLEDs. This work represents a versatile strategy using a strained system to achieve enhanced radiative emission for the development of efficient PeLEDs.

Case Report: A good response to furmonertinib second-line treatment of an advanced lung adenocarcinoma patient with a rare EGFR exon 20 N771_P772insH mutation: A case report and literature review.

Background: Lung adenocarcinoma with the classical EGFR 19 deletion and exon 21 L858R point mutations has exhibited good responses to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) treatment. However, the sensitivity of uncommon EGFR exon 20 insertion mutation to third-generation EGFR-TKIs has not been determined. Although emerging targeted therapies for EGFR exon 20 insertion mutation have been reported in recent years, such patients still have a poorer prognosis than those with typical or wild-type EGFR mutations. Case summary: Here, we report the case of a 57-year-old man with advanced non-small cell lung cancer (NSCLC) with a rare EGFR exon 20 N771_P772insH mutation. The patient was treated with furmonertinib as second-line therapy. Although his pleural effusion was more than before that during treatment, various examination results showed that the pleural effusion was closely related to hypoproteinemia; thus, local progression was not considered. His cough was significantly alleviated, and the dose was well tolerated. The patient was evaluated for a remarkable progression-free survival (PFS) of 10.0 months, a duration of response (DOR) of 8.0 months, and an overall survival (OS) of 22.0 months, which had not previously been achieved. Conclusion: The present study indicated that furmonertinib might be a good treatment option for first-line progressive NSCLC patients with EGFR exon 20 insertion mutation.

Bibliometrics and visualisation analysis of literature on varicocele: From 2002 to 2021.

Varicocele is a common disease in men, with a global incidence of approximately 25%. A comprehensive and systematic analysis of the knowledge map on it will help in assessing frontier research and identify knowledge gaps. In total, 4103 articles published from 2002 to 2021 in 1066 journals were included. They represent the current research status worldwide, potential hotspots and future research directions. In the past decades, the number of publications and citations of varicocele-related studies have increased steadily. Academic institutions in the United States played a leading role in varicocele research. The country, institution, journal and author with the most publications were the United States (779), Cleveland Clinic Foundation (132), Andrologia (246) and Agarwal A (106), respectively. The most frequently used keywords were Varicocele (1620), Male Infertility (944), Varicocelectomy (288), Testis (245), Sperm (166), Oxidative Stress (144), Azoospermia (119), Semen Analysis (118), Laparoscopy (116) and Adolescent (97). Currently, the main focus of current varicocele research is its surgical treatment method and effect on sperm quality. The frontier research hotspot is the specific mechanism of varicocele-induced decrease in sperm quality.

Current status and future perspectives of immune checkpoint inhibitors in extensive-stage small cell lung cancer.

Small-cell lung cancer (SCLC) is a type of neuroendocrine neoplasms with high aggressiveness and poor prognosis. Chemotherapy has been the standard first-line therapy for SCLC over the past several decades. In recent years, results of randomized phase III CASPIAN and IMpower-133 trials indicated that the combination of immune checkpoint inhibitors (ICIs) with platinum-etoposide chemotherapy improved the overall survival (OS) of patients with extensive stage small-cell lung cancer (ES-SCLC), which has transformed the treatment model for ES-SCLC. ICIs combined with chemotherapy has become the new first-line standard treatment of ES-SCLC with the latest research results from CASPIAN and ASTRUM-005 studies. This review summarizes the recent progress of ICIs in the treatment of ES-SCLC and expounds the mode and efficacy of immunotherapy for ES-SCLC. Future research focused on exploring basic SCLC biology and identifying novel predictive biomarkers in response to ICIs in ES-SCLC is essential. Double-ICIs treatment strategies, bispecific antibodies, and ICIs combined with other therapies, such as chemotherapy, radiotherapy, and targeted therapy, represent a new modality and show great promise for the treatment of ES-SCLC, which should achieve greater therapeutic effects through multiple synergistic mechanisms.

Older patients more likely to die from cancer-related diseases than younger with stage IA non-small cell lung cancer: a SEER database analysis.

Background: Various reports showed some conflicting data on survival at different ages. This study aimed to investigate the main cause of death in older patients with lung cancer and to perform a comparison with younger patients in order to observe the differences between these two cohorts. Methods: Outcomes of patients with stage IA non-small cell lung cancer (NSCLC) ≤3 cm who underwent lobectomy without induction therapy in the Surveillance, Epidemiology, and End Results-18 (SEER-18; January 2004 to December 2016) database were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis. Results: A total of 16,672 eligible NSCLC cases were found in the SEER database. The number of patients aged ≤60, 61-70, and ≥71 years was 3,930, 6,391, and 6,351, respectively. Among these patient groups, 527 (13.4%), 1,018 (15.9%), and 1,235 (19.4%) died of lung cancer during follow-up, while 357 (9.1%), 964 (15.1%) and 1,579 (25.2%) died of non-lung cancer diseases, respectively. The overall survival (OS) and lung cancer-specific survival (LCSS) rates of younger patients showed a significant survival advantage over older patients. After propensity-score matching (PSM) of patients aged ≤60 and ≥71 years using a ratio of 1:1, we found that 403 (12.9%) and 584 (18.7%) patients in the ≤60 and ≥71 years age groups died of lung cancer, respectively. The OS and LCSS rates of younger patients still exhibited a significant survival advantage over older patients. Conclusions: Older patients with stage IA NSCLC have a worse prognosis compared with younger patients. Also, cancer-related causes were more frequent in older patients than non-cancer-related causes.

The Sequence of Chemotherapy and Toripalimab Might Influence the Efficacy of Neoadjuvant Chemoimmunotherapy in Locally Advanced Esophageal Squamous Cell Cancer-A Phase II Study.

Background: There is no standard neoadjuvant therapy for locally advanced esophageal cancer in China. The role of neoadjuvant chemotherapy plus immunotherapy for locally advanced esophageal cancer is still being explored. Methods: This open-label, randomized phase II study was conducted at a single center between July 2019 and September 2020; 30 patients with locally advanced esophageal squamous cell carcinoma (ESCC) (T3, T4, or lymph-node positive) were enrolled. Patients were randomized according to the enrollment order at a 1:1 ratio to receive chemotherapy on day 1 and toripalimab on day 3 (experimental group) or chemotherapy and toripalimab on day 1 (control group). The chemotherapeutic regimen was paclitaxel and cisplatin. Surgery was performed 4 to 6 weeks after the second cycle of chemoimmunotherapy. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was safety and disease-free survival. Results: Thirty patients completed at least one cycle of chemoimmunotherapy; 11 in the experimental group and 13 in the control group received surgery. R0 resection was performed in all these 24 patients. Four patients (36%) in the experimental group and one (7%) in the control group achieved pCR. The experimental group showed a statistically non-significant higher pCR rate (p = 0.079). PD-L1 combined positive score (CPS) examination was performed in 14 patients; one in the control group had a PD-L1 CPS of 10, and pCR was achieved; the remaining 13 all had ≤1, and 11 of the 13 patients received surgery in which two (in the experimental group) achieved pCR. Two patients endured ≥grade 3 adverse events, and one suffered from grade 3 immune-related enteritis after one cycle of chemoimmunotherapy and dropped off the study. Another patient died from severe pulmonary infection and troponin elevation after surgery. Conclusions: Although the primary endpoint was not met, the initial results of this study showed that delaying toripalimab to day 3 in chemoimmunotherapy might achieve a higher pCR rate than that on the same day, and further large-sample clinical trials are needed to verify this. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03985670.

Wu-Zi-Yan-Zong-Wan protects mouse blood-testis barrier from Tripterygium wilfordii Hook. f. multiglycoside-induced disruption by regulating proinflammatory cytokines.

ETHNOPHARMACOLOGICAL RELEVANCE: Wu-Zi-Yan-Zong-Wan (WZYZW) is a classical traditonal Chinese herbal formula and a Chinese patent medicine used to treat male infertility. However, the chemical components of WZYZW and its mechanism are not yet fully clarified. AIM OF THE STUDY: The purpose of this study is to observe the effect and underlying mechanism of WZYZW on ameliorating blood-testis barrier (BTB) dysfunction in mice with spermatogenic dysfunction induced by administration of Tripterygium wilfordii Hook. f. multiglycosides (GTW). MATERIALS AND METHODS: WZYZW was administered by gavage to mice with GTW-induced spermatogenic dysfunction (kidney essence deficiency pattern) for 40 days. Testis tissues were obtained for subsequent histopathological analysis. Biotin tracing was used to evaluate the permeability of Sertoli cell tight junctions. The levels of proinflammatory cytokines including interleukin (IL)-6, IL-17A, IL-1α and tumor necrosis factor (TNF)-α were analyzed by ELISA. The expression levels of proteins related to tight junction including ZO-1, JAM-A and occludin were analyzed by western blotting. The ultrastructures of tight junctions were observed by transmission electron microscopy. RESULTS: WZYZW ameliorated GTW-induced testicular spermatogenic dysfunction. Levels of IL-6, IL-17A, IL-1α, and TNF-α in the groups receiving low, medium, and high doses of WZYZW decreased in a dose-dependent manner. WZYZW impeded a biotin tracer from permeating the BTB, protecting its integrity in GTW-treated mice. In addition, our results showed no significant changes in the protein expressions of ZO-1, JAM-A, and occludin after WZYZW administration compared with the GTW group. Meanwhile, WZYZW exhibited a linear arrangement and restored the typical "sandwich" structure of BTB. No acute poisoning incidences were observed in all groups during the experiment. CONCLUSIONS: Our findings demonstrate that WZYZW may ameliorate some GTW-induced BTB dysfunction, possibly by regulating proinflammatory cytokine levels. In vitro studies on the regulation of BTB permeability by WZYZW and its active components are further required.