Nasopharyngeal carcinoma (NPC) is endemic to southern China. Currently, its treatment and prognosis reply primarily on the TNM staging system and EBV-DNA testing; however, these parameters have limitations in fully capturing the tumor’s biological heterogeneity and the host's immunonutritional status. In recent years, systemic inflammatory and nutritional indices, such as the neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), prognostic nutritional index (PNI), and skeletal muscle index (SMI), have proven effective for assessing systemic inflammation and nutritional status. Accumulating evidence has demonstrated that these indicators are closely associated with treatment response, progression-free survival (PFS), and overall survival (OS) in NPC patients, and also show promise in predicting the efficacy of immune checkpoint inhibitors. This review aims to systematically elaborate on the prognostic value of these inflammatory and nutritional indicators in the context of NPC immunotherapy, to inform the development of individualized precision treatment strategies.

Objective:To explore the early diagnostic value and related mechanism of Lnc-IL7R/Jumonji domain-containing protein 3(Jmjd3)/keratinocyte growth factor(KGF)axis in inflammatory injury of acute respiratory distress syndrome(ARDS).Methods:① RT-qPCR and Western blot were used to detect Lnc-IL7R,Jmjd3,KGF mRNA and protein levels,as well as trimethyl-ation of histone H3 at lysine 27(H3K27)me3 protein level in serum of ARDS patients;ELISA was used to detect IL-1β,IL-6,TNF-α levels in serum.② Mitochondrial damage-associated molecular patterns(MTDs)was used to stimulate HBE cells and create traumatic ARDS cell model.HBE cells were divided into control group,model group(MTDs group),overexpression Lnc-IL7R group(Lnc-IL7R group),overexpression control group(NC group),overexpression Lnc-IL7R+overexpression Jmjd3 group(Lnc-IL7R+Jm-jd3 group).Chromatin immunoprecipitation(ChIP)was used to detect Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in pro-moter region;qRT-PCR and Western blot were used to detect Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,as well as H3K27me3 protein level.③ Injection of MTDs into tail vein of mice was used to create traumatic ARDS mice model.Eighty mice were divided into control group,MTDs group,Lnc-IL7R group,NC group and Lnc-IL7R+Jmjd3 group,with sixteen mice in each group.HE staining was used to detect pathological damage in lung tissue;ChIP and RT-qPCR were used to detect Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region and mRNA levels;ELISA was used to detect IL-1β,IL-6,TNF-α protein levels in BALF;Western blot was used to detect Jmjd3,KGF,H3K27me3 protein levels in lung tissue;immunohisto-chemical staining was used to detect surfactant protein C(SPC)and surfactant protein D(SPD)protein levels in lung tissue.Results:①Compared with healthy individuals,Lnc-IL7R,Jmjd3,KGF mRNA and protein levels,IL-1β,IL-6,TNF-α protein levels in serum of ARDS patients were significant increased,while H3K27me3 protein level was significant decreased(P<0.05).②Compared with control group,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,H3K27me3 protein level in HBE of MTDs group were significant decreased,while Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,Lnc-IL7R were significant increased(P<0.05);after overexpression of Lnc-IL7R,Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,KGF mRNA and protein levels,H3K27me3 protein level were significant increased,Jmjd3,IL-1β,IL-6,TNF-α mRNA and protein levels in lung tissue and BALF were significant decreased(P<0.05);overexpression of Jmjd3 could partially reverse the effects of overexpression of Lnc-IL7R on the above indicators(P<0.05).③Compared with Control group,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,H3K27me3 protein level in lung tissue of MTDs group were significant decreased,while Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,H3K27me3,SPC,SPD protein levels in lung tissue and BALF were significant increased(P<0.05);after overexpression of Lnc-IL7R,Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,KGF mRNA and protein levels,H3K27me3,SPC,SPD protein levels in lung tissue were significant increased,while Jmjd3,IL-1β,IL-6,TNF-α mRNA and protein levels in lung tissue and BALF were significant decreased(P<0.05);overexpression of Jmjd3 could partially reverse the effects of overexpression of Lnc-IL7R on the above indicators(P<0.05).Conclusion:Lnc-IL7R/Jmjd3/KGF axis participates in inflammation regulation and alveolar epithelial cell injury repair in ARDS by regulating histone methylation modifications in the promoter region.Lnc-IL7R/Jmjd3/KGF can be used for early diagnosis of ARDS.

Objective:To explore the early diagnostic value and related mechanism of Lnc-IL7R/Jumonji domain-containing protein 3(Jmjd3)/keratinocyte growth factor(KGF)axis in inflammatory injury of acute respiratory distress syndrome(ARDS).Methods:① RT-qPCR and Western blot were used to detect Lnc-IL7R,Jmjd3,KGF mRNA and protein levels,as well as trimethyl-ation of histone H3 at lysine 27(H3K27)me3 protein level in serum of ARDS patients;ELISA was used to detect IL-1β,IL-6,TNF-α levels in serum.② Mitochondrial damage-associated molecular patterns(MTDs)was used to stimulate HBE cells and create traumatic ARDS cell model.HBE cells were divided into control group,model group(MTDs group),overexpression Lnc-IL7R group(Lnc-IL7R group),overexpression control group(NC group),overexpression Lnc-IL7R+overexpression Jmjd3 group(Lnc-IL7R+Jm-jd3 group).Chromatin immunoprecipitation(ChIP)was used to detect Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in pro-moter region;qRT-PCR and Western blot were used to detect Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,as well as H3K27me3 protein level.③ Injection of MTDs into tail vein of mice was used to create traumatic ARDS mice model.Eighty mice were divided into control group,MTDs group,Lnc-IL7R group,NC group and Lnc-IL7R+Jmjd3 group,with sixteen mice in each group.HE staining was used to detect pathological damage in lung tissue;ChIP and RT-qPCR were used to detect Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region and mRNA levels;ELISA was used to detect IL-1β,IL-6,TNF-α protein levels in BALF;Western blot was used to detect Jmjd3,KGF,H3K27me3 protein levels in lung tissue;immunohisto-chemical staining was used to detect surfactant protein C(SPC)and surfactant protein D(SPD)protein levels in lung tissue.Results:①Compared with healthy individuals,Lnc-IL7R,Jmjd3,KGF mRNA and protein levels,IL-1β,IL-6,TNF-α protein levels in serum of ARDS patients were significant increased,while H3K27me3 protein level was significant decreased(P<0.05).②Compared with control group,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,H3K27me3 protein level in HBE of MTDs group were significant decreased,while Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,Lnc-IL7R were significant increased(P<0.05);after overexpression of Lnc-IL7R,Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,KGF mRNA and protein levels,H3K27me3 protein level were significant increased,Jmjd3,IL-1β,IL-6,TNF-α mRNA and protein levels in lung tissue and BALF were significant decreased(P<0.05);overexpression of Jmjd3 could partially reverse the effects of overexpression of Lnc-IL7R on the above indicators(P<0.05).③Compared with Control group,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,H3K27me3 protein level in lung tissue of MTDs group were significant decreased,while Lnc-IL7R,Jmjd3,KGF,IL-1β,IL-6,TNF-α mRNA and protein levels,H3K27me3,SPC,SPD protein levels in lung tissue and BALF were significant increased(P<0.05);after overexpression of Lnc-IL7R,Lnc-IL7R,Jmjd3,IL-1β,IL-6,TNF-α histone methylation levels in the promoter region,KGF mRNA and protein levels,H3K27me3,SPC,SPD protein levels in lung tissue were significant increased,while Jmjd3,IL-1β,IL-6,TNF-α mRNA and protein levels in lung tissue and BALF were significant decreased(P<0.05);overexpression of Jmjd3 could partially reverse the effects of overexpression of Lnc-IL7R on the above indicators(P<0.05).Conclusion:Lnc-IL7R/Jmjd3/KGF axis participates in inflammation regulation and alveolar epithelial cell injury repair in ARDS by regulating histone methylation modifications in the promoter region.Lnc-IL7R/Jmjd3/KGF can be used for early diagnosis of ARDS.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

The trillions of commensal microorganisms living in the gut lumen profoundly influence the physiology and pathophysiology of the liver through a unique gut-liver axis. Disruptions in the gut microbial communities, arising from environmental and genetic factors, can lead to altered microbial metabolism, impaired intestinal barrier and translocation of microbial components to the liver. These alterations collaboratively contribute to the pathogenesis of liver disease, and their continuous impact throughout the disease course plays a critical role in hepatocarcinogenesis. Persistent inflammatory responses, metabolic rearrangements and suppressed immunosurveillance induced by microbial products underlie the pro-carcinogenic mechanisms of gut microbiota. Meanwhile, intrahepatic microbiota derived from the gut also emerges as a novel player in the development and progression of liver cancer. In this review, we first discuss the causes of gut dysbiosis in liver disease, and then specify the pivotal role of gut microbiota in the malignant progression from chronic liver diseases to hepatobiliary cancers. We also delve into the cellular and molecular interactions between microbes and liver cancer microenvironment, aiming to decipher the underlying mechanism for the malignant transition processes. At last, we summarize the current progress in the clinical implications of gut microbiota for liver cancer, shedding light on microbiota-based strategies for liver cancer prevention, diagnosis and therapy.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

The bioactivity-guided isolation of potentially active natural products has been widely utilized in pharmaceutical discovery. In this study, by screening fungal extracts against coxsackievirus B3 (CVB3), three new aspochalasins, templichalasins A‒C (1‒3), along with six known aspochalasins (4‒9) were isolated from an active extract derived from the endophytic fungus Aspergillus templicola LHWf045. Compound 1 features a unique 5/6/5/7/5 pentacyclic ring system, while compounds 2 and 3 possess unusual 5/6/6/7 tetracyclic skeletons. Their structures were characterized through extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Additionally, we demonstrated that compound 4 can be readily converted into compounds 1‒3 under mild acidic conditions and proposed a plausible mechanism for this conversion. Bioactivity evaluation of compounds 1‒9 against CVB3 revealed the inhibitory effects of all compounds against the virus. Notably, compound 9 exhibited superior antiviral activity, surpassing the commercial drug ribavirin in selectivity index (SI) value.
Antiviral Agents/isolation & purification* ; Aspergillus/chemistry* ; Molecular Structure ; Enterovirus B, Human/drug effects* ; Endophytes/chemistry* ; Cytochalasins/isolation & purification* ; Drug Discovery ; Humans

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

The development of novel point-to-point drugs targeting resistance mechanisms is a critical and popular research field; nevertheless, success remains challenging. Therefore, given the short survival time and heightened expectations of patients with advanced NSCLC, the design of various combination therapy strategies––integrating preclinical, clinical, and real-world evidence (such as radiotherapy, chemotherapy, targeted therapy, antibody–drug conjugates, oncolytic viruses, and cell therapy)––may be a wise and practical choice to address the disease. Resistance to immunotherapy involves almost all cell types in the body, primarily cancer cells and T cells involved in immune surveillance. As a result of space limitations, this article focuses on the progress and challenges of various combined strategies for directly eliminating cancer cells. We also emphasize the realignment of treatment goals, shifting from primarily focusing on eliminating cancer cells (via chemotherapy and radiotherapy) to fully utilizing immune regulation to overcome resistance to immune checkpoint inhibitors.