Development of postoperative bronchopleural fistula after neoadjuvant immunochemotherapy in non-small cell lung cancer: case reports and review of the literature.

BACKGROUND: The advent of immune checkpoint inhibitors has dramatically changed the treatment paradigm for advanced non-small-cell lung cancer (NSCLC). Due to the complexity and diversity of stage III disease, the inclusion of immune checkpoint inhibitors (ICIs) in neoadjuvant treatment regimens is also required. However, immune-related adverse events (irAEs) limit the application of ICIs to a certain extent. Bronchopleural fistula (BPF) is a serious and fatal complication after pneumonectomy that is rarely reported, especially in patients who accept neoadjuvant immunotherapy or chemoimmunotherapy. CASE PRESENTATION: Herein, we reported four patients with postoperative BPF who received a neoadjuvant regimen of sintilimab plus chemotherapy. Postoperative BPF occurred in the late stage in three patients; one patient underwent bronchoscopic fistula repair, and the fistula was closed well after surgery, and the other two patients gradually recovered within 1-2 months after symptomatic treatment with antibiotics. One patient with BPF after left pneumonectomy died of respiratory failure due to pulmonary infection. We also reviewed the literature on the development of postoperative BPF in patients receiving immuno-neoadjuvant therapy to discuss the clinical process further, postoperative pathological changes, as well as risk factors of BPF patients. CONCLUSIONS: Central type lung cancer with stage III may be the risk factors of BPF in cases of neoadjuvant immunochemotherapy for lung cancers patients.

Small cell lung cancer with dermatomyositis: a case report.

Dermatomyositis represents an autoimmune disorder characterized by notable skin and muscular manifestations. The annual incidence of dermatomyositis stands at approximately (5~10)/1 million individuals. Notably, patients with malignant tumors exhibit an elevated risk of developing dermatomyositis compared to the general population. However, in cases where dermatomyositis co-occurs with malignancy, the efficacy of hormone therapy alone tends to be suboptimal. Moreover, reports addressing the correlation between tumor treatment and the management of dermatomyositis are scarce. A 60-year-old male patient presented with dermatomyositis, initially manifesting through symptoms such as rash, muscle weakness, and dysphagia. Despite undergoing standard hormone therapy, there was no discernible improvement in the dermatomyositis symptoms. Considering the patient's concomitant troublesome cough, further investigations were conducted, including CT, PET-CT, and pathological biopsy. These assessments confirmed the diagnosis of limited-stage small cell lung cancer (T1cN3M0 IIIB). Notably, in this patient, dermatomyositis was suspected to be a paraneoplastic syndrome associated with small cell lung cancer. Standard chemotherapy and radiotherapy were employed to treat the small cell lung cancer, resulting in partial remission after two treatment cycles. As the malignancy regressed, a notable improvement in dermatomyositis symptoms was observed, subsequently leading to a gradual reduction in the prescribed hormone dosage. In conclusion, we present a comprehensive case study of dermatomyositis as a paraneoplastic syndrome throughout the treatment process. The response to tumor therapy coincided with the amelioration of dermatomyositis symptoms. Therefore, diligent malignancy screening is imperative for patients diagnosed with dermatomyositis.

The emerging roles and mechanism of N6-methyladenosine (m6A) modifications in urologic tumours progression.

Prostate cancer (PCa), bladder cancer (BC), and renal cell cancer (RCC) are the most common urologic tumours in males. N6-methyladenosine (m6A), adenosine N6 methylation, is the most prevalent RNA modification in mammals. Increasing evidence suggests that m6A plays a crucial role in cancer development. In this review, we comprehensively analyzed the influence of m6A methylation on Prostate cancer, bladder cancer, and renal cell cancer and the relationship between the expression of relevant regulatory factors and their development and occurrence, which provides new insights and approaches for the early clinical diagnosis and targeted therapy of urologic malignancies.

OIP5-AS1 accelerates apoptosis of hippocampal neurons in cell models of epilepsy by modulating MiR-128-3p/BAX axis.

As a chronic neurological disorder, epilepsy (EP) is characterized with recurrent and unexplained epileptic seizures. Mounting evidence demonstrated that long non-coding RNAs (lncRNAs) are associated with EP. This paper intended to study the role and mechanisms of OIP5 antisense RNA 1 (OIP5-AS1) in EP.Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze relative RNA level. Cell viability was unclosed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) experiment. The activity of caspase-3/9 was investigated to measure cell apoptosis. Subcellular fractionation assay was carried out to uncover the subcellular location. RNA pulldown, luciferase reporter and RNA-binding protein immunoprecipitation (RIP) assays were applied to disclose the underlying mechanisms of OIP5-AS1.Result shows OIP5-AS1 is overexpressed in EP cell models and mainly located in cytoplasm. OIP5-AS1 knockdown impairs cell apoptosis in EP cell models. OIP5-AS1 regulates cell apoptosis in EP cell models by binding to microRNA-128-3p (miR-128-3p). OIP5-AS1 interacts with miR-128-3p to overexpress BCL2-Associated X (BAX), thereby modulating cell apoptosis in EP cell models.OIP5-AS1 accelerates apoptosis of hippocampal neurons in cell models of EP by modulating miR-128-3p/BAX axis. Investigating OIP5-AS1/miR-128-3p/BAX regulatory axis can contribute to deepening the understanding of EP.

Extended π-Conjugative Carbon Nitride for Single 1064 nm Laser-Activated Photodynamic/Photothermal Synergistic Therapy and Photoacoustic Imaging.

The synergetic photodynamic/photothermal therapy, activated via a single-second near-infrared (NIR-II) laser and guided by photoacoustic imaging (PAI), receives significant attention for precise in vivo therapy. However, due to the lack of a corresponding theranostic agent, it faces a great challenge for practical clinical implementation. Here, we present a single diagnostic and therapeutic nanoplatform named carbon nitride nanoparticles (CN-NPs) for efficient NIR-II PAI-guided photodynamic therapy (PDT)/photothermal therapy (PTT). The CN-NPs were obtained by incorporating an aromatic compound (PTCDA) with a large π-structure into melem by high-temperature polymerization. The absorption of the obtained CN-NPs was significantly enhanced compared with pristine melem. Under 1064 nm laser illumination, sufficient reactive oxygen species (ROS) generated by CN-NPs could reduce the mitochondrial membrane potential. Moreover, the CN-NPs exhibited an efficient PTT effect through improved photothermal stability and high photo-to-heat conversion efficiency (47.6%). We were also able to monitor the accumulation and metabolism of CN-NPs in vivo of mice in real time using PAI. The in vivo experiments proved that the CN-NPs could inhibit tumor growth and recurrence completely under 1064 nm. Thus, the proposed innovative strategy would open a new avenue to explore and construct NIR-II responsive nanoplatforms with enhanced performance and safety for multimodal phototheranostics.

Dephosphorylation of LjMPK6 by Phosphatase LjPP2C is Involved in Regulating Nodule Organogenesis in Lotus japonicus.

The mitogen-activated protein kinase (MAPK) LjMPK6 is a phosphorylation target of SIP2, a MAPK kinase that interacts with SymRK (symbiosis receptor-like kinase) for regulation of legume-rhizobia symbiosis. Both LjMPK6 and SIP2 are required for nodulation in Lotus japonicus. However, the dephosphorylation of LjMPK6 and its regulatory components in nodule development remains unexplored. By yeast two-hybrid screening, we identified a type 2C protein phosphatase, LjPP2C, that specifically interacts with and dephosphorylates LjMPK6 in vitro. Physiological and biochemical assays further suggested that LjPP2C phosphatase is required for dephosphorylation of LjMPK6 in vivo and for fine-tuning nodule development after rhizobial inoculation. A non-phosphorylatable mutant variant LjMPK6 (T224A Y226F) could mimic LjPP2C functioning in MAPK dephosphorylation required for nodule development in hairy root transformed plants. Collectively, our study demonstrates that interaction with LjPP2C phosphatase is required for dephosphorylation of LjMPK6 to fine tune nodule development in L. japonicus.

An MAP kinase interacts with LHK1 and regulates nodule organogenesis in Lotus japonicus.

Symbiosis receptor-like kinase (SymRK) is a key protein mediating the legume-Rhizobium symbiosis. Our previous work has identified an MAP kinase kinase, SIP2, as a SymRK-interacting protein to positively regulate nodule organogenesis in Lotus japonicus, suggesting that an MAPK cascade might be involved in Rhizobium-legume symbiosis. In this study, LjMPK6 was identified as a phosphorylation target of SIP2. Stable transgenic L. japonicus with RNAi silencing of LjMPK6 decreased the numbers of nodule primordia (NP) and nodule, while plants overexpressing LjMPK6 increased the numbers of nodule, infection threads (ITs), and NP, indicating that LjMPK6 plays a positive role in nodulation. LjMPK6 could interact with a cytokinin receptor, LHK1 both in vivo and in vitro. LjMPK6 was shown to compete with LHP1 to bind to the receiver domain (RD) of LHK1and to downregulate the expression of two LjACS (1-aminocyclopropane-1-carboxylic acid synthase) genes and ethylene levels during nodulation. This study demonstrated an important role of LjMPK6 in regulation of nodule organogenesis and ethylene production in L. japonicus.

Skin Erythema, Pigmentation and Hydration Kinetics after Ultraviolet Radiation-induced Photodamage in Southern Chinese Women.

Although there have been some studies about changes of skin erythema and pigmentation following ultraviolet radiation in other races, the relevant data in Chinese have never been achieved. Thus, we evaluated the long-time course of skin erythema, pigmentation and hydration changes after different doses of solar-simulated ultraviolet (SSUV) irradiation in 26 Chinese women for 168 days. The erythema index increased abruptly and peaked during 3 days of SSUV exposure, then slowly returned to the baseline level starting at day 7 and completely recovered during 168-day course of this study only in one minimal erythema doses (MED) SSUV irradiation. The melanin index started to slowly increase at day 3 of SSUV exposure, peaking at day 14 and gradually returned to the baseline level thereafter, but did not return to the baseline level during 168-day course in all doses. Skin hydration slowly declined at day 3 of exposure, hitting the lowest point at day 7, then slowly recovered starting at day 14 and completely returned to the baseline level at day 28 only in 1.5MED. These results will serve as baseline data on Chinese skin and provide useful references for the treatment of serious skin photodamage in Chinese.

Variant rs2237892 of KCNQ1 Is Potentially Associated with Hypertension and Macrovascular Complications in Type 2 Diabetes Mellitus in A Chinese Han Population.

KCNQ1 has been identified as a susceptibility gene of type 2 diabetes mellitus (T2DM) in Asian populations through genome-wide association studies. However, studies on the association between gene polymorphism of KCNQ1 and T2DM complications remain unclear. To further analyze the association between different alleles at the single nucleotide polymorphism (SNP) rs2237892 within KCNQ1 and TD2M and its complications, we conducted a case-control study in a Chinese Han population. The C allele of rs2237892 variant contributed to susceptibility to T2DM (odds ratio [OR], 1.45; 95% confidence interval [CI], 1.20-1.75). Genotypes CT (OR, 1.97; 95% CI, 1.24-3.15) and CC (OR, 2.49; 95% CI, 1.57-3.95) were associated with an increased risk of T2DM. Multivariate regression analysis was performed with adjustment of age, gender, and body mass index. We found that systolic blood pressure (P=0.015), prevalence of hypertension (P=0.037), and risk of macrovascular disease (OR, 2.10; CI, 1.00-4.45) were significantly higher in subjects with the CC genotype than in the combined population with genotype either CT or TT. Therefore, our data support that KCNQ1 is associated with an increased risk for T2DM and might contribute to the higher incidence of hypertension and macrovascular complications in patients with T2DM carrying the risk allele C though it needs further to be confirmed in a larger population.

Effects of mitochondrial haplogroup N9a on type 2 diabetes mellitus and its associated complications.

A case-control study was conducted with the aim of identifying the predominant haplogroups associated with type 2 diabetes mellitus (T2DM) and its complications. In addition, the role of N9a in T2DM risk and complications was analyzed. Sequencing of the entire mitochondrial DNA was conducted in 235 patients and 244 controls in cohort 1, and six haplogroups (F, B4, D4, D5, M8a and N9a) associated with T2DM were classified. The frequency of N9a was further determined in cohort 2 (440 patients and 244 controls) and examined in two combined cohorts, including 675 patients with T2DM and 649 non-diabetic controls. Multivariate logistic regression analysis and association analysis were performed to investigate the association between genotypes, T2DM and diabetic nephropathy. M8a [P=0.011; odds ratio (OR), 3.49; 95% confidence interval (CI), 1.26-9.69] and haplogroup N9a (P=0.023; OR, 2.60; 95% CI, 1.11-6.05) were associated with an increased risk of T2DM. The frequency of N9a was higher in T2DM patients compared with that in the controls (6.2% vs. 4.3%) and associated with a mild risk (P=0.10; OR, 1.51; 95% CI, 0.92-2.49). N9a was significantly associated with an increased risk of diabetic nephropathy (P=0.024; OR, 2.15; 95% CI, 1.11-4.19). Previous findings of N9a being protective against T2DM were not replicated in the present study, although this haplogroup was associated with an increased risk of diabetic nephropathy.

The tRNA(Gly) T10003C mutation in mitochondrial haplogroup M11b in a Chinese family with diabetes decreases the steady-state level of tRNA(Gly), increases aberrant reactive oxygen species production, and reduces mitochondrial membrane potential.

Mitochondrial diabetes originates mainly from mutations located in maternally transmitted, mitochondrial tRNA-coding genes. In a genetic screening program of type 2 diabetes conducted with a Chinese Han population, we found one family with suggestive maternally transmitted diabetes. The proband's mitochondrial genome was analyzed using DNA sequencing. Total 42 known nucleoside changes and 1 novel variant were identified, and the entire mitochondrial DNA sequence was assigned to haplogroup M11b. Phylogenetic analysis showed that a homoplasmic mutation, 10003T>C transition, occurred at the highly conserved site in the gene encoding tRNA(Gly). Using a transmitochondrial cybrid cell line harboring this mutation, we observed that the steady-state level of tRNA(Gly) significantly affected and the amount of tRNA(Gly) decreased by 97%, production of reactive oxygen species was enhanced, and mitochondrial membrane potential, mtDNA copy number and cellular oxygen consumption rate were remarkably decreased compared with wild-type cybrid cells. The homoplasmic 10003T>C mutation in the mitochondrial tRNA(Gly) gene suggested to be as a pathogenesis-related mutation which might contribute to the maternal inherited diabetes in the Han Chinese family.

Seasonal variability in the biophysical properties of forehead skin in women in Guangzhou City, China.

BACKGROUND: Skin appearance is influenced by biophysical parameters. Seasonal changes affect the condition of normal skin and may trigger cutaneous disorders. OBJECTIVES: This study was undertaken to measure the effects of seasonal changes on biophysical parameters in the skin of female subjects living in Guangzhou City in southern China. METHODS: A cross-sectional study was conducted in 178 healthy, adult Chinese women in whom forehead skin was examined in all four seasons between March 2007 and February 2008. Commercially available, non-invasive devices were used to measure skin hydration, sebum content, pH, and transepidermal water loss (TEWL) in a closed environment under controlled and constant conditions of temperature and humidity. Correlations between skin parameters and climate conditions were investigated. RESULTS: There were significant seasonal changes in TEWL and pH (autumn and winter > spring and summer), skin hydration (spring and summer > autumn and winter), and sebum content (spring and summer > autumn and winter). Skin hydration was correlated with average temperature and humidity. Skin TEWL and skin pH were correlated with average temperature, humidity, and ultraviolet (UV) radiation levels. Skin sebum content was correlated with average humidity. CONCLUSIONS: Facial skin physiology showed seasonal variations in China. The reasons for the changes may refer to seasonal changes in temperature, humidity, and UV radiation.