Effects of nutritional indices and inflammatory parameters on patients received immunotherapy for non-small cell lung cancer.

OBJECTIVE: This research explored the relationship between a patient's nutritional state and inflammatory markers and the prognosis of their non-small cell lung cancer (NSCLC) treatment while receiving a combination of chemotherapy and immunotherapy. METHOD: This retrospective and single-center analysis included NSCLC patients who received a combination of chemotherapy and immunotherapy at the Department of Oncology at Shanghai Lung Hospital. Patients were categorized based on malnutrition, sarcopenia, sarcopenic obesity, and advanced-lung-cancer-inflammation-index (ALI) scores after collecting nutritional and inflammatory indices. Kaplan-Meier and the Cox models were utilized to analyze survival. RESULTS: There was a significant correlation between malnutrition, sarcopenia, sarcopenic obesity, and low ALI scores with lower overall survival (OS) and progression-free survival (PFS) (p < 0.05). Low ALI score and malnutrition were independent factors influencing patient survival in terms of both OS and PFS (p < 0.01). CONCLUSION: The nutritional and inflammatory indices of immunotherapy-treated NSCLC patients substantially affect their prognosis. Assessing these variables could aid in optimizing treatment strategies and improving patient outcomes. Additional research is required to comprehend the intricate relationship between nutrition, inflammation, and cancer progression and to develop individualized therapies.

Epithelia-Sensory Neuron Cross Talk Underlies Cholestatic Itch Induced by Lysophosphatidylcholine.

BACKGROUND & AIMS: Limited understanding of pruritus mechanisms in cholestatic liver diseases hinders development of antipruritic treatments. Previous studies implicated lysophosphatidic acid (LPA) as a potential mediator of cholestatic pruritus. METHODS: Pruritogenicity of lysophosphatidylcholine (LPC), LPA's precursor, was examined in naïve mice, cholestatic mice, and nonhuman primates. LPC's pruritogenicity involving keratinocyte TRPV4 was studied using genetic and pharmacologic approaches, cultured keratinocytes, ion channel physiology, and structural computational modeling. Activation of pruriceptor sensory neurons by microRNA-146a (miR-146a), secreted from keratinocytes, was identified by in vitro and ex vivo Ca2+ imaging assays. Sera from patients with primary biliary cholangitis were used for measuring the levels of LPC and miR-146a. RESULTS: LPC was robustly pruritic in mice. TRPV4 in skin keratinocytes was essential for LPC-induced itch and itch in mice with cholestasis. Three-dimensional structural modeling, site-directed mutagenesis, and channel function analysis suggested a TRPV4 C-terminal motif for LPC binding and channel activation. In keratinocytes, TRPV4 activation by LPC induced extracellular release of miR-146a, which activated TRPV1+ sensory neurons to cause itch. LPC and miR-146a levels were both elevated in sera of patients with primary biliary cholangitis with itch and correlated with itch intensity. Moreover, LPC and miR-146a were also increased in sera of cholestatic mice and elicited itch in nonhuman primates. CONCLUSIONS: We identified LPC as a novel cholestatic pruritogen that induces itch through epithelia-sensory neuron cross talk, whereby it directly activates skin keratinocyte TRPV4, which rapidly releases miR-146a to activate skin-innervating TRPV1+ pruriceptor sensory neurons. Our findings support the new concept of the skin, as a sensory organ, playing a critical role in cholestatic itch, beyond liver, peripheral sensory neurons, and central neural pathways supporting pruriception.

[The disease characteristics and risk factors of type 2 diabetes mellitus in pedigrees].

OBJECTIVE: To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. METHODS: A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM), maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. RESULTS: No gender difference was found in the prevalence of T2DM (42.59% in male and 48.18% in female respectively, P > 0.05), nor was the newly diagnosed rate (9.89% in male and 11.82% in female, P > 0.05). The onset age was (63.3 ± 12.4) years old in the first generation [(64.4 ± 12.5) years in male and (62.3 ± 10.3) years in female], (47.1 ± 8.7) years old in the second generation [(48.2 ± 9.3) years in male and (46.1 ± 8.1) years in female], (29.6 ± 10.2) years old in the third generation [(28.9 ± 9.5) years in male and (30.0 ± 10.4) years in female]. Compared with normal glucose tolerance (NGT) subjects, newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM [(68.4 ± 12.4) kg, (69.5 ± 11.0) kg and (69.1 ± 9.6) kg] and IGR [(66.1 ± 10.7) kg, (65.9 ± 10.7) kg and (65.7 ± 10.4) kg], when compared with NGT [(61.0 ± 10.2) kg, (59.5 ± 11.0) kg and (60.1 ± 10.4) kg, all P < 0.05]. The same results were obtained with waist circumference and waist-hip ratio [(4.1 ± 12.5) cm and 0.92 ± 0.36 in newly diagnosed T2DM while (89.1 ± 10.7) cm and 0.90 ± 0.64 in IGR], when compared with NGT [(82.5 ± 10.1) cm and 0.82 ± 0.25], all P < 0.05. CONCLUSIONS: No gender difference was found in the onset characteristics of T2DM. High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.

One-step synthesis and assembly of two-dimensional arrays of mercury sulfide nanocrystal aggregates at the air/water interface.

Ordered two-dimensional (2D) arrays of ß-HgS nanocrystal aggregates were prepared successfully at the air/water interface through the interfacial reaction between Hg(2+) ions in the subphase and H(2)S in the gaseous phase under the direction of liquid-expanded monolayers of arachidic acid (AA). These 2D arrays are composed of hexagonal or quasi-hexagonal aggregates with the size of several hundreds of nanometers that consist of several tens of HgS nanocrystals with the size of several nanometers. The formed HgS nanocrystals together with AA molecules self-assembled into round aggregates due to the interactions between the species, and the aggregates self-assembled into 2D arrays further due to the attractions between them. During the self-assembly process, the soft round aggregates transformed into hexagonal or quasi-hexagonal ones. The experimental conditions, especially the phase states of the AA monolayers and temperature, have great influences on the formation of the 2D arrays. To the best of our knowledge, this is the first case to get 2D ordered arrays at the air/water interface through a one-step synthesis and assembly process.

[Regulation of Gal beta 1,3GalNAc alpha 2,3-sialyltransferase (ST3GalI) by hepatitis B virus MHBst/HBx transactivator].

Hepatitis B virus MHBst and HBx fragments were amplified to construct eukaryotic expression vector pCDNA3.1-MHBst and pCDNA3.1-HBx. ST3GalI promoter region was obtained by the method of PCR and GFP report plasmid pEGFP-N1-Psial was constructed. pCDNA3.1-MHBst or pCDNA3.1-HBx with pEGFP-N1-Psial were transiently co-transfected into QGY-7701 cells using calcium phosphate-DNA co-precipitation, respectively. The expressions of Psial-directed GFP were analyzed by FAC-Scalibur. It was found that MHBst/HBx could upregulate ST3GalI promoter activity by 35.2% and 43.8%, respectively. We report the regulation of ST3GalI by MHBst and HBx transactivators. It would be helpful to further investigate the relation between hepatitis B virus infection and sialyltransferase expression.