Anti-tumor drug research and development in non-small cell lung cancer (NSCLC) is rapidly developing, and the clinical application of high-throughput sequencing technology is also becoming widespread. Accordingly, researchers are focusing on human epidermal growth factor receptor-2 (HER-2) gene as a rare target of NSCLC, and a series of exploratory studies has been performed. Traditional chemotherapy and immunotherapy are unsatisfactory in the HER-2 mutant population, whereas the survival improvement of anti-HER-2 monoclonal antibodies and pan-HER inhibitors is limited. The development of antibody drug conjugate (ADC) ushers in a turning point for HER-2-mutated NSCLC, and new ADC drugs represented by trastuzumab deruxtecan are making a breakthrough. It opens up a new era of precision therapy for advanced HER-2-mutated NSCLC. Additionally, novel HER-2 inhibitors show very encouraging initial efficacy and safety, and clinical trials are ongoing. This review focuses on the latest progress of research on HER-2-mutated NSCLC.

Objective: To analyze the disease burden and trends of oral diseases among China’s elderly population (1990-2021) and provide evidence for developing targeted intervention strategies Methods : Using data from the Global Burden of Disease (GBD) 2021 study, we extracted prevalence, incidence, and disability-adjusted life years (DALYs) for oral conditions (permanent dental caries, edentulism, periodontal diseases, and other oral disorders) in individuals aged ≥60 years in China. Due to data limitations, other oral diseases only included DALYs and prevalence. Age-standardized rates (ASR)—including age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR), and age-standardized DALYs rate (ASDR)--were calculated. Trends were assessed via Joinpoint regression using average annual percentage change (AAPC), stratified by sex and age groups (60-64, 65-69, 70-74, 75-79, 80-84, 85-89, 90-94, 95+ years). Results: From 1990 to 2021, China’s elderly population exhibited distinct trends in oral disease burden. Overall oral diseases showed declining ASDR and ASPR, yet ASIR slightly increased. Permanent dental caries demonstrated significant rises across ASDR, ASIR, and ASPR. Edentulism showed declining ASDR and ASPR alongside stable ASIR. 95+ age group saw rising rates. Periodontal diseases remained largely stable in ASDR and ASPR but experienced a slight ASIR decline. Other oral disorders showed mild ASDR decline and stable ASPR. Notably, sex and age disparities persisted. Women consistently bore higher burdens for overall oral diseases, caries, edentulism, and other oral diseases but lower periodontal disease rates compared to men. 85-89, 90-95, 95+ age group faced rising DALYs and prevalence for overall oral diseases, while all other age groups demonstrated declining trends in both DALYs and prevalence; for permanent caries, the 60-64 age group showed the largest increases in DALY rate, incidence, and prevalence; edentulism demonstrated the most pronounced and sustained rises in DALY rate and prevalence in the 95+ group, while declining most rapidly in the 60-64 age group; for periodontal disease, both DALY rates and prevalence declined in the 90-94 and 95+ age groups, but increased across all measures (DALY rate, incidence, and prevalence) in the 70-74 and 75-79 age group; other oral conditions exhibited relatively stable burden distributions or minor changes, with no significant age-specific shifting trends observed. Conclusion From 1990 to 2021, China’s elderly oral disease burden declined overall, but caries surged, edentulism improved, periodontal diseases stabilized, and other oral diseases slightly declined. Prioritizing older women and the adults aged 85+ is critical to addressing evolving oral health needs.

Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Traditional Chinese medicine (TCM) has been an indispensable source of drugs for curing various human diseases. However, the inherent chemical diversity and complexity of TCM restricted the safety and efficacy of its usage. Over the past few decades, the combination of liquid chromatography with mass spectrometry has contributed greatly to the TCM qualitative analysis. And novel approaches have been continuously introduced to improve the analytical performance, including both the data acquisition methods to generate a large and informative dataset, and the data post-processing tools to extract the structure-related MS information. Furthermore, the fast-developing computer techniques and big data analytics have markedly enriched the data processing tools, bringing benefits of high efficiency and accuracy. To provide an up-to-date review of the latest techniques on the TCM qualitative analysis, multiple data-independent acquisition methods and data-dependent acquisition methods (precursor ion list, dynamic exclusion, mass tag, precursor ion scan, neutral loss scan, and multiple reaction monitoring) and post-processing techniques (mass defect filtering, diagnostic ion filtering, neutral loss filtering, mass spectral trees similarity filter, molecular networking, statistical analysis, database matching, etc.) were summarized and categorized. Applications of each technique and integrated analytical strategies were highlighted, discussion and future perspectives were proposed as well.

Small cell lung cancer (SCLC), characterized by early metastasis, relapse, relapse and resistance and poor prognosis, still faces difficulties in treatment. Recently, Immunotherapy is a novel treatment for SCLC, researchers are also eager to achieve a breakthrough in targeted treatment of SCLC. Genomic instability of SCLC and sensitivity to cytotoxic chemotherapy, therefore, poly ADP-ribose polymerase (PARP) inhibitors targeting DNA repair related pathways have become a hotspot in the research of SCLC targeted therapy. Studies on PARP inhibitors in SCLC have been conducted in combination with other therapeutic strategies, including the treatment of recurrent SCLC and first-line treatment,as well as maintenance treatment after induction. These studies also explored the predictive markers of PARP inhibitors in SCLC. Although the current results of PARP inhibitors in SCLC are limited, and the predictive markers are also inconsistent, we also see that PARP inhibitors could be a breakthroughfor precision medicine of SCLC.
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Objective: To evaluate the clinical application of single-arm external stent combined with free flap in the treatment of forearm fractures of Gustilo type Ⅲ. Methods: A retrospective study was conducted of the 16 patients who had been treated at Repair and Reconstruction Center, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University from September 2015 to January 2018 for open forearm fractures combined with soft tissue defects with single-arm external stent combined with free flap. They were 11 men and 5 women, aged from 18 to 64 years (average, 41.6 years). By the Gustilo classification, 9 cases were type ⅢB and 7 type ⅢC. The area of soft tissue defects at the upper arm and hand ranged from 7.5 cm×5.5 cm to 16.5 cm × 11.0 cm. Emergency debridement was performed at the primary stage. After repair of major blood vessels, nerves and tendons, the reduced fractures were fixated with a single-arm external stent. The soft tissue defects were repaired with free flaps at the secondary stage. Nine cases were repaired with a free anterolateral perforating branch flap and 7 with a free ilioinguinal flap. The single-arm external stent became the ultimate fixation mode in 5 cases but was changed into plate fixation after survival of the flaps in the other 11 cases. Complications were recorded postoperatively. At the last follow-up, the upper limb function was evaluated according to the tentative criteria for evaluation of the upper limb function proposed by the Hand Surgery Society of Chinese Medical Association. Results: Of all the free flaps, 14 survived smoothly but 2 anterolateral ones survived only after the venous crisis appearing at 24 h after operation was relieved by exploration. The 16 patients were followed up for 9 to 18 months (average, 13.5 months). The fractures united well with fine alignment of the fracture ends and recovered force line. According to the Anderson criteria for forearm fractures, 10 cases were excellent, 4 good and 2 fair after operation. According to the tentative criteria for evaluation of the upper limb function proposed by the Hand Surgery Society of Chinese Medical Association, 11 cases were excellent and 5 good. No nail infection or nonunion occurred. Conclusion In the treatment of forearm fractures of Gustilo type Ⅲ, single-arm external stent plus free flap can effectively restore the force line of upper extremity, promote bone healing, allow reasonable timing for wound repair, reduce postoperative complications like infection and osteomyelitis and facilitate functional recovery of the affected extremity.

Brain metastasis was a common metastasis site and leading cause of death in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors had improved survival of NSCLC patients with positive drive gene. It also brings good news to NSCLC patients with positive drive gene and brain metastases. However, there is still no effective treatment for NSCLC patients with drive gene-negative and brain metastases. In recent years, immunotherapy has made breakthrough progress and become important first and second line treatment options of NSCLC especially in patients with drive gene-negative. The role of immunotherapy in specific populations of NSCLC-brain metastasis patients, especially drive gene-negative patients has become the focus of attention. In this report, we review the research progress of immunotherapy in NSCLC with brain metastases, especially in driver-negative patients, analyze the limitations of existing research and future challenge.
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Brain Neoplasms ; immunology ; secondary ; therapy ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Humans ; Immunotherapy ; methods ; Lung Neoplasms ; genetics ; pathology ; Patient Selection

Objective To explore the efficiency and adverse effects of the effective EP ( etoposide+cisplatin) therapy and its subsequent maintenance therapy with different durations in patients with small cell lung cancer ( SCLC ) . Methods Clinical data of 104 SCLC patients diagnosed and treated at the Jilin Province Cancer Hospital between September 2010 and December 2013 were retrospectively analyzed.Among them, 35 patients were subsequently treated with a 4?week maintenance therapy following the original therapeutic regimen after the effective EP therapy (4?week maintenance therapy group), 35 patients were treated with a subsequent 6?week maintenance therapy ( 6?week maintenance therapy group ) , and 34 patients were treated without maintenance therapy ( control group) .52 patients were in limited stage, and 52 patients were in extensive stage. The progression?free survival (PFS), overall survival (OS) and adverse effects in the 4?week maintenance therapy group, 6?week maintenance therapy group and control group were analyzed. Results The median PFS in the control group, 4?week maintenance therapy group and 6?week maintenance therapy group was 4.0, 3.5, and 4.0 months, respectively, and the median OS was 9.0, 10.0 and 12.0 months, respectively, showing no significant difference among the groups (P>0.05 for all). The median PFS was prolonged by 2 months as compared with the control group after the 4?week maintenance therapy in the patients with complete remission in first?line chemotherapy ( P=0.041) , while the median OS was not improved ( P=0. 131). Neither the median PFS nor median OS showed statistically significant difference between each two groups in the patients with partial remission in first?line chemotherapy ( P>0.05 for all) . In the limited stage, the median PFS in the control group, 4?week maintenance therapy group, and 6?week maintenance therapy group was 5.0, 6.5, and 4.0 months, respectively, and median OS was 11.0, 13.5, and 13.0 months, respectively, the differences showed no statistical significance ( P>0.05 for all) . In the extensive stage, the median PFS in the control group, 4?week maintenance therapy group, and 6?week maintenance therapy group was 3.0, 3.0, and 3.5 months, respectively, showing significant differences ( P=0.015);the median OS was 6.5, 8.0, and 8.0 months, respectively, presenting no statistically significant differences (P=0.096). In addition, the PFS in the 6?week maintenance therapy group was significantly improved as compared with that in the control group ( P=0. 016 ) . Compared with the control group, the incidence rates of nausea ( grade 3?4 ) , vomiting, hypodynamia, leukopenia, neutropenia, and thrombocytopenia in the 4?week maintenance therapy group and 6?week maintenance therapy group were increased significantly ( P<0.05 for all) , however, the side effects were tolerable. Conclusion Prolonging the treatment cycle of EP therapy can improve the PFS in SCLC patients in first?line CR chemotherapy and extensive stage.