Objective To analyze the factors affecting the prognosis of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) undergoing immunotherapy and construct an individualized prognostic nomogram prediction model. Methods A retrospective analysis was conducted on the clinical data of 385 patients with driver gene-negative, locally advanced or metastatic NSCLC who received first-line immune checkpoint inhibitors. Univariate and multivariate Cox regression analyses were used to identify prognostic risk factors, and a prognostic nomogram model was established. The predictive performance of the model was evaluated using the concordance index (C-index), time-dependent receiver operating characteristic (ROC) curves and area under the curve (AUC), and calibration curves. The cutoff value of the nomogram was calculated to stratify patients by risk. Survival curves were calculated by Kaplan-Meier analysis. Results Age (HR=1.775, 95%CI: 1.265-2.490), degree of differentiation (HR=0.365, 95%CI: 0.257-0.519), low PD-L1 expression (HR=0.661, 95%CI: 0.455-0.960), high PD-L1 expression (HR=0.423, 95%CI: 0.297-0.603), SCC-Ag (HR=1.549, 95%CI: 1.109-2.163), and CONUT score (HR=2.527, 95%CI: 1.797-3.554) were independent risk factors affecting overall survival (OS) of patients with NSCLC undergoing immunotherapy. The nomogram prediction model constructed on the basis of these factors had a C-index of 0.767. Time-dependent ROC curves for survival showed that the AUCs for 1-, 2-, and 3-year OS were 0.830, 0.853, and 0.886, respectively. Calibration curves indicated that the nomogram-predicted survival rates were in good agreement with the actual outcomes. The cutoff value for the study’s nomogram prediction model was 136.60 points, and survival curves showed statistically significant differences between different risk groups (P<0.05). Conclusion The nomogram model established in this study can effectively predict the prognosis of patients with driver gene-negative locally advanced or metastatic NSCLC treated with first-line immunosuppressive therapy. It provides a new tool for assessing prognosis and aids clinicians in formulating individualized treatment plans.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

The abnormal accumulation, structural change, and spread of tau protein in the brain are now considered important factors in the progression of Alzheimer’s disease (AD) and many other tau-related neurodegenerative diseases. Clinical and pathological studies have shown that the amount and distribution of abnormal tau protein are closely related to synaptic damage, neuronal loss, and cognitive decline. Therefore, tau protein has become an important target for disease-modifying therapy. However, tau is difficult to target because it has no fixed structure, lacks a clear active site, undergoes many post-translational modifications, and forms different abnormal structures in different diseases and disease stages. Therefore, the effective and selective removal of harmful tau species is both a major opportunity and a major challenge in drug discovery for neurodegenerative diseases. Proteolysis-targeting chimeras (PROTACs) offer a new strategy to deal with this problem. Unlike traditional inhibitors, PROTACs do not simply block protein function. Instead, they bring the target protein close to an E3 ubiquitin ligase, which leads to ubiquitination and degradation of the target protein by the proteasome. This event-driven mechanism may be especially useful for disease-related proteins such as tau protein, which are hard to inhibit with traditional small molecules. In recent years, tau protein-targeting PROTACs and related degradation strategies have shown promising effects in cell and animal models. These effects include reducing abnormal tau protein levels, lowering synaptic toxicity, regulating disease-related signaling pathways, and improving behavioral or cognitive outcomes. These studies support targeted tau protein degradation as a promising therapeutic approach, although many problems still need to be solved before clinical use. In this review, we summarize recent progress in the development of tau protein-targeting PROTACs and discuss the main factors that affect their design and activity. We focus on the choice of tau protein-binding ligands, their binding sites, and their ability to recognize abnormal tau protein rather than normal tau protein. We also discuss the selection of E3 ligase recruiters, linker length and structure, ternary complex formation, and structure-activity relationships that influence degradation potency and selectivity. In addition, we introduce new strategies beyond traditional proteasomal degradation, including the regulation of tau protein phosphorylation and autophagy-based clearance. These approaches may be more suitable for different tau species or different stages of disease. A major challenge for tau protein-targeting PROTACs is delivery to the central nervous system. Many PROTACs have high molecular mass, large polar surface area, flexible structures, and may be removed by efflux transporters. As a result, they often have poor ability to cross the blood-brain barrier and may not reach enough free drug levels in the brain. Therefore, the therapeutic potential of tau protein-targeting PROTACs depends not only on their ability to degrade tau protein in vitro, but also on whether they can achieve long-lasting, selective, and safe target engagement in important brain regions after practical administration. Future studies should focus on improving selectivity for abnormal tau protein, understanding E3 ligase function in neural cells, designing brain-penetrant molecules, developing better delivery methods, and testing these drugs in models that better reflect human disease. Overall, tau protein-targeting PROTACs are a promising and fast-developing strategy for treating tau-related diseases. However, their successful clinical translation will require progress in chemical biology, medicinal chemistry, neuroscience, drug delivery, and translational medicine.

AIM To investigate the clinical effects of Huoxue Qingre Formula combined with radiofrequency ablation on patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis.METHODS Ninety patients were randomly assigned into control group(45 cases)for 3-month intervention of both Huoxue Qingre Formula placebo and radiofrequency ablation,and observation group(45 cases)for 3-month intervention of both Huoxue Qingre Formula and radiofrequency ablation.The changes in clinical effects,VRR,TCM syndrome score,cytokines(TNF-α,IFN-γ,IL-23,IL-1β),biochemical indices[Ca2+,25(OH)D,CRP],thyroid function indices(TSH,FT3,FT4)and safety indices were detected.RESULTS At postoperative 12 months,the observation group demonstrated higher total effective rate than the control group(P＜0.05).At postoperative 3-12 months,the two groups displayed increased VRR(P＜0.05),especially for the observation group(P＜0.05,P＜0.01).At the 7th,30th postoperative days,the two groups displayed decreased TCM syndrome score and cytokines(P＜0.05,P＜0.01),especially for the observation group(P＜0.05,P＜0.01).At the 30th postoperative day,the two groups displayed decreased Ca2+(P＜0.01)and increased 25(OH)D(P＜0.01),especially for the observation group(P＜0.01).At the 7th postoperative day,the two groups displayed increased CRP(P＜0.01),especially for the control group(P＜0.05),which were decreased at the 30th postoperative day(P＜0.05,P＜0.01),especially for the observation group(P＜0.01).No significant differences in thyroid function indices and safety indices were found between the two groups(P＞0.05).CONCLUSION For the patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis,Huoxue Qingre Formula combined with radiofrequency ablation can safely and effectively enhance nodule VRR,alleviate discomfort symptoms,reduce TCM syndrome score,inflammatory factor levels,and accelerate recovery.

Objective:To elucidate the genomic characteristics of the immunoglobulin (IG) heavy-chain variable region and light-chain variable region, the expression of subclones, and the prognostic significance in patients with CLL.Methods:Blood and/or bone marrow specimens were gathered from a cohort of 36 patients with CLL diagnosed at Jiangsu Province Hospital from December 2018 to May 2023, including 12 cases of B cell receptor (BCR) stereotyped patients. IG heavy-chain (IGH) and light-chain (IG Kappa [IGK] and IG lambda [IGL]) gene rearrangements were performed using next-generation sequencing (NGS) technology to analyze the characteristics and prognostic value in CLL.Results:NGS detection of IG variable region (IGHV) demonstrated a significant correlation and superior consistency with Sanger sequencing ( r=0.957, P < 0.001). Among the 36 patients, the IGH variant (IGHV) was observed in 9 (25.0%) but not in 27 (75.0%) participants. The incidence of the MYD88 mutation was higher among patients with mutated IGHV [1/27 (3.7%) vs 4/9 (44.4%), P=0.00]. A high incidence of trisomy 12 was observed in the IGHV #8/#8B subset [4/11 (36.4%) vs 1/25 (4.0%), P=0.023], which were more likely to develop Richter transformation [8/11 (72.7%) vs 4/25 (16.0%), P=0.002]. In the patient cohort, 36 individuals (36/36, 100.0%) used the IGK variable, whereas 15 individuals (15/36, 41.7%) employed the IGL variable (IGLV). IGLV3 - 21 reported the highest utilization rate in IGLV (5/15, 33.3%). Remarkably, patients with CLL with IGLV3-21 fragments were exclusively observed in the Binet C stage and Rai Phase Ⅲ-Ⅳ, with an incidence of del (13) (q14) at 60.0% (3/5). The median time to first treatment (TTFT) of patients with or without IGLV3 - 21 fragments was 5.2 (1.1 - 41.5) and 9.9 (0.1 - 94.4) months, respectively. Using the total reads threshold of 2.5%, 4 (4/36, 11.1%) samples were detected to have two IGHV productive clones. The median TTFT and overall survival (OS) time were 2.8 (0.9-72.7) and 12.8 months in patients with one mutated clone and 57.5 (32.0-120.7) and 51.8 months in those with two mutated clones, respectively. The median TTFT and OS time were 10.9 (0.3-94.4) and 6.3 (0.1 - 12.5) months in patients with one unmutated clone and 49.9 (22.2 - 211.1) and 30.0 (9.6 - 50.3) months in those with multiple unmutated clones, respectively ( P>0.05) . Conclusions:Detection of IG gene rearrangements using NGS technology not only facilitates the analysis of the IGHV mutation status, dominant clones, and prognostic value but also contributes to the exploration of IGK/IGL gene rearrangement fragments and the utilization of subclones. Further, it provides information about the poor prognosis of IGLV3 - 21 CLL. The shortened survival of the two unmutated clone groups in the IGHV unmutated group may indicate a poor prognosis.

Objective To explore TCM syndrome distribution law in patients with overlapping non-erosive reflux disease(NERD)and epigastric pain syndrome(EPS)gastrointestinal symptoms.Methods A multi-center,cross-sectional study was conducted to investigate the general information of 800 patients with overlapping NERD and EPS gastrointestinal symptoms in four hospitals,such as gender,age,body mass index(BMI)and four diagnostic information of TCM.Descriptive frequency analysis,factor analysis and clustering analysis were used to summarize the TCM syndrome types and distribution characteristics.Results The average age of 800 patients with overlapping NERD and EPS gastrointestinal symptoms was(44.50±14.43)years old,the average BMI was(23.17±4.80)kg/m2,and the male to female ratio was 3:5.Frequency of 95 TCM symptoms/signs≥20%.18 common factor variables were obtained based on factor analysis,and the cumulative contribution rate was 67.11%.The first three syndrome elements of disease location were liver,stomach and spleen,and the disease nature syndrome elements were qi stagnation,qi deficiency and yin deficiency.Based on the clustering analysis of 18 common factor variables,combined with expert discussion,four main TCM syndrome types were obtained,which were liver-stomach stagnation heat syndrome(213 cases,26.63%),spleen-stomach damp heat syndrome(209 cases,26.13%),spleen-stomach deficiency and cold qi stagnation syndrome(190 cases,23.75%)and qi-phlegm stagnation syndrome(188 cases,23.50%).There was no significant difference in the distribution of TCM syndrome types among patients with different genders,ages and BMI values(P>0.05).Patients with a course of disease≥2 years and those residing long-term north of the Qinling-Huaihe Line showed a significantly higher prevalence of spleen-stomach dampness-heat syndrome(P<0.05).Conclusion The syndrome elements of disease location of overlapping NERD and EPS gastrointestinal symptoms are mainly liver,stomach and spleen.The TCM syndrome types are liver-stomach stagnation heat syndrome,spleen-stomach damp heat syndrome,spleen-stomach deficiency cold qi stagnation syndrome and qi-phlegm stagnation syndrome.The course of disease and the regional differences between north and south may be the influencing factors of the distribution of syndrome types.

Objective:To investigate the clinicopathological features, diagnosis, and prognosis of aggressive natural killer-cell leukemia (ANKL).Methods:A retrospective analysis was conducted on 27 ANKL patients treated at the First Affiliated Hospital of Nanjing Medical University from 2014 to 2024. Their clinical data, histomorphology, and immunophenotype were reviewed. Kaplan-Meier analysis was used to evaluate the overall survival (OS), and COX regression analysis was performed to identify prognostic factors affecting OS.Results:Among the 27 patients, 18 were male and 9 were female, with a male-to-female ratio of 2∶1. The age ranged from 15-75 years, with a median age of 42.0 (28.5, 54.5) years. Fever and splenomegaly were the most common signs and symptoms. Most patients presented with pancytopenia, coagulation abnormalities, and liver dysfunction; and all patients had elevated EBV loads. Microscopically, 16 cases showed marked to hypercellular bone marrow proliferation, with predominant interstitial infiltration (15 cases, 55.6%), followed by sinusoidal infiltration (3 cases), diffuse infiltration (6 cases, 22.2%), mixed infiltration (interstitial and focal, 3 cases, 11.1%), focal infiltration (2 cases, 7.4%), and nodular infiltration (1 case, 3.7%). The proportion of tumor cells among nucleated cells ranged from 2% to 80%, with a median of 30%. The tumor cells displayed variable morphology. Hemophagocytosis was observed in 23 cases. Immunohistochemistry revealed that all cases expressed CD56, with mostly expressing cytotoxic molecules (granzyme B, TIA-1). The Ki-67 proliferative index ranged from 50% to 90%. CD56-EBER dual staining showed that NK cells were the primary targets of the virus. Reticulin staining showed increased fibrosis. By flow cytometry, all cases were positive for CD2 but negative for surface CD3 (sCD3), CD4, CD5 and CD57. Among them, 21 cases (95.5%) exhibited a typical phenotype of strong CD56 expression (CD56str+) with CD16 negativity (CD16-), while only one case (4.5%) showed CD16 positivity (CD16+) with dim CD56 expression (CD56dim). In killer-cell immunoglobulin-like receptor (KIR) analysis, 6 out of 17 patients (6/17) demonstrated monoclonal expression, including CD158a (4/6), CD158i (1/6), and CD158e (1/6); the remaining 11 cases (11/17) showed complete absence of KIR expression. All tested cases (17/17) were negative for T-cell receptor (TCR) protein expression. Follow-up period was from 257 days, 1 patient was lost to follow-up, and the remaining 26 patients died. Kaplan-Meier analysis revealed that OS was significantly longer in patients who received chemotherapy compared to those who did not ( P<0.05). Univariate Cox proportional hazards model analysis indicated that age, bone marrow proliferation, proportion of tumor cells among nucleated cells, absolute neutrophil count, platelet count, and triglycerides and bilirubin levels significantly affected OS ( P<0.05). Multivariate COX regression analysis identified triglycerides and bilirubin levels as independent prognostic factors for OS. Conclusion:Aggressive natural killer-cell leukemia is a rare lymphoid malignancy with very poor prognosis. Tumor cells exhibit significant morphological variation, and bone marrow infiltration patterns are diverse. Accurate recognition, early diagnosis, and timely chemotherapy are critical to improving the prognosis of patients with ANKL.

Objective:To evaluate the efficacy and long-term outcomes of fludarabine, cyclophosphamide, and rituximab (FCR) in treatment-na?ve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) .Methods:Clinical data from 68 CLL/SLL patients treated with FCR at Jiangsu Province Hospital (August 2008–May 2021) were retrospectively analyzed to assess efficacy, safety, and survival outcomes.Results:Among 68 patients [46 males, 22 females; median age 55 (47, 60) years], 13.1% (8/61) had a complex karyotype, 32.3% (20/62) had immunoglobulin heavy variable region mutated (IGHV-M) type, 6.6% (4/61) had del (17p), and 14.8% (8/54) had del (11q). Patients received a median of 6 (4, 6) FCR cycles. The overall response rate was 88.2% (60/68), including 47.0% (32/68) complete remissions. Over a median follow-up of 82 (59, 98) months, 66.2% (45/68) experienced disease progression. Median progression-free survival was 56 (21, 123) months, while median overall survival was not reached. The 5- and 10-year PFS rates were 42.6% (95% CI: 31.9–56.8% ) and 28.7% (95% CI: 19.0–43.4% ), respectively. Poor PFS was associated with del (17p) ( HR=5.04, 95% CI: 1.72–14.74, P=0.003), del (11q) ( HR=5.27, 95% CI: 2.11–13.15, P<0.001), IGHV unmutated (IGHV-UM) ( HR=4.11, 95% CI: 1.72–9.79, P=0.001), complex karyotype (CK) ( HR=3.53, 95% CI: 1.58–7.85, P=0.002), β 2-microglobulin >3.5 mg/L ( HR=2.87, 95% CI: 1.37–6.01, P=0.005). In multivariate analysis, IGHV-UM remained an independent predictor of PFS ( HR=8.63, 95% CI: 1.09–68.40, P=0.042). Sixteen patients with IGHV-M and lacking del (17p) or CK had a median PFS of 123 (58,123) months and a 5-year PFS rate of 70.7% (95% CI: 49.7–99.1% ), reaching a plateau after 5 years with no recurrences by 10 years. Common grade 3–4 adverse events included hematologic toxicity (44.1%, 30/68), infection (36.7%, 25/68), and liver dysfunction (4.4%, 3/68). Among 25 patients receiving single-agent BTK inhibitors after FCR progression, median follow-up was 45 (26, 64) months; 36% (9/25) experienced disease progression, with a median PFS time of 55 (27, 55) months. Conclusion:First-line FCR provides durable long-term benefits for patients with IGHV-M CLL without del (17p) or CK.

Objective:To investigate the trends in detection, treatment, and outcomes of rifampicin-resistant tuberculosis (TB) in Jiangsu Province from 2013 to 2023, assess the effectiveness of control policies and measures for drug-resistant TB, and provide evidence for better control of drug-resistant TB.Methods:Data and indicators related to the screening, diagnosis, treatment, and outcomes of rifampicin-resistant TB in Jiangsu Province from 2013 to 2023 were obtained from the Tuberculosis Management Information System. The Joinpoint regression method was employed to analyze the trends over this period, and annual percent change (APC) and average annual percent change (AAPC) were calculated. A comparative analysis was also conducted to evaluate the changes before and after implementing relevant policies and measures.Results:From 2013 to 2023, the number of registered rifampicin-resistant TB patients in Jiangsu Province showed a consistent upward trend (APC=AAPC=1.45%, P=0.035). The screening rates for drug resistance among new TB patients in high-risk groups and the proportion of molecular biological testing for drug resistance all exhibited increasing trends, with a notable turning point occurring in 2018. The trend of the treatment enrollment rate for rifampicin-resistant TB patients experienced a significant shift in 2020, showing a marked increase from 2013 to 2020 (APC=12.91%, P=0.008). The treatment success rate of rifampicin-resistant TB patients also showed a significant upward trend after a turning point in 2020 (APC=9.94%, P=0.004). Conclusion:From 2013 to 2023, significant progress was seen in preventing and treating rifampicin-resistant TB in Jiangsu Province, with relevant policies and measures proving to be highly effective.

Objective Utilizing patient journey mapping to decipher disease management behaviors,barriers,and needs in young and middle-aged liver transplant recipients,providing implications for self-management optimization and quality of life improvement.Methods Using purposive sampling,12 young and middle-aged liver transplant patients who attended outpatient clinics or were hospitalized in liver transplant center of a tertiary hospital in Qingdao were selected for semi-structured interviews from September to November 2024.Thematic extraction and analysis were performed using Colaizzi's 7-step analysis,ultimately resulting in the development of a patient journey map.Results The journey stages were divided into transplantation decision-making period,transplantation waiting period,perioperative period,and post-discharge management period,and the journey key elements were designed as behaviors,barriers,and needs.A total of 25 themes were extracted,including behaviors(such as referrals to higher-level hospitals,verification of treatment options),barriers(such as lack of decision-making autonomy,health information-seeking barriers),and needs(such as shared decision-making,financial assistance).Ultimately,resulting in a map of the disease management journey for young and middle-aged liver transplant recipients.Conclusion The behaviors,barriers,and needs in disease management among young and middle-aged liver transplant recipients demonstrate distinct phase-specific patterns.Healthcare providers should deliver precise and dynamic interventions tailored to each clinical phase,aiming to foster optimal self-management behaviors,address phase-specific banriers,and meet evolving patient needs throughout the transplant continuum.