Objective:To explore the efficacy of different second-line treatment strategies in the real world after progression of first-line immunotherapy and its combination therapies in patients with driver gene-negative advanced non-small cell lung cancer (NSCLC) .Methods:A retrospective analysis was conducted on the clinical data of 93 driver gene-negative advanced NSCLC patients who received first-line immunotherapy and its combination therapies from January 1, 2018 to December 31, 2023 at the First Affiliated Hospital of Xinxiang Medical University and Xinxiang Central Hospital. Patients were categorized into immune checkpoint inhibitors (ICIs) -resistant ( n=43) and ICIs-responsive ( n=50) groups according to whether progression free survival (PFS) exceeded 6 months after first-line treatment. Patients were categorized into ICIs-treated ( n=55) and non-ICIs-treated ( n=38), anti-angiogenic-treated ( n=51) and non-anti-angiogenic-treated ( n=42) groups according to the different second-line treatment strategies after progression of first-line immunotherapy and its combination therapies. The median PFS2 (mPFS2) and median overall survival (mOS) 2 after second-line treatment of each group were compared. The Kaplan-Meier method was used for survival analysis. Results:The mPFS2 and mOS2 of 93 advanced NSCLC patients who progressed after first-line ICIs treatment were 4.9 months (95% CI: 4.1-5.7 months) and 14.7 months (95% CI: 11.2-18.2 months). The mPFS2 of patients in the first-line ICIs-responsive and ICIs-resistant groups were 6.0 and 3.8 months, respectively, with no statistically significant difference ( χ2=2.00, P=0.157), and the mOS2 were 25.3 and 11.3 months, respectively, with a statistically significant difference ( χ2=12.13, P<0.001). The mPFS2 of patients in the second-line ICIs-treated group and the non-ICIs-treated group were 5.2 and 4.6 months, respectively, with no statistically significant difference ( χ2=0.16, P=0.687). The mOS2 were 15.1 and 12.7 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.930). The mPFS2 of patients in the second-line anti-angiogenic-treated and non-anti-angiogenic-treated groups were 4.5 and 6.0 months, respectively, with no statistically significant difference ( χ2=0.41, P=0.525), the mOS2 were 14.7 and 16.8 months, respectively, with no statistically significant difference ( χ2=0.01, P=0.943) . Conclusions:After progression of first-line ICIs therapy in patients with driver gene-negative advanced NSCLC, first-line ICIs-responsive patients have significantly longer OS after second-line treatment compared with ICIs-resistant patients. The efficacy of second-line therapy in patients after progression of first-line ICIs therapy does not show significant differences due to the type of treatment strategies.

Objective To evaluate the clinical efficacy of tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis in the treatment of adolescent flexible flatfoot.Methods A retrospective analysis was conducted on the clinical data of 86 children with flexible flatfoot treated at Dongguan Hospital of Guangzhou University of Chinese Medicine(Dongguan Traditional Chinese Medicine Hospital)between December 2022 and February 2024.Based on pre-treatment physician-patient communication,the children were divided into an trial group(44 cases)and a control group(42 cases).The control group received subtalar joint arthroereisis alone,while the trial group received additional tendon-regulating and bone-setting manipulation just once one day before surgery and once weekly postoperatively for one month,with a follow-up period of no less than 6 months.The Visual Analogue Scale(VAS)pain score,American Orthopaedic Foot & Ankle Society(AOFAS)ankle-hindfoot score,Tegner activity score,radiographic parameters,and static plantar pressure parameters of the two groups were observed before and after surgery.Results(1)Regarding clinical data,all surgeries were successfully completed in both groups.There were no statistically significant differences in perioperative general data,including operative time,hospital stays,and complication rates(P＞0.05).All children were followed up for no less than 6 months.The results showed that at the final follow-up,the VAS pain score,AOFAS ankle-hindfoot score,and Tegner activity score were significantly improved in both groups compared to preoperative values(P＜0.05),and the improvement in the trial group was significantly greater than that in the control group(P＜0.05 or P＜0.01).(2)Regarding radiographic parameters,at the final follow-up,the talonavicular coverage angle(TNCA),talus-first metatarsal angle(T1MT),talus-second metatarsal angle(T2MT)on weight-bearing anteroposterior radiographs,and the Meary angle between the talus and the first metatarsal as well as calcaneal Pitch angle(Pitch angle)on weight-bearing lateral radiographs were significantly improved in both groups compared to preoperative values(P＜0.05).The improvement in Meary angle,T1MT angle,and T2MT angle in the trial group was significantly greater than that in the control group(P＜0.01).However,there were no statistically significant differences in TNCA and Pitch angle between the two groups at the final follow-up(P＞0.05).(3)Regarding plantar pressure testing,at the 1-month postoperative follow-up,the forefoot load increased significantly in both groups compared to preoperative values(P＜0.05),while the midfoot load significantly decreased(P＜0.05).The increase in forefoot load and decrease in midfoot load in the trial group were significantly greater than those in the control group(P＜0.05 or P＜0.01).However,there were no statistically significant differences in hindfoot load between preoperative and postoperative values or between the two groups at the 1-month follow-up(P＞0.05).Conclusion For adolescent flexible flatfoot,tendon-regulating and bone-setting manipulation combined with subtalar joint arthroereisis can effectively restore the arch,improve foot mechanical imbalance,thereby correcting flatfoot deformity and enhancing joint motor function.

Objective To study the distribution and trend of HIV-1 drug resistance mutation in Dalian blood donors be-tween 2011 and 2020.Methods The protease-reverse transcriptase(PR-RT)region was sequenced in Dalian blood donors tested HIV-1 positive between 2011 and 2020.Drug resistance mutation(DRM)rate and level of resistance to selected drugs were analyzed by the Stanford HIV Drug Resistance Database.Results DRM were detected in 17.2%(30/174)of samples,while transmitted drug resistance(TDR)was5.7%(10/174).Between2011 and2020,DRM and TDR rates in-creased significantly in 2019 and reached their highest levels in 2020(44.4%and 22.2%,respectively).DRM carriage was associated with people with college degree or above and with local residents(P<0.05).NNRTI DRMs were the most fre-quently detected(12.6%,22/174),followed by PIs(5.7%,10/174),with V179D/E/T and M46I being the main DRMs detected.Only one HIV-1strain(0.57%,1/174)carried a NRTI DRM(L74I).The overall rate of predicted high level re-sistance to antiretroviral drugs was 6.9%(12/174),with the highest proportion of NNRTI resistance(83.3%,10/12).Two samples were classified as highly resistant to EFV and NVP,accounting for 1.1%(2/174).CRF55_01B strains showed a significantly higher DRM rate than strains of other HIV-1 genotypes(P<0.05).Conclusion Between 2011 and 2020,the rate of HIV-1 DRMs in blood donors in Dalian showed a significant upward trend,particularly in 2019-2020,with NNRTI resistance being the most common.The combination of DRMs detection before and after implementation of ART un-der the latest national ART treatment plan would improve the effectiveness of HIV-1 prevention and control locally.

This paper mainly introduced the significance of implementing palliative care for patients with chronic obstructive pulmonary disease, summarized the palliative care needs assessment tools applied to patients with chronic obstructive pulmonary disease, and discussed the factors affecting of patients′ palliative care needs and strategies to improve them, aiming to provide reference for formulating targeted intervention measures for patients with chronic obstructive pulmonary disease in the future.

The glymphatic system is a unique network of the central nervous system that facilitates the removal of metabolic waste from the brain and maintains homeostasis.The glymphatic system is relatively active during sleep,and its physiological function is affected by many factors.The application of non-invasive imaging techniques to evaluate the function of the glymphatic system has promoted the development of clinical studies.More and more studies have demonstrated the association between the function of glymphatic system and the pathogenesis of neurodegenerative diseases,cerebrovascular diseases and other central nervous system diseases.The glymphatic system is expected to become a novel target for predicting prognosis of central nervous system diseases and clinical effects.

【Objective】 To investigate the serological and molecular characteristics of HBsAg+ /HBV DNA non-reactive (NR) infections. 【Methods】 Samples tested as HBsAg+ and HBV DNA NR were confirmed by individual NAT repeat testing, viral particle concentration by PEG precipitation combined with in-house nested PCR and real-time quantitative PCR, anti-HBc testing, and HBsAg quantification. HBV sequences were compared with those from donors with chronic and occult infection as controls. 【Results】 A total of 792 195 samples were screened between January 2011 and December 2020, of which 53 (1: 14 947) were confirmed HBsAg+ /HBV DNA NR. HBV DNA was detected further in five (9.4%) samples; three S sequences and four Pre Core/Core sequences were obtained. Unique amino acid substitutions (P130T, P135Q/S, R151Q, G153S and S155F) were found in the Core protein that may affect virus packaging and replication. 【Conclusion】 Extremely low HBV DNA level was detected in plasmas of HBsAg+ /HBV DNA NR donors. Barely detectable HBV DNA might be associated with unusual mutations in the Pre Core/Core protein affecting viral replication. More sensitive HBV DNA and/or HBsAg assays may be considered to further reduce the potential HBV transfusion-transmission residual risk.

【Objective】 To investigate HIV-1 subtype distribution and trend among Dalian blood donors between 2011 and 2020, in order to provide information to improve blood safety and HIV prevention. 【Methods】 HIV RNA was purified from plasma samples of Dalian blood donors with confirmed HIV infection, which were collected between 2011 and 2020. The HIV pol gene was amplified and sequenced. HIV-1 subtypes were determined by phylogenetic analysis. 【Results】 HIV RNA was successfully genotyped in 174 samples from HIV-infected donors. The main subtypes among Dalian blood donors were CRF01_AE(69.5%), CRF07_BC(17.2%), B(5.2%), CRF02_AG(2.9%), C(1.1%), CRF55_01B(1.1%), CRF08_BC(0.6%), CRF59_01B(0.6%) and CRF79_0107(0.6%). There were still 2 cases (1.1%) unclassified. Significant difference was observed when comparing with the published national data. The prevalence of CRF01_AE strains decreased over the years, while CRF07_BC increased significantly. CRF02_AG carriers differed from donors infected with other HIV subtypes by being mostly females (40.0% vs. 2.4%), aged (median: 35y vs. 26y) and lower educational background(junior school degree or below). And 96.7% of local CRF01_AE cases were related to HIV strains, which were reported to circulate in Northeast China and in the MSM population. 【Conclusion】 HIV-1 among Dalian blood donors had unique molecular epidemiology and the trends of 07_BC increasing and 01_AE decreasing lagged behind the overall national data. Donor education on blood safety and consultation services to high risk group before donation still need improvement.

Objective To investigate the clinical applicability and different characteristics of three commonly used diagnostic methods for drug-induced liver injury from the two aspects of liver injury induced by Western medicine and liver injury induced by traditional Chinese medicine. Methods A prospective cohort study was performed for 289 hospitalized patients with acute drug-induced liver injury who were admitted to The Fifth Medical Center of Chinese PLA General Hospital from January 2015 to December 2020 and did not receive integrated traditional Chinese and Western medicine therapy, among whom 187 patients had herb-induced liver injury and 102 had Western medicine-induced liver injury. The 289 patients were diagnosed by the integrated evidence chain (IEC), Roussel Uclaf Causality Assessment Method (RUCAM), and the Structured Expert Opinion Process (SEOP) method, and related data at acute onset were collected, including general information, latency period, detailed medication, and laboratory markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase, alkaline phosphatase, and total bilirubin. A statistical analysis was performed to investigate the consistency between IEC, RUCAM, and SEOP in the diagnosis of Western medicine-induced liver injury and herb-induced liver injury and their own applicability. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data; the chi-square was used for comparison of categorical data. Results The hepatocellular type was the main type of clinical liver injury in both Western medicine-induced liver injury and herb-induced liver injury, accounting for 81.4% and 74.3%, respectively, and laboratory examination showed higher levels of ALT and AST. Western medicine-induced liver injury cases were diagnosed by IEC, RUCAM, and SEOP, with a clinical diagnosis rate of 65.7%, 100%, and 63.7%, respectively, and the constituent ratio of Western medicine-induced liver injury was 23.2%, 35.3%, and 22.5%, respectively. Herb-induced liver injury cases were diagnosed by these three methods, with a clinical diagnosis rate of 47.6%, 100%, and 29.9%, respectively, and the constituent ratio of herb-induced liver injury was 30.8%, 64.7%, and 19.4%, respectively. The consistency test of the three diagnostic methods showed that in the diagnosis of Western medicine-induced liver injury cases, there was good consistency between IEC and SEOP (Kappa=0.785, P < 0.05), while there was poor consistency between RUCAM and IEC (Kappa=0.149, P > 0.05) and between RUCAM and SEOP (Kappa=0.117, P > 0.05); in the diagnosis of herb-induced liver injury cases, there was poor consistency between RUCAM and SEOP (Kappa=0.066, P > 0.05), while there was good consistency between RUCAM and IEC (Kappa=0.026, P < 0.05) and between IEC and SEOP (Kappa=0.437, P < 0.05). Conclusion The IEC method shows good applicability for both Western medicine-induced liver injury and herb-induced liver injury, and there is good consistency between IEC and SEOP in the diagnosis of Western medicine-induced liver injury cases, while there is a relatively low level of consistency between IEC and SEOP in the diagnosis of herb-induced liver injury. There is poor consistency between RUCAM and the other two methods. In the clinical diagnosis of Western medicine-induced liver injury, IEC, RUCAM, and SEOP should be used in combination to accurately judge the causal relationship between drugs and liver injury.

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64％of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candi-date phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Por-phyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral sam-ples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.

Objective:To summarize the experience of surgical methods without repairing the fistula for 92 cases with gastrointestinal intrathoracic fistula.Methods:The surgical methods without repairing the fistula were performed through VATS, small incision assisted with VATS or thoracotomy. The focus of the surgery was to promote lung expansion, eliminate the residual cavity of chest cavity and keep effective drainage. After entering the chest cavity from the affected side, wash chest cavity with a large amount of warm normal saline and sterilize intermittently with iodophor to ensure the sterile environment in the pus cavity. Then completely remove the pleural cellulose or fiberboard on visceral pleura to promote lung expansion, eliminate the residual cavity of the chest cavity. The fistula was covered tightly and supported firmly by the visceral pleura on the lung. Multiple T-tubes were placed in thoracic cavity and fistula to keep effective postoperative drainage.Results:Among 92 cases, 85 cases were cured and the cure rate was 92.4% (85/92).7 cases died and the mortality rate was 7.61% (7/92). The 7 dead cases include 5 cases with esophagogastric anastomotic fistula (the death of 3 cases was cause by aortic esophagogastric fistula, the death of 1 case was cause by thoracic gastric tracheal fistula and 1 case was dead because of pulmonary infection and respiratory failure), 1 case with esophageal rupture (the cause of death was septic shock ), and 1 case with esophageal perforation(the cause of death was pulmonary infection and respiratory failure).Conclusion:Most of the surgeries without repairing gastrointestinal intrathoracic fistula are conducted simply through VATS or small incision assisted with VATS., which is safe and effective.