[摘 要] 目的：探讨复发/转移性鼻咽癌（NPC）接受含PD-1单抗免疫治疗的临床特征和预后影响因素。方法：回顾性分析2019年3月至2024年7月期间南部战区总医院确诊的95例NPC患者的临床资料和外周血生化及免疫学指标。预后分析采用Kaplan-Meier曲线，组间比较使用Log-rank检验，采用Cox比例风险模型进行单因素和多因素分析。结果：95例患者中男性81例，女性14例，中位年龄49.72岁（16~74岁），Ⅳ期91例（95.79%），所有患者均采用免疫治疗，联合或不联合化疗方案治疗，中位无进展生存期（mPFS）为10.5个月，客观缓解率（ORR）70.53%，疾病控制率（DCR）89.47%，接受含铂治疗方案患者PFS相对更长，且差异有统计学意义。紫杉醇 + 顺铂 + 氟尿嘧啶（TPF）对比吉西他滨 + 顺铂（GP）和紫杉醇 + 顺铂（TP）显示出更长的PFS，但差异无统计学意义。不同PD-1单抗治疗组间的PFS未显示出有统计学意义的差异。单因素及多因素Cox回归分析结果显示，肿瘤复发状态、初始血浆EBV感染状态、治疗周期数、基线外周血SII是复发/转移性NPC患者接受PD-1抑制剂治疗疗效预测的独立相关因素（均P < 0.05），并且非复发患者、初始血浆EBV DNA阳性、接受 ≥ 4治疗周期、基线外周血SII < 772.81的患者接受PD-1抑制剂治疗预后相对更好。结论：在接受PD-1抑制剂治疗的复发/转移性NPC患者中，非复发患者、初始血浆EBV DNA阳性、≥ 4治疗周期且外周血SII < 772.81者PFS相对更长，可早期识别免疫治疗效果不佳患者并精准干预。

Diabetic kidney disease（DKD） is a chronic kidney structural and functional disorder caused by diabetes. With the global prevalence of diabetes continuing to rise， DKD has gradually become a major cause of chronic kidney disease and end-stage renal disease（ESRD）， posing a serious threat to patients' quality of life and long-term health outcomes. Studies have shown that apoptosis plays a pivotal role in the development and progression of DKD， with its mechanisms involving abnormal activation of multiple signaling pathways such as Toll-like receptor 4（TLR4）/nuclear transcription factor-κB（NF-κB）/B-cell lymphoma-2（Bcl-2）/cysteinyl aspartate-specific proteinase（Caspase）-3， protein kinase R-like endoplasmic reticulum kinase（PERK）/eukaryotic initiation factor 2α（eIF2α）/activating transcript factor 4（ATF4）/CCAAT enhancer-binding protein homologous protein（CHOP）， phosphatidylinositol 3-kinase（PI3K）/protein kinase B（Akt）/glycogen synthase kinase-3β（GSK-3β）， Janus kinase 2（JAK2）/signal transducer and activator of transcription 3（STAT3）， adenosine monophosphate-activated protein kinase（AMPK）/mammalian target of rapamycin（mTOR） and silent information regulator 1（SIRT1）/tumor suppressor protein 53（p53）， thereby accelerating renal pathological damage in DKD. Extensive evidence-based medical studies have confirmed that traditional Chinese medicine（TCM）， leveraging its unique therapeutic advantages of multi-target， multi-component and multi-pathway approaches， has demonstrated remarkable efficacy and favorable safety profiles in treating DKD. Recent studies have demonstrated that active components of TCM can specifically target and modulate key effectors in apoptotic signaling pathways. Meanwhile， traditional compound formulations exert synergistic effects through multiple approaches such as replenishing deficiency and activating blood circulation， detoxifying and dredging collaterals， tonifying kidney essence， and removing stasis and purging turbidity， thereby comprehensively regulating critical pathological processes including endoplasmic reticulum stress and mitochondrial apoptosis pathways. This combined therapeutic approach of molecular targeting and holistic regulation provides novel strategies for delaying the progression of DKD. Based on this， this paper provides an in-depth analysis of key apoptotic signaling pathways and their regulatory mechanisms， while systematically summarizing recent research advances regarding the therapeutic effects of TCM active components， compound formulations， and proprietary Chinese medicines on DKD through modulation of these pathways， with particular emphasis on their underlying molecular mechanisms. These findings not only elucidate the modern scientific connotation and theoretical basis of TCM in treating DKD but also establish a solid theoretical and practical foundation for promoting the wider clinical application and further research of TCM in the field of DKD treatment.

Objective: To investigate the epidemiological characteristics, outcome patterns, and management strategies for blood donors with a positive direct antiglobulin test (DAT). Methods: A retrospective analysis was conducted on donation data from 808 386 donors from 2013 to 2023, focusing on those whose blood was discarded due to DAT positivity. Follow-up was performed on 125 DAT-positive donors, and 98 blood samples were collected. The samples were re-tested for DAT, DAT typing (IgG/C3d), and unexpected antibody screening using both the tube method and the microcolumn gel method. Results: Epidemiological characteristics: Retrospective data revealed 147 DAT-positive blood donors, yielding a positivity rate of 1/5 500. The DAT positivity rate using the tube method was 0.118‰ (49/416 893), lower than that of the microcolumn gel method at 0.25‰ (98/391 493). Among DAT-positive individuals, 44.2% (65/147) exhibited agglutination intensity<2+. Outcome analysis: The proportion of donors with positive DAT test results that converted to negative was 54.1% (53/98), with a conversion interval ranging from 8 to 117 months (mean 49.9 months). All donors in the negative conversion group had a previous DAT intensity<2+, whereas 95.6% (43/45) of the non-negative conversion group had intensity ≥2+ (P<0.001). Unexpected antibodies (anti-E, anti-M, etc.) were detected in 18 cases. Methodological differences: Review of results revealed 35 cases positive by both the DAT tube assay and microcolumn gel method. An additional 10 cases were positive by only one method: 5 were positive only by the tube assay, and 5 were positive only by the microcolumn gel method. Clinical validation: Among 14 DAT-positive donors who became negative and donated blood again, the clinical infusion efficacy of red blood cell products could be assessed in 10 cases, with 9 cases demonstrating effective infusion. Conclusion: Some DAT-positive blood donors may naturally convert to negative status, with the intensity of previous test results potentially serving as a key predictive factor for conversion. It is recommended to employ a combined approach of tube-based and microcolumn gel-based methods for retesting, concurrently screening for irregular antibodies. A tentative tiered management strategy is proposed: individuals with DAT intensity <2+ should be deferred for 12 months before retesting, while those with ≥2+ intensity should be permanently deferred.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections. Herein, we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering (SERS) and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease (MNase) in serum samples. The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) molecules to SERS-enhanced oxidized TMB (oxTMB), accompanied by the color change from colorless to blue. In the presence of S. aureus, the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads (MBs) to release alkaline phosphatase (ALP), which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away. Using this "on-to-off" triggering strategy, the target S. aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode. Meanwhile, the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis (n = 7) and healthy participants (n = 3), as well as monitored the prognostic progression of the disease (n = 2). Overall, benefiting from highly active and dense "hot spot" substrate, MNase-mediated cascade response strategy, and colorimetric/SERS dual-signal output, this methodology will offer a promising avenue for the early diagnosis of S. aureus infection.

Rapid and ultrasensitive detection of pathogen-associated biomarkers is vital for the early diagnosis and therapy of bacterial infections.Herein,we developed a close-packed and ordered Au@AgPt array coupled with a cascade triggering strategy for surface-enhanced Raman scattering(SERS)and colorimetric identification of the Staphylococcus aureus biomarker micrococcal nuclease(MNase)in serum samples.The trimetallic Au@AgPt nanozymes can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)molecules to SERS-enhanced oxidized TMB(oxTMB),accompanied by the color change from colorless to blue.In the presence of S.aureus,the secreted MNase preferentially cut the nucleobase AT-rich regions of DNA sequences on magnetic beads(MBs)to release alkaline phosphatase(ALP),which subsequently mediated the oxTMB reduction for inducing the colorimetric/SERS signal fade away.Using this"on-to-off"triggering strategy,the target S.aureus can be recorded in a wide linear range with a limit of detection of 38 CFU/mL in the colorimetric mode and 6 CFU/mL in the SERS mode.Meanwhile,the MNase-mediated strategy characterized by high specificity and sensitivity successfully discriminated between patients with sepsis(n=7)and healthy participants(n=3),as well as monitored the prog-nostic progression of the disease(n=2).Overall,benefiting from highly active and dense"hot spot"substrate,MNase-mediated cascade response strategy,and colorimetric/SERS dual-signal output,this methodology will offer a promising avenue for the early diagnosis of S.aureus infection.

Objective To explore the research status and future development trends of nursing case teaching at home and abroad,and to provide reference and guidance for the development of case teaching in nursing profession in China.Methods Data sources include the China National Knowledge Infrastructure(CNKI),Wanfang Data,and Web of Science databases.The CiteSpace software was used to visually analyze the research status and trends of nursing case teaching from January 2013 to Octo-ber 2023,covering nearly 11 years.Results A total of 2 889 valid articles were extracted.The important literature on nursing case teaching in China experienced a period of stable growth followed by rapid growth from 2013 to 2021.However,the number of publications and the number of publications in core journals on nursing case teaching abroad were higher than those in China.After 2021,both domestic and foreign publications on nursing case teaching showed a slow decline.The research on nursing case teaching in both domestic and foreign contexts is mainly conducted by universities,and the collaborative relationships between for-eign institutions and scholars are stronger than those within China.The research topics and hotspots in both domestic and foreign contexts are concentrated on the teaching applications for nursing students.Conclusion Nursing case teaching in China contin-ues to attract attention;however,compared to nursing case teaching abroad,the depth and breadth of research need to be further improved.Additionally,the collaboration between domestic authors and institutions is relatively limited.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

In situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

Objective: To analyze the improvement of executive function in children with attention deficit hyperactivity disorder (ADHD) aged 7-14 years with comprehensive intervention and drug therapy alone, to provide a basis for intervention research to improve ADHD. Methods: A total of 80 children with ADHD treated in the Third People s Hospital of Ganzhou from January 2021 to June 2022 were randomly divided into intervention group and control group. The intervention group received drug and comprehensive intervention therapy, and sensory integration training once a week for 60 to 90 min each for 12 weeks, and conduct related training for caregivers and school teachers, the control group received only drug therapy. The changes of executive function were assessed by the stroop color word association test and the Wisconsin Card Sorting Test (WCST) after 12 weeks of intervention. Results: After intervention, the results of the Stroop color word test in the intervention group (3.25±0.98, 4.92±1.40, 10.17±1.28) showed statistically significant differences ( t=12.94, 15.36, 26.34 , P <0.01) compared with those before intervention (6.47±1.92, 8.35±1.25, 16.55±1.57). There were also statistically significant differences ( t=6.76, 15.01, 16.15, P <0.01) in the control group ( 3.95 ±1.01, 5.45±1.15, 12.35±0.86) compared to those before intervention (6.17±1.87, 8.10±1.03, 16.02±1.38). Before intervention, the number of perseverative errors, non perseverative errors, and completed categories by WCST in the intervention group were (47.77±4.50, 35.50±2.37, 3.97±1.07), and in the control group were (46.45±7.34, 34.87±2.29, 3.70±1.11). After intervention, those of the intervention group and control group were (31.42±2.01, 24.75±2.05, 5.05±1.13) and (32.82±2.57, 25.55±1.04, 4.25±1.48), respectively. There were significant differences in the two groups before and after intervention ( t =21.93, 22.27 , -10.37; 10.84, 26.81, -6.90, P <0.01). After intervention, there were significant differences in the number of Stroop color word test errors, perseverative errors and non perseverative errors in WCST between the two groups ( t=-2.94, 2.29, -9.07, -2.35 , -2.06, P <0.05). Conclusion Through training for children and the therapy model of comprehensive intervention could significantly improve the executive function of children for a certain extent.

Objective:To analyze the clinical and pathological features of adolescent- onset primary nephrotic syndrome (PNS) in children (10 years≤age≤18 years), so as to explore the renal biopsy indications in adolescent-onset PNS.Methods:It was a single-center retrospective observational study. The clinical and pathological data of adolescent-onset PNS (age≥10 years) who underwent renal biopsy in Children's Hospital Affiliated to Nanjing Medical University from December 2004 to June 2022 were analyzed retrospectively.Results:A total of 110 children were included in the study, including 76 males (69.1%) and 34 females (30.9%), with the onset age ranging from 10 years to 14 years and 9 months. Forty-nine cases (44.5%) were accompanied by hematuria, including 14 cases (12.7%) of gross hematuria and 35 cases (31.8%) of microscopic hematuria. Twenty-five cases (22.7%) had hypertension, 19 cases (17.3%) had renal insufficiency, and 4 cases (3.6%) had low complement C3 at the onset. Fifty-two cases (47.3%) were steroid sensitive nephrotic syndrome and 58 cases (52.7%) were steroid resistant nephrotic syndrome. Biopsy results showed that minimal change disease(MCD) was the most common histopathological subtype (47.3%, 52 case), followed by focal segmental glomerulosclerosis (FSGS) in 22 cases (20.0%), IgA nephropathy (IgAN) in 17 cases (15.5%), membranous nephropathy (MN) in 7 cases (6.4%), mesangial proliferative glomerulonephritis in 5 cases (4.5%), IgM nephropathy in 4 cases (3.6%), membranous proliferative glomerulonephritis in 2 cases (1.8%), and C1q nephropathy in 1 case (0.9%). Among 44 children with simple type nephrotic syndrome, the pathological type was mainly MCD (77.3%), and 66 children with nephritic type nephrotic syndrome were mostly non-MCD (72.7%), such as IgAN, FSGS, MN, etc. If there are two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency or low C3 levels, the proportion of non-MCD would further increase to 92.0%(23/25). The pathological type of patient with gross hematuria or low C3-emia was non-MCD. The frequency of hematuria (69.0% vs. 17.3%, χ2=29.619, P<0.001), hypertension (31.0% vs. 13.5%, χ2=4.821, P=0.028) and renal insufficiency (24.1% vs. 9.6%, χ2=4.047, P=0.044) in non-MCD group was significantly higher than those in MCD group. Conclusions:If the clinical manifestation of PNS in adolescent over 10 years old is simple type nephrotic syndrome, the histopathological lesion is mostly MCD, and most of them are steroid sensitive. It is recommended to give hormone treatment first, and then perform renal biopsy if steroid resistance occurs; If the clinical manifestation is nephritic type nephrotic syndrome, the histopathological lesion is mostly non-MCD, especially those with gross hematuria or low C3-emia, or those have two or more clinical manifestations of persistent hematuria, hypertension, renal insufficiency and hypocomplement C3-emia, a kidney biopsy should be performed at onset.