OBJECTIVE To investigate the efficacy and safety of Wuling capsules combined with fluoxetine in the treatment of adolescents with first-episode moderate-to-severe depressive disorder accompanied by insomnia. METHODS The clinical data of 476 adolescents with first-episode moderate-to-severe depression accompanied by insomnia admitted to our hospital from June 2022 to May 2025， were retrospectively collected. According to the initial treatment regimen， patients were divided into a control group （241 cases， treated with fluoxetine alone） and an observation group （235 cases， treated with Wuling capsules combined with fluoxetine）. The depression severity （Hamilton Depression Rating Scale-17 Item and the Self-Rating Depression Scale scores）， sleep quality （Pittsburgh Sleep Quality Index score， sleep latency， wake after sleep onset， total sleep time， sleep efficiency）， serum neuroendocrine indicator （cortisol） and inflammatory markers （C-reactive protein， interleukin-6） were compared between the two groups before treatment and at 4th and 8th weeks of treatment. The effective rate at 8th weeks and the occurrence of adverse drug reactions （ADRs） were also compared between the two groups. RESULTS Before treatment， there were no significant differences in depression severity， sleep quality， serum neuroendocrine indicator， and inflammatory markers between the two groups （ P ＞0.05）. At 4th and 8th weeks， both groups showed significant improvement in these indicators compared to those before treatment， with the observation group demonstrating significantly greater improvement than the control group at the corresponding time points （ P ＜0.05）. At 8th week， the eff ective rate of the observation group was 90.21%， significantly higher than 80.50% in the control group （ P ＜0.05）. The incidence of nausea， headache， fatigue， dry mouth， and palpitations， as well as the total incidence of ADRs， did not differ significantly between the two groups （ P ＞0.05）. CONCLUSIONS Wuling capsules combined with fluoxetine can significantly improve the effective rate in adolescents with first-episode moderate-to-severe depression accompanied by insomnia， accelerate the relief of depressive symptoms， improve sleep quality， and reduce serum neuroendocrine indicator and inflammatory markers， with a favorable safety profile.

This study is designed to address the development, synthesis, and screening of non-animal-derived nanoantibody libraries. Furthermore, it seeks to elucidate the impact of framework region selection and complementarity-determining region (CDR) design on the characteristics of synthesized nanoantibody libraries. These investigations aim to establish a robust theoretical and technical foundation for enhancing the efficacy, diversity, and practical applicability of synthetic nanoantibody libraries. In this study, a new framework (IGHV3S65*01-IGHJ4*01) was identified based on the high-throughput sequencing results of natural nanobodies, and degenerate primers were designed based on the frequency of amino acids at each position in the complementarity-determining region (CDR) region to synthesize the coding fragments of nanobodies by overlap PCR. After 40 times of electro-transformation, a single-frame synthesized nanobody library (SS-Library) containing 6×10⁹ clones was obtained, and the titer of the library was demonstrated to be 10¹³ PFU/mL after rescue by the helper phage M13K07. Random 48 single colonies were picked for PCR, which revealed an insertion rate of 95.8%. Sanger sequencing results showed that 38 clones had complete sequences, none of which showed cysteines or stop codons, and no identical sequences appeared, suggesting that the library had higher diversity. The library was screened and validated with three antigens, including bovine serum albumin (BSA), acetylcholinesterase (AchE), and immunoglobulin G (IgG). Finally, 2 nanobodies against BSA, 10 against AchE, and 15 against IgG were obtained. One positive clone of each antigen was singled out for recombinant expression, and the results showed that all the three nanobodies were expressed in a soluble form. The binding activity of recombinantly expressed nanobodies was evaluated using indirect enzyme-linked immunosorbent assay (ELISA) and bio-layer interferometry (BLI). The results demonstrated that the anti-AChE and anti-IgG nanobodies exhibited specific binding to their respective antigens, with affinity constants (KD) of 294 nmol/L and 250 nmol/L, respectively. The nanobody synthetic library preparation method proposed in this study is simple and easy to use with low preference, and it is expected to be a universal nanobody discovery platform for the preparation and development of lead specific nanobodies.
Single-Domain Antibodies/biosynthesis* ; Peptide Library ; Complementarity Determining Regions/immunology* ; Animals

Lung cancer is the leading cause of cancer-related deaths worldwide. Radiation pneumonitis is a major complication in lung cancer radiotherapy. Four-dimensional computed tomography (4DCT) imaging provides dynamic ventilation information, which is valuable for lung function assessment and radiation pneumonitis prevention. Many methods have been developed to calculate lung ventilation from 4DCT, but a systematic comparison is lacking. Prediction of radiation pneumonitis using 4DCT-based ventilation is still in an early stage, and no comprehensive review exists. This paper presented the first systematic comparison of functional lung ventilation algorithms based on 4DCT over the past 15 years, highlighting their clinical value and limitations. It then reviewed multimodal approaches combining 4DCT ventilation imaging, dose metrics, and clinical data for radiation pneumonitis prediction. Finally, it summarized current research and future directions of 4DCT in lung cancer radiotherapy, offering insights for clinical practice and further studies.
Humans ; Lung Neoplasms/diagnostic imaging* ; Four-Dimensional Computed Tomography/methods* ; Radiation Pneumonitis/etiology* ; Algorithms ; Lung/radiation effects* ; Pulmonary Ventilation

Objective:To explore the characteristics of gut microbiota changes in individuals with Sarcopenic Obesity(SO)based on 16S rRNA sequencing.Methods:This cross-sectional study was conducted in Chongming District, Shanghai from April to November 2021.Fecal samples were collected from 20 elderly SO patients (case group)and 40 elderly non-SO individuals(control group)for 16S rRNA sequencing in order to analyze the diversity, structural composition, and species differences of gut microbiota, and then to predict the differential metabolic functions of the gut microbiota.Results:A total of 60 subjects were included.The case group consisted of 20 individuals(15 males and 5 females)with an average age of 73.15 ± 4.09 years; the control group included 40 individuals(20 males and 20 females)with an average age of 71.20 ± 4.12 years.The α-diversity analysis revealed that the richness indices ACE and Chao 1 of the case group were significantly lower than those of the control group( P<0.05), while the diversity indices Shannon and Simpson showed a trend of being lower in the case group, but the differences were not statistically significant( P>0.05). Principal coordinate analysis based on the Unweighted-unifrac distance metric demonstrated a statistically significant difference in β-diversity between the two groups( P=0.003). The structure and composition of the gut microbiota in the case group were altered, with a significant reduction in the relative abundance of the Blautia genus in the case group( P<0.05). LEfSe analysis identified 5 and 16 enriched microbial species in the case and control groups, respectively (Linear Discriminant Analysis score >2, P<0.05). Additionally, PICRUSt2 functional prediction revealed significant differences( P<0.05)in metabolic pathways between the two groups, including quorum sensing, fat digestion and absorption, and folate biosynthesis. Conclusions:The gut microbiota in elderly SO patients is disordered, mainly manifested as a decrease in diversity and characteristic changes in structural composition, as well as a reduction in the abundance of the beneficial bacterium Blautia.The Progression of SO is closely associated with gut microbiota metabolic disturbances, and targeting the gut microbiota is expected to become a novel therapeutic approach for SO.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Intravascular large B cell lymphoma (IVLBCL) is a rare, aggressive subtype of diffuse large B cell lymphoma, with nasal turbinate involvement being uncommon. We report a 51-year-old woman with a 1-month history of fever of unknown origin. Laboratory findings showed cytopenia, hypertriglyceridemia, elevated ferritin, increased soluble CD25, and bone marrow hemophagocytosis. No infectious cause was identified. PET-CT revealed abnormal 18F-fluorodeoxyglucose (FDG) uptake in the nasal turbinates. Turbinate biopsy revealed tumor cells localized predominantly within vascular lumens, positive for CD20, BCL6, PAX5, and MUM1, with a Ki-67 index >60%, confirming a diagnosis of IVLBCL with hemophagocytic lymphohistiocytosis (HLH). The patient received one cycle of the DEP regimen (liposomal doxorubicin, etoposide, and methylprednisolone) for HLH, followed by five cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and consolidation with auto-HSCT, achieving sustained complete remission. IVLBCL outcomes are heterogeneous; early diagnosis and prompt treatment improve survival, and R-CHOP plus auto-HSCT may be an effective strategy.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective To investigate the clinical efficacy of continuous irrigating mode of endoscopic ear sur-gery(CIM-EES)utilizing tragus cartilage-perichondrium without tympanomeatal flap elevation in repairing tympanic membrane perforation.Methods The date of 70 patients(70 ears)who underwent tympanic membrane repair under ear endoscopy from June 2020 to August 2023 were randomly selected and analyzed.They were divided into two groups according to the time of operation:CIM-EES group(observation group)of 44 cases(44 ears)and a conven-tional surgery group(control group)of 26 cases(26 ears).Both groups were repaired with tympanic membrane per-foration using the method of implanting tragus cartilage-perichondrium grafts under endoscope without tympa-nomeatal flap elevation.After 6 months of postoperative follow-up,two groups were compared in terms of operation time,frequency of the endoscopic lens scrubbing,postoperative healing rate,and hearing improvement outcomes.Results The average operation time of the observation group and the control group was 37.50±4.81 minutes and 50.31±8.21 minutes respectively,and the average number of scrubbing the endoscope was 6.77±1.51 and 35.54±7.13 respectively,there was statistical difference significance between the two groups(P＜0.01).All patients in the observation group were successfully repaired in the first stage,with the healing rate of 100％(44/44),and one patient in the control group had a postoperative small perforation that healed after secondary repair with the healing rate of 96.15％(25/26).There was no statistically significant difference between the two groups.The average 6 months postoperative air conduction threshold and air-bone conduction threshold of 0.5-4 kHz in the two groups improved compared to preoperative results(P＜0.01),with no statistically significant difference between the two groups(P＞0.05).Conclusion Endoscopic myringoplasty without tympanomeatal flap elevation under continuous irrigating mode has the advantages of high healing rate,short operation time,simple surgical operation,few post operation complications and good hearing improvement.

Objective To explore the application effect of key point nursing from the perspective of cluster analysis in preventing complications among patients with acute myocardial infarction(AMI)undergoing percutaneous coronary intervention(PCI).Methods A total of 97 AMI patients who un-derwent PCI in the cardiology department of our hospital from March 2022 to October 2023 were se-lected and divided into control group with 51 patients(March to December 2022)and observation group with 46 patients(January to October 2023)based on their admission time.The control group received routine nursing,while the observation group received key point nursing from the perspective of cluster analysis.The emergency nursing conditions,occurrence of complications during hospitaliza-tion,major adverse cardiovascular events(MACE),and satisfaction of patients were compared be-tween the two groups.Results The door-to-balloon(D2B)time,results of time to myocardial injury markers,and length of hospital stay were shorter in the observation group than those in the control group(P＜0.05).The incidence rates of reperfusion arrhythmia during surgery,total vascular com-plications after surgery,unplanned extubation,and total MACE within 6 months after surgery were lower in the observation group than those in the control group(P＜0.05).The overall satisfaction rate with nursing in the observation group was 95.65％(44/46),which was higher than 82.35％(42/51)in the control group(P＜0.05).Conclusion Key point nursing from the perspective of cluster analysis can shorten the rescue time and length of hospital stay for patients undergoing PCI,reduce the incidence of vascular complications and MACE during hospitalization,and improve satis-faction of patients.

Objective:To analyze the echocardiographic and genetic characteristics of fetuses with common arterial trunk（CAT）.Methods:A retrospective analysis was conducted on 77 480 fetal echocardiograms examined at the Maternal-Fetal Medicine center in Fetal Heart Disease of Beijing Anzhen Hospital from November 2010 to November 2024.Among them，106 fetuses were initially diagnosed with CAT，and 95 cases were ultimately confirmed（0.1%，95/77 480）. The echocardiographic and genetic features of CAT fetuses were analyzed. According to the modified Van Praagh classification，CAT was divided into types A1-A4［with ventricular septal defect（VSD）］and B1-B4（without VSD）based on the origin of the pulmonary artery branches and the presence or absence of a VSD. Additionally，CAT was categorized into isolated and complex types based on the presence of associated intracardiac or extracardiac anomalies.Results:① Among the 95 confirmed CAT fetuses，type A accounted for 90.5%（86/95），and type B accounted for 9.5%（9/95）. All 9 type B CAT fetuses exhibited no overriding of the arterial trunk ， with 8 cases showing left ventricular hypoplasia accompanied by mitral atresia or absence.② Of the 95 CAT fetuses，14 were isolated（14.7%，14/95） ， and 81 were complex（85.3%，81/95）.The main associated intracardiac anomalies included：single ventricle（22 cases），complete atrioventricular septal defect（12 cases），anomalous pulmonary venous drainage（10 cases），right aortic arch with mirror-image branching（16 cases），and persistent left superior vena cava（14 cases）. ③ Genetic testing was performed in 31 fetuses，with 18 showing positive results，primarily 22q11.21 deletion syndrome（29.0%，9/31）. Conclusions:Apart from VSD，the most common intracardiac anomaly associated with CAT fetuses is single ventricle. Type B CAT without trunk overriding is often associated with left ventricular hypoplasia and mitral atresia or absence. The most frequent genetic abnormality in CAT fetuses is 22q11.21 deletion syndrome. Prenatal echocardiography should clarify the CAT subtype and associated anomalies，and genetic testing is strongly recommended for perinatal counseling and prognostic evaluation.