BACKGROUND:Previously,a SENP1 gene-silenced human alveolar epithelial cell line was successfully constructed in vitro,and the role of SENP1 in hyperoxic lung injury was investigated at the cellular level.OBJECTIVE:To construct a mouse model of alveolar type II epithelial cell-specific knockout of SENP1 gene based on the Cre-loxP recombinase system.METHODS:SENP1flox/-mice were self-crossed to obtain SENP1flox/flox and SENP1flox/-mice;Sftpc-Cre+/+mice were crossed with wild-type mice to obtain more Sftpc-Cre+/-mice.Sftpc-Cre+/+or offspring Sftpc-Cre+/-mice were crossed with SENP1flox/-or offspring SENP1flox/flox mice to obtain SENP1flox/-Sftpc-Cre+/-double heterozygous mice.SENP1flox/-Sftpc-Cre+/-mice were then crossed with SENP1flox/flox mice to obtain SENP1flox/floxSftpc-Cre+/-mice.The genomic DNA was extracted by tail clipping and amplified by PCR.The amplified product was subjected to agarose gel electrophoresis to determine the mouse genotypes.Lung tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were subjected to immunofluorescence double-labelling and western blot assay to verify the knockdown effect of SENP1 gene.Heart,liver,lung and kidney tissues of SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice were stained with hematoxylin-eosin to observe the histomorphology of each organ in the two groups of mice.RESULTS AND CONCLUSION:SENP1flox/floxSftpc-Cre+/-mice were correctly screened by agarose gel electrophoresis.Immunofluorescence double-labeling experiments showed that the mean fluorescence intensity of SENP1 was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with that of SENP1flox/flox mice(P<0.01)and no significant co-localization of SENP1 and Sftpc was observed(P<0.01).Western blot results showed that SENP1 protein expression was reduced in lung tissues of SENP1flox/floxSftpc-Cre+/-mice compared with SENP1flox/flox mice(P<0.001).Hematoxylin-eosin staining showed no significant alterations in the histomorphology of heart,liver,lung and kidney tissues in SENP1flox/flox and SENP1flox/floxSftpc-Cre+/-mice.This study successfully constructed alveolar type II epithelial cell-specific knockout SENP1 gene mice using the Cre-loxP recombinase system,which provides a good tool for the subsequent study of the role of SENP1 gene in lung diseases such as bronchopulmonary dysplasia and idiopathic pulmonary fibrosis,in which alveolar type II epithelial cells are the main damage cells.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective To analyze the law of acupoint selection and compatibility of acupuncture and moxibustion and the application law of acupuncture and moxibustion in the treatment of lactational mastitis using complex network technology.Methods The clinical research literature about acupuncture and moxibustion treatment of lactational mastitis was retrieved from CNKI,CBM,Wanfang Data,VIP and PubMed from the establishment of the databases to March 15,2025.The literature was screened according to the standards to build a prescription database of acupuncture and moxibustion treatment of lactational mastitis.SPSS Modeler 18.0 software was used to analyze association rules,and Gephi 0.9 software was used for complex network analysis.Results A total of 108 articles were included.141 acupuncture and moxibustion prescriptions were extracted,involving 74 acupoints,with a total use frequency of 677 times.The high-frequency acupoints were Jianjing,Danzhong,Rugen,Zusanli,Neiguan,etc.Specific acupoints were mainly composed of Wushu acupoints(169 times,21.10%);the acupoints were mainly distributed in the limbs(36);the most frequently used meridian was stomach meridian(168 times,24.82%).The combination of acupoints with the highest correlation was Jianjing-Neiguan-Rugen.Complex network analysis identified 22 core acupoints,with the most commonly used acupuncture method being filiform needle acupuncture(79 times).Conclusion Acupuncture and moxibustion treatment of lactational mastitis pays special attention to the selection of stomach meridian.The compatibility mode is mainly from top to bottom,and the corresponding acupoints are selected according to syndrome differentiation.

OBJECTIVES: Prolonged invasive mechanical ventilation is associated with increased risks of severe complications such as retinopathy of prematurity and bronchopulmonary dysplasia. Although neonatal intensive care unit (NICU) follow the principle of early extubation, extubation failure rates remain high, and reintubation may further increase the risk of adverse outcomes. This study aims to identify risk factors and short-term prognosis associated with first extubation failure in neonates, to provide evidence for effective clinical intervention strategies. METHODS: Clinical data of neonates who received invasive ventilation in the NICU of Children's Hospital of Nanjing Medical University from January 1, 2019, to December 31, 2021, were retrospectively collected. Neonates were divided into a successful extubation group and a failed extubation group based on whether reintubation occurred within 72 hours after the first extubation. Risk factors and short-term outcomes related to extubation failure were analyzed. RESULTS: A total of 337 infants were included, with 218 males (64.69%). Initial extubation failed in 34 (10.09%) infants. Compared with the successful extubation group, the failed extubation group had significantly lower gestational age [(31.37±5.14) weeks vs (34.44±4.07) weeks], age [2.5 (1.00, 8.25) h vs 5 (1.00, 22.00) h], birth weight [(1 818.97±1128.80) g vs (2 432.18±928.94) g], 1-minute Apgar score (6.91±1.90 vs 7.68±2.03), and the proportion of using mask oxygenation after extubation (21% vs 46%) (all P<0.05). Conversely, compared with the successful extubation group, the failed extubation group had significantly higher rates of vaginal delivery (59% vs 32%), caffeine use during mechanical ventilation (71% vs 38%), dexamethasone use at extubation (44% vs 17%), the highest positive end-expiratory pressure level within 72 hours post-extubation [6(5.00, 6.00) cmH₂O vs 5 (0.00, 6.00) cmH₂O] (1 cmH₂O=0.098 kPa), the highest FiO₂ within 72 hours post-extubation [(34.35±5.95)% vs (30.22±3.58)%], and duration of noninvasive intermittent positive pressure ventilation after extubation [0.5 (0.00, 42.00) hours vs 0 (0, 0) hours] (all P<0.05). Multivariate analysis identified gestational age <28 weeks (OR=5.570, 95% CI 1.866 to 16.430), age at NICU admission (OR=0.959, 95% CI 0.918 to 0.989), and a maximum FiO₂≥35% within 72 hours post-extubation (OR=4.541, 95% CI 1.849 to 10.980) as independent risk factors for extubation failure (all P<0.05). Additionally, the failed extubation group exhibited significantly higher incidences of necrotizing enterocolitis grade II or above, moderate-to-severe bronchopulmonary dysplasia, severe bronchopulmonary dysplasia, retinopathy of prematurity, treatment abandonment due to poor prognosis, and discharge on home oxygen therapy (all P<0.05). Total hospital length of stay and total hospitalization costs were also significantly increased in the failed extubation group (all P<0.05). CONCLUSIONS Gestational age <28 weeks, younger age at NICU admission, and FiO₂≥35% after extubation are high-risk factors for first extubation failure in neonates. Extubation failure markedly increases the risk of adverse clinical outcomes.
Humans ; Infant, Newborn ; Male ; Female ; Airway Extubation/adverse effects* ; Risk Factors ; Retrospective Studies ; Respiration, Artificial/methods* ; Intensive Care Units, Neonatal ; Prognosis ; Gestational Age ; Bronchopulmonary Dysplasia ; Infant, Premature ; Treatment Failure ; Intubation, Intratracheal

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [⁶⁴Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [⁶⁴Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [⁶⁴Cu]QM-2303 from the bloodstream. Administration of a single dose of [¹⁷⁷Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [⁶⁴Cu]/[¹⁷⁷Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.

INTRODUCTION: Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD. METHODS: In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging. RESULTS: A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline. CONCLUSIONS: Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies. REGISTRATION ClinicalTrials.gov , NCT07034222.
Humans ; Alzheimer Disease/drug therapy* ; Male ; Female ; Aged ; Middle Aged ; Cognitive Dysfunction/drug therapy* ; Aged, 80 and over ; Amyloid beta-Peptides/metabolism* ; Biomarkers ; East Asian People

OBJECTIVE: To compare clinical effect of arthroscopic double row fixation and single row fixation in treating Ideberg typeⅠA scapular glenoid fracture. METHODS: From June 2018 to December 2022, 26 patients with Ideberg typeⅠA scapular glenoid fracture treated with shoulder arthroscopy were divided into single-row anchor group and double-row anchor group according to the fixation method of fracture block. There were 12 patients in single-row anchor group, including 7 males and 5 females, aged from 25 to 53 years old with an average of (38.42±9.61) years old;the time from injury to operation ranged from 2 to 7 days with an average of (4.75±1.82) days. There were 14 patients in double-row anchor group, including 10 males and 4 females, aged from 21to 53 years old with an average of (37.36±10.19) years old;the time from injury to operation ranged from 1 to 8 days with an average of (4.21±2.01) days. The changes of shoulder joint flexion, abduction, lateral lateral rotation, Constant-Murley shoulder function score and Rowe scores were compared between two groups before operation and 1 year after operation. The percentage of bone mass in pelvis area before operation and the percentage of bone defect in pelvis area at the latest follow-up were compared between two groups. RESULTS: All patients were followed up for 12 to 15 months with an average of (13.08±1.17) months in single-row anchor group and 12 to 15 months with an average of (13.29±1.07) months in double-row anchor group, with no statistical significance between two groups (P>0.05). The results of anterior flexion, abduction and lateral lateral rotation in single-row anchor group were(86.67±6.62) °, (79.50±5.68) °, (38.17±1.70) ° before operation, and (162.50±4.52)°, (169.17±3.35)°, (50.67±10.20)° at 1 year after operation; while in double-row anchor group were (84.14±5.48) °, (81.71±5.20) °, (39.29±3.63) ° before operation and (162.29 ± 5.53) °, (167.14±3.61) °, (56.93±9.56) ° at 1 year after operation;the difference between two groups before operation and 1 year after operation was statistically significant (P<0.05). There were no significant difference between two groups (P>0.05). Constant-Murley scores and Rowe scores in single-row anchor group were (55.42±3.75), (43.75±18.49) before operation and (94.83±2.21), (95.42±4.50) at 1 year after operation, respectively;while in double-row anchor group were (54.50±7.88), (41.79±18.25) before operation and (94.36±4.73), (95.00±4.80) at 1 year after operation;there was no significant difference in Constant-Murley score and Rowe score between two groups before operation and 1 year after operation (P>0.05). There was significant difference in the percentage of bone mass in pelvis area between two groups before operation (P>0.05). There was no significant difference in the percentage of bone defect in the shoulder area between single-row anchor group(4.42±1.51)% and double-row anchor group (2.71±1.44)% at 1 year after operation (P<0.05). CONCLUSION Both single and double row fixation techniques for the treatment of Ideberg typeⅠA scapular glenoid fracture could receive satisfactory functional recovery. However, double-row fixation has more advantages in reducing bone resorption of fracture mass.
Humans ; Female ; Male ; Middle Aged ; Arthroscopy/methods* ; Adult ; Scapula/surgery* ; Case-Control Studies ; Fractures, Bone/physiopathology* ; Fracture Fixation, Internal/methods* ; Shoulder Joint/physiopathology* ; Range of Motion, Articular

OBJECTIVE: The aim of this study is to analyze the clinical features and genetic etiology of a patient with multiple morphological abnormalities of the sperm flagella (MMAF) retrospectively. METHODS: A severely oligospermic patient from the Reproductive Center of the First Affiliated Hospital of Ningbo University was selected as the study subject. Clinical data and examination results were collected. High-throughput sequencing and bioinformatics were used to analyze the genetic etiology. And Sanger sequencing was employed to validate findings in the family. Transmission electron microscopy (TEM) was used to observe the sperm ultrastructure, and immunofluorescence analysis was performed to examine the localization of FSIP2 protein in the sperm. RESULTS: The patient presented with severe oligospermia, and sperm morphology displayed MMAF. TEM revealed fibrous sheath and 9+2 microtubule structural disruptions in the sperm. Sequencing identified compound heterozygous variants in the FSIP2 gene (c.17798C > T, c.5927T > G), inherited from the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, the variants were classified as pathogenic. The patient's spouse underwent intracytoplasmic single sperm injection, resulting in one embryo, but no clinical pregnancy occurred after embryo transfer. CONCLUSION This study reported the mutation of FSIP2 gene c.17798C > T, c.5927T > G in a patient with MMAF. These findings expand the mutational spectrum of the FSIP2 gene and provide insights for genetic and assisted reproductive counseling for patients with MMAF.
Humans ; Male ; Sperm Tail/pathology* ; Heterozygote ; Oligospermia/genetics* ; Spermatozoa ; Mutation ; Infertility, Male/genetics* ; Adult ; Pedigree ; Retrospective Studies ; Sperm Injections, Intracytoplasmic

Objective To analyze the law of acupoint selection and compatibility of acupuncture and moxibustion and the application law of acupuncture and moxibustion in the treatment of lactational mastitis using complex network technology.Methods The clinical research literature about acupuncture and moxibustion treatment of lactational mastitis was retrieved from CNKI,CBM,Wanfang Data,VIP and PubMed from the establishment of the databases to March 15,2025.The literature was screened according to the standards to build a prescription database of acupuncture and moxibustion treatment of lactational mastitis.SPSS Modeler 18.0 software was used to analyze association rules,and Gephi 0.9 software was used for complex network analysis.Results A total of 108 articles were included.141 acupuncture and moxibustion prescriptions were extracted,involving 74 acupoints,with a total use frequency of 677 times.The high-frequency acupoints were Jianjing,Danzhong,Rugen,Zusanli,Neiguan,etc.Specific acupoints were mainly composed of Wushu acupoints(169 times,21.10%);the acupoints were mainly distributed in the limbs(36);the most frequently used meridian was stomach meridian(168 times,24.82%).The combination of acupoints with the highest correlation was Jianjing-Neiguan-Rugen.Complex network analysis identified 22 core acupoints,with the most commonly used acupuncture method being filiform needle acupuncture(79 times).Conclusion Acupuncture and moxibustion treatment of lactational mastitis pays special attention to the selection of stomach meridian.The compatibility mode is mainly from top to bottom,and the corresponding acupoints are selected according to syndrome differentiation.