Objective To compare the clinical efficacy and safety differences between the triple immunosuppressive regimen of mizoribine (MZR) or mycophenolate mofetil (MMF) combined with tacrolimus (Tac) and glucocorticoids of kidney transplant recipients in one year after transplantation. Methods A single-center retrospective cohort study design was adopted. The clinical data of 156 patients who underwent the first allogeneic kidney transplantation at the Third Hospital of Peking University from January 2022 to December 2024 were included. The patients were divided into the MZR group (78 cases) and the MMF group (78 cases) based on the initial immunosuppressive regimen after transplantation. The baseline data, medication use in one year after transplantation, blood routine indicators, adverse events and clinical outcomes were compared between the two groups. For the repeated-measurement longitudinal data, repeated-measurement analysis of variance was used to evaluate the main effects of the groups, time and their interaction effects. Results At the primary efficacy endpoint, there were no statistically significant differences in the one-year survival rate, graft survival rate and incidence of acute rejection between the two groups (all P > 0.05). In terms of medication patterns and laboratory test indicators, there were significant time main effects and "time × group" interaction effects for Tac dosage (all P < 0.05). The Tac dosage in the MZR group was lower than that in the MMF group from 2 to 3 months after transplantation, and it was higher in the MZR group than in the MMF group from 7 to 12 months and one year after transplantation. White blood cell count in the MZR group was higher at one month after transplantation, and the platelet count was higher one year after transplantation (all P < 0.05). In terms of infection, the incidence of novel coronavirus and Pneumocystis jirovecii pneumonia infections in the MZR group was lower (all P < 0.05). In terms of metabolic indicators, the post-transplantation uric acid level was better in the MZR group than in the MMF group, but the total cholesterol level was higher one year after transplantation (all P < 0.05). In terms of liver function, there was a brief and mild increase in transaminase in the early stage after transplantation in the MZR group. Conclusions During the one-year follow-up after transplantation, both the MZR and MMF regimens demonstrate comparable immunosuppressive efficacy and overall safety in Chinese kidney transplant recipients. The MZR regimen shows clear advantages in reducing specific infection risks, alleviating bone marrow suppression and improving uric acid metabolism, but its potential impact on blood lipids needs to be monitored. Therefore, the MZR regimen may be an effective and safe alternative immunosuppressive option for kidney transplant recipients, especially those with high infection risk, poor hematological tolerance, or comorbid hyperuricemia.

Objective To evaluate the diagnostic efficacy of the Kaiser score for ultrasound(US)BI-RADS 4A lesions and the potential to avoid unnecessary biopsies.Methods Data of patients who underwent breast US and magnetic resonance imaging(MRI)between May 2019 and June 2023 were retrospectively collected,and all cases were confirmed by puncture biopsy or surgical pathology.The diagnostic efficacy of Kaiser score and MRI BI-RADS classification for US BI-RADS 4A lesions was calculated and compared using pathologic findings as the gold standard.Results A total of 119 lesions(74 benign and 45 malignant lesions)were found in the 119 patients.The diagnostic efficacy of the Kaiser score was significantly better than that of the MRI BI-RADS classification(AUC:0.88 vs.0.65,P＜0.000 1).The concordance of the Kaiser score results with the pathologic findings and the inter-observer concordance were better than that of the MRI BI-RADS classification.Unnecessary biopsies could be avoided in 87.8％(65/74)and 33.8％(25/74)of the cases when the Kaiser score and the MRI BI-RADS classification were applied for the diagnosis of US BI-RADS 4A lesions,respectively.Conclusion The Kaiser score can provide a diagnostic basis for risk stratification of US BI-RADS 4A lesions,and its diagnostic efficacy and inter-observer agreement are superior to those of MRI BI-RADS classification.

Perimenopausal anxiety and depression state fall under the categories of"visceral agitation"and"perimenopausal syndrome"in traditional Chinese medicine(TCM).Grounded in the theory of"Yang transforms qi,yin shapes form",this study posits that the pathogenesis of this condition is complex,often presenting with concurrent deficiency and excess syndromes,and is closely associated with yang deficiency-induced stagnation and qi stagnation leading to mental decline.The pathological mechanism is summarized as yang deficiency being the root and qi stagnation the manifestation.This article proposes a"yang-oriented treatment"approach for perimenopausal anxiety-depression disorders,employing a stepwise integrated acupuncture protocol termed"One Needling,Two Moxibustion,Three Consolidation":"One Needling"prioritizes regulating qi flow via acupuncture to soothe the liver and harmonize the spirit;"Two Moxibustion"utilizes refined moxibustion to warm yang,resolve stagnation,and activate yang circulation;"Three Consolidation"combines bloodletting therapy to remove stasis and regenerate tissues with intradermal needle embedding to stimulate yang and regulate visceral functions.This synergistic protocol aims to nourish the heart-mind,awaken the orifices of consciousness,alleviate perimenopausal anxiety and depressive symptoms,and consolidate therapeutic efficacy.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

Objective To analyze the clinical features,therapeutic effects and relapse factors of anti-myelin oligodendrocyte glycoprotein-IgG antibody associated diseases(MOGAD)in adult patients.Methods The clinical data of 15 adult patients with MOGAD were retrospectively analyzed.The patients were divided into conventional treatment group and plasma exchange group according to the treatment.The efficacy was analyzed by comparing the scores of mRS and expanded disability status scale(EDSS)before and after treatment.And the patients were divided into single course group and relapse course group according to the course of disease,and the relapse-related factors were analyzed.Results There were 10 patients in the conventional treatment group and 5 patients in the plasma exchange treatment group,and the mRS and EDSS of the two groups were significantly lower after treatment than those before treatment(all P＜0.05).There were no significant differences in mRS and EDSS scores between the plasma exchange group and the conventional treatment group after treatment(all P＞0.05).There were 11 patients in the unidirectional course group and 4 patients in the relapsing course group.There were no significant differences between the two groups in gender,age,severity of disease,clinical phenotype,antibody titer,and treatment plan in the acute stage(all P＞0.05).The detection rate of OCB in CSF of patients with relapse course was significantly higher than that of patients with single course.The proportion of patients with maintenance oral hormone duration＜6 months in recurrent disease course group was significantly higher than that in single disease course group(all P＜0.05).Conclusions MOGAD patients respond effectively to glucocorticoid pulse therapy and double filtration plasmapheresis during the acute phase,with a favorable prognosis.MOGAD have a risk of recurrence,those who present with encephalitis at the onset,have positive OCB in CSF,and have a shorter duration of oral glucocorticoid maintenance treatment may be more prone to recurrence.Acute-phase treatment with double filtration plasmapheresis may reduce the recurrence rate.

Perimenopausal women are more susceptible to fire pathogen disturbances,often resulting in the restlessness of the mind owing to the deficiency and decline of the thoroughfare and conception vessels,as well as the insufficiency of the essence and blood of the viscera.CHENG Zhongling's theory of thief and child fire in Medical Insights proposes that thief fire primarily arises from exogenous pathogen invasion and improper diet,leading to syndromes such as food retention in the stomach or phlegm-fire stagnation.In contrast,child fire is generated endogenously,often owing to liver and kidney deficiency,resulting in an imbalance of water and fire and liver dysfunction,leading to excessive fire transformation.This theory provides a novel perspective for understanding the pathogenesis of perimenopausal insomnia.An in-depth exploration of the role of thief fire and child fire in perimenopausal insomnia is presented,along with a detailed discussion of corresponding treatment strategies.For the invasion of thief fire,therapeutic approaches include ascending and dispersing stagnant fire,clearing and moistening to remove interior heat,purging the heat accumulation to unblock the bowels,and subduing the fire and nourishing yin to eliminate depression.When child fire disturbs the spirit,treatment methods involve smoothing and relieving the liver qi to clear the stagnant heat,nourishing the true yin to restrain the yang,warming and nurturing the primordial qi and harmonizing the nutrient and defensive qi,and guiding and reducing the deficient heat to remove the floating fire.Clinical practice necessitates precise identification of thief and child fire,thorough investigation of exogenous pathogens and internal damage,and careful differentiation between deficiency and excess,as well as the superficial and internal aspects.Strict adherence to the treatment principle of"nourishing the child fire can drive out the thief fire,but driving out the thief fire should not harm the child fire"ensures a balanced approach.By harmonizing the yin and yang of the viscera and allowing the mind to be at ease,this strategy effectively alleviates perimenopausal insomnia.The application of these principles provides a practical and feasible theoretical foundation and practical guidance for the treatment of perimenopausal insomnia using traditional Chinese medicine.

The phrase"wood element characterized by spreading harmony"from the Huangdi Neijing five-phase theory summarizes the fundamental nature and functions of the wood element,emphasizing the crucial significance of the harmonious virtue of wood in promoting the generation and transformation of all things.In human physiology,"wood element characterized by spreading harmony"corresponds to the harmonious spreading of liver-gallbladder qi,ensuring smooth liver qi regulation and proper functioning of the ascending-descending movement mechanisms.Bipolar disorder,categorized in traditional Chinese medicine as"depression"or"manic depressive psychosis,"primarily arises from hepatic wood dysfunction.Insufficient wood qi dispersion typically manifests as a depressive phase,whereas excessive dispersion leads to a manic phase,with alternating manic-depressive phase indicating qi movement disorder.By integrating wood qi characteristics,disease pathogenesis of bipolar disorder,and our team's clinical experience in treating emotional disorders,this study developed an integrated acupuncture and moxibustion diagnosis and treatment approach for bipolar disorder,focusing on soothing the liver and regulating spirit,structured as"acupuncture-moxibustion-consolidation."Based on the physiological characteristics of"wood element characterized by spreading harmony,"from liver failing to controll conveyance and dispersion:depressive phase should apply warm-nourishing growth method,manic phase should suppress hyperactive liver for tranquillizing mind method,and alternating manic-depressive phase should apply harmonized rigidity-flexibility method.These methods aim to regulate the spirit of the heart and brain,harmonize the qi movement of the spleen and stomach,and replenish the essence and blood of the liver and kidney.Clinical application through syndrome differentiation has demonstrated satisfactory therapeutic outcomes.

Objective:To construct patient-derived xenograft (PDX) models from head and neck squamous cell carcinoma (HNSCC) patients, to explore the effect of immune reconstitution timing on the PDX modeling and immune microenvironment in humanized immune system mice (huHSC-NCG-hIL15), and to provide a reliable animal model for research on the mechanisms of head and neck squamous carcinoma and for studies on immune therapy drug interventions.Methods:This study enrolled 28 HNSCC patients (25 laryngeal carcinomas, 3 hypopharyngeal carcinomas). PDX models were established in Balb/c nude (nu) mice, NSG mice, and humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Fresh HNSCC samples were transplanted into Balb/c nu and NSG mice to generate PDX models, with subsequent analysis of success-associated factors. One successfully established PDX tumor was subsequently implanted into humanized immune system-reconstituted huHSC-NCG-hIL15 mice. Tumor transplantation was performed at distinct immune reconstruction timepoints (2 vs. 7 weeks post-reconstitution), and tumor growth patterns were monitored. Flow cytometry and multiplex immunohistochemical staining were utilized to characterize immunological profiles in peripheral lymphoid organs and tumor microenvironments. Hematoxylin-eosin (HE) staining was employed to assess histomorphological concordance between primary patient tumors and PDX model tissues. Results:HNSCC PDX models were successfully established. NSG mice exhibited a higher and more stable tumor take rate compared to Balb/c nu mice (pilot study: 4/10 vs. 3/10 cases; mean take rate 60%-80% vs. 20%-60 %). The PDX success rate in NSG mice was 46.4% (13/28). In the huHSC-NCG-hIL15 mice model with immune reconstitution at 7 weeks, tumors grew significantly faster, and the PDX modeling process was shorter (617 mm3 at day 70 in 7-week cohort vs.280 mm3 in 2-week cohort). Flow cytometry analysis of the immune microenvironment showed that at 7 weeks of immune reconstitution, the proportions of B cells in the spleen and tumor tissues(2-week vs. 7-week: spleen 16.2% vs. 61.7%, tumor 26.0% vs. 38.8%) and myeloid cells in the spleen (2-week vs. 7-week: spleen 47.2% vs. 88.1 %) were significantly higher, while mice at 2 weeks post-reconstitution showed a higher proportion of T cells (2-week vs. 7-week: spleen 13.2% vs. 9.3%, tumor 4.8% vs. 2.5%). HE results demonstrated that the tumor tissues in PDX models maintained a high degree of morphological similarity to the primary tumors in both NSG and huHSC-NCG-hIL15 mouse models. Conclusion:The HNSCC PDX modeling protocol demonstrates operational feasibility and high reproducibility, establishing this model as a robust platform for mechanistic and immunotherapeutic studies.

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.

The phrase"wood element characterized by spreading harmony"from the Huangdi Neijing five-phase theory summarizes the fundamental nature and functions of the wood element,emphasizing the crucial significance of the harmonious virtue of wood in promoting the generation and transformation of all things.In human physiology,"wood element characterized by spreading harmony"corresponds to the harmonious spreading of liver-gallbladder qi,ensuring smooth liver qi regulation and proper functioning of the ascending-descending movement mechanisms.Bipolar disorder,categorized in traditional Chinese medicine as"depression"or"manic depressive psychosis,"primarily arises from hepatic wood dysfunction.Insufficient wood qi dispersion typically manifests as a depressive phase,whereas excessive dispersion leads to a manic phase,with alternating manic-depressive phase indicating qi movement disorder.By integrating wood qi characteristics,disease pathogenesis of bipolar disorder,and our team's clinical experience in treating emotional disorders,this study developed an integrated acupuncture and moxibustion diagnosis and treatment approach for bipolar disorder,focusing on soothing the liver and regulating spirit,structured as"acupuncture-moxibustion-consolidation."Based on the physiological characteristics of"wood element characterized by spreading harmony,"from liver failing to controll conveyance and dispersion:depressive phase should apply warm-nourishing growth method,manic phase should suppress hyperactive liver for tranquillizing mind method,and alternating manic-depressive phase should apply harmonized rigidity-flexibility method.These methods aim to regulate the spirit of the heart and brain,harmonize the qi movement of the spleen and stomach,and replenish the essence and blood of the liver and kidney.Clinical application through syndrome differentiation has demonstrated satisfactory therapeutic outcomes.