Objective To evaluate the effect of a multidisciplinary collaborative quality control management (hereinafter referred to as "QC management") on improving the performance of biological safety cabinets in hospital. Methods A total of 63 ClassⅡbiological safety cabinets in active use at Peking University Third Hospital were selected as the study subjects using the before-after study mode. Conventional management was implemented on the biological safety cabinets from 2018 to 2021. QC management was used in 2022. The compliance of biological safety cabinets management norm and performance differences under the two models were compared. Results The median and the 25th and 75th percentiles [M(P₂₅, P₇₅)] of the service life among these 63 biological safety cabinets were 3 (1,6) years. The overall performance pass rate and inflow velocity pass rate of biological safety cabinets were higher in the QC management than that in the conventional management (90.5% vs 65.1%, 96.8% vs 84.1%, both P<0.05). However, there was no significant difference in downflow velocity, high-efficiency particulate air filter integrity, cleanliness, airflow smoke pattern, noise, and illumination pass rates of biosafety cabinets before and after the implementation of QC management (79.4% vs 88.9%, 90.5% vs 100.0%, 96.8% vs 100.0%, 85.7% vs 100.0%, 100.0% vs 100.0%, and 85.7% vs 96.8%, respectively; all P>0.05). Conclusion sQC management improves the standardization of biological safety cabinet management and key performance indicators in hospital.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation and joint damage, accompanied by the accumulation of plasma cells, which contributes to its pathogenesis. Understanding the genetic alterations occurring during plasma cell differentiation in RA can deepen our comprehension of its pathogenesis and guide the development of targeted therapeutic interventions. Here, our study elucidates the intricate molecular mechanisms underlying plasma cell differentiation by demonstrating that PRDX1 interacts with DOK3 and modulates its degradation by the autophagy-lysosome pathway. This interaction results in the inhibition of plasma cell differentiation, thereby alleviating the progression of collagen-induced arthritis. Additionally, our investigation identifies Salvianolic acid B (SAB) as a potent small molecular glue-like compound that enhances the interaction between PRDX1 and DOK3, consequently impeding the progression of collagen-induced arthritis by inhibiting plasma cell differentiation. Collectively, these findings underscore the therapeutic potential of developing chemical stabilizers for the PRDX1-DOK3 complex in suppressing plasma cell differentiation for RA treatment and establish a theoretical basis for targeting PRDX1-protein interactions as specific therapeutic targets in various diseases.

Natural antimicrobial peptides (AMPs) are promising candidates for the development of a new generation of antimicrobials to combat antibiotic-resistant pathogens. They have found extensive applications in the fields of medicine, food, and agriculture. However, efficiently screening AMPs from natural sources poses several challenges, including low efficiency and high antibiotic resistance. This review focuses on the action mechanisms of AMPs, both through membrane and non-membrane routes. We thoroughly examine various highly efficient AMP screening methods, including whole-bacterial adsorption binding, cell membrane chromatography (CMC), phospholipid membrane chromatography binding, membrane-mediated capillary electrophoresis (CE), colorimetric assays, thin layer chromatography (TLC), fluorescence-based screening, genetic sequencing-based analysis, computational mining of AMP databases, and virtual screening methods. Additionally, we discuss potential developmental applications for enhancing the efficiency of AMP discovery. This review provides a comprehensive framework for identifying AMPs within complex natural product systems.

Objective To investigate the synergistic therapeutic effects of HER2 antibody-drug conjugate(HER2-ADC)combined with anti-PD-1 antibody(anti-PD-1)on HER2-expressing bladder cancer and elucidate its regulatory mechanisms on the tumor immune microenvironment.Methods Orthotopic tumor models were established in 40 female C57BL/6 mice(6～8 weeks old,body mass 18～22 g)using MB49 bladder cancer cells overexpressing human HER2.When tumors reached 100 mm3,the mice were randomized into(n=10)control(intraperitoneal injection of 1.0 mL PBS),anti-PD-1(200 μg per mouse every 3 d),HER2-ADC(2.5 mg/kg once weekly),and combination groups(same regimens as above monotherapy).Tumor volume and body mass were measured every 3 d during 28-day treatment.Tumor growth kinetics and survival rates were analyzed.Post-treatment survival was monitored until natural death to determine median survival time(n=5).At day 28,blood and tumor samples(n=5)were collected to detect myeloid-derived suppressor cells(MDSCs;CD11b?Gr1?)and regulatory T cells(Tregs;CD4?CD25?FOXP3?)with flow cytometry,tumor-infiltrating CD3?T,CD8?T,and FOXP3?T cells with immunohistochemical assasy,and liver/kidney functions[alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(CRE)]and tissue damage indicators[lactate dehydrogenase isoenzyme(LDH-L)].Results In 28 d after treatment,the combination group obtained significantly smallest tumor volume than the control group and the 2 monotherapy groups(all P<0.01).The longest median survival was observed in the combination group(65 d,P<0.01),followed by the HER2-ADC group(55 d),anti-PD-1 group(53 d)and control group(41 d).After 28 d of treatment,the combination group exhibited obviously the smallest peripheral proportions of MDSCs/Tregs,most tumor-infiltrating CD3?T/CD8?T cells,and less FOXP3?T cells when compared with the 2 monotherapy groups and control group(all P<0.05).While,the 2 monotherapy groups had smaller MDSCs/Tregs proportions than the control group(P<0.05).No significant differences were observed among the 4 groups in serum ALT,AST,BUN,CRE,or LDH-L levels,and all of them were within normal ranges.Conclusion HER2-ADC combined with anti-PD-1 suppresses the growth of orthotopic bladder tumor,probably through their synergic effects on down-regulating MDSCs/Treg and enhancing CD8?T cell infiltration.

TCM believes that spleen deficiency is the root cause of emotional abnormalities in chronic fatigue syndrome (CFS), and clinical treatment often involves the heart, liver and kidney. TCM therapy has a significant efficacy in CFS emotional abnormalities. It is mostly treated with oral administration of TCM, acupuncture, moxibustion and massage therapy. It may play a therapeutic role by improving oxidative stress and immune inflammation, regulating nerve-endocrine, controlling energy metabolism and other ways. It is suggested to establish the syndrome differentiation standard of CFS emotional abnormality in the future, so as to improve the accuracy of syndrome differentiation and treatment; form a perfect treatment guide or expert consensus to guide the standardized application of various internal and external treatment methods; explore objective indicators based on the pathogenesis, and focus on the morphological and functional changes of disease target brain regions with the help of neuroimaging techniques, so as to improve the diagnosis and prognosis evaluation of CFS; based on the guidance of TCM theory, improve the CFS emotional abnormal animal modeling method.

TCM functional exercises are the important means of TCM to prevent and cure diseases. By adjusting the bones and muscles externally, adjusting the heart and organs internally, promoting blood circulation, improving sleep disorders, enhancing metabolism and immune capacity, the aim of preventing and treating diseases, prolonging life span, and strengthening the body is achieved. TCM exercises have a significant effect on the treatment of various types of fatigue such as chronic fatigue syndrome, Exercise-induced fatigue, post-stroke fatigue, and cancer-related fatigue.

Objective:To construct 3D-bioprinted organoid artificial skin derived from adult stem cells and investigate their effects on repair of skin defect in mice.Methods:The cell suspension mixture was prepared with human skin keratinocytes, fibroblasts and vascular endothelial cells with a ratio of 2∶1∶1 and cultured in ultra-low attachment plates, and morphological changes of cell spheres were observed with an inverted phase contrast microscope. After 7 days of culture, cell spheres were collected and immunofluorescence staining was performed to characterize the expression and structural distribution of the epidermis, dermis and blood vessels. The artificial skin composed of skin organoids were printed through 3D printing and morphology of printed artificial skin and dressing was observed. Ten immunodeficient balb/c female mice were divided into hydrogel group and organoid group, with 5 mice in each group with the method of random number table. The full-thickness skin defect model with a diameter of 1 cm was established in all mice, and the wound was covered with the hydrogel dressings in hydrogel group and with 3D-printed skin organoids of the same size in organoid group. Wound healing and healing rate of the two groups were observed at 0, 4, 8, 12 and 16 days after modeling. At 16 days after modeling, HE staining was performed on wound skin samples to observe the epidermal keratosis and dermal epidermal junction of the wound surface and Masson staining to observe the density of collagen fibers and dermal fiber thickness of the wound surface.Results:(1) The cell suspension mixture of keratinocytes, fibroblasts and vascular endothelial cells could self-aggregate into cell spheres in the ultra-low attachment plates, and it was observed with the inverted phase contrast microscope that the volume of cell spheres gradually increased with the extension of culture time. (2) Immunofluorescence staining of the cell spheres showed that epidermal markers such as keratin (K)1, K10, and K14 were expressed in the outer layer of the cell spheres, and dermal markers such as vimentin (VIM) and vascular markers CD31 were expressed in the core, which indicated the epidermis was located in the outer layer of the sphere, and the dermis and blood vessels were located in the core of the sphere, with the same structural characteristics of the skin organoids. (3) The 3D-printed organoid artificial skin and hydrogel dressing were round and transparent, with a diameter of 10 mm and a thickness of 1 mm. (4) As shown in the general observation of the wound surface, the wound area of both groups decreased with the extension of treatment time. The wound of the organoid group healed faster, which showed obvious epithelization at 4 days after modeling and basic wound healing at 16 days after modeling. At 0 day after modeling, there was no obvious difference in the appearance of wound surface between the two groups. At 4 and 8 days after modeling, the wound healing rates were (31.7±1.0)% and (52.4±5.4)% in the organoid group, and (24.3±6.8)% and (45.4±7.0)% in the hydrogel group ( P>0.05). At 12 and 16 days after modeling, the wound healing rates were (78.6±8.0)% and (91.1±5.6)% in the organoid group, and were (58.5±5.4)% and (71.9±7.8)% in the hydrogel group ( P<0.01). (5) HE staining showed that in the organoid group epidermal keratinization was found better, with the epidermis being more intact and well attached to the dermis. Epidermal keratinization was not complete in hydrogel group and the epidermis and dermis were obviously separated. Masson staining showed the formation of collagen fiber structures in the wound surface of both groups, which were blue and reticular. The collagen fiber structure was more compact and the dermal fiber thickness was smaller in the organoid group, while the collagen fiber structure was loose and the dermal fiber thickness was greater in the hydrogel group. Conclusions:Adult stem cells of skin can successfully form skin organoids in 3D culture conditions and organoid artificial skin can be constructed with 3D bioprinting technology. Compared with hydrogel dressing, 3D-bioprinted organoid artificial skin can significantly improve the healing rate in mice, with better epidermal keratinization and closer attachment of the epidermis to the dermis. Moreover, the collagen fiber structure of the wound is more compact, with smaller dermal fiber in thickness.

Objective:To treat the Crohn's disease(CD)patients with ustekinumab(UST),to eva-luate their clinical and endoscopic remission,and to evaluate their transmural response(TR)and trans-mural healing(TH)condition using intestinal ultrasonography(IUS).Methods:Retrospective analysis was made on patients diagnosed with CD in Peking University People's Hospital from January 2020 to Au-gust 2022,who were treated with UST for remission induction and maintenance therapy.All the patients were evaluated on both week 8 and week 16/20 after treatment,including clinical,biochemical indica-tors,colonoscopy and IUS examination.Results:A total of 13 patients were enrolled in this study,inclu-ding 11 males and 2 females.The minimum age was 23 years,the maximum age was 73 years and the mean age was 36.92 years.All the patients were in the active stage of disease before treatment,and the average Best Crohn's disease activity index(Best CDAI)score was 270.12±105.55.In week 8,the Best CDAI score of the patients decreased from 270.12±105.55 to 133.16±48.66(t=4.977,P＜0.001).Eight patients achieved clinical remission while 5 patients remained in the active stage.Nine patients underwent colonoscopy evaluation.The average simple endoscopic score for Crohn's disease(SES-CD)score decreased from 10.71±7.14 before treatment to 6.00±7.81(t=2.483,P=0.048)in week 16/20.Four patients achieved endoscopic remission while 5 patients did not.In week 8,5 pa-tients achieved TR,2 patients achieved TH,the other 6 patients did not get TR or TH.In week 16/20,6 patients achieved TR,3 patients achieved TH while the other 4 patients did not get TR or TH.There was no significant statistical difference in the TR effect of UST between small intestine and colon lesions(Fisher test,P＞0.999).The rate of UST transmural response in the patients who had had previous bio-logical agent therapy was lower than those with no previous biological agent therapy,but there was no sig-nificant statistical difference(Fisher test,P=0.491).Conclusion:After treatment of UST,the clinical and endoscopic conditions of the CD patients had been improved,and some patients could achieve clini-cal remission and endoscopic remission.UST had good TR and TH effects on CD.TR might appear in week 8,and the TR effect increased in week 16/20.There was no significant statistical difference in the TR effect between small intestine and colon lesions.TR effect of UST was better in the patients who had no previous biological agent therapy than those who had had other biological agents,but the result had no significant statistical difference.

Purpose The aim of this study is to investigate the relationship between the expression of kinesin family member C1(KIFC1)in endometrioid carcinoma and clinicopathological features and prognosis of endometrioid carcinoma patients.Methods The expression of KIFC1 in 30 cases of paracancer-ous endometrium and 95 cases of endometrioid carcinoma was detected by immunohistochemical SP method.qRT-PCR and Western blot were used to detect the expression level of mRNA and protein of KIFC1 in 30 pairs of fresh cancer tissues and ad-jacent non-cancer tissues.Furthermore,the relationship between KIFC1 protein expression and survival time was analyzed by TC-GA database,and their clinicopathologic features were analyzed.Results The immunohistochemistry results showed the positive rate of KIFC1 in endometrioid carcinoma(61.05％)was signifi-cantly higher than that in the neighboring noncancerous tissue(13.33％),and the difference was statistically significant(P＜0.05).The expression of KIFC1 was correlated with myometrial invasion,FIGO stage and lymphatic metastasis(all P＜0.05).The relative expression of KIFC1 mRNA in endometrioid carci-noma(2.99±0.59)was significantly higher than that in the neighboring noncancerous tissue(1.00±0.29),and there was significant difference(P＜0.05).The relative expression of KIFC1 protein in endometrioid carcinoma(1.70±0.36)was significantly higher than that in the neighboring noncancerous tissue(0.72±0.17),and there was significant difference(P＜0.05).Furthermore,elevated KIFC1 expression was positive-ly correlated with a poorer prognosis.Conclusion KIFC1 is upregulated in endometrioid carcinoma and associated with poor prognosis of patients,KIFC1 was expected to be a potential ther-apeutic target and prognostic indicator for endometrioid carcino-ma.