Laboratory animals are the "living" tools of medical research. Through animal experiments, people can gain continuous insights into the laws of life, reveal the essence of diseases, develop vaccines and drugs for prevention and treatment, and play an important role in the technological development of fields related to human health. The environmental conditions of laboratory animals have a direct impact on their health, quality, and the results of animal experiments. The higher the degree of environmental control, the more reliable the experimental results are in terms of quality. Therefore, environmental control of laboratory animal facilities is important for ensuring that laboratory animals live under required conditions, which is a key factor for conducting effective animal experiments. This article analyzes the current status of environmental testing of laboratory animal facilities in Sichuan Province, briefly summarizing their number, area, and other basic information, and provides detailed statistics on the ability of institutions to conduct environmental testing for laboratory animal facilities in Sichuan Province. It also summarizes the testing requirements for laboratory animal facility environments based on national standards, regulatory requirements, and the quality control needs of facility users. In the analysis of testing indicators for laboratory animal facilities, based on testing data from 40 laboratory animal facilities in Sichuan Province, it was found that static pressure difference is the indicator most prone to non-compliance, followed by illumination and air exchange rate. Using barrier environments as examples, common problems in the process of environmental testing for laboratory animal facilities are summarized in six aspects: testing personnel, instruments, methods, technical materials, testing environment, and reports, and targeted suggestions are proposed. These suggestions help improve environmental control in laboratory animal facilities, and provide practical reference and guidance for relevant testing institutions, as well as laboratory animal producers and users in the industry.

The life view of "human life is the most important" in Traditional Chinese Medicine (TCM) originates from the people-oriented theory of Chinese traditional culture, the benevolence thought of Confucianism, the rebirth thought of Taoism and the compassion thought of Buddhism. Taking the life view of "human life is the most important" as the starting point, it has formed medical ethics thoughts such as the social responsibility of saving the world, the medical practice purpose of treating all patients equally, the meticulous working attitude, the diligent and tireless learning attitude, and the exploration spirit of widely exploring the medical roots, which still has important educational significance. Therefore, the life view of "human life is the most important" should be integrated into the medical ethics education of medical students, and the medical ethics literacy of medical students should be improved through the following ways: strengthen the vocational ideal education of saving the dying and healing the wounded, and enhance the sense of social responsibility of medical students; consolidate the theme of life first classroom education and improve the professional identity of medical students; enrich and innovate the practice forms of protecting life, pay attention to the practicality of medical ethics education.

BACKGROUND:Currently,there have been a variety of conservative and surgical treatment plans for spontaneous osteonecrosis of the knee,achieving excellent results.However,a broad consensus on indication and guide of surgical treatment has not been announced.In clinical practice,there is still a misunderstanding that unicondylar replacement or total knee arthroplasty should be performed upon the discovery of spontaneous osteonecrosis of the knee,while an urgent need for universal access to the concept of stepwise therapy. OBJECTIVE:To summarize and find the factors leading to the poor effect of conservative treatment in spontaneous osteonecrosis of the knee,which occurred on the medial femoral condyle,from the literature and clinical cases,at the same time,combined with the Koshino stage,to propose the strategy of stepwise spontaneous osteonecrosis of the knee treatment on the medial femoral condyle. METHODS:A systematic search of the literature database was conducted to summarize the factors leading to poor outcomes of conservative treatment in spontaneous osteonecrosis of the medial femoral condyle.Meanwhile,according to the Clinical&Health Records for analytics&Sharing system,the cases receiving conservative and surgical treatment in spontaneous osteonecrosis of the medial femoral condyle in the Department of Orthopedics of Guangdong Provincial Hospital of Chinese Medicine from January 2017 to January 2023 were analyzed retrospectively,then the causes of success and failure in typical cases were summarized and analyzed. RESULTS AND CONCLUSION:(1)Early diagnosis and treatment of spontaneous osteonecrosis of the knee were very important for prognosis.For sudden knee pain in some patients,if no obvious abnormality was found in the X-ray examination,and the symptoms persisted and could not be relieved for more than 1 week,an MRI examination was recommended to detect early spontaneous osteonecrosis of the knee.(2)The X-ray images of Koshino stage 1 and stage 2 of spontaneous osteonecrosis of the medial femoral condyle were difficult to be distinguished,which needed to be probed by MRI.MRI images of Koshino stage 1 were mainly characterized by bone marrow edema,and an osteonecrosis area with a clear boundary was not formed,while MR images of Koshino stage 2 showed a necrotic area with a clear boundary.(3)Five factors leading to the poor effect of conservative treatment on spontaneous osteonecrosis of the medial femoral condyle were summarized:a.The necrotic area was＞5 cm2;b.The necrotic area accounted for more than 40%of the condyle;c.relative compression percentage of medial meniscus≥33%(with or without medial meniscus injury and subchondral bone marrow edema);d.MRI depth of necrotic area(anterior-posterior diameter of sagittal necrotic area)＞20 mm;e.varus deformity of lower limb＞6°.(4)Conservative treatment of spontaneous osteonecrosis of the knee in Koshino stage 1 was good.For spontaneous osteonecrosis of the knee in Koshino stage 2,conservative treatment was preferred or combined with drilling decompression.If there was no relief or improvement of symptoms or in MRI after 3 months,while the patient had any of the previous five factors,then knee preservation surgery should be considered.For spontaneous osteonecrosis of the knee in Koshino stage 3 and stage 4,knee preservation surgery should be selected based on the previous five factors,including age,gender and activity level of the patient.Total knee arthroplasty was used for spontaneous osteonecrosis in Koshino stage 4,which was associated with symptomatic patellofemoral arthritis,valgus alignment,or necrotic area,which greatly affected the stability of unicondyle prosthesis.

The immune microenvironment plays a key role in the development and progression of tumors.In recent years,with the rapid advancement of high-throughput sequencing technologies,researchers have gained a deeper under-standing of the composition and function of immune cells in the tumor microenvironment.However,traditional bulk sequenc-ing technologies are limited in resolving heterogeneity at the single-cell level,constraining a comprehensive understanding of the complexity of the tumor microenvironment.The advent of single-cell RNA sequencing technology has brought new opportunities to uncover the heterogeneity of the immune microenvironment in lung cancer.Currently,T-cell-centered im-munotherapy in clinical settings is prone to side effects affecting prognosis,such as immunogenic drug resistance or immune-related pneumonia,with the key factor being changes in the interactions between immune cells and tumor cells in the tumor microenvironment.Single-cell RNA sequencing technology can reveal the origins and functions of different subgroups within the tumor microenvironment from perspectives such as intercellular interactions and pseudotime analysis,thereby discovering new cell subgroups or novel biomarkers,providing new avenues for uncovering resistance to immunotherapy and monitoring therapeutic efficacy.This review comprehensively discusses the newest research techniques and advancements in single-cell RNA sequencing technology for unveiling the heterogeneity of the tumor micro environment after lung cancer immunotherapy,offering insights for enhancing the precision and personalization of immunotherapy.

Objective To analyze the characteristics of time in range(TIR)and its relationship with oxidative stress(OS)and insulin resistance status(HOMA-IR)in patients with type 2 diabetes mellitus(T2DM)and sleep apnea-hypopnea syndrome(OSAHS).Methods According to apnea-hypopnea index(AHI),165 T2DM in patients were divided into simple T2DM group(AHI<5 times/h,n=43),T2DM combine OSAHS mild group(OSAHS-G,5≤AHI<15 times/h,n=51),T2DM combined OSAHS moderate group(OSAHS-M,15≤AHI≤30 times/h,n=40)and T2DM combine OSAHS severe group(OSAHS-S,AHI>30 times/h,n=31).TIR was calculated by dynamic blood glucose monitoring.Superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and other indexes were detected and analyzed.Results Compared with simple T2DM group,the levels of HOMA-IR,8-iso-PGF2a and Ox-LDL were higher in T2DM combined OSAHS-G,OSAHS-M or OSAHS-S group,while the levels of TIR,SOD and GSH-Px were lower(P<0.05).Pearson correlation analysis showed that TIR was positively correlated with the levels of SOD and GSH-Px(P<0.05 or P<0.01),and negatively correlated with the levels of 8-iso-PGF2a,Ox-LDL,HbA1c,HOMA-IR and the severity of OSAHS(P<0.01).Logistic regression analysis showed that TIR,SOD and GSH-Px were protective factors for severe OSAHS in T2DM patients,while 8-iso-PGE2a and Ox-LDL were the risk factors for severe OSAHS.Conclusions The glucose level fluctuates greatly in patients with T2DM and OSAHS.Insulin resistance and oxidative stress are factors that affect the normalization of TIR.

Objective To investigate the effects of calcitriol intervention on PI3K/AKT signaling pathway and wound healing in rats with diabetic foot ulcer(DFU).Methods Thirty-two male SD rats were divided into normal control(Con)group,DFU group,calcitriol low dose(L)group and calcitriol high dose(H)group.A circular wound of 5 mm in diameter and deep to the fascia was made on the dorsum of the left foot of rats in each group.HE staining was used to evaluate the histopathological changes of the wounds.Immunohistochemical method was selected to compare the distribution of CD34-positive cells and the expression of p-PI3K and p-AKT in traumatic tissues of each group.ELISA was adopted in the detection of serum IL-6,IFN-γ,TNF-α and IL-7.RT-PCR was used to detect the mRNA expression of PI3K and AKT in each group,and western blot was used to detect the protein expression of PI3K,p-PI3K,AKT,p-AKT and VEGF.Results Compared with Con group,the expressions of IL-6,IFN-γ,TNF-α,IL-7,CD34,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K,p-AKT/AKT increased,while PI3K protein expression decreased in DFU,L and H groups(P<0.05),VEGF and AKT protein expression decreased in DFV and L groups(P<0.05).Compared with DFU group,the expressions of VEGF,AKT and PI3K protein increased(P<0.05),while the expressions of p-PI3K/PI3K,p-AKT/AKT decreased in L and H groups(P<0.05),IL-6 decreased in L group(P<0.05),and CD34 expression increased in H group(P<0.05),while IL-6,IFN-γ,TNF-α and IL-7,PI3K mRNA,AKT mRNA,p-AKT protein and p-PI3K protein expression decreased(P<0.05).Compared with L group,the expressions of CD34,VEGF,AKT and PI3K protein increased(P<0.05),while IL-6,PI3K mRNA,AKT mRNA,p-AKT protein,p-PI3K protein,p-PI3K/PI3K and p-AKT/AKT decreased in H group(P<0.05).Conclusions Calcitriol intervention may reduce the activity of the PI3K/AKT signaling pathway,inhibit inflammation,promote neovascularization,and facilitate wound healing in rats with DFU.

Objective For the development of the electronic patient-reported outcome measures(ePRO)for stroke,the scale′s equivalence,i.e,differential item functioning(DIF)was assessed,aiming to compare whether paper-and mobile-based collection methods affect the participants′responses.Methods The patient information was collected using the developed App,and the DIF was detected using the mean and covariance structure(MACS)model to analyse whether the scale maintained a good measurement equivalence after changing to mobile-based from paper-based.Results Items PHD7,PHD8,PHD14,PSD3,PSD9,SOD1,and SOD6 exhibited uniform DIF(P1＜α1),PHD9,PHD10,PHD11,PHD12,SOD5,and THD1 exhibited non-uniform DIF(P2＜α2),and SOD7 and THD2 exhibited both uniform and non-uniform DIF.The DIF between the different measurement modalities existed for the above 15 items;however,it was within the acceptable limit.Conclusion The mPRO patient follow-up system developed in this study by assessing the DIF between the scale′s different data collection methods confirmed that mobile-based data collection did not affect the participants′response,and the measurement method shift did not affect the scale measurement equivalence.The system yielded accurate and reliable measurements that can be used in clinical practice and optimized in its application course.

BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

Objective:To investigate the clinical characteristics of patients with rheumatic diseases and abnormal liver function, as well as determine the proportion and severity of liver function abnormalities.Methods:Cross-sectional study. Data were collected from patients registered in the Chinese Rheumatism Date Center from 2011 to 2021. The rheumatic diseases analyzed in this study were rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjogren syndrome (SS), ankylosing spondylitis (AS), and gout. Patient data, including demographic characteristics [ such as age, sex, body mass index,(BMI), and smoking history], liver function test results [including alanine aminotransferase (ALT), aspartate aminotransferase, alkaline phosphatase(ALP), and total bilirubin], and use of anti-rheumatic immune drugs and liver-protective drugs, were collected and compared between groups with normal and abnormal liver functions. In addition, the proportions of abnormal liver function were compared between sex and age groups.Results:A total of 116 308 patients were included in this study, including 49 659 with RA, 17 597 with SLE, 9 039 with SS, 11 321 with AS, and 28 692 with gout. The lowest proportion of liver function abnormalities was observed in patients with RA[11.02% (5 470/49 659)], followed by those with SS[17.97% (1 624/9 039)] and AS [18.22% (2 063/11 321) ], whereas patients with SLE [21.14% (3 720/17 597) ] and gout [28.73% (8 242/28 692)] exhibited the highest proportion of these abnormalities. Elevated ALT, mostly classified as grade 1, was the most commonly noted liver function abnormality, whereas elevated ALP was the least common. Some patients who took liver-protective drugs had normal liver function, with the lowest percentage observed in patients with gout [7.45% (36/483) ] and ranging from 21.7% to 30.34% in patients with RA, SLE, SS, and AS. The proportion of liver function abnormalities was higher in males than in females for all disease types [RA: 13.8%(1 368/9 906) vs. 10.3%(4 102/39 753); SLE: 33.6% (479/1 424) vs. 20.0% (3 241/16 173); SS: 25.4%(111/437) vs. 17.6%(1 513/8 602); AS: 20.1%(1 629/8 119) vs. 13.6% (434/3 202); and gout: 29.3% (8 033/27 394) vs. 16.1% (209/1 298)]. In RA, SLE, and AS, the proportions of liver function abnormalities were similar across all age groups. In SS, the proportion of liver function abnormalities increased with age [<40 years: 14.9%(294/1 979); 40-59 years: 18.1%(858/4 741); ≥60 years: 20.4%(472/2 319)], whereas a reversal of this trend was observed in gout [<40 years: 34.9%(4 294/12 320); 40-59 years: 25.5%(2 905/11 398);≥60 years: 21.0%(1 042/4 971)].Conclusions:The proportions of combined liver function abnormalities in patients with rheumatologic diseases were high, and the utilization rates of liver-protective drugs were low. It is necessary to pay more attention to monitoring patients′ liver function, timely administer liver-protective drugs, and optimize liver-protective regimens during the treatment of rheumatic diseases.

Objective:To explore the relationship between low serum albumin levels and its duration on first episode of peritonitis in peritoneal dialysis (PD) patients.Methods:PD patients who were regularly followed up in the Pearl River Delta region from September 1, 2000 to July 6, 2021 in Shunde Hospital of Southern Medical University, Nanfang Hospital of Southern Medical University, and Foshan First People′s Hospital were retrospectively selected. The patients were divided into low serum albumin group (LSA group, mean albumin<35 g/L), moderate serum albumin group (MSA group, 35 g/L≤mean albumin<40 g/L) and high serum albumin group (HSA group, mean albumin≥40 g/L) according to the mean albumin of the patients, and the differences among the three groups were compared. The Kaplan-Meier survival analysis method was used to compare the risk of peritonitis events in different mean albumin groups and different durations of hypoalbuminemia. The multivariate Cox regression model was used to analyze the relationship between serum albumin levels and duration of hypoalbuminemia and new-onset peritonitis.Results:A total of 1 853 PD patients were included in this study, aged (49.72±15.34) years, and 1 036(55.9%) males. There were 551 patients (29.7%) in the LSA group, 920 patients (49.7%) in the MSA group, and 382 patients (20.6%) in the HSA group. The median follow-up was 37 (15, 66) months and there were 508 patients (27.4%) with new-onset peritonitis during the follow-up. Compared with the LSA group, the incidence of new peritonitis in the MSA group and HSA group was lower ( χ2=14.053, P<0.001; χ2=21.857, P<0.001), but there was no significant difference in the incidence of new peritonitis between the HSA group and MSA group. The Kaplan-Meier survival analysis showed that the cumulative incidence of peritonitis in the LSA group was significantly higher than that in the MSA group and HSA group (Log-rank χ2=22.128, P<0.001). Compared with PD patients with normal serum albumin, the patients with longer duration of hypoalbuminemia tended to have a higher incidence of new peritonitis. Multivariate Cox regression analysis showed that the mean albumin<35 g/L (LSA group/MSA group, HR=1.495, 95% CI 1.198-1.866, P<0.001; LSA group/HSA group, HR=1.459, 95% CI 1.104-1.928, P=0.008) was an independent risk factor of new-onset peritonitis in PD patients and the prolongation of duration of hypoalbuminemia had a significantly higher risk of new-onset peritonitis ( HR=1.013, 95% CI 1.003-1.024, P=0.014). Conclusion:The mean albumin<35 g/L and prolong duration of hypoalbuminemia are independent risk factors of PD-related peritonitis in PD patients.