ObjectiveTo investigate the effect of Yaoshu Zhuyu Fang on the regulation of the microRNA-17-5P (miR-17-5P)/murine double minute 2 (MDM2)/p53 axis in the proliferation and apoptosis of rat intervertebral disc annulus fibrosus cells, and its potential molecular mechanism. MethodsIntervertebral disc annulus fibrosus tissues were obtained from 8-week-old SPF-grade male SD rats, and annulus fibrosus cells were isolated and obtained by enzyme digestion and mechanical dispersion. Annulus fibrosus cells were divided into 6 groups: Group C was the blank control group, in which annulus fibrosus cells were not treated with interleukin-1β (IL-1β) but were cultured in RPMI 1640 complete medium. Group β was the degeneration model group constructed by treating annulus fibrosus cells with 10 ng/mL IL-1β for 24 h. Group β+B was the IL-1β + blank serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% blank serum for 24 h. Group β+W was the IL-1β + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. Group β+I was the IL-1β + miR-17-5P inhibitor group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor. Group β+I+W was the IL-1β + miR-17-5P inhibitor + Yaoshu Zhuyu Fang-containing serum group, in which annulus fibrosus cells were first treated with IL-1β to construct the degeneration model, then transfected with miR-17-5P inhibitor, and finally treated with RPMI 1640 medium containing 5% Yaoshu Zhuyu Fang-containing serum for 24 h. CCK-8 assay was used to detect cell survival rate. Flow cytometry was used to detect cell apoptosis. Real-time quantitative PCR was used to detect the expression levels of miR-17-5P, MDM2 mRNA, and p53 mRNA in cells. Western blotting was used to detect the protein expression levels of MDM2 and p53 in cells. Dual-luciferase reporter system was used to analyze the targeting relationship between miR-17-5P and MDM2. ResultsCompared with Group C, Group β showed a significant decrease in cell survival rate (P<0.001), a significant increase in cell apoptosis rate (P<0.001), significantly increased expression of miR-17-5P, p53 mRNA, and p53 protein (P<0.001), and significantly decreased expression of MDM2 mRNA and protein (P<0.001). Compared with Group β, Group β+W, Group β+I, and Group β+I+W showed significantly increased cell survival rate, significantly decreased apoptosis rate, significantly decreased expression of miR-17-5P, p53 mRNA, and p53 protein, and significantly increased expression of MDM2 mRNA and protein (P<0.001). Moreover, changes in the above indicators were greater in Group β+I+W (P<0.001). Circular RNA Interactome predicted that miR-17-5P had specific binding sites with the 3' untranslated region (3'UTR) of MDM2. Transfection of miR-17-5P mimic significantly reduced the luciferase expression level of co-transfected luciferase reporter plasmid containing wild-type MDM2 3'UTR (P<0.05), but had no significant effect on luciferase expression in cells co-transfected with luciferase reporter plasmid containing mutant MDM2 3'UTR (P>0.05). ConclusionYaoshu Zhuyu Fang down-regulates the expression of miR-17-5P, promotes the synthesis of MDM2 protein, thereby down-regulates p53, promotes proliferation, and inhibits the apoptosis of rat intervertebral disc annulus fibrosus cells.

Bone marrow suppression is one of the common adverse reactions to radiotherapy and chemotherapy. Anticancer treatments such as radiotherapy and chemotherapy first directly damage the patient′s peripheral blood cells, impairing qi and blood; further, they damage the actively proliferating cell populations in the bone marrow, impairing yin and blood; and then they interfere with hematopoietic stem cells, impairing essence and blood. This process is rapid and intense, consistent with the characteristics of " acute deficiency syndrome" , marked by sudden onset, rapid changes, critical condition, complexity and variability, multiple complications, and poor prognosis. Given this, its diagnosis and treatment should differ from those of general deficiency syndromes. This paper advocates the principles and ideas of diagnosis and treatment such as " preventing first and treating early to prevent changes; supplementing for deficiency and strengthening vital qi to eliminate pathogenic factor; urgent rescue for critical conditions, no time to lose; and comprehensive supplementing throughout the process, with severe cases requiring singular action" . This approach is intended to provide theoretical reference and practical guidance for bone marrow suppression after radiotherapy and chemotherapy.

Objective To understand the clinical distribution characteristics and drug-resistance genotypes of carbapenem-resistant Pseudomonas aeruginosa(CRPA)in a tertiary hospital in Shanghai,so as to guide the rational use of antibiotics,reduce bacterial resistance and control nosocomial infections.Methods A total of 94 consecutive and non-redundant CRPA strains isolated from clinical specimens were collected in The First Affiliated Hospital of Naval Medical University between Jan.1,and Dec.31,2019.The distribution of CRPA across departments and sample sources were analyzed.Antimicrobial susceptibility testing against 13 antibiotics was determined using the VITEK 2 Compact automated microbiology analyzer and the Kirby-Bauer disk diffusion method.Polymerase chain reaction(PCR)was employed to detect genes encoding extended-spectrum β-lactamase resistance gene,carbapenemase resistance gene,and porin resistance gene.Homology analysis of selected isolates was performed using kSNP3,a k-mer-based software,for single nucleotide polymorphism(SNP)analysis.An evolutionary tree was constructed to assess genetic relationships.Additionally,multilocus sequence typing(MLST)was performed using the Pseudomonas aeruginosa typing scheme from the PubMLST database.Results Among the 94 CRPA isolates,high resistance rates were observed for carbapenems,including imipenem(92.6%,87 strains)and meropenem(87.2%,82 strains).In contrast,low resistance rates were detected for aminoglycosides,such as amikacin(10.6%,10 strains),gentamicin(20.2%,19 strains),and tobramycin(20.2%,19 strains).The top 3 departments in terms of isolate distribution were the Emergency Intensive Care Unit(9.6%,9 strains),Department of Cerebrovascular Surgery(8.5%,8 strains),and Department of Respiratory Medicine(8.5%,8 strains).PCR analysis of 94 CRPA strains detected outer membrane protein D2(OprD2)gene deletion in 47(50.0%)strains,13(13.8%)strains were positive for blaKPC,4(4.3%)strains for blaVIM,2(2.1%)strains for blaIMP,1(1.1%)strain for blaNDM,12(12.8%)strains for blaTEM,4(4.3%)strains for blaPER,and 2(2.1%)strains for blaGES,while blaOXA-48,blaBIC,blaSIM,blaVEB,and blaSHV were not detected.MLST identified 36 different sequence types(STs),with ST463 and ST274 being the most common,and 2 new ST(ST4023 and ST4024)were identified for the first time.Conclusion CRPA strains carry multiple resistance genes and exhibit concurrent resistance to several commonly used clinical antibiotics.The resistance is primarily associated with the presence of blaKPC,blaVIM and blaTEM genes and the deletion of OprD2 gene.Clinical monitoring of CRPA should be strengthened,and rational use of antimicrobial agents is essential to control its spread within the hospital.

Objective To investigate the current situation of off-label use of immune checkpoint inhibitors(ICIs)in China and the cognition of medical staff.Methods From August 31 to September 9,2022,a nationwide survey questionnaire was sent to medical staff in the form of electronic questionnaire.The questionnaire included 13 questions,covering four dimensions:Drug allocation,current situation of medication beyond the instructions,cognition of medication beyond the instructions and current situation of medication beyond the instructions.Results A total of 745 questionnaires were collected.75.70％of respondents reported off-label use of ICIs in their hospitals,with the most common type being off-label indications.The primary reasons for such practices included support from authoritative domestic and international guidelines,clinical research data validation,and approved indications in foreign regulatory documents.85.37％of respondents believed off-label use could offer new hope for patients,while 68.86％considered it unlikely to increase adverse reactions.44.97％of respondents' hospitals had not established off-label use registration systems for ICIs.88.86％of respondents emphasized the need for stricter regulations governing off-label use of immunotherapeutic agents.Conclusion Off-label use of ICIs is common,and there is a lack of unified guidance in clinical practice.It is urgent to form norms and consensus on the management of off-label use of ICIs.

Turning to critical illness is a common stage of various diseases and injuries before death. Patients usually have complex health conditions, while the treatment process involves a wide range of content, along with high requirements for doctor′s professionalism and multi-specialty teamwork, as well as a great demand for time-sensitive treatments. However, this is not matched with critical care professionals and the current state of medical care in China. Telemedicine, which shortens the distance of medical professionals and the gap of disease diagnosis and treatments in various regions through electronic information, can effectively solve the current problem. Therefore, there is an urgent need to develop a standardized, high-quality visualization telemedicine round system .Therefore, experts have been organized to search domestic and foreign literature on telemedicine round for critically ill patients and to form this consensus based on clinical experiences so as to further improve the level of critical care treatments in regions.

OBJECTIVE To develop a prediction model for durable clinical benefit （DCB） in patients with advanced esophageal squamous cell carcinoma （ESCC） receiving programmed death-1 （PD-1） inhibitor. METHODS The clinical data of patients with advanced ESCC who received PD-1 inhibitor in Jieyang People’s Hospital were retrospectively collected between January 2020 to December 2023. Predictors were screened by least absolute shrinkage and selection operator （Lasso） regression， and a multivariable Logistic regression model was developed to predict DCB. A nomogram was constructed based on the model. Internal validation of the prediction model was performed by using the Bootstrap method， and the model was evaluated by the receiver operating characteristic （ROC） curve， calibration curve， and decision curve analysis. RESULTS A total of 91 patients with advanced ESCC were included. The results of Lasso regression combined with Logistic regression analysis indicated that the baseline lymphocyte monocyte ratio （LMR） [odds ratio （OR）＝1.97， 95% confidence interval （CI）： 1.15-3.36， P＝0.013]， albumin （ALB） content （OR＝1.35， 95%CI： 1.13-1.60， P＜0.001）， body mass index （BMI） category 1 [normal vs. low： OR＝ 0.28， 95%CI （0.09-0.96）， P＝0.042]， BMI category 2 [overweight-obesity vs. low： OR＝0.08， 95%CI （0.01-0.59）， P＝0.013]， and treatment regimen [monotherapy vs. monotherapy combination therapy： OR＝0.07， 95%CI （0.01-0.50）， P＝0.008] were predictive factors for patients with advanced ESCC to achieve DCB when treated with PD-1 inhibitor. A prediction model was constructed based on the above indicators. Internal validation of the model using the Bootstrap method showed an area under the curve of 0.831 （95%CI： 0.746-0.904）， with specificity of 74.4% and sensitivity of 75.0%. The Hosmer-Lemeshow test yielded χ2＝ 9.930， P＝0.270， and the calibration curve slope was close to 1. The decision curve analysis demonstrated that the model exhibited good clinical utility within a threshold range of 0.1 to 1.0. CONCLUSIONS The prediction model based on baseline LMR， ALB content， BMI， and treatment regimen demonstrates robust predictive performance and clinical utility for assessing therapeutic efficacy of PD-1 inhibitor in the treatment of advanced ESCC.

Objective:To investigate auricular acupressure combined with massage-tapping exercises on body indicators, blood lipids, and liver function in patients with obesity-related fatty liver disease.Methods:This retrospective study included 78 patients with obesity-related fatty liver disease admitted to Hangzhou Hospital of Traditional Chinese Medicine from April to December 2023. The patients were divided into two groups based on different treatment methods: the conventional group (36 patients receiving conventional interventions) and the combined group (36 patients receiving auricular acupressure combined with massage-tapping exercises in addition to conventional interventions). The total response rates, physical indicators (body weight, body mass index), blood lipid levels (triglycerides, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), and liver function indicators (aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase were recorded and compared between the two groups.Results:The total response rate in the combined group was 94.87% (37/39), which was significantly higher than the 76.92% (30/39) in the conventional group ( χ2 = 5.19, P < 0.05). After intervention, the combined group showed lower body weight [(70.42 ± 8.32) kg vs. (75.84 ± 8.46) kg], lower body mass index [(24.32 ± 1.26) kg/m2 vs. (25.48 ± 1.30) kg/m2], lower triglycerides [(1.62 ± 0.42) mmol/L vs. (2.94 ± 0.78) mmol/L], lower total cholesterol [(5.24 ± 0.54) mmol/L vs. (6.72 ± 0.66) mmol/L], lower low-density lipoprotein cholesterol [(2.14 ± 0.46) mmol/L vs. (2.78 ± 0.50) mmol/L], lower aspartate aminotransferase [(35.32 ± 4.38) U/L vs. (40.16 ± 5.14) U/L], lower alanine aminotransferase [(31.05 ± 4.20) U/L vs. (37.24 ± 4.56) U/L], and lower gamma-glutamyltransferase [(43.35 ± 8.74) U/L vs. (57.62 ± 9.04) U/L] levels compared with the conventional group. The combined group showed higher high-density lipoprotein cholesterol level compared with the conventional group [(1.85 ± 0.26) mmol/L vs. (1.26 ± 0.30) mmol/L]. All differences were statistically significant ( t = 2.85, 4.00, 9.31, 10.84, 5.88, 4.48, 6.24, 7.09, 9.28, all P < 0.05). Conclusions:The combination of auricular acupressure and massage-tapping exercises is effective in treating obesity-related fatty liver disease in patients. This approach can regulate physical indicators, improve lipid metabolism, and enhance liver function, making it a method worth promoting in clinical practice.

With the extended survival period of breast cancer patients and the increasing health demands, the concomitant diseases of breast cancer have gradually attracted the attention of both doctors and patients, and it is imperative to conduct comprehensive management of these diseases, in which the general practitioners, as the more comprehensive and complex medical talents, have not yet played their due roles. In this article, we report two cases of comprehensive management of concomitant diseases of breast cancer through collaboration of general practitioners and specialists (integrated general and specialist care). The role and function of general practitioners in this process were deeply analyzed, and the establishment of a consultation-liaison general practice model to further promote the role of integrated general and specialist care in integrated oncology care was advocated.

With the improvement of diagnosis and treatment level, most breast cancer patients survive in a chronic state for a long time, and the issue of concomitant diseases of breast cancer (CDBC) has become increasingly prominent. All-round and full-cycle management of these comorbidities can help improve patients’ quality of life and prognosis. General practice, with its long-term, comprehensive and responsible health care that is person-centered, family-based, community-wide and oriented to the maintenance and promotion of overall health, presents new opportunities for the health management of CDBC. This article will explore the application of consultation-liaison general practice through the integrated general and specialist care in the comprehensive management of CDBC, aiming to raise people’s awareness of it and promote the development of consultation-liaison general practice and the management model of the "Internet plus general practitioner team" , which will surely contribute to the all-round management of concomitant diseases in breast cancer patients.