OBJECTIVES: To study the therapeutic mechanism of Tuihuang Mixture against cholestasis. METHODS: Forty-eight Wistar rats were randomized equally into blank group, model group, ursodeoxycholic acid group and Tuihuang Mixture group. Except for those in the blank group, all the rats were given α‑naphthylisothiocyanate (ANIT) to establish rat models of cholestasis, followed by treatments with indicated drugs or distilled water. Serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL of the rats were determined, and hepatic expressions IL-1β, IL-18, FXR, NLRP3, ASC, Caspase-1 and GSDMD were detected using q-PCR, ELISA or Western blotting. Histopathological changes of the liver tissues were observed using HE staining. RESULTS: The rat models of cholestasis had significantly increased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL with increased mRNA and protein expressions of IL-1β and IL-18, decreased protein and mRNA expressions of FXR, and increased protein expressions of NLRP3 and Caspase-1 and mRNA expressions of NLRP3, ASC, Caspase-1 and GSDMD in the liver tissue, showing also irregular arrangement of liver cells, proliferation of bile duct epithelial cells and inflammatory cells infiltration. Treatment of the rat models with Tuihuang Mixture significantly decreased serum levels of ALT, AST, ALP, γ-GT, TBA and TBIL, lowered IL-1β and IL-18 and increased FXR protein and mRNA expressions, and reduced NLRP3, ASC, Caspase-1 and GSDMD proteins and NLRP3, ASC and Caspase-1 mRNA expressions in the liver tissue. Tuihuang Mixture also significantly alleviated hepatocyte injury, bile duct epithelial cell proliferation and inflammatory cell infiltration in the liver of the rat models. CONCLUSIONS Tuihuang Mixture can effectively improve cholestasis in rats possibly by inhibiting NLRP3 inflammatosome-mediated pyroptosis via regulating FXR.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein ; Rats ; Receptors, Cytoplasmic and Nuclear/metabolism* ; Cholestasis/drug therapy* ; Rats, Wistar ; Inflammasomes/metabolism* ; 1-Naphthylisothiocyanate ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Interleukin-18/metabolism* ; Caspase 1/metabolism* ; Interleukin-1beta/metabolism* ; Liver/metabolism*

Nonalcoholic fatty liver disease （NAFLD） has become the most common chronic liver disease in the world， and it is also one of the main causes of liver cirrhosis and hepatocellular carcinoma， so it is particularly important to curb the development and progression of NAFLD in a timely manner. However， due to its complex pathogeneses， there are currently no effective methods for radical treatment. As a new generation of probiotics， Akkermansia muciniphila （Akk bacteria） can improve metabolic disorders of the body， and more and more studies have shown that Akk bacteria have a potential therapeutic effect on metabolic diseases， especially NAFLD. Therefore， this article briefly reviews the mechanism of action of Akk bacteria in NAFLD， in order to provide new ideas for improving the treatment of NAFLD and creating new therapies.

N7-methylguanosine （m⁷G） is one of the most popular RNA modifications at present and has attracted wide attention from researchers in China and globally. By influencing the metabolism of various RNA molecules （including messenger RNA， ribosomal RNA， microRNA， and transfer RNA）， m⁷G modification actively participates in many biological processes such as cell proliferation， differentiation， and apoptosis. More and more evidence has shown that m⁷G plays a key role in the development of cancer， and abnormal m⁷G levels are closely associated with the development and progression of cancer by regulating the expression of multiple oncogenes and tumor suppressor genes. Hepatocellular carcinoma is the most common gastrointestinal tumor in China， and current treatment methods tend to have an unsatisfactory therapeutic effect. At present， the potential molecular mechanism of m⁷G modification in hepatocellular carcinoma remains unclear. This article reviews the potential mechanism of action of m⁷G modification in hepatocellular carcinoma and the m⁷G-related diagnosis and treatment strategies.

Purpose: Neoadjuvant therapy modality can increase the operability rate and mitigate pathological risks in locally advanced cervical cancer, but treatment response varies widely. It remains unclear whether genetic alterations correlate with the response to neoadjuvant therapy and disease-free survival (DFS) in locally advanced cervical cancer. Materials and Methods: A total of 62 locally advanced cervical cancer (stage IB-IIA) patients who received neoadjuvant chemoradiation plus radical hysterectomy were retrospectively analyzed. Patients’ tumor biopsy samples were comprehensively profiled using targeted next generation sequencing. Pathologic response to neoadjuvant treatment and DFS were evaluated against the association with genomic traits. Results: Genetic alterations of PIK3CA were most frequent (37%), comparable to that of Caucasian populations from The Cancer Genome Atlas. The mutation frequency of genes including TERT, POLD1, NOS2, and FGFR3 was significantly higher in Chinese patients whereas RPTOR, EGFR, and TP53 were underrepresented in comparison to Caucasians. Germline mutations were identified in 21% (13/62) of the cohort and more than half (57%) had mutations in DNA damage repair genes, including BRCA1/2, TP53 and PALB2. Importantly, high tumor mutation burden, TP53 polymorphism (rs1042522), and KEAP1 mutations were found to be associated with poor pathologic response to neoadjuvant chemoradiation treatment. KEAP1 mutations, PIK3CA-SOX2 co-amplification, TERC copy number gain, and TYMS polymorphism correlated with an increased risk of disease relapse. Conclusion We report the genomic profile of locally advanced cervical cancer patients and the distinction between Asian and Caucasian cohorts. Our findings highlight genomic traits associated with unfavorable neoadjuvant chemoradiation response and a higher risk of early disease recurrence.

Objective:To investigate the feasibility of contracted nursing services for disabled persons.Methods:A qualitative study on the feasibility of contracted nursing services for disabled persons was conducted from August 2020 to October 2020 with the phenomenological method. Community nurses were selected with the purpose of sampling method from Yuetan and Baizhifang Community Health Service Centers in Beijing Xicheng District for semi-constructed interviews, and 12 community nurses were finally interviewed according to the principle of information saturation. The research team took field notes, audio recordings and transcriptions of the interviews, coded to refine the themes, and fed back with the respondents to confirm the accuracy of the themes.Results:All the interviewed nurses thought that the contents of basic medical and public health required by the Guidance manual of contracted services of family doctors for disabled persons (the manual) including basic documentation, appointments, pre-diagnosis and post-diagnosis services, home care, rehabilitation nursing guidance, referral services and extended nursing services for the disabled and their families could be completed. All interviewees said that the manual had a guiding role in contracted services for disabled persons. Eight interviewed nurses believed that the manual involved referral services and rehabilitation care, but the technical guidance content did not meet the actual work needs and it should be supplemented and improved; 9 interviewees pointed out that there was a lack of communication with various types of disabled people in service practice, especially for those with vision, hearing, mental disabilities and disabled children; 7 interviewees said that it the free home care for the disabled was not sustainable. Conclusion:The contracted nursing services for disabled persons are feasible and the manual has a guiding role for the practice,and some contents need to be added in the manual to further improve service capacity for disabled people.

Objective:To investigate the status quo of communication between contracted family doctor team and the disabled.Methods:Using convenience sampling, family doctor team members of 80 community health centers (CHCs) in Beijing were selected to participate in a questionnaire survey from April to June 2022. The questionnaire included the basic information of team members, the choice of communication methods and targets, the acquisition of communication knowledge and skills and so on.Results:A total of 365 team members participated in the survey. The most common type of disability was physical disability (78.08%,285/365). All participants met communication obstacles with disabled people in contracted health service, and hearing and speech disabilities were the most common (70.14%, 256/365). Only 13.42% (49/365) chose to directly communicate with the disabled themselves; 84.93% (310/365) used "increase the volume and slow down" method when communicating with the disabled, and 38.63% (141/365) chose "write and convey multiple messages at the same time". Most of participants (84.38%, 308/365) indicated the need for professional training in communication with persons with disabilities.Conclusion:There are communication obstacles between family doctor team members and the disabled during contracted services. More relevant professional training are urgently needed for contracted family doctor team to improve the abilities to communicate with the disabled.

Objective:To compare magnetic resonance imaging (MRI)-based and computed tomography (CT)-based target volume delineation and dose coverage in partial breast irradiation (PBI) for patients with breast cancer, aiming to explore the application value of MRI localization in PBI after breast-conserving surgery.Methods:Twenty-nine patients with early breast cancer underwent simulating CT and MRI scans in a supine position. The cavity visualization score (CVS) of tumor bed (TB) was evaluated. The TB, clinical target volume (CTV), planning target volume (PTV) were delineated on CT and MRI images, and then statistically compared. Conformity indices (CI) between CT- and MRI-defined target volumes were calculated. PBI treatment plan of 40 Gy in 10 fractions was designed based on PTV-CT, and the dose coverage for PTV-MRI was evaluated.Results:The CVS on CT and MRI images was 2.97±1.40 vs. 3.10±1.40( P=0.408). The volumes of TB, CTV, PTV on MRI were significantly larger than those on CT, (24.48±16.60) cm 3vs. (38.00±19.77) cm 3, (126.76±56.81) cm 3vs. (168.42±70.54) cm 3, (216.63±81.99) cm 3vs. (279.24±101.55) cm 3, respectively, whereas the increasing percentage of CTV and PTV were significantly smaller than those of TB. The CI between CT-based and MRI-based TB, CTV, PTV were 0.43±0.13, 0.66±0.11, 0.70±0.09( P<0.001), respectively. The median percentage of PTV-MRI receiving 40 Gy dose was 81.9%(62.3% to 92.4%), significantly lower than 95.6%(95.0%~97.5%) of PTV-CT. Conclusions:The CVS between CT and MRI is not significantly different, but the MRI-based TB, CTV, PTV are significantly larger than CT-based values. The PTV-MRI is of underdose if PBI treatment plan is designed for PTV-CT. As a supplement of CT scan, MRI can enhance the accuracy of TB delineation after breast-onserving surgery.

Objective:To evaluate the clinical efficacy of radiotherapy in the treatment of extracranial metastatic breast cancer, and to investigate the significance and prognostic factors of whole-lesion radiotherapy (WLRT).Methods:Clinical data of 85 patients with extracranial metastatic breast cancer treated with radiotherapy between 2014 and 2019 were retrospectively analyzed. Thirty-six patients were assigned into the WLRT group and 49 in the non-WLRT group. The local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan- Meier method, log-rank test and univariate prognostic analysis. Cox proportional hazards model was used for multivariate prognostic analysis. Results:The median follow-up time was 26.7 months. The 2-year LC, PFS, OS rates were 77%, 26%, 77%, respectively. The 2-year LC (91% vs. 67%, P=0.001), PFS (47% vs. 8%, P<0.001), OS rates (84% vs. 71%, P=0.010) in the WLRT group were significantly higher than those in the non-WLRT group, respectively. Multivariate analysis demonstrated that WLRT was an independent favorable prognostic factor for the LC, PFS and OS. Furthermore, bone metastasis alone was associated with improved LC and positive hormone receptor status was correlated with improved OS. Conclusions:WLRT has the potential to prolong the survival of patients with extracranial metastatic breast cancer. The patients with bone metastases alone obtain better LC, whereas those with negative hormone receptor status has worse OS.

Multi-disciplinary team(MDT)mode is regarded as the key to standardized diagnosis and treatment of malignant tumors. The model, however, encounters such roadblocks in the current form of MDT organization, as costly clinical resources and time consumption, low efficiency, poor management of participating experts in MDT, and lack of enforceability of the therapeutic decisions made. This paper summarized the practical MDT experiences of the Affiliated Cancer Hospital of Shandong First Medical University. It introduced the construction of an intranet-based MDT system covering a large proportion of newly diagnosed malignant tumor patients, and the practices and achievements of such MDT management system under hospital administrative guidance. The authors proposed to use reporting ratio as the main assessment indicator in promoting MDT, and that to define the performance, responsibilities and rights in MDT practice. These measures aim at to upgrading individual behaviors of doctors to organizational behaviors of hospitals, and providing cancer patients with more standardized, comprehensive and personalized diagnosis and treatment decisions.

Objective:To analyze the efficacy of chest wall boost radiotherapy in stage T 4 breast cancer patients after modified radical mastectomy. Methods:A retrospective analysis was performed on the data of 148 stage T 4 breast cancer patients who were admitted from 2000 to 2016 and received radiotherapy after modified radical mastectomy. There were 57 cases in the chest wall boost radiotherapy group and 91 cases in the conventional dose group. Radiotherapy was performed by conventional+ chest wall electron beam, three-dimensional conformal+ chest wall electron beam, intensity modulated radiotherapy+ chest wall electron beam irradiation. EQD 2 at the boost group was >50Gy. All patients received neoadjuvant chemotherapy. Kaplan-Meier method was used to analyze survival; Logrank was used to test differences; and Cox model was used to do multivariate prognostic analysis. Results:The median follow-up time was 67.2 months. The 5-year rates of chest wall recurrence (CWR), locoregional recurrence (LRR), disease-free survival (DFS), and overall survival (OS) were 9.9%, 16.2%, 58.0%, and 71.4%, respectively. The 5-year rates of CWR, LRR, DFS, and OS with and without chest wall boost radiotherapy were 14% vs. 7%, 18% vs. 15%, 57% vs. 58%, 82% vs. 65%( P>0.05), respectively. Multivariate analysis showed that chest wall boost radiotherapy had no significant effect on prognosis ( P>0.05). Among 45 patients in the recurrent high-risk group, boost radiotherapy seemed to have higher OS rate ( P=0.058), DFS rate ( P=0.084), and lower LRR rate ( P=0.059). Conclusions:Stage T 4 breast cancer patients had strong heterogeneity. Chest wall boost radiotherapy did not apparently benefit all patients. For patients with 2-3 high risk factors including positive vascular tumor embolus, pN 2-N 3, and hormone receptor negative, chest wall boost radiotherapy showed a trend of improving efficacy.