Palliative care,as the most special way to treat malignant tumors,is not only conducive to improving the quality of life and life value of patients,as well as alleviating the physical and mental pain of patients and their families,but also can help to relieve their financial burden and effectively avoid the waste of limited public resources.However,in the actual promotion of palliative care services,various ethical issues are encountered,such as the dignity of death,the need for psychological care,and the patient's right to independent decision-making.From the perspective of bioethics,by analyzing different types of practical disputes,this paper revealed their inherent ethical problems,and proposed specific countermeasures from the aspects of defending patient dignity,breaking the limitations of traditional cognition,and establishing a field model for joint decision-making between doctors and patients,so as to build a palliative care service model that suits China's national conditions and safeguard the patients'life rights and interests with malignant tumors.

AIM:The paper is to explore a rapid and simple method for the culture of mouse primary thyroid cells.METHODS:Mouse thyroid cells were isolated by enzyme digestion and cultured with improved medium,and their morphology,characteristics and secretory function were observed within 14 d.RESULTS:In the cultures,the active pri-mary cells were obtained from the thyroid tissue after digestion for 25 min;adherent growth was observed on the 2nd day.And secondary follicles appeared from the 5th to 7th day.Over 95%cells were detected with thyroglobulin.The secretion of total triiodothyronine and total thyroxine maintains over 60%in 7 d.The expression levels of specific genes can still maintain more than 50%in 10 d.CONCLUSION:Mouse thyroid primary cells can be rapidly cultured by this method,and the cells can be used for studying thyroid endocrine secretion within 7 d and studying thyroid genes within 10 d.

Objective To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway.Methods Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients.Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer.CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting.Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid,and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay,EdU assay,and cell cycle assay;the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting.Results Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them(P>0.05),but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis.Immunohistochemistry,qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells(P<0.01),and its overexpression strongly inhibited cell proliferation,caused cell cycle arrest,and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1.Conclusion Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

AIM:To investigate the activation of Cl-channels by sodium taurocholate(NaTC)in mouse pan-creatic acinar cells.METHODS:The single isolated pancreatic acinar cells from FVB/N mice were prepared using colla-genase digestion method.Whole-cell patch clamp technique was performed to record the currents.Intracellular adenosine triphosphate(ATP)dependence of the channels was examined via eliminating ATP from the pipette solution.Anion per-meability of the channels was investigated with ion-exchange method.The pharmacological characteristics of the channels was confirmed by two Cl-channel blockers.The volume sensitivity of the channels was detected using 47%hypertonic bathing solution.Extracellular Ca2+dependence of activating the channels was examined through eliminating Ca2+from the bathing solution.Intracellular reactive oxygen species(ROS)level was detected by an oxidation-sensitive fluorescent probe,2',7'-dichlorofluorescin diacetate.The experiment was repeated 6 times in each group.RESULTS:Extracellular application of 5 mmol/L sodium taurocholate induced a Cl-current,exhibiting the properties of outward-rectification,a se-lectivity sequence of I->Br-≥Cl->gluconate-and intracellularATP dependence(P<0.01).The currents were inhibited by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid disodium salt hydrate(DIDS)and tamoxifen and by 47%hypertonicity stimulation(P<0.01).When ROS production was scavenged by N-acetyl-L-cysteine,the sodi-um taurocholate-induced Cl-currents were unaffected.The effect of sodium taurocholate on ROS production did not alter with the treatment with DIDS.Sodium taurocholate failed to induce Cl-currents when Ca2+was absent in extracellular bath-ing solution(P>0.05).CONCLUSION:Sodium taurocholate activates Cl-channels in mouse pancreatic acinar cells,which is dependent on extracellular Ca2+but not ROS pathway.

Hepatocellular carcinoma is the most common malignancy of the liver and poses serious health burdens on China and the whole world. However， most patients with hepatocellular carcinoma are already in the advanced stage at the time of diagnosis， with fewer opportunities for surgery and limited treatment options. In recent years， the advances in molecular targeted therapies have brought new hope for patients with advanced hepatocellular carcinoma. Among these therapies， lenvatinib is the second first-line drug after sorafenib approved by the US Food and Drug Administration for the treatment of advanced hepatocellular carcinoma， and it has attracted widespread attention for its powerful anti-tumor properties. However， the efficacy of lenvatinib is severely limited by its drug resistance. This article reviews the research advances in the molecular mechanisms of lenvatinib resistance in hepatocellular carcinoma and discusses possible ways to improve the efficacy of lenvatinib， so as to improve its efficacy.

Objective To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway.Methods Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients.Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer.CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting.Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid,and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay,EdU assay,and cell cycle assay;the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting.Results Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them(P>0.05),but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis.Immunohistochemistry,qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells(P<0.01),and its overexpression strongly inhibited cell proliferation,caused cell cycle arrest,and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1.Conclusion Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.

To assess the protective effects of luteolin(LT)on liver fibrosis in rats with autoimmune hepatitis(AIH)and to explore the underlying mechanisms,total of 62 rats were recruited and randomly divided into normal control group(CT),AIH model group(AIH),LT low-dose group(LT L),LT medium-dose group(LT M),LT high-dose group(LT H)and prednisolone group(PSL),with 10 rats in each group.The rat in CT group were injected with an equivalent volume of physiological saline via the tail vein,when the rat in the other groups were received tail vein injection of concanavalin A(Con A)dissolved in physiological saline to induce the AIH model.Then,the rat in LT L,M,and H groups were administered intraperitoneal injections of LT dissolved in physiological saline(at doses of 5,25,and 50 mg/kg,respectively),and the rat in the PSL group received intraperitoneal injections of PSL dissolved in physiological saline(at a dose of 10.0 mg/kg),while the rat in the CT and AIH groups received equivalent volumes of physiological saline intraperitoneally.All treatments were administered twice daily for 7 consecutive days.The day after the last treatment,liver function indices,peripheral blood lymphocyte subsets,and hepatic hydroxyproline content were measured.Furthermore,Masson staining was used to assess the liver fibrosis was assessed using,and Western blot analysis was performed to detect the expression levels of activated nuclear factor κB(NF-κB),phosphorylated NF-κB(p-NF-κB),inhibitor of nuclear factor κBα(IκBα),and phosphorylated IκBα(p-IκBα)proteins in liver tissue.Compared to the CT group,the AIH group exhibited significantly higher serum levels of alanine aminotransferase(ALT),total bilirubin(TBIL),CD4+T lymphocyte ratio,CD4+/CD8+ratio,and hepatic hydroxyproline content(P<0.05),while albumin(ALB)levels and the CD8+T lymphocyte ratio were significantly lower(P<0.05).LT in all doses could reverse these changes mentioned above in AIH rats in a dose-dependent manner(P<0.05),and no significant differences were observed between the LT H group and the PSL group in these parameters(P>0.05).Masson staining results revealed that liver fibrosis in the LT groups was less severe than that in the AIH group,with a clear dose-dependent effect.The PSL group exhibited similar antifibrotic effects to the LT H group.Furthermore,the AIH group showed significantly higher levels of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios in liver tissue,as compared to the CT group(P<0.05),while LT could suppress the increase of p-NF-κB p65/NF-κB p65 and p-IκBα/IκBα ratios(P<0.05)in a dose-dependent manner(P<0.05),and no significant differences in these ratios were observed between the LT H group and the PSL group(P>0.05).Taken together,Luteolin can improve liver function and immune function,and alleviate liver fibrosis by inhibiting the NF-κB pathway in AIH rats.

China has classified the Corona Virus Disease 2019(COVID-19) as a statutory category B infectious disease and managed it according to Category B since January 8, 2023.In view that Omicron variant is currently the main epidemic strain in China, in order to guide the treatment of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection in children with the times, refer to the Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial 10 th Edition), Expert Consensus on Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fourth Edition) and the Diagnosis and Treatment Strategy for Pediatric Related Viral Infections.The Expert Consensus on the Diagnosis, Treatment and Prevention of Novel Coronavirus Infection in Children (Fifth Edition) has been formulated and updated accordingly on related etiology, epidemiology, pathogenic mechanism, clinical manifestations, auxiliary examination, diagnosis and treatment, and added key points for the treatment of COVID-19 related encephalopathy, fulminating myocarditis and other serious complications for clinical reference.

The characteristic genetic abnormality of neuroendocrine neoplasms (NENs), a heterogeneous group of tumors found in various organs, remains to be identified. Here, based on the analysis of the splicing variants of an oncogene Focal Adhesion Kinase (FAK) in The Cancer Genome Atlas datasets that contain 9193 patients of 33 cancer subtypes, we found that Box 6/Box 7-containing FAK variants (FAK^6/7) were observed in 7 (87.5%) of 8 pancreatic neuroendocrine carcinomas and 20 (11.76%) of 170 pancreatic ductal adenocarcinomas (PDACs). We tested FAK variants in 157 tumor samples collected from Chinese patients with pancreatic tumors, and found that FAK^6/7 was positive in 34 (75.6%) of 45 pancreatic NENs, 19 (47.5%) of 40 pancreatic solid pseudopapillary neoplasms, and 2 (2.9%) of 69 PDACs. We further tested FAK splicing variants in breast neuroendocrine carcinoma (BrNECs), and found that FAK^6/7 was positive in 14 (93.3%) of 15 BrNECs but 0 in 23 non-NEC breast cancers. We explored the underlying mechanisms and found that a splicing factor serine/arginine repetitive matrix protein 4 (SRRM4) was overexpressed in FAK^6/7-positive pancreatic tumors and breast tumors, which promoted the formation of FAK^6/7 in cells. These results suggested that FAK^6/7 could be a biomarker of NENs and represent a potential therapeutic target for these orphan diseases.
Female ; Humans ; Alternative Splicing ; Breast Neoplasms/metabolism* ; Carcinoma, Pancreatic Ductal/pathology* ; Focal Adhesion Protein-Tyrosine Kinases/therapeutic use* ; Nerve Tissue Proteins/genetics* ; Neuroendocrine Tumors/genetics* ; Oncogenes ; Pancreatic Neoplasms/metabolism*

Objective:To determine the effects of preperitoneal balloon (PPB) tamponade with different volumes of fluid on hemodynamically unstable pelvic fracture-associated arterial and venous hemorrhage in a swine model.Methods:A model of open-book pelvic fracture with injuries to external iliac vessels was established in 18 female 12-month old Bama miniature pigs. After the successful establishment of hemodynamically unstable pelvic fracture with vascular injury was confirmed by contrast agent imaging, the animals were randomized into 3 even groups ( n=6): a control group (group C) subjected to PPB tamponade with 0 mL fluid injected, group T1 subjected to PPB tamponade with 500-mL fluid injected, and group T2 subjected to PPB tamponade with 1,000-mL fluid injected. The 3 groups were compared in terms of 60-min survival rate, balloon pressure, peritoneal pressure, bladder pressure, 70-min survival rate, blood loss, and infusion volume. Results:There was no statistically significant difference in the basic hemodynamic or other experimental indicators among the 3 groups before experiment, indicating comparability ( P>0.05). The 60-min survival rate in group T2 was 100.0% (6/6), significantly higher than those in group C and group T1 [0.0% (0/6), 0.0% (0/6)] ( P<0.05). After fluid injection, the balloon pressure and preperitoneal pressure in group T2 were respectively (127.2±4.7) mmHg and (34.5±3.6) mmHg, significantly higher than those in group T1 [(78.7±3.8) mmHg and (13.7±2.8) mmHg] and in group C [0 mmHg and (9.0±1.4) mmHg], and the 2 indicators in group T1 were significantly higher than those in group C (all P<0.05). After fluid injection, there was no statistically significant difference among groups C, T1, and T2 in bladder pressure [(6.7±1.0) mmHg, (5.8±1.9) mmHg, and (6.0±1.1) mmHg] or in bleeding volume [(1,163.0±191.3) mL, (1,212.0±148.4) mL, and (975.0±133.2) mL] (all P≥ 0.05). The infusion volume in group T1 [(1,250.0±225.8) mL] was significantly larger than that in group C [(951.7±177.8) mL] ( P<0.05). No colorectal or bladder injuries were found by the anatomy of the experimental animals in 3 groups. Conclusions:PPB tamponade with 1,000-mL fluid injected in a swine model can efficiently control pelvic fracture-associated arterial and venous hemorrhage, and increase the 60-min survival rate with no colorectal or bladder injuries.