Background::Liver cancer is largely resistant to chemotherapy. This study aimed to identify the effective chemotherapeutics for β-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1 ( CTNNB1), the most frequently altered proto-oncogene in hepatic neoplasms. Methods::Constitutive β-catenin-activated mouse embryonic fibroblasts (MEFs) were established by deleting exon 3 ( β-cateninΔ(ex3)/+ ), the most common mutation site in CTNNB1 gene. A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibited β-cateninΔ(ex3)/+ but not for wild-type MEFs. Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis. The efficacy and selectivity of methotrexate (MTX) on β-catenin-activated human liver cancer cells were determined in vitro. Immuno-deficient nude mice subcutaneously inoculated with β-catenin wild-type or mutant liver cancer cells and hepatitis B virus ( HBV); β-cateninlox(ex3)/+ mice were used, respectively, to evaluate the efficacy of MTX in the treatment of β-catenin mutant liver cancer. Results::MTX was identified and validated as a preferential agent against the proliferation and tumor formation of β-catenin-activated cells. Boosted nucleotide synthesis was the major metabolic aberration in β-catenin-active cells, and this alteration was also the target of MTX. Moreover, MTX abrogated hepatocarcinogenesis of HBV; β-cateninlox(ex3)/+ mice, which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer. Conclusion::MTX is a promising chemotherapeutic agent for β-catenin hyperactive liver cancer. Since repurposing MTX has the advantages of lower risk, shorter timelines, and less investment in drug discovery and development, a clinical trial is warranted to test its efficacy in the treatment of β-catenin mutant liver cancer.

Objective:To retrieve, screen, evaluate and synthesize evidence related to the management of pregnant women during pregnancy after cervical cerclage to provide a basis for clinical practice.Methods:According to the "6S" evidence resource pyramid model, the system searched of all evidence on the management of pregnant women after cervical cerclage in databases suchas UpTo Date, BMJ Best Clinical Practice, International Guidelines Network, American Guidelines Network, World Health Organization website, Yimaitong, Metz Medical website, Clinical Guidelines website, American College of Obstetricians and Gynaecologists, Royal College of Obstetricians and Gynaecologists of the United Kingdom, Canadian College of Obstetricians and Gynaecologists, French College of Obstetricians and Gynaecologists, European Association of Perinatal Medicine, Cochrane Library, the Joanna Briggs Institute (JBI), the Centre for Evidence-Based Health Care Database, PubMed, Embase, Scopus, Web of Science, CNKI, Wanfang Database, VIP Database, and China Biomedical Literature Database, including best dicision practices, guidelines, expert consensus, evidence summary, systematic reviews, Meta-analysis. The search time limit was the establishment of the database to March 1, 2023, and the evidence was extracted and summarized according to the theme after the two researchers independently evaluate the quality of the literature.Results:A total of 8 studies were selected, including 2 expert consensuses, 2 systematic reviews and 4 guidelines. Through literature reading, evidence extraction and classification, 23 pieces of best evidence were summarized from seven aspects: systematic management, activity management, medication management, health behavior management, pregnancy supervision, supervision of the timing of cerclage removal and supervision of psychological state.Conclusions:The best evidence quality and autuority of pregnancy management for pregnamt women after cervical cerclage surgery summarized in the study are high. It was recommended to strengthen the management of pregnant women during pregnancy after cervical cerclage, dynamically and continuously assess the pregnancy status of pregnant women, and prudently selected evidence to improve the prenatal examination process, ensure the safety of mothers and babies, and reduce the occurrence of complications. Overall, effective management of pregnant women during pregnancy after cervical cerclage required a combination of many factors to ensure the health and safety of the mother and baby.

This case report described an 80-year-old male patient with Parkinson disease(PD)complicated with myasthenia gravis(MG).Six years ago,the patient was diagnosed with PD based on the motor symptoms including bradykinesia and static tremor and treated with levodopa-benserazide and piribedil sustained-release tablets.He was admitted to the hospital due to left eyelid ptosis one month ago.The result of Neostigmine test was positive and anti-acetylcholine receptor(AChR)antibodies of serum was positive,which met the diagnostic criteria for myasthenia gravis(MG).The symptom of MG improved significantly after treatment with glucocorticoid and pyridostigmine but the PD symptoms worsened.The symptoms of PD were improved after withdrawal of pyridostigmine and use of the levodopa-benserazide and his condition maintained stable at 3 years of follow-up.The PD complicated with MG was fairly rare.We also reviewed the literature on the possible comorbidity mechanism and treatment strategies to improve the comprehensive understanding and ability of diagnosis and treatment of clinicians.

AIM: To observe the clinical efficacy of Fuzheng Xiaoliu Granules in the treatment of stage II primary liver cancer and to explore its mechanism of action from the perspective of metabolomics. METHODS: Sixty patients with stage II primary liver cancer who achieved complete remission (CR) after comprehensive interventional therapy were randomly divided into treatment group and placebo group, with 30 patients in each group. They were treated for one year and observed for one year. The one-year recurrence rate, traditional chinese medicine (TCM) syndrome score, alpha-fetoprotein and child-pugh grade were compared between the two groups. The serum metabolites of the two groups before and after treatment were screened by ultra-high liquid chromatography-mass spectrometry technology, and the metabolic pathways and related biological pathways were analyzed. RESULTS: The one-year recurrence rate of the treatment group was significantly lower than that of the placebo group, and the overall improvement rate of TCM syndrome score was significantly better than that of the placebo group (P<0.05). There was no statistical significance in the comparison of alpha-fetoprotein and child-pugh grade between the two groups after treatment (P>0.05). Metabolomics results showed that there were 39 and 33 different metabolites in the treatment group before and after treatment and in the two groups after treatment, respectively. After enrichment analysis and topological analysis of the different metabolites, it was found that Fuzheng Xiaoliu Granules could affect amino acid metabolism, fatty acid metabolism and purine metabolism and other metabolic pathways. Before and after treatment in the treatment group and after treatment in the two groups, there were the same differential metabolites and metabolic pathways in the two comparison results. The same differential metabolites with FOLD CHANGE>1 include Stearic acid, Hypoxanthine, Kynurenic acid, Arachidonic acid, and N-Arachidonoyl Dopamine. The same metabolic pathways with Impact>0.1 include Arachidonic acid metabolism and Histidine metabolism. CONCLUSION: Fuzheng xiaoliu granules can effectively reduce the recurrence rate of stage II liver cancer patients after comprehensive intervention and improve the TCM syndrome. It may inhibit the activation of PI3K/Akt and ERK signaling pathways by regulating the content of metabolites involved in metabolic pathways such as amino acids and fatty acids, thereby delaying tumor recurrence.

Objective:To investigate the risk factor of hepatocellular carcinoma (HCC) with vessels encapsulating tumor clusters (VETC) and the application value of its risk scoring model.Methods:The retrospective cross-sectional study was conducted. The clinicopathological data of 149 patients with HCC who were admitted to two medical centers, including 97 cases in the Jiangnan University Medical Center and 52 cases in the Affiliated Xingtai People′s Hospital of Hebei Medical University, from January 2017 to April 2020 were collected. There were 116 males and 33 females, aged (58±12)years. There were 74 cases with VETC and 75 cases without VETC. Observation indica-tors: (1) clinical characteristics of patients with and without VETC; (2) imaging features of patients with and without VETC; (3) multivariable analysis of HCC patients with VETC; (4) construction of VETC related risk scoring model and its performance evaluation; (5) postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Count data were described as absolutes, and comparison between groups was conducted using the chi-square test and continuous correction chi-square test. Variables of clinical and imaging characteristics with statistically signifi-cant were included in the multivariate analysis. Multivariate analysis was conducted using the Logistic regression model of backward stepwise selection. VETC related risk scoring model was constructed based on the results of Logistic regression model. The receiver operating characteristic (ROC) curve was drawn, and the area under curve (AUC), the sensitivity, specificity, accuracy and their 95% confidence interval ( CI) were calculated. The maximizing Youden index was the optimal cutoff value for VETC prediction. The Hosmer Lemeshow goodness of fit test was used to assess the consistency between VETC risk scoring model predicted VTEC status and the true VETC status. The Kaplan-Meier method was used to calculate survival rates and draw survival curves. The Log-rank test was used for survival analysis. Results:(1) Clinical characteristics of patients with and without VETC. Cases with postoperative albumin <36 g/L were 57 in patients with VETC, versus 68 in patients without VETC, respectively, showing a significant difference between them ( χ2=5.13, P<0.05). (2) Imaging features of patients with and without VETC. Cases with lesion imaging presence as nonperipheral washout, cases with lesion imaging presence as mosaic architecture, cases with lesion imaging presence as intratumoral hemorrhage, cases with lesion imaging presence as corona enhancement, cases with lesion imaging presence as non-smooth tumor margin, cases with lesion imaging presence as peritumoral enhancement in arterial phase, cases with lesion imaging presence as intratumoral arteries, cases with lesion imaging presence as peritumoral hypointensity in hepatobiliary phase, cases with lesion imaging enhancement type as uniform low enhancement, uniform high enhance-ment, heterogeneous enhancement with septations and heterogeneous enhancement with irregular ring-like structures, cases with intratumoral necrosis or ischemic, cases with tumor diameter >5 cm were 73, 35, 33, 15, 39, 28, 42, 27, 4, 5, 27, 38, 45, 46 in patients with VETC, versus 64, 16, 13, 3, 19, 15, 9, 13, 9, 35, 5, 26, 10, 10 in patients without VETC, respectively, showing significant differences in the above indicators between them ( χ2=8.92, 11.15, 12.97, 9.28, 11.74, 5.77, 33.14, 6.96, 41.79, 36.05, 37.86, P<0.05). (3) Multivariable analysis of patients with VETC. Results of multivariable analysis showed that lesion imaging enhancement as heterogeneous enhancement with septations, lesion imaging enhancement as heterogeneous enhancement with irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm were independent risk factors influen-cing patients with VETC ( odds ratio=4.18, 7.62, 4.23, 4.08, 95% CI as 1.60?11.60, 2.00?31.70, 1.71?10.90, 1.60?10.80), P<0.05). (4) Construction of VETC related risk scoring model and its performance evaluation. The VETC related risk scoring model was constructed as (heterogeneous enhancement with septations, presence: 1.0, absence: 0)+(heterogeneous enhancement with irregular ring-like structures, presence: 1.5, absence: 0)+(intratumoral necrosis or ischemia, presence: 1.0, absence: 0)+(main tumor diameter >5 cm, presence: 1.0, absence: 0). The AUC, sensitivity, specificity, and accuracy of VETC related risk scoring model were 0.86 (95% CI as 0.80?0.92), 79.7% (95% CI as 69.2%?87.3%), 80.0% (95% CI as 69.6%?87.5%) and 79.9% (95% CI as 72.7%?85.5%), respectively. Results of Hosmer-Lemeshow goodness of fit test showed a good consistency between VETC risk scoring model predicted VETC status and true VETC status ( P>0.05). (5) Postoperative early tumor recurrence of patients with and without VETC who were confirmed by risk scoring model and histopathological examination. All 149 patients were followed up for 29(range, 26?35)months. The time to tumor recurrence and 2-year cumulative tumor recurrence rate of 149 patients were 29(range, 24?33)months and 43.0%, respectively. The 2-year tumor cumulative recurrence rate of patients with and without VETC predicted by risk scoring model was 47.8% and 37.9%, respectively, showing a significant difference between ( χ2=3.90, P<0.05). The 2-year cumulative tumor recurrence rate of patients with and without VETC confirmed by postoperative histopathological examination was 47.4% and 38.1%, respectively, showing a significant difference between ( χ2=4.20, P<0.05). Conclusions:Lesion imaging enhancement as heterogeneous enhancement with septations or irregular ring-like structures, intratumoral necrosis or ischemia and tumor diameter >5 cm are independent risk factors influen-cing HCC patients with VETC. The proposed risk scoring model based on those three risk factors achieves an optimal preoperative diagnostic performance.

Objective:To investigate the value of the extrahepatic bile duct and main pancreatic duct segment patterns on magnetic resonance cholangiopancreatography (MRCP) for differentiating the periampullary carcinoma (PAC).Methods:The clinicopathologic data of 125 patients with PAC who were admitted to Wuxi No.2 People’s Hospital from June 2013 to December 2021 were retrospectively analyzed, including 72 males and 53 females, aged (64.9±8.6) years. According to its anatomy, the extrahepatic bile duct (B) was divided into suprapancreatic and intrapancreatic (including ampullary) segments, and the main pancreatic duct (P) was divided into tail-body and head segments. MRCP patterns: i. the extrahepatic bile duct or main pancreatic duct visible without dilatation, ii. cutoff of the distal extrahepatic bile duct or main pancreatic duct with upstream dilatation, iii. cutoff of the intrapancreatic or head segment with upstream dilatation and remnant intrapancreatic or head segments invisible, iv. cutoff of the intrapancreatic or head segment with upstream dilatation and nondilated remnant intrapancreatic or head segments, were represented as 0, 1, 2, and 3, respectively. Segment patterns of B1/P0+ B1/P1, B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3, B3/P0, and B0/P0+ B2/P0 on MRCP were compared in PAC patients.Results:Of the 125 patients, there were 57 (45.6%) with pancreatic head carcinoma, 36 (28.8%) with ampullary carcinoma, 20 (16.0%) with distal cholangiocarcinoma, and 12 (9.6%) with periampullary duodenal carcinoma. Segment patterns of B0/P2+ B0/P3+ B2/P2+ B2/P3+ B3/P3 were found in 52 patients with pancreatic head carcinoma (91.2%, 52/57), with a significant difference between PAC (χ 2=110.66, P<0.001). Segment patterns of B1/P0+ B1/P1were found in 36 patients with ampullary carcinoma (100.0%, 36/36), fallowed by 11 (91.7%, 11/12) with periampullary duodenal carcinoma, with a significant difference between PAC (χ 2=129.95, P<0.001). Segment pattern of B3/P0 presented in 16 patients with distal cholangiocarcinoma (80.0%, 16/20), with a significant difference between PAC (χ 2=62.45, P<0.001). The segment patterns of B0/P0+ B2/P0 were only seen in 3 of 57(5.3%) patients with pancreatic head carcinoma. Conclusion:On MRCP, cutoff of the head segment with upstream dilatation and remnant head segment invisible or nondilated indicates the pancreatic head carcinoma. Cutoff of the intrapancreatic segment with upstream dilatation, remnant intrapancreatic segment visible, and main pancreatic duct nondilated, indicates the distal cholangiocarcinoma. And cutoff of the distal extrahepatic segment with upstream dilatation and main pancreatic duct dilatation or not, indicates the ampullary or periampullary duodenal carcinoma.

There is still a lack of effective strategies for the prevention and treatment of liver cancer, and a deep understanding of its pathogenesis may help to develop new treatment methods. Due to the abnormal changes of lipid metabolism in the development and progression of liver cancer, such process is closely associated with the "phlegm-turbidity" theory in traditional Chinese medicine (TCM). Starting from the changes of lipid metabolism in hepatocellular carcinoma microenvironment, this article discusses the association of the abnormal changes of lipid metabolism in tumor cells and immune cells with the "phlegm-turbidity" theory and the clinical efficacy of phlegm-eliminating therapies in clinical practice. Since the "phlegm-turbidity" theory in TCM plays an important role in the pathogenesis and pathological changes of liver cancer, the analysis of its theoretical connotation helps to clarify pathological mechanism, thereby providing a theoretical basis for the role of TCM in the prevention and treatment of liver cancer.

It is a new attempt to interpret the essence of doctor-patient relationship and reveal the mechanism of doctor-patient conflict by using game theory. According to James Cass’s philosophy theory of finite and infinite games, this paper applies the four elements of finite and infinite games: "goal-actor-rule-boundary". Combined with the four elements of game theory, the doctor-patient relationship was systematically interpreted, and the evolution model of finite games and infinite games was constructed. This paper held that the essence of doctor-patient relationship is an infinite game in theory, the nature of doctor-patient relationship is a finite game in reality, and doctor-patient conflict is the result of the evolution of the finite game of doctor-patient relationship. Based on the finite game evolution model, this paper analyzed the causes of doctor-patient conflict in the specific narrative of doctor-patient conflict, and pointed out that the doctor-patient relationship can only be resolved by changing their "game view", so as to achieve the transcendence of the doctor-patient relationship from finite game to infinite game.

Objective:To investigate the value of machine learning-based computed tomography (CT) images radiomics analysis in preoperative evaluation of surgical portal vein-superior mesenteric vein (PV-SMV) invasion in patients with pancreatic ductal adenocarcinoma (PDAC).Methods:The retrospective study was conducted with 156 consecutive PDAC patients who were underwent surgery at the Affiliated Wuxi No.2 People's Hospital of Nanjing Medical University between January 2010 and July 2021. There were 95 males and 61 females, with the age of (65.7±8.2) years. Patients were randomly split into training set and validation set by a ratio of 3∶2. Minimum redundancy maximum relevance was used to select radiomic features, which were extracted from contrast-enhanced CT images. Five machine learning classifiers were developed, and those models' area under the curve (AUC) values were compared with the conventional radiologic-feature-based evaluation.Results:Ninety-four and 52 patients were included into the training set and validation set, respectively. Their PV-SMV invasion rates were confirmed by intraoperative exploration with 31.9%(30/94) and 40.3%(25/61), respectively. Five models: LASSO regression, random forest, support vector machine, k-nearest neighbor and Naive Bayesian, were established based on ten features from CT images radiomics, and LASSO regression model achieved the highest AUC value compared with the other four models (all P<0.05). Compared with the conventional radiologic evaluation, the LASSO regression model had higher AUC (0.920 vs. 0.752) and sensitivity (92.0% vs. 86.5%)(both P<0.05). Conclusion:Machine learning-based CT images radiomics analysis can be used to evaluate PV-SMV invasion status preoperatively in PDAC. The LASSO regression model showed better performance than the conventional radiologic evaluation.

The oral cavity of each person is home to hundreds of bacterial species.While taxa for oral diseases have been studied using culture-based characterization as well as amplicon sequencing,metagenomic and genomic information remains scarce compared to the fecal microbiome.Here,using metagenomic shotgun data for 3346 oral metagenomic samples together with 808 published samples,we obtain 56,213 metagenome-assembled genomes(MAGs),and more than 64％of the 3589 species-level genome bins(SGBs)contain no publicly available genomes.The resulting genome collection is representative of samples around the world and contains many genomes from candi-date phyla radiation(CPR)that lack monoculture.Also,it enables the discovery of new taxa such as a genus Candidatus Bgiplasma within the family Acholeplasmataceae.Large-scale metagenomic data from massive samples also allow the assembly of strains from important oral taxa such as Por-phyromonas and Neisseria.The oral microbes encode genes that could potentially metabolize drugs.Apart from these findings,a strongly male-enriched Campylobacter species was identified.Oral sam-ples would be more user-friendly collected than fecal samples and have the potential for disease diagnosis.Thus,these data lay down a genomic framework for future inquiries of the human oral microbiome.