Hepatocellular carcinoma (HCC) poses a significant hazard to public health in China because of its high incidence, high mortality, and high rate of advanced stages. Early detection and treatment of HCC by screening for high-risk populations is instrumental for enhancing survival rates among patients with HCC in China. Liver resection, local ablation, interventional therapy, radiotherapy, and drug therapy are all effective treatments for patients with HCC, and appropriate treatments can be selected based on different tumor stages. However, the condition of patients with HCC in China is complicated, and no single specialty offers the complete spectrum of care. The disease-centered multidisciplinary team for HCC is a crucial method to prolong the survival of patients with HCC and optimize their quality of life. Recent advancements in different disciplines have brought new opportunities in HCC treatments and altered multidisciplinary management approaches. Meanwhile, new challenges have emerged, and many problems have yet to be addressed.

Nonalcoholic fatty liver disease(NAFLD)is the most common chronic liver disease,with a global prevalence of approximately 30.05% to 32.4% .It is closely associated with various other diseases.In recent years,microRNAs(miRNAs)have played a crucial role as non-invasive biomarkers in understanding the pathogenesis and diagnosis of NAFLD.miRNAs play significant roles in both lipid metabolism and insulin resistance,exerting specific regulatory functions in the development and progression of NAFLD.miRNAs are small RNA molecules that regulate the gene expression and protein synthesis by controlling the transcription and translation of target genes.This article provides a comprehensive overview of the roles and mechanisms of miRNAs in lipid metabolism,insulin resistance,and the occurrence and development of NAFLD.

Objective:To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC).Methods:This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ 2 test or Fisher′s exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results:According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant( χ 2=4.459, P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant( χ 2=4.410, P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95% CI: 5.8 to 13.2 months) and 7.3 months (95% CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95% CI: 12.5 to 33.9 months) and 15.9 months (95% CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion:Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

Objective:To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC).Methods:This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ 2 test or Fisher′s exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results:According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant( χ 2=4.459, P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant( χ 2=4.410, P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95% CI: 5.8 to 13.2 months) and 7.3 months (95% CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95% CI: 12.5 to 33.9 months) and 15.9 months (95% CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion:Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

A series of chemotherapeutic drugs that induce DNA damage, such as cisplatin (DDP), are standard clinical treatments for ovarian cancer, testicular cancer, and other diseases that lack effective targeted drug therapy. Drug resistance is one of the main factors limiting their application. Sensitizers can overcome the drug resistance of tumor cells, thereby enhancing the antitumor activity of chemotherapeutic drugs. In this study, we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms. We found that the alcohol withdrawal drug disulfiram (DSF) could significantly enhance the antitumor activity of DDP. JC-1 staining, propidium iodide (PI) staining, and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells. Subsequent RNA sequencing combined with Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism: DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia (FA) repair pathway, exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs. Thus, our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP. This might provide an effective and safe solution for combating DDP resistance in clinical treatment.
Female ; Male ; Humans ; Cisplatin/pharmacology* ; Disulfiram/pharmacology* ; Testicular Neoplasms/drug therapy* ; Fanconi Anemia/drug therapy* ; Alcoholism/drug therapy* ; Drug Resistance, Neoplasm ; Cell Line, Tumor ; Substance Withdrawal Syndrome/drug therapy* ; Apoptosis ; Antineoplastic Agents/therapeutic use* ; Cell Proliferation

Primary liver cancer is the fourth most common malignancy and the second most common cause of cancer death in China, which poses a serious threat to the life and health of the Chinese people. Hepatocellular carcinoma (HCC) represents more than 90% of the pathology of primary liver cancer, among them around 60% of patients are at the intermediate-advanced stage when diagnosed. Therefore, increasing the rate of resection via conversion therapies is particularly important to improve the prognosis of these patients. Vascular interventional therapies represented by transarterial chemoembolization and hepatic arterial infusion chemotherapy are important treatment methods for HCC patients in intermediate-advanced stage, showing good rates of tumor response and surgical conversion. Combined with research data at home and abroad, the authors analyze research progress of vascular interventional therapy in the conversion therapy of HCC, review the history and the strategies of conversion therapies based on vascular interventional therapy in this article.

Objective:To investigate the efficacy of venlafaxine combined with transcranial direct current stimulation in the treatment of postpartum depression and its effects on neurological function.Methods:A total of 135 patients with postpartum depression who were admitted to Wenzhou Seventh People's Hospital from November 2019 to October 2021 were included in this study. They were randomly divided into observation ( n = 70) and control ( n = 65) groups. The control group was treated with venlafaxine alone, and the observation group was treated with an IS200 intelligent electrical stimulator based on the treatment used in the control group. The two groups were treated for 4 weeks. Clinical efficacy and neurological function were compared between the two groups. Results:Total response rate in the observation group was significantly higher than that in the control group (98.57% vs. 89.23%, χ2 = 7.61, P < 0.05). After treatment, the scores of Edinburgh Postnatal Depression Scale and Hamilton Depression Scale in the observation group were (8.03 ± 0.79) points and (9.03 ± 3.98) points, respectively, which were significantly lower than (11.74 ± 0.98) points and (14.68 ± 3.79) points in the control group ( t = 3.28, 4.65, both P < 0.05). Standard deviation of heart rate variability, root mean square of successive differences between adjacent NN intervals, ratio of low frequency to high frequency, activity of the autonomic nervous system in the observation group were (32.38 ± 0.93) ms, (27.86 ± 0.78) ms, 1.79 ± 0.19, (86.65 ± 1.21) points, respectively, which were significantly higher than (27.84 ± 0.88) ms, (25.79 ± 0.81) ms, 1.38 ± 0.14, (82.94 ± 1.19) points in the control group ( t = 4.09, 3.72, 2.98, 4.09, all P < 0.05). Conclusion:Venlafaxine combined with transcranial direct current stimulation for treatment of postpartum depression can enhance clinical efficacy and remarkably improve patient's neurological function.

Primary liver cancer is the fourth most common malignancy and the second most common cause of cancer death in China, posing a serious threat to the health of Chinese people. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancers, among them 66% of patients are with intermediate-advanced HCC. Therefore, prevention strategies and conversion therapies to patients with intermediate-advanced HCC are particularly important. Hepatic arterial infusion chemotherapy (HAIC) is one of the important treatment methods to treat intermediate-advanced HCC. The tumor objective response rates and surgery conversion rates of HAIC-based conversion therapies are promising. The authors review the history of HAIC and the HAIC-based conversion therapies in this article.

Currently, the definition, classification and Chinese nomenclature of intra-hepatic cholangiocarcinoma (ICC) are controversial. Whether ICC belongs to liver cancer or carcinoma of bile duct is debatable, and the two terms"intrahepatic cholangiocarcinoma"and"cholangiocellular carcinoma"are simultaneously used without distinction, bringing great confusions to clinical practice. Based on authoritative literatures at home and abroad, the authors give suggestions on the definition, classification and Chinese nomenclature of ICC, as well as the classification of carcinoma of bile duct, which recommend that the Chinese translation of "cholangiocarcinoma" should be "epithelial carcinoma of bile duct (cholangiocellular carcinoma)", the mass-forming type ICC should be classified as primary liver cancer, naming as"intrahepatic cholangiocarcinoma"and the periductal-infiltrating type and intraductal-growing type ICCs still be classified as carcinoma of bile duct, naming as"perihilar cholangiocarcinoma". The authors recommend to classify carcinoma of bile duct into: perihilar cholangiocarcinoma, hilar cholangiocarcinoma, and distal cholangiocarcinoma.

Pharmaceutical cocrystals are multicomponent systems in which at least one component is an active pharmaceutical ingredient and the others are pharmaceutically acceptable ingredients. Cocrystallization of a drug substance with a coformer is a promising and emerging approach to improve the performance of pharmaceuticals, such as solubility, dissolution profile, pharmacokinetics and stability. This review article presents a comprehensive overview of pharmaceutical cocrystals, including preparation methods, physicochemical properties, and applications. Furthermore, some examples of drug cocrystals are highlighted to illustrate the effect of crystal structures on the various aspects of active pharmaceutical ingredients, such as physical stability, chemical stability, mechanical properties, optical properties, bioavailability, sustained release and therapeutic effect. This review will provide guidance for more efficient design and manufacture of pharmaceutical cocrystals with desired physicochemical properties and applications.