Shenyang Medical College

Wang P., Han Y., Lv Z., Miao L., Wang M., Liu Z., Feng T., Gao M., Shi Y., Cai R., Sun Z., Bian J.

Zhang M., Lv P., Wang L., Wang J., Yang J.

Luan T., Jin Y., Wu D., Wei W., Yang J., Wang J.

Jiang H., Xu S., Xiang X., Zhao M., Wang Y., Liu X., Liu B., Chen Q.

Bai S., Jichao S., Zhiyao L., Lingke G., Kewen L., Hongli Y., Diancheng Z., Zhongzhou D., Zhang M., Yao J., Ke L., Tianshu L.

Chen X., Shen A., Niu S., Xiao M., Zhang J., Lu T., He Z., Li S., Yang W.

Zhan X., Chen X., Feng M., Yao K., Yang K., Jia H.

Sun Y., Wang R., Wang C., Shao X., Zheng X., Li H., Chi Y., Deng B., Li Y., Jin S., Qi X.

Lopinavir/ritonavir, an anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drug, may be associated with the development of liver injury. In this paper, we reported an elderly female patient with drug-induced liver injury secondary to lopinavir/ritonavir, which was evaluated for their causality using the updated Roussel Uclaf Causality Assessment Method (RUCAM) of 2016. She had a RUCAM score of 8 which was equivalent to a probable causality grading. Her clinical course was complicated by persistent hepatocyte secretion failure (PHSF), followed by septic shock and SARS-CoV-2 re-infection during her hospitalization. Her response to any medical intervention, including ursodeoxycholic acid, glutathione, methylprednisolone sodium succinate, rifampicin, artificial liver support, and endoscopic nasobiliary drainage (ENBD) was very poor, and her family members refused liver transplantation. Finally, she died. In summary, this case suggests the possibility that lopinavir/ritonavir can cause DILI and even PHSF in our clinical practice.

Yu W., Huang R., Sun S., Bu L., Chen X., Di Y., Lin S., Li Q., Yang Y., Ye X., Wang W., Ren R., Xi L., Zhang R., Li Y., et. al.

Multimorbidity and physical function in older adults have been identified as associated with coronavirus disease 2019 (COVID-19) outcomes. This study aimed to investigate whether multimorbidity affects the association of impaired functional independence (FI) with critical COVID-19 among older inpatients during the peak of Omicron infection in China. This is a multicentre, retrospective cohort study in northeastern China. Patients aged ≥ 60 years, who were diagnosed with COVID-19 at the time of admission or during hospitalisation. The Barthel index was used to assess FI. Patients were classified into independent, mildly dependent, moderately dependent, and severely dependent groups. Disease severity was classified as critical, severe, and non-severe and combined into severe or critical and non-severe. Binary logistic regression analysis was used to investigate any correlation between FI and disease severity. Patients were further stratified by presence or absence of multimorbidity. In this study, of 1598 patients, 530 (33.17%) developed severe or critical infections during the entire hospital stay. Patients with severe dependency had 7.39 times (95% CI: [4.60, 12.15]) higher risk of serious or critical infections than those without dependency. An interaction was noted between reduced FI and multimorbidity (p for interaction < 0.001). Compared to non-multimorbid patients (OR = 3.71, 95% CI: [1.58, 9.16]), multimorbid patients (OR = 10.04, 95% CI: [5.63, 18.57]) had a more pronounced risk of severe or critical infection. Our results provide further scientific evidence on the association between FI, multimorbidity, and disease severity in older COVID-19 patients, contributing to future health decision-making for COVID-19 and other infectious diseases.

Fu X., Yu Z., Fang F., Zhou W., Bai Y., Jiang Z., Yang B., Sun Y., Tian X., Liu G.

Ovarian cancer (OC) is the most deadly gynecological tumor. OC cells utilize cellular metabolic reprogramming to gain a survival advantage, particularly through aberrant lipid metabolic process. As the primary ingredient in exogenous cannabinoids, cannabidiol (CBD) has been confirmed to exhibit antitumor activity in preclinical studies. However, it is still unclear whether CBD can disrupt fatty acid metabolism and induce apoptosis in OC cells. In this study, we have demonstrated that CBD significantly inhibits the proliferation of OCs through a cannabinoid receptor type 1 (CB1R)-mediated manner. Fatty acid metabolic profiling and flow cytometry analysis revealed that CBD has the ability to decrease fatty acid levels and significantly suppress the transcription of genes involved in fatty acid uptake and synthesis in ES-2 cells. In addition, the analysis from RNA-seq and real-time RT-PCR revealed that CBD activated the endoplasmic reticulum (ER) stress pathway. Conversely, by supplementation with unsaturated fatty acid or blocking CB1R, ER stress or reactive oxygen species (ROS) signals with specific inhibitors could significantly relieve CBD induced, dose-dependent, ER stress associated apoptosis, G0-G1 phase arrest, and mitochondrial dysfunction. Taken collectively, these data indicate that CBD may disrupt lipid metabolism, and lead to ER stress-related apoptosis in OCs. Our findings may provide a theoretical mechanism for anti-ovarian cancer using CBD.

Zhou L., Guo Q., Yu L., Chen W., Chen H., Zhou X., Li J., Yang T., Cong R., Liu Y., Xiao J., Lu H., Xiao M., Li F., Zhang Y., et. al.

ABSTRACTChina experienced another outbreak of acute hemorrhagic conjunctivitis (AHC) in 2023, with a total of 195 297 recorded cases. This marks the third nationwide outbreak in nearly two decades, following previous outbreaks in 2007 and 2010. Descriptive epidemiological analysis shows that the number of cases in 2023 peaked in September, similar to the last two outbreaks. The age groups with the highest incidence rate of the three outbreaks in 2007, 2010, and 2023 are 15–20, 10–15, and 10–15 years old, respectively. Students are the main occupational group in the three outbreaks. Hainan, Guangxi, and Guangdong were the top three regions with high incidence rates in the three outbreaks. In 2023, the incidence rate in Hainan Province is the highest ever. Pathogenetic analyses show that the pathogens isolated during the 2023 outbreak were identified as the GIV genotype of CVA24v. Seven different recombination patterns were identified in the recombination analysis of the Chinese strains in 2023 and representative strains of global outbreaks since 1988. These patterns mainly involved the recombination signals of EV‐C96 and PV in the 5′ untranslated region and 3C and 3D regions. Although recombination events of CVA24v are rarely reported, its recombination was consistently present through systematic analysis in this study. This study comprehensively analyzed the 2023 AHC re‐emerging data and isolated CVA24v sequences, providing valuable data for future CVA24v molecular epidemiology studies.

Xiao M., Shen A., Chen X., Lu T., Zhang J., Li S., Yang W.

Zhu Y., Xu H., Yu C., Jiang W., Hou X., Ma M., Wu J.

Alzheimer’s disease (AD) is one of the most common diseases of the central nervous system in the middle-aged and elderly population. It is a neurodegenerative disorder, and its main clinical symptoms include the loss of established memories, a decline in learning capacity, and the buildup of β-amyloid peptides. The disease is often accompanied by neurodegenerative changes and the formation of neurofibrillary tangles. However, the number of drugs available for the clinical treatment of AD remains limited. Currently, existing medications are not effective in completely curing the disease or stopping its progression. Due to their excellent biocompatibility and biodegradability, polymers have been widely used as drug delivery carriers in various fields including cancer therapy and wound healing. The use of polymers enables targeted drug delivery and prolonged release profiles. In recent years, researchers have made significant progress in utilizing polymers such as polyethylene glycol, poly (lactic-co-glycolic acid) (PLGA), and chitosan (CS) to deliver drugs and blood-brain barrier receptor ligands for the treatment of AD. Moreover, many polymers with inherent therapeutic properties have been developed, including the already marketed GV-971 as well as experimental polymers such as PLGA and CS oligosaccharide. This review summarizes the applications of polymers in AD treatment over the past few years and highlights their current limitations to help researchers better understand current advancements in polymer development and identify future research directions.

Wang J., An J., Tian L., Jin Y., Li Y., Ding P., Yun W., Zhang Y., Zhao S.

Objective: The objective of this study is to examine the impact of KW-2478 combined with DDP on colorectal cancer cells both in vitro and in vivo and to elucidate the molecular mechanism of KW-2478 in colorectal cancer. Methods: qRT-PCR and Western blot were employed to assess HSP90 mRNA and protein expression in normal intestinal epithelial and colorectal cancer cells. DLD-1 and HCT116 were selected for the experiment. CCK-8 was used to detect cytotoxicity; apoptosis rate was measured using flow cytometry; Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. HCT116 was used to construct a subcutaneous tumor model in nude mice. After treatment with KW-2478 and DDP, the growth rate, volume, and weight of the tumor were observed. The expression of Ki67 was detected by immunohistochemistry. Apoptosis of tumor cells was detected using TUNEL. Western blot was employed to measure the expression levels of apoptotic and PI3K/AKT/mTOR pathway proteins. Results: HSP90 mRNA and protein levels were elevated in colorectal cancer cells compared to normal colorectal epithelial cells. HSP90 mRNA and protein expression levels were also significantly elevated in HCT116 and DLD-1 cells compared to other colorectal cancer cells. In DLD-1 and HCT116 cells, KW2478 and DDP inhibited cell viability. The combination of KW2478 and DDP exhibited a significantly higher inhibitory effect compared to either KW2478 or DDP alone. DDP markedly triggered apoptosis in HCT116 and DLD-1. KW2478 at 3 μg/ml and 6 μg/ml induced apoptosis in HCT116 cells but not in DLD-1 cells. The combination of KW2478 and DDP induced a significantly higher apoptosis rate as compared to either KW2478 or DDP alone. Treatment of HCT116 and DLD-1 with KW2478 or DDP alone increased Bax, Caspase9, and Caspase3 protein expression, while decreasing BCL-2. The KW2478+DDP combined treatment group exhibited more significant changes. Phosphorylation of PI3k, AKT, and mTOR decreased in the KW2478 or DDP treatment groups, with more significant changes observed in the KW2478 + DDP combination group. The growth rate, volume, and weight of subcutaneous tumors in the KW2478 or DDP treatment groups were significantly lower than control, and the KW2478+DDP combination group was more affected. Ki67 expression in subcutaneous tumors was reduced in the KW2478 or DDP treatment groups compared to the vehicle control group, with the lowest expression observed in the KW2478 + DDP combination group. The fluorescence intensity of subcutaneous tumors was higher in both the KW2478 and DDP treatment groups compared to the vehicle control group, and the KW2478 + DDP combination group exhibited the strongest fluorescence intensity among them. Conclusion: The combination of KW2478 and cisplatin inhibits colorectal cancer cell proliferation and induces apoptosis by regulating the PI3K/AKT/mTOR pathway.

Zhao X., Shang L., Shen C.