Complete remission in a pretreated, microsatellite-stable, KRAS-mutated colon cancer patient after treatment with sintilimab and bevacizumab and platinum-based chemotherapy: a case report and literature review.

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.

Effects of acupuncture in the treatment of occipital neuralgia: A systematic review and meta-analysis.

BACKGROUND: Acupuncture is used to treat subjects with occipital neuralgia, which is 1 of the main causes of occipital pain; however, its effect is conflicting. Hence, the current study aims to evaluate the effects of acupuncture in the treatment of occipital neuralgia. METHODS: In a systematic search of PubMed, Embase, OVID, China National Knowledge Infrastructure, Cochrane Library, Chinese Biomedical Literature Database, Wanfang databases, and Google Scholar until July 2021, 15 studies aimed to evaluate the effects of acupuncture in the treatment of occipital neuralgia were included. Human-related trials were considered in different languages. The size of the study was not considered a limit for its inclusion and the study intervention should focus on comparing the impact of acupuncture in the intervention group compared with the control group.The odds ratio (OR) and the mean difference (MD) with 95% confidence intervals (CIs) were calculated with a random or fixed-effect model for different subgroup analyses. Publication bias was assessed using the Egger test, while the risk of bias was assessed using the Review manager software. RESULTS: Acupuncture had a significantly higher effective rate of treatment (OR, 5.40; 95% CI, 2.48 to 11.77, P < .001) compared to control in the treatment of occipital neuralgia and lower visual analogue scale (MD, -2.45; 95% CI, -2.69 to -2.21, P < .001). Acupuncture plus medication had a significantly higher effective rate of treatment (OR, 3.96; 95% CI, 2.10 to 7.47, P < .001) compared to medication in the treatment of occipital neuralgia. Acupuncture analysis for safety issues showed a significant reduction of adverse events compared with the medication group. CONCLUSION: Acupuncture alone or acupuncture plus medication had a significantly beneficial effect on the effective rate of treatment, safety and visual analog scale compared to medication in the treatment of occipital neuralgia. Further studies are required to validate these findings.

Preclinical evidence of Yinchenhao decoction on cholestasis: A systematic review and meta-analysis of animal studies.

Cholestasis is an important cause of liver fibrosis and cirrhosis. Yinchenhao decoction has been used as a well-known traditional Chinese medicine used in the treatment of cholestasis for over 2,000 years. The purpose of this systematic review is to evaluate the preclinical evidence of Yinchenhao decoction on cholestasis models. The following databases were searched from inception to February 2020. Chinese National Knowledge Infrastructure, VIP medicine information system, Wanfang Database, PubMed, Web of Science, Embase and the Cochrane Library were searched. The content concerned Yinchenhao decoction on different animal model experiments for the treatment of cholestasis. The methodological quality of the included studies was assessed based on the SYstematic Review Center for Laboratory animal Experimentation Animal Experiment Bias Risk Assessment Tool. A meta-analysis was conducted with RevMan 5.3 software according to the Cochrane tool. Nineteen studies on a total of 404 animals were included with five kinds of experimental animal models. The results showed that serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin and total bile acid in the group treated with Yinchenhao decoction were significantly lower than those in the model group (P < 0.00001). The alanine aminotransferase (ALT), aspartate aminotransferase and alkaline phosphatase levels in the Yinchenhao decoction group were also significantly reduced (P < 0.00001). The subgroup analysis of the different models showed that Yinchenhao decoction had a significant effect on the bile duct ligation model, and there was a significant reduction in TBIL, DBIL and ALT levels (P < 0.00001) in ANIT-induced cholestasis. After 24 hours of Yinchenhao decoction treatment, there was no significant difference in TBIL levels (P = 0.34), but after 48 and 72 hours of treatment, the TBIL levels were significantly reduced compared with the model group (P < 0.00001). There was no significant difference in DBIL after 48 hours of administration (P = 0.26), but compared with the model group, Yinchenhao decoction could significantly reduce the DBIL levels after 48 hours of treatment (P < 0.0003). Yinchenhao decoction could significantly reduce the ALT levels after 24, 48 and 72 hours (P < 0.006). Yinchenhao decoction was able to significantly reduce the levels of TBIL, DBIL and ALT on different rat species: Wistar and Sprague Dawley (P = 0.0001; P = 0.0002). The preclinical evidence indicated that Yinchenhao decoction might be a potent and promising agent for cholestasis. Moreover, this conclusion should be further confirmed with more well-designed researches.

Animal model of intrahepatic metastasis of hepatocellular carcinoma: establishment and characteristic.

One of the most important and striking characteristics of hepatocellular carcinoma (HCC) with intrahepatic metastasis, is that it results in extremely poor prognosis. Animal models have become a fundamental and very useful in research for disease study. However, some limitation has arisen from these model systems. We have therefore established a model of HCC with intrahepatic metastasis and noticed some differential appearances in different HCC cell lines. Luciferase-transfected HCC cell lines MHCC97-H and PLC/PRF/5 were inoculated into SCID mice via spleen. Observation the intrahepatic metastasis by bioluminescence imaging in vivo and comparing of the differential formation of metastatic lesions between different HCC cell lines by incorporating physical anatomy was done. Animal models for HCC intrahepatic metastasis were well established. However, there were some clearly noticed differences between MHCC97-H and PLC/PRF/5 cell lines. The group of MHCC97-H cell line readily metastasis in the liver, whereas group PLC/PRF/5 cell line developed extensive intrahepatic metastasis and formed large tumor in situ in the spleen. MHCC97-H and PLC/PRF/5 cell lines can be used to successfully establish a model of HCC intrahepatic metastasis with distinctive characteristics, which provides an important direction for the study of the mechanism of HCC intrahepatic metastasis, and may hopefully provide a basis for clinical treatment.

Prediction of progression of chronic atrophic gastritis with Helicobacter pylori and poor prognosis of gastric cancer by CYP3A4.

BACKGROUND AND AIM: It has been well documented that Helicobacter pylori (H. pylori) infection is a risk factor for aggravating gastric mucosal atrophy. However, the exact molecular mechanism mediating this process is not fully elucidated. The purpose of this study was to identify biomarkers, which may predict the risk for progression of chronic atrophic gastritis (CAG) with H. pylori. METHODS: GSE27411 was downloaded from the Gene Expression Omnibus. The differentially expressed genes (DEGs) between H. pylori-infected samples without CAG and H. pylori-infected CAG samples were analyzed. Gene Ontology and pathway enrichment analyses were performed, followed by protein-protein interaction network construction. We used immunohistochemistry analysis to identify DEGs in 20 chronic gastritis, 20 CAG, and 22 gastric cancer (GC) specimens. RESULTS: A total of 303 upregulated and 26 downregulated DEGs were identified. The pathways enriched by upregulated DEGs were mainly related to fat digestion and absorption, peroxisome proliferator-activated receptor signaling pathway, and chemical carcinogenesis. Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) had the highest degrees in protein-protein interaction network. Moreover, the positive rates of CYP3A4 protein expression in chronic gastritis, CAG, and GC were 10% (2/20), 55% (11/20), and 77.3% (17/22), respectively (P < 0.001). The Kaplan-Meier analysis revealed that elevated expression of CYP3A4 was significantly associated with worse overall survival and first progression, respectively (P < 0.0001). CONCLUSION: According to the findings of this study, the expression of CYP3A4 might be related to the potential carcinogenic transformation of CAG to GC. Therefore, CYP3A4 may be biomarkers to predict progression of CAG and poor prognosis of gastric cancer.

Molecular mechanism of Helicobacter pylori-induced autophagy in gastric cancer.

Helicobacter pylori (H. pylori) is a gram-negative pathogen that colonizes gastric epithelial cells. The drug resistance rates of H. pylori have dramatically increased, causing persistent infections. Chronic infection by H. pylori is a critical cause of gastritis, peptic ulcers and even gastric cancer. In host cells, autophagy is stimulated to maintain cellular homeostasis following intracellular pathogen recognition by the innate immune defense system. However, H. pylori-induced autophagy is not consistent during acute and chronic infection. Therefore, a deeper understanding of the association between H. pylori infection and autophagy in gastric epithelial cells could aid the understanding of the mechanisms of persistent infection and the identification of autophagy-associated therapeutic targets for H. pylori infection. The present review describes the role of H. pylori and associated virulence factors in the induction of autophagy by different signaling pathways during acute infection. Additionally, the inhibition of autophagy in gastric epithelial cells during chronic infection was discussed. The present review summarized H. pylori-mediated autophagy and provided insights into its mechanism of action, suggesting the induction of autophagy as a novel therapeutic target for persistent H. pylori infection.

[Preventive strategy for post-ERCP pancreatitis].

Endoscopic retrograde cholangiopancreatography (ERCP) is an irreplaceable measure with minimally invasive diagnosis and treatment of endoscopy for biliary and pancreatic diseases, but the related complications associated with ERCP are the highest among the endoscopic procedures. Post-ERCP pancreatitis (PEP) is one of the most common complications with life-threatening in severe cases. Early active prevention can effectively reduce the incidence of post-ERCP pancreatitis. At present, measures including preoperative rectal non-steroidal anti-inflammatory drugs and prophylactic pancreatic stent placement, have definite effective strategy in clinic. Aggressive hydration with lactated Ringer's solution is also a safe and effective way to prevent PEP.