Objective To investigate the effects of metformin(Met)on the proliferation of pancreatic cancer cells under different glucose concentration culture conditions,and to find the potential role of miR-139-5p in the process.Methods PANC-1 cells were treated with different concentrations of metformin(0/5/10/20 mmol/L)in 25 mmol/L(high-glucose group,HG)or 5 mmol/L(normal-glucose group,NG)glucose culture,cell proliferation,apoptosis,migration and cell cycle were detected after 48 h.The expression of miR-139-5p was quantitatively detected by RT-qPCR,and the miR-139-5p mimics were transfected into PANC-1 cells to clarify the role of miR-139-5p.Results Metformin inhibited the proliferation,promoted apoptosis,and induced S phase and G2/M phase arrest of PANC-1 cells under in high glucose and normal glucose culture conditions,and its anti-proliferation and pro-apoptosis effects were more significant in the normal glucose groups.The expression of miR-139-5p was up-regu-lated by metformin treatment in normal but not in high glucose culture.Further studies showed that miR-139-5p mimics inhibited of PANC-1 cells proliferation without metformin pre-incubation and enhanced the anti-prolifera-tion effect of 5 mmol/L metformin.The pro-apoptotic effect of 10 mmol/L metformin in normal glucose culture conditions.Conclusions In normal-glucose culture conditions,metformin can inhibit proliferation,induce apop-tosis and cell cycle arrest of PANC-1 cells more significantly than in higher-glucose culture,which may be partly related to the up-regulation of miR-139-5p.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

Objective To investigate the value of serum markers in the early diagnosis of liver cirrhosis with minimal hepatic encephalopathy (MHE). Methods A prospective analysis was performed for 81 patients who were hospitalized and treated in General Hospital of Ningxia Medical University from April 2020 to February 2022, and all these patients were diagnosed with hepatitis B cirrhosis based on clinical manifestation, laboratory examination, and radiological examination or liver biopsy. According to digital connection test A (NCT-A) and digital symbol test (DST), these patients were divided into simple cirrhosis group with 45 patients and MHE group with 36 patients. Related indices were measured, including liver function [alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (TBil)], albumin, blood ammonia, cholinesterase, and prothrombin time. The independent samples t -test was used for comparison of normally distributed continuous data between two groups; the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups; the chi-square test was used for comparison of categorical data between groups. The logistic regression analysis and the area under the ROC curve (AUC) were used to investigate the predictive factors for MHE. Results Compared with the simple cirrhosis group, the MHE group had a significant increase in NCT-A score ( Z =-7.110, P < 0.001) and a significant reduction in DST score ( t =12.223, P < 0.001). The univariate analysis showed that there were significant changes in AST, albumin, prothrombin time, cholinesterase, and blood ammonia in the patients with MHE ( Z =-2.319, -2.643, -1.982, -6.594, and -5.331, all P < 0.05), while the multivariate analysis showed that only cholinesterase and blood ammonia were significant predictive factors (all P < 0.05) and were correlated with Child-Pugh score (all P < 0.05). Cholinesterase, blood ammonia, and their combination had an AUC of 0.925, 0.845, and 0.941, respectively, in the diagnosis of MHE, with an optimal cut-off value of 2966, 60, and 0.513, respectively. Conclusion Blood ammonia, cholinesterase, and their combined measurement have a potential clinical value in the early diagnosis of liver cirrhosis with MHE.

BACKGROUND: Epidermal growth factor receptor (EGFR) and cellular-mesenchymal to epithelial transition factor (c-Met) are widely expressed on cancer cells. There is a synergistic effect of EGFR and HGF/c-Met pathways on proliferation, downstream activation of signal transduction and an additive effect. Studies show that combination of both signaling pathways could potentially be targeted in a synergistic fashion. Amivantamab, a bispecific monoclonal antibody targeting EGFR and c-Met, yielded robust and durable responses in a variety of clinicals trials. However, few researches have reported its efficacy in Chinese non-small cell lung cancer (NSCLC) patients. This study was conducted to evaluate the effectiveness and tolerance of Amivantamab in NSCLC patients with EGFR/MET gene abnormalities at Peking University Cancer Hospital. METHODS: The study enrolled NSCLC patients who received Amivantamab in our hospital between August 2020 and December 2021, and analyzed the response, survival, and treatment-related adverse events. RESULTS: Fifteen patients were enrolled in this research, and six of them received Amivantamab treatment and the other nine patients received Amivantamab plus Lazertinib treatment. The rates of partial response (PR), stable disease (SD), and progressive disease (PD) were 46.7% (7/15), 46.7% (7/15) and 6.7% (1/15), respectively. The overall response rate (ORR) and disease control rate (DCR) were 28.6% (2/7) and 100.0% (7/7) in seven patients with EGFR exon 20 insertion, respectively. The ORR and DCR were 40.0% (2/5) and 100.0% (5/5) in five post-osimertinib EGFR-mutant patients, respectively. After a median follow-up of 8.7 months, the median progression-free survival and overall survival were not reached. The most common treatment-related adverse events were rash (86.7%), paronychia (80.0%), and infusion-related reactions (60.0%), and most of them were graded as 1 to 2. Grade 3 to 4 adverse events included rash (33.3%), alanine aminotransferase elevation (13.3%), gamma-glutamyl transpeptidase elevation (13.3%), peripheral edema (6.7%), thromboembolism (6.7%), interstitial lung disease (6.7%), and thrombocytopenia (6.7%). CONCLUSIONS Amivantamab was effective in Chinese NSCLC patients with EGFR exon 20 insertion and post-Osimertinib EGFR-mutant patients, similar to the results of clinical trials conducted in western countries. Amivantamab was well tolerated and emphases should be put on adverse events such as rash, paronychia, and infusion-related reactions.
Antibodies, Bispecific ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Exanthema/drug therapy* ; Humans ; Lung Neoplasms/genetics* ; Mutation ; Paronychia/drug therapy* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To evaluate the clinical efficacy of off-midline closure technique in the treatment of chronic pilonidal sinus.Methods:From July 2014 to July 2018, 59 patients suffered from chronic pilonidal sinus treated by off-midline closure were admitted to the Department of Proctology, Linyi Central Hospital, including 34 males and 25 females. According to the size and scope of the chronic pilonidal sinus, the off-midline flap was designed and sutured.Results:In this group of 59 patients, there were 52 cases of primary healing and 7 cases of incision complications, such as partial incision dehiscence and subcutaneous effusion. After follow-up for 2 years, no recurrence was observed. The scar was not obvious after wound healing. The patient was satisfied with the postoperative appearance.Conclusions:Using the off-midline closure technique to treat chronic pilonidal sinus can deviate from the midline to make the suture tension-free and the gluteal groove elevated. It not only effectively reduce the complication rate in patients, but also has high cure rate, low recurrence rate and does not affect appearance.

Objective:To explore the clinical characteristics and follow-up outcomes of a pedigree of maturity onset diabetes of the young (MODY) induced by a novel mutation of glucokinase (GCK).Methods:The clinical features and laboratory data of a pedigree diagnosed with GCK-MODY in Peking Union Medical College Hospital was analyzed. Genomic DNA was extracted, and Sanger sequencing was performed to detect the gene mutation of the family members. The proband and her father were followed up for 3 years. Wanfang and PubMed were used to search literatures on follow-up studies for treatment of GCK-MOYD.Results:Both the proband and her father were found to have a novel mutation on the GCK gene located in exo10 c.1348G.T (p. Ala450Thr). The proband was treated with diet and exercise control only. At the end of the follow-up, her fasting plasma glucose (FPG, 6.8 mmol/L), 2 h postprandial plasma glucose (2hPG, 7.4 mmol/L), and glycated hemoglobin (HbA1c, 6.3%) were all within the control targets. Additionally, the levels homeostasis model assessment of insulin resistance (HOMA-IR) tended to improved comparing to that at baseline (4.09 to 2.32), and glucose disposition index (DI) was improved compared with baseline (16.22 to 20.05). As to the proband′s father, the treatment with insulin plus acarbose was converted to sulfonylureas monotherapy. His FPG and 2hPG mostly were within the target range, and the levels of HbA1c were significantly reduced by 0.5%-0.7% when compared to that at baseline. The HOMA-IR or islet beta cell function was comparable to those at baseline.Conclusions:Screening patients whose clinical performance meets GCK-MODY and their family members with proper genetic testing is of great importance to reduce misdiagnosis of GCK-MODY, so as to obtain a better glucose control without unnecessary over-treatment and protect islet beta cell function.

Objective To evaluate the influence of graphic type health education combined with empowerment theory on phonetic function and swallowing function in tongue cancer patients after surgery. Methods A total of 86 tongue cancer patients after surgery in the First Affiliated Hospital of Zhengzhou University from June 2014 to June 2017 were selected by convenience sampling method, and divided into control group and experimental group, with 43 cases in each group. The control group received graphic type health education, while the experimental group received graphic type health education combined with empowerment theory. The phonetic function and swallowing function were collected and compared before and after intervention between two groups. Results Before the intervention, there was no statistical significance in the difference of patients' phonetic function between the two groups (P＞0.05). However, after the intervention, the phonetic function improved than before, and it in the experimental group was higher than that in the control group (P＜0.05). The difference in swallowing function between the two groups was not statistically significant before the intervention (P＞ 0.05). After the intervention, swallowing function of the two groups were higher than those before intervention, and the experimental group was higher than that of the control group (P＜0.05). Conclusions Graphic type health education combined with empowerment theory is helpful for the recovery of phonetic function and swallowing function in tongue cancer patients after surgery,it is worthy of clinical promotion.

Objective To observe the clinical effects of hyperbaric oxygen (HBO) combined with Fufanghuangbai liquid on wound healing after perianal abscess surgery.Methods One hundred and fifty-eight patients with perianal abscess were randomly divided into the observation group and the control group.The patients of the groups were all treated with conventional surgical treatment and external drug application,but the observation group was supplemented with HBO combined with the spraying of Fufanghuangbai liquid on the wound surface.Clinical effects of the 2 groups were closely observed,and wound healing time,granulation growth,seriousness of pain and edema,as well as wound surface effusion were compared between the 2 groups.Results Wound healing time of the observation group (24.91 ± 5.17) days was significantly shorter than that of the control group (31.23 ± 6.01) days,with statistical significance (P ＜ 0.05).Wound edema and granulation growth on the 7th,14th and 21st days after surgery for the observation group were all superior to those of the control group (P ＜ 0.05).Three days after surgery,there were no significant differences in the seriousness of pain and wound surface effusion,when comparisons were made between the 2 groups (P ＜ 0.05).On the 7th and 14th days after surgery,improvement in the above 2 indicators in the treatment group was significantly better than those of the control group,and statistical significance could be seen,when comparisons were made between the 2 groups(P ＜ 0.05).Conclusion HBO combined with Fufanghuangbai liquid could produce good therapeutic effects on the alleviation of wound edema,relief of pain,reduction of wound surface effusion in the treatment of perianal abscess after surgery,and at the same time,it could shorten hospitalization days and improve patient life quality.For this reason,it was worth further clinical popularization.

Objective To observe the clinical effects of hyperbaric oxygen (HBO) combined with Fufanghuangbai liquid on wound healing after perianal abscess surgery.Methods One hundred and fifty-eight patients with perianal abscess were randomly divided into the observation group and the control group.The patients of the groups were all treated with conventional surgical treatment and external drug application,but the observation group was supplemented with HBO combined with the spraying of Fufanghuangbai liquid on the wound surface.Clinical effects of the 2 groups were closely observed,and wound healing time,granulation growth,seriousness of pain and edema,as well as wound surface effusion were compared between the 2 groups.Results Wound healing time of the observation group (24.91 ± 5.17) days was significantly shorter than that of the control group (31.23 ± 6.01) days,with statistical significance (P ＜ 0.05).Wound edema and granulation growth on the 7th,14th and 21st days after surgery for the observation group were all superior to those of the control group (P ＜ 0.05).Three days after surgery,there were no significant differences in the seriousness of pain and wound surface effusion,when comparisons were made between the 2 groups (P ＜ 0.05).On the 7th and 14th days after surgery,improvement in the above 2 indicators in the treatment group was significantly better than those of the control group,and statistical significance could be seen,when comparisons were made between the 2 groups(P ＜ 0.05).Conclusion HBO combined with Fufanghuangbai liquid could produce good therapeutic effects on the alleviation of wound edema,relief of pain,reduction of wound surface effusion in the treatment of perianal abscess after surgery,and at the same time,it could shorten hospitalization days and improve patient life quality.For this reason,it was worth further clinical popularization.

Objective To investigate the clinical value of blood oxygenation level-dependent functional magnetic resonance imaging(BOLD-fMRI)in the protection of visual function during postoperative radiotherapy for occipital lobe gliomas. Methods Twenty-eight patients with occipital lobe gliomas receiving postoperative radiotherapy from 2014 to 2016 were enrolled as subjects. All patients underwent computed tomography(CT) simulation,conventional MRI,and BOLD-fMRI before radiotherapy. The location and scope of the visual cortex on 3DT1anatomical images were used to guide the labeling of the visual cortex on simulated CT images. A visual cortex protective radiotherapy plan and a conventional radiotherapy plan were made by intensity-modulated radiotherapy. The feasibility of the visual cortex protective radiotherapy plan was evaluated using conformity index(CI),homogeneity index(HI),Dmax,and Dmeanfor planning target volume(PTV)and Dmaxand Dmean to the visual cortex. Results For the two plans, if the effective dose to target volume was guaranteed and the doses to conventional organs at risk were acceptable, there were no significant differences in CI or HI for PTV between them(P=0.874,P=0.602).Compared with the conventional radiotherapy plan,the Dmaxand Dmeanto the ipsilateral visual cortex were reduced by 8.40% and 9.25%, respectively, while the Dmaxand Dmeanto the contralateral visual cortex were reduced by 13.26% and 14.77%, respectively, in the protective radiotherapy plan. Conclusions With a guaranteed prescribed dose to target volume and BOLD-fMRI used as a guide, the visual cortex protective radiotherapy, compared with the conventional plan, can reduce the dose to the visual cortex and protect the corresponding functional areas.