[Advances in basic research on choline and central nervous system development and related disorders].

Choline is an essential nutrient that plays an integral role in all stages of the life cycle, with increasing interest in the relationship between choline and neurodevelopment. Choline is a major component in the synthesis of phospholipids, phosphatidylcholine and sphingolipids, and is an essential nutrient for methyl metabolism, acetylcholine synthesis and cell signaling. Choline plays an important role in neurogenesis and neural migration during fetal development, potentially influencing the development and prognosis of neurological disorders, but its mechanism of action is not yet clear. This article reviews the source and metabolism of choline, the effects and mechanism of choline on neurodevelopment and central nervous system related disorders.

[Application and evaluation of artificial intelligence TPS-assisted cytologic screening system in urine exfoliative cytology].

Objective: To explore the application of manual screening collaborated with the Artificial Intelligence TPS-Assisted Cytologic Screening System in urinary exfoliative cytology and its clinical values. Methods: A total of 3 033 urine exfoliated cytology samples were collected at the Henan People's Hospital, Capital Medical University, Beijing, China. Liquid-based thin-layer cytology was prepared. The slides were manually read under the microscope and digitally presented using a scanner. The intelligent identification and analysis were carried out using an artificial intelligence TPS assisted screening system. The Paris Report Classification System of Urinary Exfoliated Cytology 2022 was used as the evaluation standard. Atypical urothelial cells and even higher grade lesions were considered as positive when evaluating the recognition sensitivity, specificity, and diagnostic accuracy of artificial intelligence-assisted screening systems and human-machine collaborative cytologic screening methods in urine exfoliative cytology. Among the collected cases, there were also 1 100 pathological tissue controls. Results: The accuracy, sensitivity and specificity of the AI-assisted cytologic screening system were 77.18%, 90.79% and 69.49%; those of human-machine coordination method were 92.89%, 99.63% and 89.09%, respectively. Compared with the histopathological results, the accuracy, sensitivity and specificity of manual reading were 79.82%, 74.20% and 95.80%, respectively, while those of AI-assisted cytologic screening system were 93.45%, 93.73% and 92.66%, respectively. The accuracy, sensitivity and specificity of human-machine coordination method were 95.36%, 95.21% and 95.80%, respectively. Both cytological and histological controls showed that human-machine coordination review method had higher diagnostic accuracy and sensitivity, and lower false negative rates. Conclusions: The artificial intelligence TPS assisted cytologic screening system has achieved acceptable accuracy in urine exfoliation cytologic screening. The combination of manual screening and artificial intelligence TPS assisted screening system can effectively improve the sensitivity and accuracy of cytologic screening and reduce the risk of misdiagnosis.

[The moderating effect analysis of mindfulness on perceived stress and job burnout of medical staff].

Objective: To explore the moderating mechanism of mindfulness on perceived stress and job burnout of medical staff. Methods: From November 2020 to March 2022, 1626 medical staff were investigated by questionnaires. Chinese Version Perceived Stress Scale (CPSS), Maslach Burnout Inventory-Human Service Survey (MBI-HSS) and Mindful Attention Awareness Scale (MAAS) were used to evaluate the perceived stress, three dimensions of job burnout[depersonalization (DP), emotional exhaustion (EE), personal accomplishment (PA) ], and mindfulness level of medical staff. The Spearman rank correlation analysis was used to analyze the correlation between mindfulness and perceived stress, job burnout of medical staff. And the SPSS PROCESS macro program was used to test the moderating effect of mindfulness on perceived stress and job burnout. Results: Among the 1626 medical staff, 57.38% had perceived stress with health risk (933/1626), and 63.84% (1038/1626) had job burnout, among them, with 618 (38.01%), 274 (16.85%), and 146 (8.98%) experiencing mild, moderate and severe job burnout, respectively. The scores of mindfulness among medical staff were significantly correlated with perceived stress and various dimensions of job burnout (EE, DP and PA) (r(s)=-0.155, -0.351, -0.315, 0.307, P<0.001). Mindfulness had a moderating effect between perceived stress and job burnout, which was achieved through three moderating pathways: perceived stress-mindfulness-EE, perceived stress-mindfulness-DP and perceived stress-mindfulness-PA (ΔR(2)=0.073, 0.06, 0.006, P<0.001) . Conclusion: Medical staff have a high level of job burnout, mindfulness plays a moderating role between perceived stress and job burnout. Specific measures can be taken to improve the level of mindfulness in medical staff, so as to prevent and alleviate job burnout of medical staff.

[Evaluation considerations for using surrogate endpoints in anticancer clinical trials].

The prolongation of patient's overall survival is the accepted as gold standard to prove clinical values of anti-cancer drugs. However, if overall survival is taken as the primary endpoint in clinical trials for cancer types with a relatively good prognosis in the process of new anti-cancer drug research and development, the time to market the drugs will be prolonged due to the long follow-up time. In addition, overall survival is often interfered by confounding factors such as follow-up treatment. Therefore, regulatory agencies have established an accelerated review model using surrogate endpoints for the approval of new anti-cancer drugs, but there are still some problems in the use of surrogate endpoints in cancer clinical trials. From the perspective of new drug review, the authors expounds the key points of confirming and rationally using surrogate endpoints in clinical trials of anti-cancer drugs, which will improve the level of clinical trials of new anti-cancer drugs and accelerate the development of anti-tumor drugs.

[Clinical trials on intrathecal pemetrexed treated leptomeningeal metastases from solid tumors].

Objective: To investigate the feasibility, safety and efficacy of intrathecal pemetrexed (IP) treated for patients with leptomeningeal metastases (LM) from solid tumors. Methods: Forty-seven patients receiving pemetrexed intrathecal chemotherapy in the First Hospital of Jilin University from 2017 to 2018 were selected. The study of pemetrexed intrathecal chemotherapy adopted the classical dose-climbing model and included 13 patients with meningeal metastasis of non-small cell lung cancer who had relapsed and refractory after multiple previous treatments including intrathecal chemotherapy. Based on the dose climbing study, 34 patients with meningeal metastasis of solid tumor who did not receive intrathecal chemotherapy were enrolled in a clinical study using pemetrexed as the first-line intrathecal chemotherapy combined with radiotherapy. Kaplan-Meier method and Log rank test were used for survival analysis, and Cox regression model was used for influencing factor analysis. Results: The dose climbing study showed that the maximum tolerated dose of pemetrexed intrathecal chemotherapy was 10 mg per single dose, and the recommended dosing regimen was 10 mg once or twice a week. The incidence of adverse reactions was 10 cases, including hematological adverse reactions (7 cases), transaminase elevation (2 cases), nerve root reactions (5 cases), fatigue and weight loss (1 case). The incidence of serious adverse reactions was 4, including grade 4-5 poor hematology (2 cases), grade 4 nerve root irritation (2 cases), and grade 4 elevated aminotransferase (1 case). In the dose climbing study, 4 patients were effectively treated and 7 were disease controlled. The survival time was ranged from 0.3 to 14.0 months and a median survival time was 3.8 months. The clinical study of pemetrexed intrathecal chemotherapy combined with radiotherapy showed that the treatment mode of 10 mg pemetrexed intrathecal chemotherapy once a week combined with synchronous involved area radiotherapy 40 Gy/4 weeks had a high safety and reactivity. The incidence of major adverse reactions was 52.9% (18/34), including hematologic adverse reactions (13 cases), transaminase elevation (10 cases), and nerve root reactions (4 cases). In study 2, the response rate was 67.6% (23/34), the disease control rate was 73.5% (25/34), the overall survival time was ranged from 0.3 to 16.6 months, the median survival time was 5.5 months, and the 1-year survival rate was 21.6%. Clinical response, improvement of neurological dysfunction, completion of concurrent therapy and subsequent systemic therapy were associated with the overall survival (all P<0.05). Conclusions: Pemetrexed is suitable for the intrathecal chemotherapy with a high safety and efficacy. The recommended administration regimen was IP at 10 mg on the schedule of once or twice per week. Hematological toxicity is the main factor affecting the implementation of IP. Vitamin supplement can effectively control the occurrence of hematological toxicity.

[Rethinking the marketing strategy of anti-tumor drugs by single-arm trials supported].

Single-arm trial refers to a clinical trial design that does not set up parallel control group, adopts open design, and does not involve randomization and blind method. These features, on the one hand, speed up the process of clinical trials, significantly shorten the time to market and meet the needs of patients with advanced malignancies, but also lead to the uncertainty of single-arm clinical trials themselves. Recently, the US Food and Drug Administration held a meeting of the oncologic drug advisory committee to discuss six tumor indications that have been accelerated approved, which once again triggered the discussion of single-arm trials. The basis of accelerated approval by single-arm trial is actually a compromise on the level of evidence-based medical evidence requirements after assessing the benefit risk. Therefore, the sponsor should strictly grasp the applicable conditions of single-arm trial in anti-tumor drugs and conduct single-arm trial scientifically. Post-marketing clinical trial should be implement as early as possible to ensure the benefit of patients. Based on the characteristics of single-arm trial, combined with two guidance relevant to single-arm trial issued by National Medical Products Administration recently, this article is supposed to propose and summarize the strategy of single-arm trial supporting the marketing of anti-tumor drugs.

[Basic immunization of vaccines is fundamental, and booster immunization is the guarantee: Booster immunization and its public health value].

Booster immunization is the following vaccination after a period of vaccine primary immunization schedule in order to maintain immunity against a certain pathogen. In this article, the immunological mechanism of booster immunization is elaborated, and the effectiveness and public health value of booster immunization for common vaccines is discussed. Subsequently, three hot issues of general concern in booster immunization are addressed, and the public health viewpoint that "Primary immunization of vaccines is fundamental, and booster immunization is the guarantee" is emphasized, so as to raise awareness of the importance and necessity of booster immunization as well as to provide scientific evidences for vaccine immunization practice.

[Rotavirus gastroenteritis and its vaccination].

Rotaviruses infection is one of the main causes of diarrhea among infants and children in the world, resulting in rotavirus gastroenteritis, which is very harmful and has caused a huge disease burden and no specific drug treatment. This paper reviews the rotavirus etiology, epidemiological characteristics, disease burden of rotavirus gastroenteritis and rotavirus vaccines. RV in group A is the main cause of acute gastroenteritis in infants, people at all ages are generally susceptible to RV, 3 to 24 months infants have the most severe symptoms of diarrhea, RVGE epidemic is seasonal and peaks in winter, increasing RV vaccination can reduce the incidence and mortality of rotavirus diarrhea in infants to reduce the burden of corresponding disease. This article focuses on RV vaccines currently in use and their effect on preventing RV infection, and put forward thoughts and suggestions on technical issues related to the application of RV vaccine in China. Provide support for improving the RV vaccine immunization strategy and Chinese-specific immunization strategy for eventually incorporating RV vaccine into the national child immunization program.

[Molecular epidemiological characterization of group A rotavirus in domestic sewage in Jinan from 2016 to 2018].

Objective: To understand the detection of group A rotavirus (RVA) in domestic sewage and its molecular epidemiological characteristics, and further explore the feasibility and necessity of RVA environmental surveillance. Methods: From 2016 to 2018, we collected domestic sewage samples monthly in Jinan city, and concentrated them via anion membrane adsorption-elution method. Then RNA extraction and RVA VP7 and VP4 coding region RT-PCR amplification were performed. After purification, TA cloning and sequencing, homology analysis and phylogenetic analysis were conducted on the obtained sequences. Results: RVA G gene was detected in 31 of the 36 sewage samples (86.1% detection rate); RVA P genotype was detected in 33 samples (91.7% detection rate). A total of 536 RVA sequences were obtained, of which 225 G-type sequences belonged to 6 genotypes, and the G9 accounted for 92.4% (208/225); 311 P-type sequences were obtained, which belonged to 4 genotypes. The dominant P[8] accounted for 50.1% (156/311), followed by P[4] with 41.8% (130/311). Phylogenetic analysis shows that there were multiple transmission chains circulating in the dominant genotypes G9 and P[8]. Conclusion: The genotype, homology, and phylogenetic characteristics of sequences obtained from domestic sewage in Jinan area were described, which further confirmeing that RVA environmental surveillance is not feasible but also necessary.

[Clinical research and drug review of epidermal growth factor receptor tyrosine kinase inhibitors in advanced non-small cell lung cancer].

Lung cancer is the most frequently diagnosed cancer and the most common cause of cancer mortality in China. Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. The mutation rate of epidermal growth factor receptor (EGFR) gene is relatively high, accounts for 32%~38% of all NSCLC. During the last decade, the application of EGFR specific tyrosine kinase inhibitors (TKI) significantly improved prognosis of NSCLC patients with sensitive EGFR mutations. Thus, the research and development of third generation EGFR-TKI have entered the period of rapid development. The fourth generation EGFR-TKI which targeting EGFR C797S has even begun clinical development in China. This review will discuss the clinical research and drug review of EGFR-TKI from the perspective of drug review.

[Epidemiological characteristics and medical expenses of acute occupational poisoning hospitalization in 5 monitoring counties (cities, districts) of Shandong Province from 2012 to 2018].

The data were drawn from injury hospitalization surveillance system in Shandong province. From 2012 to 2018, 164 cases of acute occupational poisoning were reported from five surveillance counties (cities, districts), accounting for 6.11% (164/2 683) of total accidental poisoning cases. The annual average reported incidence of acute occupational poisoning hospitalization was 1.15/100 000. The number of male cases was 3.3 times that of females (126 vs 38). The poisoning cases mainly occurred between January to May in a year and 5-7 AM within a day. Those cases were mainly caused by irritating gases (92 cases, 56.10%) and asphyxiating gases (53 cases, 32.32%), of which chlorine (71 cases) and carbon monoxide (50 cases) were the main reasons. The average hospitalization medical cost of acute occupational poisoning cases was 7 278.81 RMB per case.

[Comparison on CMR characteristics and clinical prognosis between hypertrophic cardiomyopathy patients with and without left ventricular apical aneurysms].

Objective: To compare the imaging characteristics and long-term prognosis in hypertrophic cardiomyopathy(HCM) patients with or without left ventricular apical aneurysm(LVAA). Methods: Retrospectively analyzed the clinical data from 18 patients diagnosed as HCM complicating with LVAA(HCM-LVAA group), hospitalized and underwent cardiac magentic resonance (CMR) examination in Fuwai Hospital between December 2012 and December 2016. Eighteen age and gender matched patients with HCM diagnosed by CMR served as control(HCM group). Outpatient and in-hospital clinical data as well as follow up results were compared. The major adverse cardiovascular events were defined as malignant arrhythmia events (including sudden cardiac death, ventricular flutter/ventricular fibrillation) and heart failure events (including heart transplantation, progressive heart failure). Results: Compared with HCM group, patients in HCM-LVAA group had a more positive family history of HCM(P=0.04), higher incidence of ST-T segment changes and abnormal Q wave in electrocardiograms (both P<0.01), the CMR derived left ventricular end-diastolic transverse diameter and end-diastolic volume index were also significantly higher (both P<0.05), and delayed enhancement was more significant ((25.26±10.60)% vs. (15.78±7.33)%, t=3.12, P=0.004) in HCM-LVAA group. Moreover, the left ventricular ejection fraction ((54.4±10.6)% vs. (67.5±7.6)%, t=-4.28, P<0.000 1) and the thickness of the apical wall ((3.11±1.05) mm vs. (5.46±1.94) mm, t=-4.49, P<0.000 1) were significantly lower in HCM-LVAA group than in HCM group. The mean follow-up duration was (3.46±1.64) years, 4 patients in HCM-LVAA group (22.2%) developed 4 cardiovascular events, including 1 sudden cardiac death, 3 progressive heart failures. One patient in HCM group developed progressive heart failure. Conclusion: The prognosis of the HCM complicating with LVAA patients is worse than that of HCM patients without LVAA, and the amount of late gadolinium enhancement is higher than that of HCM patients without LVAA.

[Clinical and cardiac magnetic resonance features of apical hypertrophic cardiomyopathy patients complicating with left ventricular apical aneurysm].

Objective: To evaluate the clinical and cardiac magnetic resonance (CMR) features of apical hypertrophic cardiomyopathy (ApHCM) patients complicating with left ventricular apical aneurysm (LVAA). Methods: CMR confirmed 25 ApHCM patients complicating with LVAA from January 2010 to December 2017 in Fuwai hospital were included in this study, and the baseline clinical data and CMR characteristics were retrospectively analyzed. There were 14 pure ApHCM (hypertrophy limited at the apical segments) complicating with LVAA patients and 11 mixed ApHCM (predominantly apical hypertrophy along with thickening of contiguous non-apical left ventricular region) with LVAA patients. Results: In this patient cohort,age of 84% (21/25) patients ranged between 20-70 years old, and 68% (17/25) were male. There were 68% (17/25) patients with complaint of chest distress symptom, 56% (14/25) with complaint of chest pain, 32% (8/25) with complaint of palpitation,16% (4/25) with complaint of dyspnea, and 12% (3/25) presented as syncope. ST-T segment changes of electrocardiogram were observed in all patients, and giant negative T waves were detected in 80% patients (20/25). The rate of missed diagnosis by echocardiography for detecting ApHCM and LVAA was 16% (4/25) and 68% (17/25), respectively. CMR showed discrete thin-walled dyskinetic or akinetic segment of the most distal portion of the left ventricular chamber in ApHCM patients with LVAA. Transmural late gadolinium enhancement of the aneurysmal rim was detected in 76% (19/25) patients, and the maximum transverse dimension of aneurysm was bigger in patients with transmural late gadolinium enhancement than in patients without transmural late gadolinium enhancement ((22.0±10.8)mm vs. (11.7±4.0) mm, P=0.033). Conclusion: ApHCM with LVAA patients have distinct cardiac clinical features, and CMR is the most useful tool for the accurate and objective evaluation of this disease.

[Clinical exploratory application of robotic resection of tumor in segment â §: a report for 7 cases].

Objective: To investigate the feasibility and security of robotic resection of tumor in segment Ⅷ primarily. Methods: The clinicopathologic data of 7 patients who underwent robotic resection of tumor in segment Ⅷ using daVinci robotic system in the Department of Hepato-pancreato-biliary Surgical Oncology, Chinese PLA General Hospital from June 2016 to December 2016 were retrospectively analyzed. The lesion size, the tumor malignance degree mean operation time, intraoperative blood loss and the rate of conversion to laparotomy, postoperative hospital stay, mobidity and motality of all the 7 patients were collected. Results: All the 7 operations were successfully performed with radical resection.The mean tumor diameter was (4.6±1.2)cm. The mean operation time, intraoperative blood loss and postoperative hospital stay were(120.7±21.7)min, (100±106.7)ml, and(7.3±1.8)days respectively.All the patients were discharged successfully with no severe complications. Conclusions: According to our experiences, as a new operationmodel of minimally invasive surgery, robotic resection of tumor in segment Ⅷ has manyadvantages in laparoscopic like less trauma, less intraoperative bleeding, light postoperative pain, shorter postoperative hospital stay and so on. There are some certain advantages in exposure of Ⅷ segment under robotic surgery system. Robotic surgery system is safe and feasible for tumorresection of segmentⅧ, andhas clinical promoting value and application prospect.

Obvious emphysema on computed tomography during an acute exacerbation of chronic obstructive pulmonary disease predicts a poor prognosis.

BACKGROUND: Emphysematous change on computed tomography (CT) during the stable phase of chronic obstructive pulmonary disease (COPD) is reported to correlate with COPD prognosis. Acute exacerbation of COPD (AECOPD) is associated with a high risk of mortality and a poor prognosis. AIMS: This study aims to study the relationship between prognosis and emphysematous changes on CT during an AECOPD. METHODS: Histories were recorded, and CT acquired for 106 patients who visited the emergency department for an AECOPD. Emphysematous change was quantified by measuring the percentage of low-attenuation areas (LAA%) in the entire lung on CT images with a threshold of -950 Hounsfield units. Other factors that could influence AECOPD prognosis were also recorded on admission and analysed. At follow ups conducted in 1 year, patient survival, the modified Medical Research Council (mMRC) Dyspnoea Scale, and performance status (PS) were evaluated, and a COPD Assessment Test (CAT) was completed. RESULTS: The 1-year follow up was completed by 103 of 106 patients. The median LAA% was significantly higher in non-survivors (11%, n = 16) than in survivors (5.69%, n = 87) (P = 0.006) at the 1-year follow up. LAA% was significantly correlated with mMRC grade (r = 0.285, P = 0.008), PS (r = 0.397, P < 0.001) and CAT score (r = 0.27, P = 0.017) at the 3-month follow up, and with mMRC grade (r = 0.405, P < 0.001) and PS (r = 0.377, P < 0.001) at the 1-year follow up. LAA% > 7.5% was a significant predictor of 1-year mortality, higher mMRC and PS at the 3-month and 1-year follow ups, after adjustment for other prognostic predictors. CONCLUSION: Obvious emphysematous changes on CT (LAA% > 7.5%) during an AECOPD predicts a poor prognosis independent of other known indicators.

Combination of edaravone and neural stem cell transplantation repairs injured spinal cord in rats.

This study sought to observe the effect of the combination of edaravone and neural stem cell (NSC) transplantation on the repair of complete spinal cord transection in rats. Eighty adult female Sprague-Dawley (SD) rats were used to establish the injury model of complete spinal cord transection at T9. Animals were divided randomly into four groups (N = 20 each): control, edaravone, transplantation, and edaravone + transplantation. The recovery of spinal function was evaluated with the Basso, Beattie, Bresnahan (BBB) rating scale on days 1, 3, and 7 each week after the surgery. After 8 weeks, the BBB scores of the control, edaravone, transplantation, and combination groups were 4.21 ± 0.11, 8.46 ± 0.1, 8.54 ± 0.13, and 11.21 ± 0.14, respectively. At 8 weeks after surgery, the spinal cord was collected; the survival and transportation of transplanted cells were observed with PKH-26 labeling, and the regeneration and distribution of spinal nerve fibers with fluorescent-gold (FG) retrograde tracing. Five rats died due to the injury. PKH-26-labeled NSCs had migrated into the spinal cord. A few intact nerve fibers and pyramidal neurons passed the injured area in the transplantation and combination groups. The numbers of PKH-26-labeled cells and FG-labeled nerve fibers were in the order: combination group > edaravone group and transplantation group > control group (P < 0.05 for each). Thus, edaravone can enhance the survival and differentiation of NSCs in injured areas; edaravone with NSC transplantation can improve the effectiveness of spinal cord injury repair in rats.

A pooled analysis of MRI in the detection of bone marrow infiltration in patients with malignant lymphoma.

AIM: To explore the role of magnetic resonance imaging (MRI) in detecting bone marrow infiltration of malignant lymphoma through a systematic review and meta-analysis. MATERIALS AND METHODS: Studies that evaluated the diagnostic performance of MRI in detecting bone marrow infiltration of malignant lymphoma were acquired from the MEDLINE, EMBASE, Cancerlit, and Cochrane Library database, from February 1987 to May 2012. Pooled estimation and subgroup analysis data were obtained by statistical analysis. RESULTS: A total of 13 studies involving 634 patients who fulfilled all of the inclusion criteria were considered for the analysis. No publication bias was found (p = 0.70). The pooled sensitivity of MRI was 0.82 [95% confidence intervals (CI): 0.70-0.90] and the pooled specificity was 0.79 (95% CI: 0.72-0.84). Overall, positive likelihood ratios (LR+) was 3.9 (95% CI: 2.8-5.4) and negative likelihood ratios (LR-) was 0.23 (95% CI: 0.13-0.41). In patients with high pre-test probabilities, MRI enabled confirmation of bone marrow involvement; in patients with low pre-test probabilities, MRI enabled exclusion of bone marrow involvement. Worst-case-scenario (pre-test probability, 50%) post-test probabilities were 80% and 18% for positive and negative MRI results, respectively. In subgroup analysis, MRI performed with 1.5 T devices had higher pooled specificity (0.80, 95% CI: 0.71-0.88) than the MRI with ≤1 T (0.78, 95% CI: 0.71-0.85; p < 0.05). The pooled sensitivity of MRI with diffusion-weighted imaging (DWI) was 0.65 (95% CI: 0.39-0.92) and the pooled specificity was 0.83 (95% CI: 0.69-0.97). The sensitivity and specificity of MRI without DWI was 0.85 (95% CI: 0.76-0.94) and 0.79 (95% CI: 0.72-0.85), respectively. CONCLUSION: A limited number of small studies indicate that MRI can serve as a valuable tool for detecting bone marrow infiltration of malignant lymphoma. Results were most promising when performing MRI using high field strength devices. MRI with DWI is shown to be more specific than conventional MRI techniques. This deserves further investigation in future studies.

[A cross-sectional survey and analysis of the pain status and its influencing factors in diabetic foot ulcer patients].

Objective: To investigate the pain status in diabetic foot ulcer (DFU) patients and analyze its influencing factors. Methods: A single-center cross-sectional survey research method was used. From May 2021 to February 2022, DFU patients who were admitted to the Fourth Medical Center of PLA General Hospital and met the inclusion criteria were selected and investigated. The scores of the heaviest pain, the least pain, the average pain, and the current pain in pain degree and the total score and the scores of influence on patients' daily life, mood, walking ability, daily work, relationship with others, sleep, and life interest in pain-related effects and the total score of patients were evaluated by the brief pain inventory. A self-designed general data questionnaire was used to collect the data including patients' gender, age, education level, body mass index, self-care ability, diabetes course, wound Wagner grade, bacterial culture result of wound specimen, and the levels of glycated hemoglobin, albumin, prealbumin, hemoglobin, and leukocyte count. Patients were classified according to general data, and the total scores of pain degree and pain-related effects were counted. Data were statistically analyzed with Kruskal-Wallis test and Mann-Whitney U test. The indicators with statistically significant differences in univariate analysis were selected for generalized linear model analysis to screen the independent risk factors of pain severity and pain-related effects in DFU patients. Results: A total of 44 questionnaires were sent out, and 42 valid questionnaires were collected, with effective recovery of 95.45%. The scores of the heaviest pain, the least pain, the average pain, and the current pain in DFU patients were 5 (0, 10), 2 (0, 6), 3 (0, 8), and 2 (0, 8), respectively, and the total score of the pain severity was 11 (0, 24); the scores of pain-related effects on patients' daily life, mood, walking ability, daily work, relationship with others, sleep, and life interest were 4 (0, 10), 4 (0, 10), 5 (0, 10), 5 (0, 10), 3 (0, 10), 4 (0, 10), and 4 (0, 10), respectively, and the total score of pain-related effects was 30 (0, 63). In 42 DFU patients, most patients were male, aged 39-87 (67±10) years, most patients had education level of junior high school, most patients had diabetes for more than 20 years, half of patients' wounds were Wagner grade 4, most patients had body mass index and leukocyte count within normal limits, most patients had partial dependence on self-care ability, the bacterial culture results of wound specimen in the vast majority of patients were positive, about half of the patients had abnormal level of albumin, and most patients had abnormal levels of glycosylated hemoglobin, prealbumin, and hemoglobin. Univariate analysis of the above general data showed that total scores of pain severity among patients with different hemoglobin levels and leukocyte counts were statistically significant different (with Z values of -2.05 and -2.55, respectively, P<0.05), and the total scores of pain-related effects on patients with different hemoglobin levels, leukocyte counts, and bacterial culture results of wound specimen were statistically significant different (with Z values of -2.66, -2.02, and -2.12, respectively, P<0.05). Generalized linear model analysis showed that leukocyte count was an independent risk factor for pain severity and pain-related effects in 42 DFU patients (with 95% confidence intervals of 0.28-11.87 and 5.67-36.99, respectively, standardized regression coefficient values of 6.17 and 21.33, respectively, both P values <0.05). The bacterial culture result of wound specimen was an independent risk factor for pain-related effects in 42 DFU patients (with 95% confidence interval of 2.92-39.09, standardized regression coefficient value of 21.00, P<0.05). Conclusions: DFU patients often suffer pain, and the bacterial culture results of wound specimen and leukocyte count are the main factors affecting the pain of DFU patients.

Wnt/ß-catenin signaling regulates MAPK and Akt1 expression and growth of hepatocellular carcinoma cells.

In hepatocellular carcinoma (HCC), Wnt/ß-catenin, Ras/MAPK and PI3K/AKT signaling pathways form a complex network and play important roles during HCC genesis and development. To study their relationship and the influence on cell growth, the siRNA directed against ß-catenin was transfected into HCC HepG2 cells. ß-catenin mRNA and protein levels were measured respectively at various times by RT-PCR and Western blot. Furthermore, HCC cell growth was measured by MTT assay. Finally, MAPK family and Akt1 protein levels were also measured by Western blot. After the transfection, ß-catenin mRNA levels were markedly inhibited at 24 h and increased gradually at 48, 72 and 96 h; ß-catenin protein levels decreased gradually at 24, 48 and 72 h and slightly increased at 96 h. HCC cell growth was inhibited from 24-72 h, but this inhibition decreased at 96 h. ERK1/2 (p42/p44 MAPK), JNK/SAPK, p38 MAPK, and Akt1 protein levels showed no change following transfection, while their phosphorylated protein levels showed changes. Thus, siRNA directed against ß-catenin markedly decreased ß-catenin gene expression and inhibited cell growth. Wnt/ß-catenin signaling pathway might regulate Ras/MAPK and PI3K/Akt signaling pathways through regulation of the phosphorylation state of ERK1/2, JNK/SAPK and Akt1 protein in HCC HepG2 cells. These pathways might compensate for the inhibitory effect of ß-catenin, thereby affecting tumor cell growth and others downstream factors.