Linxian County in Henan Province, Northern China is known as the region with the highest incidence and mortality rate of esophageal cancer worldwide. Since 1959, the Henan medical team has conducted field work on esophageal cancer prevention and treatment in Linxian. Through three generations of effort exerted by oncologists over 65 years of research on esophageal cancer prevention and treatment in Linxian, the incidence rate of esophageal squamous cell carcinoma in this area has dropped by nearly 50%, and the 5-year survival rate has increased to 40%, reaching the international leading level. This article aims to summarize the history, present opportunities and new challenges, and explore the experience of esophageal cancer prevention and treatment in Linxian (referred to as the “Linxian experience”), providing reference and guidance to cancer prevention and treatment research in China.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective To explore the material basis and mechanism of the Chinese medicine Shenmajingfu granules in the treatment of cerebral infarction. Methods The potential active ingredients and targets of Shenmajingfu granules were retrieved through TCMSP, ETCM database and TCM Database. The related target genes of cerebral infarction were searched from OMIM database. The common targets of Shenmajingfu granules and cerebral infarction were obtained by the intersection method. Cytoscape was used to construct active components of Shenmajingfu granules-targets network. Protein-protein interaction network was constructed by STRING software. DAVID database was used for GO and KEGG enrichment analysis. Results The 183 potential active ingredients of Shenmajingfu granules were screened out. 1785 potential targets were screened in the TCMSP database, including 30 targets related to cerebral infarction. These target genes were mainly involved in the inflammatory response and apoptosis process, involving the TNF signaling pathway, HIF-1 signaling pathway and NF-κB signaling pathway. Conclusion The therapeutic effect of Shenmajingfu granules on cerebral infarction may be related to the regulation of inflammatory response, improvement of impaired neurological function and protection of cerebral ischemia-reperfusion injury.

Objective To explore the material basis and mechanism of the Chinese medicine Dingqing tablets in the treatment of leukemia.Methods The potential active ingredients of Dingqing tablets were retrieved through TCMSP and HERB Database and the targets of herbs were screened by Swiss TargetPrediction databases.The treatment targets of leukemia were searched from the GeneCards,OMIM and Disgenet databases.The protein-protein interaction network was used to construct the interactive target regulation function of Dingqing tablets and leukemia by STRING software,and the core subnetworks were filtered by the MCODE plug-in.A component-target pathway network was constructed by GO and KEGG enrichment analysis of the highest scoring Gene cluster 1 gene in the DAVID database.Molecular docking of the active components and core targets of Dingqing tablets was performed by AutoDock and the results were visualized.Results A total of 82 active ingredients and 439 targets of action of Dingqing tablets,and 1 878 leukemia-related targets were obtained through database retrieval,in which 169 common targets of active ingredients and diseases were mapped.Based on the degree values,the main active ingredients were determined as quercetin,luteolin,kaempferol,etc.The PPI core network indicated that the key targets for treating leukemia included TP53,MMP9,TNF,AKT1,CASP3,etc.The gene enrichment analysis of sub-networks and the component-target pathway network diagram showed that Dingqing tablets might exert therapeutic effects on leukemia by regulating signaling pathways such as TNF and IL-17.The molecular docking results showed fairly strong binding activity between the active ingredients and the targets.Conclusion The active ingredients of Dingqing tablets may participate in TNF,IL-17,and other signaling pathways by regulating genes such as TP53,AKT1,and CASP3,thereby exerting therapeutic effects on leukemia.

Objective We tried to investigate the effects of human umbilical cord mesenchymal stem cell exosomes(hUCMSC-Exos)on the proliferation of human dermal papilla cells(HDPCs)and the mechanism of hUCMSC-Exos promoting hair growth.Methods HDPCs were isolated using two-step enzymatic method and cul-tured in vitro.Human umbilical cord mesenchymal stem cells(hUC-MSCs)were cultured.Cell culture supernatant was collected,and exosomes were isolated and extracted using high-speed centrifugation.Electron microscopy,particle size,and surface marker identification were performed on them.Dihydrotestosterone(DHT)induces HDPCs and establishment of an androgenic alopecia cell model.Co-culture hUCMSC-Exos with HDPCs,cell proliferation experiment(EdU)was used to detect the relative activity of induced HDPCs.Real-time qPCR was used to detect the expression level of alkaline phosphatase(ALP),and Western blot was used to detect β-catenin,Wnt10b,GSK-3β expression at the protein level.Results The obtained primary HDPCs,hUC-MSCs,and hUCMSC-Exos were all conformed to the characteristics of dermal papilla cells,mesenchymal stem cells,and exosomes.The num-ber of EdU positive cells significantly increased,and exosomes could effectively promote the proliferation of HDPCs(P<0.05),enhance the vitality of HDPCs and alleviate the damage caused by DHT(P<0.05).Real-time qPCR showed that exosomes could enhance the expression level of ALP gene(P<0.05)and hair follicle induction ability.Western Blot confirmation β-catenin,Wnt10b,GSK-3β were differences in expression at the protein level(P<0.05).Conclusions HUCMSC-Exos could promote DHT induced proliferation of HDPCs,enhance their hair follicle regeneration and repair ability,and its mechanism may be related to the activation of Wnt/β-catenin signaling pathway.

Objective To observe the protective effect of Shenmajing formula on brain tissue of mice with cerebral ischemic injury and explore the possible mechanism. Methods Thirty SPF-grade C57 BL/6 male mice were randomly divided into model control group, Shenmajing group and nimodipine group, and the animal models of cerebral ischemic injury in mice were prepared by electrocoagulation. The protein expression level in endothelial progenitor cells were detected by Western blot. Results Compared with the model control group, the infarct volume of mice in the Shenmajing group was significantly reduced, and the migration, adhesion and tubule formation ability of endothelial progenitor cells were significantly improved, and the expression level of BDNF protein in endothelial progenitor cells was significantly increased. Conclusion The protective effect of Shenmajing granules on brain tissue of mice with cerebral ischemic injury could be closely related to the regulation of BDNF expression in endothelial progenitor cells and improvement of endothelial progenitor cell function of bone marrow origin.

Objective To describe the characteristics and registration status of clinical trials of new drugs for nonalcoholic steatohepatitis (NASH), and to provide a reference for the design and implementation of clinical trials of new drugs for NASH. Methods The U.S. Clinical Trials Database, China Clinical Trial Registry, and Center for Drug Evaluation, National Medical Products Administration, were searched for clinical trials of new drug registration and interventional studies with NASH as the indication published up to August 6, 2021, using NASH in English and Chinese characters as the keywords, and liver cirrhosis was excluded. Two researchers independently searched and screened the articles to extract relevant information. Results A total of 196 clinical trials of new drug registration or interventional studies for NASH were included, among which there were 174 trials registered abroad and 22 trials registered in China, and the number of registrations tended to increase year by year. The numbers of phase Ⅰ, phase Ⅰ/Ⅱ(including Ⅰb/Ⅱa), phase Ⅱ, phase Ⅱ/Ⅲ, and phase Ⅲ clinical trials were 45(23.0%), 8(4.1%), 112(57.1%), 4(2.0%), and 19(9.7%), respectively. The main drug types included farnesoid X receptors, fibroblast growth factors, peroxisome proliferator-activated receptor agonists, and glucagon-like peptide-1, with numbers of 16(8.16%), 14(7.14%), 11(5.61%), and 13(6.63%), respectively. The clinical trials of innovative drugs for NASH initiated by the sponsors in European and American regions accounted for the highest proportion, and there was a gradual increase in the number of clinical trials of innovative drugs in China in recent years, with a similar distribution of single-center and multicenter clinical trials. As for the trials with NASH patients as subjects, the numbers of trials with pathology, imaging, and clinical diagnosis as the main inclusion criteria were 125, 66, and 42, respectively. Phase Ⅰ clinical trials used safety, tolerability, and pharmacokinetic parameters as the main assessment indices, while phase Ⅱ and phase Ⅲ clinical trials often used safety and efficacy as the main assessment indices. The number of clinical trials for the registration of innovative drugs for NASH was relatively low but kept increasing in China, and there were fewer clinical trials of innovative traditional Chinese medicine drugs compared with innovative chemical drugs. Conclusion There is a significant increase in the registration of international clinical trials of innovative drugs for NASH, and most of these trials are in the early phases, with large differences in inclusion criteria and assessment indices, a lack of unified evaluation indices, and relatively few trials with new designs. There are fewer clinical trials of innovative drugs for NASH in China than in European and American countries, and the number of such trials is gradually increasing in China.

Objective:To evaluate the clinical effectiveness and safety of three different non-invasive ventilation strategies in initial treatment of neonatal respiratory distress syndrome(RDS).Methods:A total of 111 premature infants with RDS who were admitted to the NICU from Jan 2019 to Dec 2019 were divided into nasal continuous positive airway pressure(NCPAP)group( n=35), bi-level positive airway pressure(BiPAP)group( n=30)and nasal intermittent positive pressure ventilation(NIPPV)group( n=46)as an initial respiratory support.A retrospective study was conducted to compare pH, PaCO 2, PaO 2, P/F value(PaO 2/FiO 2)before 4 to 6 hours after treatment, the incidence of non-invasive ventilation failure, non-invasive ventilation time, invasive ventilation time, duration of oxygen therapy and the incidence of complications among the three groups. Results:Four to 6 hours after treatment, the blood gas indexes of pH, PaO 2 and P/F were significantly higher and PaCO 2 was significantly lower than those before the treatment in the three groups ( P<0.05). PaO 2 and P/F in both BiPAP group and NIPPV group were higher than those in NCPAP group ( P<0.05). PaCO 2 was lower in BiPAP group than that in NCPAP group ( P<0.05), but there were no statistical differences of the blood gas indexes between BiPAP group and NIPPV group ( P>0.05). The incidence of non-invasive ventilation failure was significantly lower in the BiPAP group and NIPPV group than that in NCPAP group ( P<0.012 5), while no signifficant difference was observed between BiPAP group and NIPPV group ( P>0.05). Moreover, no signifficant differences were found among three groups regarding non-invasive ventilation time, ventilation time of successful non-invasive ventilation, invasive ventilation time, duration of oxygen therapy and the incidence rates of bronchopulmonary dysplasia, necrotizing enterocolitis, periventricular-intraventricular hemorrhages, retinopathy of prematurity( P>0.05). Conclusion:NIPPV and BiPAP as an initial respiratory support for RDS in preterm infants augment the beneficial effects of NCPAP contributing to improvement of oxygenation, reduction of the rate of intubation within five days postnatal life without the relevant complications.

Objective:To compare the changes of corneal asphericity and higher-order aberrations after smart pulse technology-assisted transepithelial photorefractive keratectomy (Smart) for low and moderate myopia and to investigate the changes in the shape of the front corneal surface in patients with different diopters.Methods:A non-randomized controlled study design was used.Ninety-eight eyes of 54 patients with moderate or low myopia who underwent Smart surgery in Tianjin Medical University Eye Hospital from November 2018 to March 2019 were included.The 41 eyes of 23 patients with low myopia were set as the low-myopia group, and 57 eyes of 31 patients with moderate myopia were assigned as the moderate-myopia group.The Pentacam anterior segment analysis system was used to measure Q value, index of surface variance (ISV), corneal higher-order aberration (HOA), corneal vertical coma (Z 3-1), corneal horizontal coma (Z 31) and spherical aberration (Z 40) before surgery, 1 month and 3 months after surgery.The anterior surface morphology was compared between the low-myopia and moderate-myopia group.Pearson correlation analysis was used to analyze the correlations between measurement parameters.The study protocol was approved by an Ethics Committee of Tianjin Medical University Eye Hospital (No.2019KY-17). Written informed consent was obtained from each patient before surgery. Results:Corneal Q value, ISV, HOA and Z 40 were 0.445±0.191, 26.973±5.611, 0.671±0.142 and 0.384±0.188, respectively, in the low-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.273±0.817, 13.784±2.376, 0.433±0.687 and 0.231±0.062 (all at P<0.05). Corneal Q value, ISV, HOA and Z 40 were 0.693±0.203, 34.038±5.773, 0.874±0.216 and 0.520±0.129, respectively, in the moderate-myopia group at one month after surgery, which were significantly increased than corresponding preoperative values of -0.309±0.104, 14.838±3.992, 0.409±0.081 and 0.228±0.089 (all at P<0.05). Corneal Q values, ISV, HOA and Z 40 in the moderate-myopia group were higher than those in the low-myopia group at different time points after surgery, showing significant differences between the two groups (all at P<0.05). There was no significant difference in postoperative 1-month and 3-month corneal Z 3-1 and Z 31 between the two groups (both at P>0.05). The results of correlation analysis showed that there were no significant differences in ΔQ value and ΔISV between the two groups, both of which were negatively correlated with spherical equivalent (ΔQ value: low-myopia group: r=-0.364, P=0.044; moderate-myopia group: r=-0.589, P<0.01; ΔISV: low-myopia group: r=-0.298, P=0.039; moderate-myopia group: r=-0.409, P=0.022). ΔQ value and ΔZ 40 were positively correlated in the moderate-myopia group ( r=0.348, P=0.009); there was no significant correlation between ΔQ value and ΔZ 40 in the low-myopia group ( r=0.180, P=0.266). Conclusions:The corneal high-order aberrations and ISV after Smart are increased in comparison with preoperative values in the low-myopia and moderate-myopia eyes, and the corneal Q values change from negative to positive.The effect of Smart on corneal asphericity is less in the low-myopia eyes.

Objective:To study the influence of different feeding patterns on mother-to-child transmission (MTCT) of hepatitis B virus (HBV) in pregnant women with high viral loads who received antiviral medication during pregnancy to the day of delivery.Methods:This prospective cohort study was conducted in Beijing You'an Hospital. From January 1, 2019, to March 31, 2020, and 574 pregnant women with positive hepatitis B surface antigen (HBsAg) and HBV DNA>2×10 5 IU/ml were enrolled. All participants received tenofovir, telbivudine, lamivudine, or propofol tenofovir from 24-28 weeks of gestation and discontinued on the day of delivery, and their neonates were postnatally given routine passive-active immunoprophylaxis. Based on the feeding patterns, the subjects were divided into three groups: breastfeeding ( n=257), bottle-feeding ( n=241) and mixed feeding groups ( n=76). The follow-up data were obtained from liver functions and HBV DNA level of the mothers at 6-8 weeks postpartum and HBV serological markers of infants at 7-12 months. One-way ANOVA, Student-Newman-Keuls, Chi-square test or Fisher exact test, and repeated measures ANOVA were used to analyze the data. Results:The average maternal HBV DNA levels before antiviral treatment did not differ significantly between the three groups [(7.90±0.67), (7.82±0.70), (7.83±0.70) log 10 IU/ml, F=0.912, P>0.05]. HBV DNA level before delivery in the mixed feeding group was slightly lower than that in the breastfeeding and bottle-feeding group [(3.87 ±1.08) vs (4.21±1.17) and (4.30±1.28) log 10 IU/ml, q= 3.052 and 3.831, both P<0.05], while the comparison between the latter two groups showed no significant differences ( P>0.05). After delivery, HBV DNA level in the bottle-feeding group was slightly lower than that in the breastfeeding group [(7.42±0.93) vs (7.69±0.90) log 10 IU/ml, q=4.583, P<0.05]. Among 580 infants (including six pairs of twins), only one bottle-fed infant (0.4%, 1/243) was infected with HBV through MTCT, and none in the breastfeeding or mixed feeding group ( P=0.553). Conclusions:For pregnant women with high viral loads of HBV who have received antiviral medication during pregnancy, although HBV DNA level will rebound after discontinuation upon delivery, breastfeeding is recommended considering it does not increase the risk of MTCT.