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.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

ObjectiveTo characterize the evidence distribution and methodological quality of randomized controlled trials （RCTs） on oral Chinese herbal medicine （CHM） for atopic dermatitis （AD） based on evidence mapping. MethodsSeven databases （CNKI， Wanfang Data， VIP， CBM， Cochrane Library， PubMed， and Embase） and the Chinese Clinical Trial Registry were searched for the RCTs in Chinese and English. Evidence distribution was presented graphically and textually， and methodological quality was assessed via the Cochrane Risk of Bias tool （ROB 1.0）. ResultsA total of 168 RCTs were included. The number of annual publications showing an increasing trend， and 72.6% RCTs had sample sizes of 51-100 participants. The studies evaluated 108 distinct CHM interventions categorized as decoctions， granules， Chinese patent medicines， and extracts. Compound Glycyrrhizin was the most frequently used， followed by Xiaofengsan and Chushi Weiling decoction. Among the RCTs， 57.1% had the treatment courses of 4-8 weeks. Outcome measures predominantly focused on clinical response rate， skin lesion severity scores， and adverse events， with less attention to TCM symptom scores， skin barrier function， and relapse rates. The overall risk of bias was generally high. ConclusionWhile CHM for AD is a research hotspot and demonstrates clinical advantages， the related studies have problems such as unclear clinical positioning， poor research standardization and methodological quality， and insufficient prominence of TCM clinical advantages. Large-sample， methodologically rigorous， and high-quality studies are needed to enhance the evidence base for CHM in treating AD.

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

[Purpose]To analyze the trend of bladder cancer incidence and age at diagnosis in can-cer registration areas of Jiangsu Province from 2009 to 2019.[Methods]The data of bladder can-cer incidence from 2009 to 2019 were collected from 16 cancer registries in Jiangsu Province,and quality control indicators of the data were evaluated.The crude rate(CR)of incidence,age-standar-dized incidence rate by Segi world standard population(ASIRW),age-specific incidence rate,mean age at diagnosis,mean standardized age at diagnosis,and age-specific incidence composi-tion ratio were calculated.Incidence trends were analyzed using Joinpoint software and the average annual percentage change(AAPC)was calculated.Birth cohort models were constructed and can-cer incidence rates were calculated for people born from 1929 to 2019 and the incidence trends were analyzed.The linear regression models were used to analyze the relationship of average age at onset,standardized average age of onset with year of onset.[Results]The CR of bladder cancer in Jiangsu Province increased from 4.27/105 in 2009 to 7.04/105 in 2019.The CR and ASIRW showed upward trends(CR:AAPC=4.62％,ASIRW:AAPC=1.92％,both P＜0.001).Sex-specific analysis showed that the incidence rate was higher in male(AAPC=5.32％)than that in female(AAPC=1.98％).Birth cohort results indicated a significant upward trend in incidence rates among age groups of 60 years old above,and the fastest increase was in those aged 80 years old and above(AAPC=3.27％,P=0.007).From 2009 to 2019,the average age of bladder cancer onset in Jiangsu Province showed a significant rising trend,increasing by an average of 0.17 years old annually,but the standardized average age of onset showed no significant change after adjusting for age structure.[Conclusion]The incidence rate of bladder cancer showed an increasing trend from 2009 to 2019 in Jiangsu Province,with a significantly higher incidence rate in male than that in female.

Deficient mismatch repair(dMMR)is currently recognized as a biomarker for predicting the efficacy of immune checkpoint inhib-itors(ICIs),and domestic and foreign guidelines recommend first-line immunotherapy for patients with solid dMMR tumors.For rectal can-cer,only 5%of patients are classified as dMMR/microsatellite instability-high(MSI-H),and most have"immune desert type"or mismatch re-pair proficient(pMMR)/microsatellite stabilization(MSS)diseases,which respond poorly to ICIs.Therefore,recently,the synergistic effect of immune drugs and neoadjuvant chemoradiotherapy has been the focus of basic and clinical research.An increasing number of clinical trials of phase Ⅱ/Ⅲ immuno-total neoadjuvant therapy(iTNT)have emerged,and the management of locally advanced rectal cancer(LARC)has begun to enter the non-operative treatment era.Furthermore,an increasing number of studies support the efficacy of neoadjuvant immun-otherapy in patients with dMMR/MSI-H LARC,which exempts such patients from surgery and chemoradiotherapy as follow-up treatment and results in a pivot in the treatment paradigm of a watch-and-wait strategy.Regarding the LARC with pMMR/MSS,the preliminary iTNT findings support ICIs as a shift from an initial posterior-line palliative scheme to a first-line selection strategy and the continuation of large-scale clinical trials.However,no definitive conclusion has been reached regarding the best iTNT application for LARC.Recent studies have shown that short-course radiotherapy and sequential neoadjuvant chemotherapy,combined with immunotherapy,can achieve good short-term outcomes.Finally,identifying other new biomarkers may facilitate the identification of patients with pMMR/MSS who are sensitive to immune drugs(especially for low rectal cancer).In the future,the treatment strategy of LARC should be combined with the stratification of clinical recurrence risk and patient willingness for organ retention to achieve stratified and accurate treatment.This article will review the re-lated research background,basic and clinical research progress and existing problems of iTNT in LARC.

Objective To explore the effects of wogonin on cognitive function and neuroinflamma-tion in VaD rats by regulating AMPK/SIRT1 pathway.Methods 90 VaD rats were randomly di-vided into model group,low-,medium-and high-dose wogonin groups(50,100,200 mg/kg),and high dose+AMPK inhibitor(20 mg/kg)group,18 animals per group.Another 18 normal rats served as sham operation group.ELISA was utilized to measure the contents of IL-1β,TNF-α and IL-6 in hippocampal tissues.Western blotting was conducted to detect the expression of Iba-1,p-AMPK,AMPK and SIRT1 in hippocampal tissues.Results Compared with the sham operation group,the model group had longer escape latency,and elevated contents of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression level of Iba-1 protein in hippocampal tissue,shorter stay time at original platform,and lower expression of p-AMPK/AMPK and SIRT1 in hippocampal tissues(P＜0.05).Treatment of three doses of wogonin,in a dose-dependent man-ner,reduced escape latency,and decreased levels of IL-1β,TNF-α and IL-6,number of Iba-1 posi-tive cells and expression of Iba-1 protein in hippocampal tissue,but longer stay time at original platform,and enhanced expression of p-AMPK/AMPK and SIRT1 protein in hippocampal tissue when compared with the model group(P＜0.05).The high dose+AMPK inhibitor group showed longer escape latency(47.64±5.39 s vs 26.45±3.27 s),shorter stay time at original platform(21.78±3.51 s vs 35.22±5.02 s),increased levels of IL-1β,TNF-α and IL-6,number of Iba-1 positive cells and expression of Iba-1 protein in hippocampal tissue,and lower expression levels of p-AMPK/AMPK and SIRT1 in hippocampal tissue when compared with the high-dose group(P＜0.05).Conclusion Wogonin may improve cognitive function and hippocampal tissue patho-logical damage in VaD rats by activating the AMPK/SIRT1 pathway,and inhibit neuroinflammation.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.