Application progress of artificial intelligence in the diagnosis of esophageal cancer / 中国胸心血管外科临床杂志

@#Esophageal cancer is an aggressive malignancy with high morbidity and poor prognosis. Symptoms of early esophageal cancer are insidious and difficult to detect, while advanced esophageal obstruction, lesion infiltration and metastasis seriously affect patients’ quality of life. Early detection and treatment can help to increase the survival chance of patients. Recently, artificial intelligence (AI) has shown remarkable success in diagnosis of esophageal cancer, highlighting the great potential of new AI-assisted diagnostic modalities. This paper aims to review recent progress of AI in the diagnosis of esophageal cancer and to prospect its clinical application.

Thoughts of syndrome differentiation and treatment of precancerous lesions of chronic atrophic gastritis based on the theory on hidden pathogen / 国际中医中药杂志

Precancerous lesions of gastric cancer (PLGC) is a pathological change accompanied by intestinal metaplasia and dysplasia on the basis of chronic atrophic gastritis. It is also an important stage of "inflammation-cancer transformation" on gastric mucosa. Paying attention to the intervention of PLGC has important value and significance for the secondary prevention of gastric cancer. PLGC has the characteristics of occult onset, toxin damaging collaterals, and long course of disease, which is highly consistent to the pathogenesis characteristics of incubative pathogenic factors. Based on the relevance of incubative pathogenic factors and PLGC, treatment of PLGC from the perspective of incubative pathogenic factors should be mainly strengthening the spleen and stomach, and combined with the methods of regulating qi and dissipating dampness, and removing blood stasis and detoxification. It should also pay attention to the prognosis.Paying attention to the body-mind treatment can reduce the re-occurrence , so as to provide a new way of thinking for treating PLGC from incubative pathogenic factors.

Application of Theory of ''Pathogen Invading Nutrient and Blood Aspects'' in Precancerous Lesions of Gastric Cancer / 中国实验方剂学杂志

Gastric cancer is one of the most common malignant tumors of the digestive system， with a high incidence， a low overall survival rate， and poor prognosis after treatment. It has become a major public health problem that threatens the lives and health of people. Since the pathogenesis of gastric cancer is still not fully unraveled， it is difficult to implement primary prevention. Therefore， the research on secondary prevention of gastric cancer， i.e.， precancerous lesions of gastric cancer， is extremely important and has become the focus of many researchers. Precancerous lesions of gastric cancer are the key pathological links in the transformation of inflammatory lesions of gastric mucosa into gastric cancer， including chronic atrophic gastritis， intestinal metaplasia， and dysplasia. Relevant studies have confirmed that with the aggravation of gastric mucosal lesions， the incidence and risk of gastric cancer also increase. Therefore， early diagnosis and effective intervention in the pathological link of gastric precancerous lesions is a key measure to prevent and reduce the incidence of gastric cancer， with great significance. More studies have shown that traditional Chinese medicine （TCM） can truncate and reverse the pathological grading of gastric mucosa， and can also effectively improve the clinical symptoms and quality of life of patients， with few adverse reactions and low recurrence rate， which has unique advantages and characteristics. The theory of ''pathogen invading nutrient and blood aspects'' was first proposed by WU Youxing， a febrile disease doctor， in Treatise on Pestilence （《温疫论》）. It was originally used for the treatment of syndrome changes in the late stage of febrile epidemics， but after being enriched and developed by different doctors， it is now mostly used to guide the treatment of various chronic diseases. Precancerous lesions of gastric cancer are a common and difficult disease in clinical practice. Its evolution process is characterized by asthenia in origin and sthenia in superficiality and deficiency-excess in complexity， which is consistent with the core pathogenesis of ''pathogen invading nutrient and blood aspects''， namely， positive deficiency and intruding pathogen， and intruding pathogen cementation in the blood vessels. They are also interlinked in terms of treatment principles. Therefore， with the theory of ''pathogen invading nutrient and blood aspects'' as the breakthrough point， this article expounded the intervention effect of TCM on precancerous lesions of gastric cancer from the perspective of this theory， reflecting its important guidance and application value and providing new ideas for clinical treatment of diseases.

Risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the risk factors of recurrence and canceration for premalignant vocal fold lesions after surgery, and to provide a reasonable basis for preoperative evaluation and postoperative follow-up. Methods:This study retrospective analyzed the relationship between clinicopathological factors and clinical outcome（recurrence, canceration, recurrence-free survival, and canceration-free survival） in 148 patients undergoing surgical treatment in Chongqing General Hospital from 2014 to 2017. Results:The five-year overall recurrence rate was 14.86% and the overall recurrence rate was 8.78%. Univariate analysis showed that smoking index, laryngopharyngeal reflux and lesion range were significantly associated with recurrence（P<0.05）, and smoking index and lesion range were significantly associated with canceration（P<0.05）. Multivariate logistic regression analysis showed that smoking index ≥600 and laryngopharyngeal reflux were independent risk factors for recurrence（P<0.05）, and smoking index ≥600 and lesion range ≥1/2 vocal cord were independent risk factors for canceration（P<0.05）. The mean carcinogenesis interval for the postoperative smoking cessation group was significantly longer（P<0.05）. Conclusion:Excessive smoking, laryngopharyngeal reflux and a wide range of lesions may be related to postoperative recurrence or malignant progression of precancerous lesions in the vocal cord, and further large-scale multi-center prospective randomized controlled studies are needed to clarify the effects of the above factors on recurrence and malignant changes in the future.

Effect and mechanism of Xihuang Pills on rats with precancerous lesions of breast / 中国中药杂志

The purpose of this study was to explore the effect and mechanism of Xihuang Pills on rats with precancerous lesions of the breast. Of 48 healthy female rats, 8 were randomly selected as blank group, and the other 40 were treated with 7,12-dimethylbenzanthracene(DMBA) combined with estrogen and progestin to establish a model of precancerous lesions of the breast. The successfully modeled rats were randomly divided into a model group, a tamoxifen group(1.8 mg·kg~(-1)·d~(-1)), a Xihuang Pills low-dose group(0.3 g·kg~(-1)·d~(-1)), a medium-dose group(0.6 g·kg~(-1)·d~(-1)) and a high-dose group(1.2 g·kg~(-1)·d~(-1)). After 30 days of admi-nistration, the histopathological changes of viscera and breast were observed by haematoxylin and eosin(HE) staining, and the visceral index was calculated. Enzyme linked immunosorbent assay(ELISA) was used to detect the contents of estradiol(E_2) and progesterone(P) in serum. The protein expressions of vascular endothelial growth factor(VEGF) and fibroblast growth factor 2(FGF2) were detected by immunohistochemistry. The protein expressions of VEGF, vascular endothelial growth factor receptor 2(VEGFR2), phosphorylated-vascular endothelial growth factor receptor 2(p-VEGFR2), B-cell lymphoma-2(Bcl-2), and Bcl-2 associated X protein(Bax) were detected by Western blot and the mRNA expressions of VEGF, FGF2, CXC-chemokine receptor 4(CXCR4), cysteine aspartic acid-specific protease(caspase-3), and stromal cell-derived factor 1(SDF-1) were detected by real-time polymerase chain reaction(RT-PCR). HE staining revealed that the model group had some liver and kidney damages and severe hyperplastic mammary tissue, while the Xihuang Pills high-dose group had mild hyperplasia. Compared with the model group, the Xihuang Pills groups had lo-wer ovarian coefficient(P<0.05 or P<0.01) and Xihuang Pills high-dose group had lower uterine coefficient(P<0.01). ELISA results showed that compared with the model group, expressions of E_2 and P in Xihuang Pills high-dose group were significantly decreased(P<0.05 or P<0.01). Immunohistochemistry, Western blot and RT-PCR indicated that compared with the conditions in the model group, the protein and mRNA expressions of VEGF and FGF2 in the Xihuang Pills groups were down-regulated(P<0.05 or P<0.01), and the protein expression of Bcl-2 was lowered(P<0.01); there was a decrease in the protein expressions of VEGFR2 and p-VEGFR2(P<0.01), a down-regulation in the mRNA expressions of CXCR4 and SDF-1(P<0.01), while an increase in the mRNA expression of caspase-3(P<0.01) in both Xihuang Pills medium-dose and high-dose groups; the protein expression of Bax in Xihuang Pills high-dose group was increased(P<0.01). The above results indicated that Xihuang Pills can effectively intervene in precance-rous lesions of the breast, and the mechanism may be related to the regulation of E_2 and P secretion as well as the inhibition of angiogenesis and chemokine receptor expression, thus controlling the occurrence of precancerous lesions of the breast in rats.

Comparison of in vivo plasma pharmacokinetics and urine excretion of main components in Xihuang Formula in rats with precancerous lesions of breast cancer / 中国中药杂志

The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.

Mechanism of Qi-invigorating and Blood-activating Therapy in Mediating Autophagy of Precancerous Lesions of Atrophic Gastritis by miR216b/Beclin1 / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Qi-invigorating and blood-activating therapy on the miR216b/Beclin1 pathway in mice with atrophic precancerous lesions of gastric cancer （PLGC） and analyze its mechanism in autophagy of PLGC. MethodSeventy-five healthy male SPF KM mice were randomly divided into a blank group and a model group. Mice in the model group were given 1-methyl-3-nitroso-1-nitrosoguanidine （MNNG） solution （150 mg·L-1） for free drinking and gavage and ranitidine solution （0.03 g·kg-1） daily for 12 weeks. According to the random control table， mice were divided into a model group， a Qi-invigorating group （3.5 g·kg-1 of Astragali Radix）， a blood-activating group （0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， a Qi-invigorating and blood-activating group （3.5 g·kg-1 of Astragali Radix + 0.7 g·kg-1 of Notoginseng Radix et Rhizoma powder）， and a folic acid group （2 mg·kg-1）. The corresponding drugs were given to mice in each group for 8 weeks and then the tissues were collected. Hematoxylin-eosin （HE） staining was carried out to observe the changes in gastric mucosa. Western blot was used to detect the protein expression of microtuble-associated protein 1 light chain 3 （LC3）Ⅰ， LC3Ⅱ， and Beclin1. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Beclin1 and miR-216b. ResultPathological observation showed that as compared with the blank group， the intrinsic glands of gastric mucosa decreased with atrophy and intestinal metaplasia in the model group， which were improved in all treatment groups， and the improvement of the Qi-invigorating and blood-activating group was the most obvious. As compared with the blank group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of the model group was significantly decreased （P<0.05）. As compared with the model group， the content of LC3Ⅰ， LC3Ⅱ， LC3Ⅱ/LC3Ⅰ， and Beclin1 protein in gastric tissues of each treatment group was increased （P<0.05， P<0.01）. The increase was most obvious in the Qi-invigorating and blood-activating group. As compared with the blank group， the mRNA expression of Beclin1 in the model group was decreased （P<0.05）， and that of miR216b was increased （P<0.05）. As compared with the model group， the mRNA expression of Beclin1 was increased and that of miR216b was decreased in each treatment group （P<0.05）， and the changes were the most obvious in the Qi-invigorating and blood-activating group. ConclusionThe mechanism of the Qi-invigorating and blood-activating therapy， represented by Astragali Radix and Notoginseng Radix et Rhizoma， in treating PLGC may be through inhibiting the expression of miR216b and activating Beclin1， thus promoting autophagy and repairing gastric mucosa.

Value of serum pepsinogen Ⅰ, Ⅱ and gastrin-17 in screening precancerous lesions of gastric cancer in physical examination population / 中国医师进修杂志

Objective:To evaluate the value of serum pepsinogen Ⅰ and Ⅱ combined with gastrin-17 in screening precancerous lesions of gastric cancer in physical examination population.Methods:Serum pepsinogen, gastrin-17 and Helicobacter pylori (Hp) antibody were detected in 18 354 physical examination people from July to December 2017 in Wenrong Hospital, Hengdian, Dongyang. The patients were divided into youth group (18 to 39 years old), middle-aged group (40 to 59 years old) and elderly group (≥60 years old) according to their ages. The correlation between the serological level of the above indexes and age was analyzed; according to the new ABC method, the test results were divided into groups A, B, C and D. The patients in group C and D were examined by gastroscopy. The differences of gastric mucosal atrophy or intestinal metaplasia and other precancerous lesions detected by gastroscopy in different age groups were compared.Results:Finally, 18 354 cases were enrolled, including 9 614 males and 8 740 females. With the increase of age, the proportion of group C and D increased gradually. In group C, 181 cases underwent gastroscopy, including 39 cases of atrophic gastritis, 29 cases of intestinal metaplasia and 3 cases of dysplasia/intraepithelial neoplasia, the detection rate of precancerous lesions was 39.23%; in group D, 94 cases underwent gastroscopy, including 22 cases of atrophic gastritis and 13 cases of intestinal metaplasia, the detection rate of precancerous lesions was 37.23%. The proportion of gastric precancerous lesions in group C and D was 29.63% in the young group, 69.70% in the middle-aged group and 71.58% in the old group, respectively. There was significant difference compared with the young group ( P<0.01); atypical hyperplasia occurred in 2.02% and 9.47% of the middle-aged group and the elderly group. Conclusions:The combined detection of serum pepsinogen Ⅰ and Ⅱ and gastrin-17 levels is of great value in the screening of precancerous lesions of gastric cancer; when this method used for early gastric cancer screening in healthy population, it is necessary to consider the influence of age for the risk stratification of gastric cancer.

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Cervical precancerous lesions at the Tchibanga Regional Hospital and the University Hospital in Gabon in 2018: smartphone as a screening tool for diagnosis

Background: Cervical precancerous lesions are disorders that can induce discoloration changes. Their detection is difficult in remote areas in the absence of adequate equipment. The objectives were to evaluate Smartphone performance in diagnosing cervical precancerous lesions in Tchibanga, Gabon. Methods: It was an interventional cross-sectional study to evaluate the validity and reliability of the smartphone as a tool for diagnosing atypical changes in the cervix. Study period was between July 1, 2017, to February 28, 2018, at the Tchibanga Regional Hospital (CHRT) and the University Hospital (CHU). The variability between examiners was determined according to Cohen's Kappa formula. The Gold standard test was the cytology. Results: Compared to the examiner -1, the examiner - 2 found a high percentage of inflammations as atypical transformations: 15.3% versus 9%. With regard to smartphonic impressions, the examiner-1 found the normal impressions almost equal to that of the examiner-2, 72.9% versus 72.2%. The concordance between positive smartphonic impressions was 93.8% and 95.5% between negative smartphonic impressions, with k = 0.86. Conclusion: In view of the above, the concordance between positive and negative smart phonic impressions was 93.8 and 95.5% with k = 0.86. The performance parameters being good, there is a need to use the smartphone as a tool for the diagnosis of precancerous lesions

Establishment and clinical validation of an artificial intelligence YOLOv51 model for the detection of precancerous lesions and superficial esophageal cancer in endoscopic procedure / 中华肿瘤杂志

Objective: To construct the diagnostic model of superficial esophageal squamous cell carcinoma (ESCC) and precancerous lesions in endoscopic images based on the YOLOv5l model by using deep learning method of artificial intelligence to improve the diagnosis of early ESCC and precancerous lesions under endoscopy. Methods: 13, 009 endoscopic esophageal images of white light imaging (WLI), narrow band imaging (NBI) and lugol chromoendoscopy (LCE) were collected from June 2019 to July 2021 from 1, 126 patients at the Cancer Hospital, Chinese Academy of Medical Sciences, including low-grade intraepithelial neoplasia, high-grade intraepithelial neoplasia, ESCC limited to the mucosal layer, benign esophageal lesions and normal esophagus. By computerized random function method, the images were divided into a training set (11, 547 images from 1, 025 patients) and a validation set (1, 462 images from 101 patients). The YOLOv5l model was trained and constructed with the training set, and the model was validated with the validation set, while the validation set was diagnosed by two senior and two junior endoscopists, respectively, to compare the diagnostic results of YOLOv5l model and those of the endoscopists. Results: In the validation set, the accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the YOLOv5l model in diagnosing early ESCC and precancerous lesions in the WLI, NBI and LCE modes were 96.9%, 87.9%, 98.3%, 88.8%, 98.1%, and 98.6%, 89.3%, 99.5%, 94.4%, 98.2%, and 93.0%, 77.5%, 98.0%, 92.6%, 93.1%, respectively. The accuracy in the NBI model was higher than that in the WLI model (P<0.05) and lower than that in the LCE model (P<0.05). The diagnostic accuracies of YOLOv5l model in the WLI, NBI and LCE modes for the early ESCC and precancerous lesions were similar to those of the 2 senior endoscopists (96.9%, 98.8%, 94.3%, and 97.5%, 99.6%, 91.9%, respectively; P>0.05), but significantly higher than those of the 2 junior endoscopists (84.7%, 92.9%, 81.6% and 88.3%, 91.9%, 81.2%, respectively; P<0.05). Conclusion: The constructed YOLOv5l model has high accuracy in diagnosing early ESCC and precancerous lesions in endoscopic WLI, NBI and LCE modes, which can assist junior endoscopists to improve diagnosis and reduce missed diagnoses.

Clinical research progress and implications of therapeutic vaccines for cervical cancer and precancerous lesions: a qualitative systematic review / 中华肿瘤杂志

Objective: To systematically summarize and analyze the clinical research progress of therapeutic vaccines for cervical cancer or precancerous lesions. Methods: English databases (PubMed, Embase, Web of Science, Cochrane library, Proquest, and ClinicalTrails.gov) and Chinese databases (SinoMed, CNKI, WanFang, and VIP Database) were systematically searched to collect literature on therapeutic vaccines for cervical cancer or precancerous lesions from inception to February 18, 2021. After screening, we evaluated the risk of bias of included studies, and combed the basic information of the literature, research designs, information of vaccines, study patients, outcome indicators and so on, qualitatively summarized the clinical research progress. Results: A total of 71 studies were included in this systematic review, including 14 random controlled trials, 15 quasi-random controlled trials, 4 cohort studies, 1 case-control study, 34 case series studies and 3 case reports. The study patients included women aged 15~79 with cervical cancer or precancerous lesions in 18 countries from 1989 to 2021. On the one hand, there were 40 studies on therapeutic vaccines for cervical precancerous lesions (22 867 participants), involving 21 kinds of vaccines in 6 categories. Results showed 3 marketed vaccines (Cervarix, Gardasil, Gardasil 9) as adjuvant immunotherapies were significant effective in preventing the recurrence of precancerous lesions compared with the conization only. In addition, MVA E2 vaccine had been in phase Ⅲ clinical trials as a specific therapeutic vaccine, with relative literature showing it could eliminate most high-grade precancerous lesions. Therapeutic vaccines for precancerous lesions all showed good safety. On the other hand, there were 31 studies on therapeutic vaccines for cervical cancer (781 participants), involving 19 kinds of vaccines in 7categories, with none had been marketed. 25 studies were with no control group, showing the vaccines could effectively eliminate solid tumors, prevent recurrence, and prolong the median survival time. However, the vaccines effectiveness couldn't be statistically calculated due to the lack of a control group. As for the safety of therapeutic vaccines for cervical cancer, 9 studies showed that patients experienced serious adverse events after treatments, where 7 studies reported that serious adverse events occurred in patients couldn't be ruled out as the results of therapeutic vaccines. Conclusions: The literature review shows that the literature evidence for the therapeutic vaccines for cervical precancerous lesions is relatively mature compared with the therapeutic vaccines for cervical cancer. The four kinds of vaccines on the market are all therapeutic vaccines for precancerous lesions, but they are generally used as vaginal infection treatments or adjuvant immunotherapies for cervical precancerous lesions, not used for the specific treatments of cervical precancerous lesions. Other specific therapeutic vaccines are in the early stage of clinical trials, mainly phase Ⅰ/Ⅱ clinical trials with small sample size. The effectiveness and safety data are limited, and further research is still needed.

Endoscopic submucosal dissection for early hypopharyngeal carcinoma and precancerous lesions / 中华消化内镜杂志

Objective:To evaluate the efficacy and safety of endoscopic submucosal dissection (ESD) for early hypopharyngeal carcinoma and precancerous lesions.Methods:Clinical data of 41 patients who received ESD for early hypopharyngeal carcinoma and precancerous lesions from August 2013 to August 2019 in the Department of Endoscopy of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively analyzed. Main outcome measurements included operation completion rate, operation time, en bloc resection rate, R0 resection rate, complication rate and recurrence.Results:ESD was successfully completed in all 41 cases, with a success rate of 100.0% and a mean time of 49.1 min (ranged 10-110 min). Fifty-four lesions underwent en bloc resection, with an en bloc resection rate of 98.2% (54/55), of which 41 had negative horizontal and vertical margins, and the R0 resection rate was 74.5% (41/55). During the operation of 55 lesions, there was a small amount of blood oozing on the wound surface, and electrocoagulation with thermal biopsy forceps could successfully stop the bleeding. No perforation occurred, and 2 cases (4.3%) had delayed bleeding after ESD, and hemostasis was successful under emergency endoscopy. Postoperative endoscopy showed that 1 case (2.2%) had esophageal entrance stenosis, and the obstruction was relieved after repeated water balloon dilatation. The follow-up period ranged from 3 to 72 months, and the median time was 18 months. One case was found to have mucosal lesions in the same part of the hypopharynx and received ESD treatment again. Follow-up to October 2020, no residual lesions and recurrence were found.Conclusion:ESD is a safe and effective option for the treatment of early hypopharyngeal carcinoma and precancerous lesions, which is worthy of clinical application.

Clinical research progress of Traditional Chinese Medicine treating precancerous lesions of gastric cancer with syndrome differentiation / 国际中医中药杂志

Traditional Chinese Medicine (TCM) has certain advantages in the treatment of precancerous lesions of gastric cancer (PLGC) based on the holistic concept and the thought of syndrome differentiation. Currently, it is generally divided into 6 kinds of syndromes: liver and stomach qi stagnation syndrome, liver and stomach heat stagnation syndrome, spleen and stomach weakness syndrome (including spleen and stomach qi deficiency syndrome with coldness), spleen and stomach damp heat syndrome, stomach yin deficiency syndrome and blood stasis in stomach collateral syndrome. Clinically, the doctor should treat PLGC patients according to different syndrome types by using Chinese medicine prescription, which could improve the gastric mucosal pathological state, gastroscopy and clinical symptoms, to rehibit the development of precancerous lesions, reduce the incidence rate of gastric cancer. In the future, the doctors shouldreach the consensus of treating PLGC with TCM diagnosis, and focus on the research of TCM compounds or monomers with obvious curative effect, increase the times of follow-up, and evaluate the long-term curative effect.

Therapeutic effects of lamb′s tripe extract and vitamin B12 capsule on precancerous lesions of gastric mucosa in rats / 中华消化杂志

Objective:To explore the therapeutic effects of lamb′s tripe extract and vitamin B12 (hereinafter referred to as lamb′s tripe) capsule on precancerous lesions of gastric mucosa in rats.Methods:Thirty-two rats of the 42 Wistar rats (model group) were selected for modelling, and in model group six rats died due to gavage, 10 rats were sacrificed for observing the results of modeling, and the left 16 rats were divided into administration group (eight rats) and non-administration group (eight rats). After modeling, five of the 10 rats without modelling treatment were selected as the normal control of the model group, the other five (negative control group) rats were included in drug intervention experiment. The drug intervention program was as follows: in administration group, rats were gavaged with lamb′s tripe 0.2 g/kg once per day for three months; in non-administration group and negative control group, rats were gavaged with 0.9% sodium chloride solution 0.2 g/kg once per day for three months. One rat died in each for the administration group and non-administration group due to gavage. Body weight gain, pH value of gastric juice and pathological changes of gastric mucosa of the three groups were evaluated. The number of nodules on gastric mucosal surface and the incidence and scores of precancerous lesions (intraepithelial neoplasia) in gastric mucosal were analyzed. The therapeutic effects of lamb′s tripe capsule on gastric mucosal precancerous lesions in rats were evaluated. Independent sample t test , Mann Whitney U test and chi-square test were used for statistical analysis. Results:The body weight gain of rats at the 6th week in the administration group was higher than that of rats in the non-administration group ((508.26±33.96) g vs. (495.50±23.01) g), and the pH value of gastric juice of rats in the administration group was lower than that of rats in the non-administration group (3.07±0.55 vs. 4.45±0.72), and the differences were statistically significant (both P<0.05). The number of proliferative nodules on the gastric mucosal surface of the rats in the administration group was less than that of rats in the non-administration group (the ratio of gastric fundus: 6.00(3.00, 7.00) vs. 11.00(7.00, 13.00); the ratio of gastric antrum: 0.00(0.00, 1.00) vs. 3.00(2.00, 4.00); the ratio of whole stomach: 7.00(3.00, 10.00) vs. 15.00(13.00, 17.00)), and the differences were statistically significant ( U=43.50, 49.00, 49.00, all P<0.05). The score of gastric mucosal precancerous lesions in the administration group was lower than that in the non-administration group(1.00±0.00 vs.1.14±0.38), and the incidence of precancerous lesions in the administration group was lower than that in the non-administration group (1/7 vs. 5/7), and the differences were statistically significant ( t=2.45, χ2=4.67, both P=0.031). Conclusions:Lamb′s tripe capsule can significantly inhibit the progression of precancerous lesions of gastric mucosa in rats, so as to play a role in preventing the occurrence of gastric cancer.

Construction and evaluation of a predictive model for esophageal stenosis after endoscopic submucosal dissection of early esophageal cancer and precancerous lesions / 中华消化内镜杂志

Objective:To investigate the risk factors of esophageal stenosis after endoscopic submucosal dissection (ESD) of early esophageal cancer and precancerous lesions, and to construct and assess a predictive model for esophageal stenosis.Methods:Data of 421 patients with early esophageal cancer or precancerous lesions who underwent ESD and were confirmed by pathology in the First Affiliated Hospital of Zhengzhou University between January 2015 and April 2020 were retrospectively analyzed.Eighty-nine cases developed postoperative esophageal stenosis (stenosis group) and 332 cases did not (non-stenosis group). Risk factors of esophageal stenosis were investigated by univariate and multivariate logistic regression analysis. Independent risk factors were used as predictors to construct a nomogram model by using the lasso algorithm.The accuracy of the model was evaluated by the consistency index (C-index) and the calibration curve. Bootstrap was applied to internal verification to avoid over-fitting of the model.Results:Univariate analysis showed that postoperative pathology, depth of infiltration, median long and short diameters of the specimen, circumferential resection range, and muscularis propria injury were related to postoperative esophageal stenosis( P<0.05). Further multivariate logistic regression analysis showed that the resection range≥1/2 of the circumference (VS <1/2 circumference: P<0.01, OR=48.453, 95% CI: 11.288-207.983), muscularis propria injury( P<0.01, OR=4.671, 95% CI: 2.283-9.557)and longitudinal length≥50 mm (VS <50 mm: P=0.008, OR=2.741, 95% CI: 1.299-5.785) were independent risk factors for esophageal stenosis after ESD. The nomogram model was constructed through the lasso algorithm by taking the longitudinal length, circumferential resection range, and muscularis propria injury as the predictive factors. The C-index of the nomogram was 0.934 (95% CI: 0.909-0.959)and was 0.931 after 100 times of Bootstrap internal sampling, which meant the prediction probability of the model in the calibration curve was in good agreement with the actual observation probability. Conclusion:Circumferential resection range ≥1/2, muscularis propria injury, and longitudinal length≥50 mm are independent risk factors for post-ESD esophageal stenosis. The nomogram model constructed by the above three indicators as predictors shows an ideal prediction effect on esophageal stenosis after ESD for early esophageal cancer and precancerous lesions, which is helpful to establish a standard plan for early intervention in patients at high risk of stenosis after ESD.

Explore Mechanism of Modified Si Junzitang in Improving Acidic Microenvironment and Reversing Gastric Precancerous Lesions Based on MCT4/CD147 / 中国实验方剂学杂志

Objective:To observe the effect of modified Si Junzitang on the level of lactic acid in gastric mucosa and the expression of Carboxylic acid transporter 1（MCT1）， monocarboxylic acid transporter 4（MCT4）， and extracellular matrix metalloproteinase inducer （CD147）in rats with gastric precancerous lesions（GPL）. Method:Seventy-four SD male rats were randomly divided into normal group （12 rats） and model group （62 rats）. <italic>N</italic>-methyl-<italic>N'</italic>-nitro-<italic>N</italic>-nitrosoguanidine（MNNG）-ammonia compound method was used to establish GPL rat models， and at the 9^th week， the model rats were randomly divided into model group， folic acid group（2.7 mg·kg^-1）， modified Si Junzitang high， medium and low dose groups（12.6， 6.3， 3.15 g·kg^-1）， with 12 rats in each group. After intragastric administration for 12 weeks， the general conditions of the rats were observed. Hematoxylin-eosin（HE）staining was used to observe the histopathological changes of gastric mucosa in rats， chemical colorimetry was used to detect the content of lactic acid in gastric mucosa； immunohistochemistry and real-time polymerase chain reaction（Real-time PCR）were used to detect MCT1， MCT4， CD147 protein and mRNA expression in gastric mucosal tissues. Result:Modified Si Junzitang significantly improved the pathological manifestations in GPL rats such as gastric mucosal epithelial gland structure， disorder of arrangement and cell atypia. Compared with the normal group， the lactic acid content of the gastric mucosa tissue in the model group increased significantly（<italic>P</italic><0.01）， and the protein and mRNA expressions of MCT1， MCT4， CD147 significantly increased（<italic>P</italic><0.05， <italic>P</italic><0.01）. Compared with the model group， the lactic acid content in each dose group of modified Si Junzitang was significantly reduced（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the protein expression levels of MCT4 and CD147 were also significantly reduced in each dose group of modified Si Junzitang（<italic>P</italic><0.05， <italic>P</italic><0.01）. The mRNA expression of MCT4 was significantly reduced in the middle and high dose groups（<italic>P</italic><0.05， <italic>P</italic><0.01）， and the mRNA expression of CD147 was significantly reduced in the high dose group（<italic>P</italic><0.05）. Modified Si Junzitang showed no significant regulatory effect on MCT1. Conclusion:Modified Si Junzitang can significantly improve the abnormal histopathology of gastric mucosal epithelium in GPL model rats. Its mechanism may be related to down-regulating the overexpression of MCT4 and CD147， inhibiting lactic acid outflow， and improving the acidic microenvironment of gastric mucosal epithelium.

Mechanism of Traditional Chinese Medicine in Prevention and Treatment of Precancerous Lesions of Gastric Cancer： An Exploration Based on Gastric Microenvironment / 中国实验方剂学杂志

At present， the incidence and mortality of gastric cancer in China are 10.26% and 12.45%， ranking the second and third places， respectively， in the incidence and mortality of malignant tumors in China. Cancer often goes through three stages： precancerous lesions， carcinoma in situ， and invasive carcinoma. It is of great significance to advance cancer prevention and control to the stage of precancerous lesions. The popularization of digestive endoscopy-assisted diagnosis and treatment has enabled the timely diagnosis and treatment of early gastric cancer and severe dysplasia. However， the endoscopic mucosal resection is not suitable for most precancerous lesions of gastric cancer （PLGC）， and the effective drugs are not available. The long-term clinical dynamic monitoring has imposed considerable physical and mental burdens on patients. Gastrointestinal microenvironment is a dynamic balance system composed of gastrointestinal flora， chemical barrier， mechanical barrier， immune barrier， and gastrointestinal nerves. The imbalance of gastric microenvironment has been proved to be the key mechanism of PLGC. According to traditional Chinese medicine （TCM）， PLGC is a result of long-term interaction between deficient healthy Qi and excessive pathogens. In syndrome differentiation and treatment， PLGC is often believed to be developed from chronic gastritis. Besides， the inflammation-cancer transformation model put forward by Correa and the evolution of its TCM pathogenesis are also considered. Guided by the basic treatment principle of reinforcing healthy Qi to eliminate pathogenic factors， we determined the basic therapeutic methods as follows： invigorating spleen， clearing heat， and resolving dampness. At the same time， such methods as soothing liver and regulating Qi， resolving phlegm and dissipating mass， activating blood and resolving stasis， clearing heat and removing toxin， and tonifying deficiency can be combined based on the results of syndrome differentiation. After discussing the correlation between the imbalance of gastric microenvironment and PLGC and summarizing TCM intervention methods and mechanisms against PLGC from the perspective of gastric microenvironment regulation， this paper believed that TCM improved the gastric microenvironment by regulating the disorder of gastric flora， eliminating the gastric mucosal inflammation， and relieving the abnormal immune response， thereby preventing and controlling the PLGC.

Mechanism of Biejiajian Wan in Reversing EMT in Rat Hetapic Oval Cells via Wnt/ β-catenin Pathway / 中国实验方剂学杂志

Objective:To study the effect of Biejiajian Wan on the epithelial-mesenchymal transition （EMT） of rat hepatic oval cells induced by transforming growth factor- β1（TGF-β1）， in order to explore its mechanism in reversing EMT. Method:WB-F344 cells were divided into five groups： blank group， TGF-β1 model group （10 μg·L-1TGF-β1）， low-dose group （10 μg·L-1TGF-β1+0.55 g·kg-1Biejiajian Wan）， medium-dose group （10 μg·L-1TGF-β1+1.1 g·kg-1Biejiajian Wan）， high-dose group （10 μg·L-1TGF-β1+2.2 g·kg-1Biejiajian Wan）. Except blank group， TGF-β1 was used to induce WB-F344 cells in all of the remaining groups to construct an EMT model. After the cells were treated with low， medium and high doses of Biejiajian Wan serum， the changes of migration ability of WB-F344 cells were detected by cell scratching test. The expressions of E-cadherin， N-cadherin and Vimentin were detected by Western blot. Real-time PCR was used to detect the changes in the expression of β-catenin mRNA. The expression of β-catenin was detected by cell immunofluorescence assay. Result:Compared with normal WB-F344 cells， the intercellular space of WB-F344 cells became loose from tight， and the morphology changed from cobblestone to fibroblast after TGF-β1 induced WB-F344 cells for 4 days， and the expression of E-cadherin protein decreased， while the expression of N-cadherin protein increased （P<0.01）， indicating that the EMT model of WB-F344 cells was successfully built. Compared with the blank group， the migration ability of WB-F344 cells in TGF-β1 model group was enhanced （P<0.01）， compared with TGF-β1 model group， Biejiajian Wan could significantly inhibit the migration ability of WB-F344 cells； specifically， the low-dose group had no statistical significance， and the medium and high-dose groups had statistical significance （P<0.05）. Western blot results showed that compared with the blank group， the expression of E-cadherin decreased， whereas those of N-cadherin and Vimentin increased in the TGF-β1 model group （P<0.01）， compared with TGF-β1 model group， E-cadherin protein expression was increased in the low， medium and high-dose groups， while the expressions of N-cadherin and Vimentin was decreased； specifically， the low-dose groups had no statistical significance， and the medium and high dose groups had statistical significance （P<0.05，P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expression of β-catenin in the TGF-β1 model group was increased （P<0.05）， whereas compared with TGF-β1 model group， the mRNA expression of β-catenin in the low， medium and high-dose groups of Biejiajian Wan was reduced （P<0.01）. The results of cellular immunofluorescence showed that compared with the blank group， the fluorescence expression of β-catenin in the cell nucleus was enhanced in the TGF-β1 model group； and compared with the TGF-β1 model group， the expression of β -catenin in the cell nucleus of the low， medium and high-dose groups of Biejiajian Wan decreased， and the inhibitory effect of Biejiajian Wan on β-catenin in the cell nucleus was positively correlated with its concentration. Conclusion:Biejiajian Wan may reverse the EMT process that TGF-β1 induced WB-F344 cells， and inhibit the migration of WB-F344 cells by inhibiting Wnt/β-catenin signaling pathway.

Expression of K-Ras, p53 and Ki-67 in Precancerous and Cancerous Lesions of Colorectum.

The immunological assessment at molecular profiling of K-Ras, p53 and Ki-67 along with EGFR, BRAF and others like BCL-2 has been the focus of several workers. The incidence of colorectal adenomatous polyp with dysplastic changes and colorectal carcinoma per se in the context of Indian population as per the ICMR registry, New Delhi, India, is significant. We wanted to study precancerous lesions (adenoma, polyp) and adenocarcinoma of colorectum for the expression of K-Ras, p53 and Ki-67 in biopsy or surgical specimen of colon by immunohistochemistry for its occurrence. We also wanted to study the intratumor heterogeneity of aforesaid expression for the purposes of prognostication and correlation with other clinicopathological parameters. MethodsThis is a cross sectional study conducted in the Surgical Pathology and Division of Immunohistochemistry, Department of Pathology, Jawaharlal Nehru Medical College, Sawangi (Meghe), Wardha, Maharashtra, India, for a duration of 2 years. Total seventy patients of all ages and genders suspected of 1) precancerous lesions of adenomas and polyps (35 cases) and 2) adenocarcinoma on colonoscopic biopsy or surgical specimens (35 cases) were included in the study. The expression of K-Ras, p53 and Ki-67 as primary objectives along with EGFR, BRAF and others like BCL-2 as secondary objectives were recorded, tabulated and compared for the purposes of predictive parameters in colorectal neoplastic lesions. ResultsMost of the cases of CRC were over the age of 50 years and Male:Female ratio was 5:3.Twenty-five cases of group 2 (CRC) showed positive IHC for K-Ras. p53 was detected in 28 cases and high Ki-67 index was observed in all 32 cases of CRC. The comparative statistics in the pilot study showed that the immunoexpression of K-Ras, p53 and Ki-67 is significantly higher in group 2 (CRC) compared to cases in group 1 (polyps) and group 3 (normal). ConclusionsExpression of K-Ras, p53 and Ki-67 is likely to be the distinguishing tissue biomarkers between benign and malignant colorectal disease process as well as have prognostic and predictive value in colorectal cancer. The addition of EGFR, BRAF and BCL-2 would help in determining the pathogenesis and offer targeted therapeutic intervention.