ObjectiveTo observe the effects of Huqi Zhengxiao Formula （槲芪癥消方） on the survival rate and quality of life of patients with stage Ⅲ hepatitis B-associated primary liver cancer （PLC） with syndrome of healthy qi deficiency and toxic stasis accumulation after transcatheter arterial chemoembolisation （TACE） treatment. MethodsOne hundred and twenty-six patients with stage Ⅲ hepatitis B-associated PLC who were identified as syndrome of healthy qi deficiency and toxic stasis accumulation after TACE treatment were selected， and were randomly assigned to 63 cases each of the treatment group and the control group in a ratio of 1∶1 by using the random number table method； the control group was given symptomatic supportive treatments with western internal medicine， and the treatment group was given the addition of Huqi Zhengxiao Formula on the basis of the control group. All patients were treated for a period of 48 weeks， and were followed up at weeks 4， 8， 12， 24， 36， and 48 of the treatment process. The primary effectiveness index was the 1-year survival rate， and the secondary effectiveness index was the Karnofsky score and the traditional Chinese medicine （TCM） syndrome score. Survival analysis was performed using the Kaplan-meier method， and Log-rank test was used to compare the differences between the survival curves of each group. ResultsSix withdrawals in the treatment group and seven withdrawals in the control group， and finally 57 patients in the test group and 56 patients in the control group were included in the statistical analysis. The 1-year survival rate of patients in the treatment group was 56.1% （32/57）， which was higher than that of 33.9% （19/56） in the control group （P = 0.033）. The mean survival time was （275.30±15.50） days in the treatment group， higher than （227.16±17.11） days in the control group （P = 0.039）. Thirty-two patients in the treatment group and 19 patients in the control group completed the Karnofsky score and TCM symptom score at each time point. At weeks 4， 8， 12 and 36， the difference in the Karnofsky score between the two groups was not statistically significant （P＞0.05）； at weeks 24 and 48， the Karnofsky score in the treatment group was higher than that in the control group at the same time point （P＜0.05）； analysis of variance of repeated measurements found that the downward trend of the Karnofsky score in the treatment group was slower than that in the control group （F = 4.47， P = 0.037）. The difference between the TCM symptom scores of the two groups at each follow-up observation point was not statistically significant （P＞0.05）； there was a tendency for the TCM symptom scores of the two groups to increase， but the ANOVA of repeated measurements found that the difference between the two groups was not statistically significant either （F = 0.31， P = 0.58）. Concusion The oral administration of Huqi Zhengxiao Formula can improve the survival rate， prolong the survival time， and improve the quality of life of patients with stage Ⅲ hepatitis B-associated PLC with syndrome of healthy qi deficiency and toxic stasis accumulations after TACE treatment.

ObjectiveTo investigate the possible mechanism of electroacupuncture at "Neiguan" （PC6） and "Zhongwan" （RN12） in the treatment of functional dyspepsia （FD）. MethodsSPF male SD rats were randomly divided into model group， Neiguan （PC6） group， Zhongwan （RN12） group， and Neiguan-Zhongwan （PC6-RN12） group， with 8 rats in each group. Except for the normal group， the other groups of rats were cogavaged with 0.1% sucrose iodoacetamide solution combined with small platform standing training to establish FD rat models. After successful modeling， the rats in the normal group and model group were tied up for 30 min/d for 7 days； the Neiguan group， Zhongwan group， and Neiguan-Zhongwan group were treated with electroacupuncture intervention at "Neiguan" （PC6）， "Zhongwan" （RN12）， and "Neiguan" - "Zhongwan" （PC6-RN12） acupoints， respectively， using continuous wave， frequency of 2 Hz， current intensity of 1 mA， 30 min/d， and continuous intervention for 7 days. The general condition of rats in each group was observed. After treatment， the body weight and food intake of rats were measured， and the gastric emptying rate was calculated； HE staining was performed on the gastric antrum tissue of rats to observe the histopathologic changes； the expressions of calcitonin gene-related peptide （CGRP） and Ghrelin protein in gastric antrum were detected by Western Blot； the metabolites in gastric antrum tissues were detected by liquid chromatography-mass spectrometry （LC-MS）， and differential metabolites were screened by correlation analysis， then Metabo Analyst 5.0 and KEGG databases were used for metabolic pathway analysis. ResultsUnder light microscope， the gastric antrum structure was complete and the glands were abundant. No obvious inflammation and edema were found in gastric mucosa. Compared with the normal group， the body weight， food intake， and gastric emptie rate of rats in model group decreased， the expression of Ghrelin protein decreased and the expression of CGRP protein increased in gastric antrum tissue （P＜0.01）. Compared with model group， the body weight， food intake， and gastric emptance rate of rats in Neiguan group， Zhongwan group and Neiguan-Zhongwan group all increased， CGRP protein expression decreased in Neiguan group， and Ghrelin protein expression increased and CGRP protein expression decreased in Zhongwan group and Neiguan-Zhongwan group （P＜0.01 or P＜0.05）. Compared with Neiguan-Zhongwan group， Ghrelin protein expression decreased and CGRP protein expression increased in Neiguan group and Zhongwan group （P＜0.05 or P＜0.01）. Metabolomics results showed that compared with normal group， the content of metabolites adenosine diphosphate ribose， adenosine monophosphate and adenosine diphosphate in gastric antrum tissue of model group decreased； compared with model group， the contents of adenosine diphosphate， adenosine diphosphate and citicoline in Neiguan group increased， the contents of nicotine adenine dinucleotide， cytidine diphosphate ethanolamine and citicoline in Zhongwan group increased， and the contents of adenosine diphosphate， cytidine diphosphate and citicoline in Neiguan-Zhongwan group increased （P＜0.05 or P＜0.01）. Compared with model group， the main metabolic pathways of different metabolites in PC6-RN12 group were glycerophospholipid metabolism， taurine and hypotaurine metabolism， purine metabolism， starch and sucrose metabolism. ConclusionElectroacupuncture at “Neiguan” and “Zhongwan” acupoints can effectively regulate gastrointestinal motility and improve FD symptoms in FD rats， and the effect is better than that of "Neiguan" or "Zhongwan" acupoints alone. The mechanism may be related to the influence of related metabolites on energy metabolism， glucose metabolism and nucleotide metabolism， thereby regulating gastrointestinal motility hormones.

Objective:To explore the role of tripartite motif-containing protein 21(TRIM21)in chronic apical periodontitis(CAP)and its potential mechanism.Methods:Human CAP tissue and normal periodontal tissue were collected.The expression of inflamma-tory factors(IL-1 β,IL-6,TNF-a,TGF-β1),osteoclast related genes(TRAP,RANKL,CTSK),macrophage polarization related genes(CD86,iNOS,CD206,Arg1)and TRIM21 were detected by RT-qPCR.TRIM21 protein was detected by immunohistochemical staining,and the osteoclasts was detected by tartrate resistant acid phosphatase(TRAP)staining.The inflammation cell model was es-tablished by stimulating Raw264.7 cells with lipoteichoic acid(LTA)or lipopolysaccharide(LPS),and the expression of the above factors was detected.The bone marrow-derived macrophages(BMDMs)extracted from wild-type and TRIM21-/-mice stimulated by LPS were used to verify the expression of the above factors by RT-qPCR,the osteoclasts were detected by TRAP staining,and the po-larization of macrophages was detected by immunofluorescence staining.Results:In CAP tissue the expression of inflammatory factors,osteoclast related genes,CD86,iNOS and TRIM21 increased,while CD206 and Arg1 decreased,and osteoclasts were more than that in normal tissue.The stimulation of LTA/LPS promoted the proliferation of Raw264.7 cells,and the expression of these factors in cells was consistent with that in tissues.After LPS stimulation,BMDMs of TRIM21-/-mice had lighter inflammation,lower expression of os-teoclast specific genes,fewer osteoclasts and lower M1 polarization than those of wild type mice.Conclusion:TRIM21 might promote the progress of CAP by promoting M1 polarization of macrophages.

Objective:To investigate the risk factors for positive margins after endoscopic submucosal dissection (ESD) for early gastric cancer and precancerous lesions, and to follow up the recurrence.Methods:The endoscopic, clinical and pathological data of 489 patients with early gastric cancer or precancerous lesions treated by ESD in Fujian Provincial Hospital from January 2015 to December 2020 were retrospectively collected. They were categorized into a negative group (371 cases), a low-grade intraepithelial neoplasia (LGIN)-positive group (79 cases), and a high-grade intraepithelial neoplasia (HGIN) or cancer-positive group (39 cases) according to the different margins. Logistic regression was used to analyze the risk factors for positive margins, the Kaplan-Meier method and log-rank test to compare the risk of recurrence in different margin groups, and the Cox proportional risk regression model to explore the associated factors that caused recurrence in those with positive margins.Results:In the 489 patients, the positive resection margin rate was 24.1% (118/489), of which HGIN or cancer accounted for 33.1% (39/118). LGIN-positive margin was more likely to occur for lesions larger than 10 cm 2 ( OR=1.58, 95% CI: 1.13-2.08, P=0.033), in the presence of ulcers ( OR=2.92, 95% CI: 1.37-4.54, P=0.012) and for 1-2 years of ESD experience [ OR=1.69 (1-2 years VS 5-6 years), 95% CI: 1.51-1.94, P=0.026]. Those located in the upper 1/3 of the stomach [ OR=3.64 (upper 1/3 VS lower 1/3), 95% CI: 1.27-5.50 P=0.010] and submucosal infiltration (SM1 VS M1+M2: OR=2.37, 95% CI: 1.04-5.72, P=0.028; SM2 VS M1+M2: OR=6.08, 95% CI: 1.31-12.75, P=0.002) were high risk factors for HGIN/cancer-positive margin. Postoperative follow-up was completed in 337 patients, with a median follow-up time of 26.0 (22) months. The overall cumulative recurrence was 5.3% (18/337), 2.1% (5/239) in the negative margin group, 8.3% (6/72) in the LGIN-positive margin group, and 26.9% (7/26) in the HGIN/cancer-positive group, with statistically significant differences among the 3 groups ( P<0.05). Risk factors for recurrence in the positive margin group included positive basal margins ( HR=5.17, 95% CI: 1.47-14.09, P=0.011) and SM1 invasion ( HR=4.82, 95% CI: 1.38-14.77, P=0.013). Conclusion:Positive margins after ESD for early gastric cancer and precancerous lesions are related to lesion location, size, presence of ulceration, depth of infiltration, and endoscopists' experience. The overall risk of recurrence is higher in those with positive margins than in those with negative margins. Additional treatments need to be considered comprehensively for those with submucosal invasion and positive basal margins.

Objective: To explore the potential mechanism of acupuncture and moxibustion in treating Crohn disease (CD) by evaluating the changes in histamine and inflammatory factors in the skin tissue at Tianshu (ST25) of rats.Methods: Fifty-eight Sprague-Dawley rats were randomly divided into a normal group (n=14) and a CD-modeling group (n=44). Rats in the CD-modeling group received enema with 2,4,6-trinitrobenzene sulfonic acid plus ethanol to establish CD models. The enema was repeated once every 7 d for a total of 4 times. After modeling, four modeled rats and four normal rats were randomly selected for model identification. After the CD model was successfully established, the remaining rats in the CD-modeling group were randomly divided into a model group, an acupuncture group, a moxibustion group, and a Western medication group, with ten rats in each group. The rats in the acupuncture and moxibustion groups were treated with acupuncture or moxibustion at Tianshu (ST25) and Shangjuxu (ST37); the rats in the Western medication group were treated with mesalazine enteric-coated tablets by gavage for continuous 7 d. After the intervention, the colon tissue of rats in each group was collected. After gross observation, hematoxylin-eosin (HE) staining was performed to further observe the pathological changes. The expression of histamine in the skin tissue at Tianshu (ST25) was detected by enzyme-linked immunosorbent assay. The expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18, IL-10, and IL-6 in the skin tissue at Tianshu (ST25) was detected by Western blotting. Results: Compared with the normal group, the colonic wall of rats in the model group showed cobblestone-like changes, local ulcers, and polyps in dark red and thickening and hardening. HE staining showed local loss of mucosal epithelial layer and formation of slit-like ulcers, destruction of mucosal glands, edema, and infiltration of inflammatory cells in lamina propria and submucosa, and occasional formation of sarcoid-like granuloma. The levels of histamine and IL-6 were significantly up-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly down- regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the model group. Compared with the model group, the pathomorphological damage of the colon tissue of rats in the acupuncture group, moxibustion group, and Western medication group was significantly improved. The levels of histamine and IL-6 were significantly down- regulated (P<0.01, P<0.05), and the level of IL-10 was significantly up-regulated (P<0.01) in the skin at Tianshu (ST25) of rats in the acupuncture group. The levels of histamine and IL-6 were significantly down-regulated (P<0.01, P<0.05), and the levels of TNF-α, IL-18, and IL-10 were significantly up-regulated (P<0.01 or P<0.05) in the skin tissue at Tianshu (ST25) of rats in the moxibustion group. The level of histamine was significantly down-regulated (P<0.01), and the levels of IL-18 and IL-10 were significantly up-regulated (P<0.05, P<0.01) in the skin tissue of rats in the Western medication group. Compared with the acupuncture group, the level of IL-10 in the skin tissue at Tianshu (ST25) of rats in the moxibustion group was significantly up-regulated (P<0.01). Conclusion: The inflammatory responses in the skin tissue at Tianshu (ST25) may be the external manifestation of CD. Significant differences in the regulation of inflammatory responses in the skin tissue at Tianshu (ST25) between acupuncture and moxibustion exist, which may be caused by the differences in the stimulation characteristics between acupuncture and moxibustion.

Objective:To analyze genioglossus (GG) activation responses to the negative pressure of upper airway cavity during awake and different sleep stages in patients with different obstructive sleep apnea (OSA) graduation.Methods:This prospective cohort study started from August 2019 to January 2021, recruited 42 male OSA patients aged from 21 to 59 (38.77±8.42) years. After completing whole night polysomnography (PSG) and upper airway CT, each subject underwent drug-induced sleep with simultaneous monitoring of genioglossal electromyography (GGEMG) and pressure of epiglottis (P epi). Subjects were divided into three groups of mild OSA(7 males), moderate OSA(12 males), and severe OSA(23 males). The differences in upper airway CT measurements, parameters of GGEMG and P epi during awake and induced sleep were compared. Statistical analysis was conducted by SPSS 21.0. Results:There was no significant difference in the GGEMG parameters between the mild and moderate groups. In wakefulness, the peak phasic GGEMG of the severe group was higher than the mild group ( t=1.249, P=0.025), with no statistically difference in the corresponding P epi. In the sleep onset, the GGEMG parameters and P epi in severe group were higher than the other two groups. Linear regression analysis of the maximum GGEMG and maximum P epi at the end of obstructive apnea (OA) in all moderate plus severe patients ( n=35) was shown nonlinear correlation ( r=0.28, P=0.694). The airway length of the glossopharyngeal cavity was linearly correlated with the maximum P epi of OA ( r=0.468, R2=0.219, P=0.005). Conclusions:The individual difference of GG activation in OSA patients is related to the severity of the disease (frequency of respiratory events) and negative pressure stimulation. In moderate and severe OSA patients, GG activity is not in harmony with the corresponding negative pressure stimulation, which may be one of the mechanisms leading to the aggravation of OSA.

Objective:To investigate the clinical and genetic characteristics of patients with late-onset subtypes (adolescent or adult) of Krabbe disease.Methods:The clinical data of 7 patients with Krabbe disease admitted to Shanghai Jiao Tong University Affiliated Sixth People′s Hospital and Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from September 2006 to June 2021 were analyzed and Sanger sequencing of the galactosylceramidase (GALC) gene (NM_000153) and detection of the activity of GALC were conducted. A total of 61 cases of Krabbe disease reported in domestic literature were reviewed and summarized.Results:Among the 7 patients with Krabbe disease, there were 4 males and 3 females. All of them had lower limb weakness or walking difficulty as the initial symptoms, and presented as spastic paraplegia. The symptoms were relatively mild in patients with late onset. There were 4 out of 5 patients undergoing magnetic resonance imaging examination, who showed abnormal signals: 2 had brain atrophy and the remaining 2 had white matter lesions. A total of 5 GALC gene mutations were detected by genetic analysis. Among these, c.1901T>C (p.L634S), c.908C>T(p.S303F) and c.461C>A(p.P154H) are known variants, while c.50_51insTT (p.M17Ifs) and c.1130delT(p.L337X) are novel variants reported for the first time in this paper.Conclusions:Krabbe disease is a rare neurodegenerative disease with phenotypic heterogeneity, which is inherited in an autosomal recessive mode. The severity of clinical manifestations of Krabbe disease is correlated with the age of onset.

Objective:To understand the molecular epidemic characteristics and genes of human astrovirus (HAstV) in infantile diarrhea patients in Jilin province from 2017 to 2020.Methods:Fecal samples of hospitalized infants with diarrhea under 5 years of age from January 2017 to December 2020 were collected. The nucleic acids of fecal samples were amplified by reverse transcription-polymerase chain reaction (RT-PCR), the positive amplification products were sequenced, and the phylogenetic tree was constructed.Results:A total of 2 019 fecal samples were collected, of which 71 were positive for HAstV, with a positive rate of 3.5%. Among the cases with positive samples of HAstV, 42 had mixed infection with other viruses causing diarrhea, accounting for 59.2% of the total number of positive cases, half of which were mixed infection with rotavirus and HAstV. From 2017 to 2020, the positive rates of HAstV were 4.69%, 1.98%, 5.93% and 0.43% per year, respectively. There were two epidemic peaks every year and one epidemic peak year every two years. The positive rate of 36-47 months old was the highest, followed by 0-2 months old. A total of 55 sequences were obtained in this study. Phylogenetic tree analysis showed that they all belonged to classical HAstV, including 42 HAstV-1a subtypes, 8 HAstV-1b subtypes and 5 HAstV-5 subtypes.Conclusions:HAstV is one of the important pathogens of diarrhea in children under 5 years of age in Jilin province. The epidemic law has obvious seasonal and age differences. The dominant strain is HAstV-1a.

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.

Guided by the development of new medical science proposed by Ministry of Education and the "Education and Training Plan for Excellent Doctors 2.0", shifted from treatment-oriented to whole life-health cycle, we have explored curriculum ideological and political education in metabolic-related curriculum chain. Firstly, we constructed a core teaching team and had the training of curriculum ideological and political education. The top-level design was made with the integration of moral education into medical education. Secondly, the syllabus was comprehensively revised, containing the connotation of "morality education". The elements relevant to curriculum ideological and political education hidden behind professional courses were excavated. Finally, the mixed teaching mode of online combining with offline was carried out. Metabolism-related curriculum chain, focused on "metabolism, diabetes, obesity and patient education", formed a progressive link from basic medical science to practice to clinical, strengthening the "prevention, treatment and health care" based "one health" philosophy and giving full play to the implicit curriculum ideological and political education hidden behind professional courses. Our practice shows that the implementation of curriculum ideological and political education in metabolism-related curriculum has been accepted by students, and curriculum ideological and political education has been become part of professional courses. The "gene chimera" mode for curriculum ideological and political education incorporation into professional courses needs to be infiltrated imperceptibly, and the effect will be visualized in the future.