AIM:To investigate the anti-fibrotic effect of Panax notoginseng saponins(PNS)in arecoline(ANE)-induced oral submucous fibrosis,and to analyze the effect of PNS on nuclear factor E2-related factor 2(Nrf2)/glu-tamate-cysteine ligase catalytic subunit(GCLC)signaling pathway.METHODS:CCK-8 assay was used to evaluate the effects of different concentrations of PNS and arecoline on the survival rate of human immortalized keratinocyte cell line Ha-CaT.The results of CCK-8 were used to select 75 mg/L arecoline,and 25,50 and 100 mg/L PNS as subsequent experi-mental concentrations.The cells were set as blank control group,model group,and low,medium and high doses(25,50 and 100 mg/L)of PNS groups.The protein and mRNA expressions of collagen type I(COL-I),E-cadherin,Nrf2,GCLC and glutathione reductase(GR)in each group were detected by Western blot and RT-qPCR.Immunofluorescence method was used to detect the entry of Nrf2 into the nucleus.Biochemical kits were used to detect the content of glutathione(GSH),nicotinamide adenine dinucleotide phosphate(NADPH)and malondialdehyde(MDA),and superoxide dis-mutase(SOD)activity in each group of cells.DCFH-DA fluorescent probe was used to detect the content of intracellular reactive oxygen species(ROS).RESULTS:Compared with the blank control group,the protein and mRNA expression of COL-I in the model group was up-regulated,and the protein and mRNA levels of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were down-regulated.The content of NADPH,MDA and ROS in the cells increased,and the content of GSH and the activity of SOD was significantly reduced.Compared with the model group,the protein and mRNA expression of COL-I was down-regulated,and the protein and mRNA expression of E-cadherin,Nrf2,GCLC,nuclear Nrf2 and GR were up-regulated in PNS 50 and 100 mg/L groups.Compared with the model group,the content of NADPH,MDA and ROS in cells decreased,and the content of GSH and the activity of SOD was significantly enhanced(P<0.05 or P<0.01).CON-CLUSION:Panax notoginseng saponins have anti-fibrosis effects in HaCaT cells,and their mechanism may be related to the activation of Nrf2/GCLC signaling pathway,thereby resisting oxidative stress and improving oral submucosal fibrosis.

Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.

Early childhood caries (ECC) is a significant chronic disease of childhood and a rising public health burden worldwide. ECC may cause a higher risk of new caries lesions in both primary and permanent dentition, affecting lifelong oral health. The occurrence of ECC has been closely related to the core microbiome change in the oral cavity, which may be influenced by diet habits, oral health management, fluoride use, and dental manipulations. So, it is essential to improve parental oral health and awareness of health care, to establish a dental home at the early stage of childhood, and make an individualized caries management plan. Dental interventions according to the minimally invasive concept should be carried out to treat dental caries. This expert consensus mainly discusses the etiology of ECC, caries-risk assessment of children, prevention and treatment plan of ECC, aiming to achieve lifelong oral health.
Child ; Child, Preschool ; Consensus ; Dental Caries/prevention & control* ; Dental Caries Susceptibility ; Humans ; Oral Health

Objective:To study the optimal timing of laparoscopic cholecystectomy (LC) after percutaneous transhepatic gallbladder drainage (PTGBD) for grade Ⅱ-Ⅲ acute cholecystitis.Methods:A multicenter, single blind and randomized controlled study was conducted at Shanghai Fifth People's Hospital Affiliated to Fudan University, Shanghai Pudong Hospital, and Shanghai Minhang District Central Hospital from October 2018 to September 2021. Patients who underwent LC after PTGBD were divided 1∶1 into the early group and the late group. LC was performed 4-6 weeks after PTGBD in the early group and 7-8 weeks after PTGBD in the late group. Gender, age, AC grade, complications after PTGBD, body mass index, complications before LC, operation time of LC, intraoperative bleeding, total treatment cost, conversion rate to open surgery and complications after LC were compared between the two groups. The 36-Item Short Form Health Survey (SF-36) before and after LC was also compared.Results:Of 248 patients who were eligible for the study, there were 52 males and 196 females, with ages ranging from 18 to 89 years, and mean ±s.d. of (52.5 ± 20.2) years. There were 126 patients in the early group and 122 patients in the late group. There were no significant differences in gender, age, AC grade, body mass index and complications before LC between the two groups (all P>0.05). The preoperative score of SF-36 in the early group was significantly better than that in late group, and the complications of PTGBD in the late group were significantly higher than the early group (both P<0.05). The operation time and total treatment cost of the early group were significantly less than those of the late group (37.2±12.8 min vs. 48.5±19.7 min, 20 856±2 136 yuan vs. 2 2207±2 049 yuan) (both P<0.05). The intraoperative bleeding volume of LC in the early group was [ M( Q1, Q3)] 40 (40, 60) ml and the late group was [ M( Q1, Q3)] 35 (25, 40) ml. The difference was also significant ( P<0.05). There was no significant differences in the conversion rates to open surgery, complications and SF-36 scores after LC between the two groups (all P>0.05). Conclusion:LC should be performed 4-6 weeks after PTGBD for grade Ⅱ-Ⅲ acute cholecystitis. Although the amount of intraoperative bleeding was higher, the operation time was shorter, the burden on patients was reduced and there was more rapid recovery.

Objective:To establish and evaluate a nomogram for long-term survival of patients with intrahepatic cholangiocarcinoma (ICC) after radical resection.Methods:The data of ICC patients who underwent radical resection for the first time at Zhongshan Hospital, Fudan University from January 2014 to December 2017 were retrospectively analyzed. Of 167 patients who were enrolled, there were 104 males and 63 females, with the age of (60.3±10.9) years. Tumor tissues were collected for immunohistochemical staining and interpretation. Univariate Cox regression, LASSO regression and multivariate Cox regression were used to analyze influencing factors of postoperative long-term survival after ICC. R software was used to construct a nomogram in predicting ICC prognosis.Results:Cox regression analysis showed that TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression to be independent risk factors associated with poor long-term survival after radical resection. The prognostic nomogram model of ICC was constructed based on these factors. The C-index was 0.821. The nomogram model consistency index had a high degree of prognostic differentiation. The 45° diagonal of the 3-year postoperative calibration curve which represented the actual survival fitted well with the segmented line which represented the predicted survival of the nomogram. The area under the receiver operating characteristic curve of the nomogram model was higher than that of AJCC TNM staging (0.894 vs. 0.803, z=4.10, P<0.001). The nomogram model was more effective in predicting postoperative survival of ICC patients than the TNM staging. Conclusion:TNM staging, poorly differentiated tumor, positive resection margin, positive mucin 5 expression and abnormal P53 expression were independent risk factors for postoperative survival of ICC. The nomogram model could better evaluate long-term prognosis of ICC patients after radical resection than the traditional TNM staging system.

In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 ac-tivities in human blood and kidney should be considered. In summary, a selective and sensitive biolu-minescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.

Objective:To compare the caries experience and the kinds of dental treatment between children with autism spectrum disorders (ASD) and children without systemic disease who were all treated under general anesthesia.Methods:Totally 103 children with ASD who received dental treatments under general anesthesia in 13 professional dental hospitals around China from April to November 2016 were included in the present study. A group of 97 children without systemic disease, according to the age, gender and application propensity score matching method, were chosen as controls, who received dental treatments under general anesthesia between January 2015 to November 2018 in the same hospitals as the children with ASD. Decay missing filling tooth (DMFT/dmft, DMFT for permanent teeth and dmft for primary teeth) indices of two groups of children and the contents of the dental treatments under general anesthesia were analyzed.Results:No significant difference of DMFT/dmft index ［ M( Q25, Q75)］ was found between children with ASD group ［0 (0, 3)/11(8, 14)］ and control group ［0 (0, 3)/9(7, 13)］ ( P>0.05). The average number of dental treatments under general anesthesia and the average number of endodontic treatment in children with ASD were 13 (11, 15) and 3 (2, 6) teeth respectively, while those in the control group were 12 (9, 14) and 2 (1, 4) teeth respectively, the differences were statistically significant ( P<0.01, P<0.05). Conclusions:No significant difference was found between children with ASD and the normal controls who receive dental treatments under general anesthesia in DMFT/dmft index, but the treatment needs of children with ASD is relatively higher, and their tooth decay is relatively severer.

Objective: To investigate the diagnostic value of some antibodies in peritoneal fluid of patients with gastric cancer and malignant epithelioid mesothelioma in serous effusion. Methods: One hundred and eighty-two cases of serous effusion were collected at Jilin Cancer Hospital, from July 2012 to July 2016. The expression of GLUT1, CDX2, Villin, calretinin and WT1 was evaluated using SP immunocytochemical technique in peritoneal fluid samples collected from 98 patients with gastric cancer and 74 patients with reactive mesothelial cells. The expression of GLUT1, calretinin and WT1 was also evaluated in serous effusion from 10 patients with mesothelioma. Results: The sensitivity of GLUT1, CDX2 and Villin in adenocarcinoma cells was 91.8%(90/98), 68.4% (67/98) and 88.8%(87/98), respectively. The specificity was 95.9% (71/74), 100.0%(74/74) and 100.0% (74/74), respectively. The sensitivity of calretinin and WT1 for reactive mesothelium was 93.2% (69/74) and 79.7% (59/74), respectively. The specificity was 96.9% (95/98) and 100.0% (98/98), respectively. The sensitivity of GLUT1, calretinin and WT1 for mesothelioma was 9/10, 9/10 and 7/10. The reactivity of GLUT1, CDX2, Villin, calretinin and WT1 showed a significant difference (P<0.01) between adenocarcinoma cells and reactive mesothelium. The reactivity of GLUT1 showed a significant difference (P<0.01) between mesothelioma and reactive mesothelium. Conclusions The optimal combination is a panel of GLUT1, CDX2, Villin, calretinin and WT1 for differential diagnosis between adenocarcinoma cells and reactive mesothelium in peritoneal fluid of patients with gastric cancer. Whereas GLUT1, calretinin and WT1 is the best for differential diagnosis between reactive mesothelium and mesothelioma in serous effusions.

Objective To evaluate the role of Toll-like receptor 4 (TLR4) in mechanical ventilation-induced activation of microglias in the hippocampi of mice.Methods Forty-two healthy male TLR4 gene knocked out C57BL/10ScNJNju mice and 42 wild type C57BL/6 mice,aged 10-12 weeks,weighing 20-25 g,were used in the study.The mice of either group were divided into 2 subgroups (n =21 each) using a random number table:spontaneous breathing subgroup (subgroup SB) and mechanical ventilation subgroup (subgroup MV).In subgroup SB,the mice were exposed to isoflurane for 6 h in an anesthesia chamber.After tracheal intubation,the mice were mechanically ventilated for 6 h when anesthesia was maintained with isoflurane in subgroup MV.Twelve mice were selected from each subgroup at 1 and 3 days after ventilation,fear conditioning test was performed to assess the cognitive function,and the rate of freezing time was recorded.Three mice in each subgroup were sacrificed at 1 day after ventilation,and the brains were removed to observe the morphological changes of microglias (by double immunofluorescent staining) and to count CD11b positive cells and co-expression of TLR4 with CD11b (TLR4/CD11b) positive cells in hippocampal microglias.Six mice in each subgroup were sacrificed at 1 day after ventilation,and the hippocampi were isolated for determination of the content of tumor necrosis factor-alpha (TNF-α) in hippocampal tissues by enzyme-linked immunosorbent assay.Results Compared with subgroup SB of wild type group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and TLR4/CD1 1b positive cells were increased,and the content of TNF-α was increased in subgroup MV of wild type group (P＜0.05),and the number of CD1 1b positive cells and content of TNF-α were significantly increased in subgroup MV of geue knockout group (P＜0.05).Compared with subgroup SB of gene knockout group,the rate of freezing time was significantly decreased at 1 and 3 days after ventilation,and the number of CD1 1b positive cells and content of TNF-α were increased in subgroup MV of gene knockout group (P＜0.05).Compared with subgroup MV of wild type group,the rate of freezing time was significantly increased at 1 and 3 days after ventilation,and the number of CD11b positive cells and content of TNF-α were decreased in subgroup MV of gene knockout group (P＜0.05).Conclusion The mechanism by which mechanical ventilation induces activation of microglias in hippocampi is partially related to TLR4 in mice.

Objective: To evaluate the reliability and validity of warning signs checklist developed by the National Health and Family Planning Commission of the People′s Republic of China (NHFPC), so as to determine the screening effectiveness of warning signs on developmental problems of early childhood. Method: Stratified random sampling method was used to assess the reliability and validity of checklist of warning sign and 2 110 children 0 to 6 years of age(1 513 low-risk subjects and 597 high-risk subjects) were recruited from 11 provinces of China. The reliability evaluation for the warning signs included the test-retest reliability and interrater reliability. With the use of Age and Stage Questionnaire (ASQ) and Gesell Development Diagnosis Scale (GESELL) as the criterion scales, criterion validity was assessed by determining the correlation and consistency between the screening results of warning signs and the criterion scales. Result: In terms of the warning signs, the screening positive rates at different ages ranged from 10.8%(21/141) to 26.2%(51/137). The median (interquartile) testing time for each subject was 1(0.6) minute. Both the test-retest reliability and interrater reliability of warning signs reached 0.7 or above, indicating that the stability was good. In terms of validity assessment, there was remarkable consistency between ASQ and warning signs, with the Kappa value of 0.63. With the use of GESELL as criterion, it was determined that the sensitivity of warning signs in children with suspected developmental delay was 82.2%, and the specificity was 77.7%. The overall Youden index was 0.6. Conclusion The reliability and validity of warning signs checklist for screening early childhood developmental problems have met the basic requirements of psychological screening scales, with the characteristics of short testing time and easy operation. Thus, this warning signs checklist can be used for screening psychological and behavioral problems of early childhood, especially in community settings.