Objective: To explore the association between mediterranean diet (MD) patterns and dental caries among children and adolescents with neurodevelopmental disorders (NDD), so as to provide a basis for developing scientific anti caries strategies related to diet. Methods: From December 2021 to June 2024, a questionnaire survey, a three day 24 hour dietary review survey, oral health examination, physical development measurement and Childhood Autism Rating Scale (CARS) evaluation were conducted involving 147 children and adolescents aged 2-22 years with NDD from nine special education schools and rehabilitation institutions in Tianjin. Group comparisons were carried out using the Mann-Whitney U test, Chi-square test, or Fisher s exact probability method. The correlation between dietary quality and dental caries was analyzed by adopting multiple linear regression analysis and restricted cubic spline. Results: There were 46 children and adolescents (31.3%) in the non dental caries group and 101 children and adolescents (68.7%) in the dental caries group. The number of decayed missing and filled teeth (dmft) was 2.0 (4.0), and the MD score was 4.0 (2.0) points. There were 62 children and adolescents (42.2%) in the low MD scores group and 85 children and adolescents (57.8%) in the high MD scores group. There was no significant difference in MD scores between NDD children in the non dental caries group and those in the dental caries group [nondental caries group:4.0(2.0), dental caries group:4.0(2.0), Z= -0.14, P >0.05]. The MD scores and dmft exhibited increasing and then decreasing trend ( P total =0.02, P non lineary = 0.04 ). Children and adolescents with NDD in the MD high scores group had a lower number of dmft than those in the MD low scores group ( β= -2.00 , 95%CI =-3.39 to -0.62, P <0.05). However, in children and adolescents with NDD and CARS scores ≥30, the above association was insignificant ( β=-0.63, 95%CI=-0.29-0.15, P >0.05). Conclusion Children and adolescents with NDD who have dietary patterns similar to the Mediterranean diet, are found to have fewer dental caries, and this is observed among those with no or mild symptoms of autism spectrum disorder.

Objective Narcolepsy type 1 （NT1） is known to be associated with low levels of hypocretin-1 （Hcrt-1） in cerebrospinal fluid （CSF）. The standard method for Hcrt-1 measurement is radioimmunoassay （RIA） with imported reagents， but this antibody-dependent method is limited to radiation safety-certified lab， gradual radioactivity degradation， and slow turn-around time. The purpose of this study is to explore a non-radioactive， faster， and antibody independent domestic method in China for Hcrt-1 detection. Methods Repeated testing of cerebrospinal fluid from 14 clinically diagnosed NT1 patients and 10 non-narcolepsy patients was performed using liquid chromatography-tandem mass spectrometry （LC-MS/MS）technology，including the establishment and optimization of fundamental methodological procedures. The main steps involved the addition of non-radioactive isotope-labeled internal standards to the cerebrospinal fluid， followed by solid-phase extraction， mass spectrometry signal acquisition， and quantitative analysis. The results were then compared with the corresponding radioimmunoassay（RIA） findings. Results The LC-MS/MS method showed faster speed， and good linearity across a wider range of synthesized standard（5~2 500 pg/ml）， and good repeatability. Although this absolute-quantitation-based LC-MS/MS method and RIA method have different reading values in Hcrt-1 quantitation， they both can segregate NT1 group from non-NT1 group well. Conclusion Although larger cohorts are needed to set up a standard method in China，LC-MS/MS method is proved to be an easier， safer， faster， and possibly more accurate method for Hcrt-1 quantitation and detection for NT1 diagnosis.
Narcolepsy ; Radioimmunoassay

OBJECTIVE To investigate the types of neurons that influence the head twitch response(HTR)induced by 5-hydroxytryptaminergic(5-HTergic)psychedelic mescaline in mice.METHODS①Adult male C57BL/6J mice were randomly divided into the normal control group and mescaline(1.56,3.125,6.25,12.5,25 and 50 mg·kg-1)groups,with 15 mice in each group.The drugs of the corresponding groups were ip given,and the HTR frequency of mice was recorded for 30 min.② 5-HT 2A receptor(5-HT2AR)gene bilateral LoxP homozygous mice(5-HT2A flox/flox)were hybridized with calmodulin depen-dent protein kinaseⅡα cyclization recombination enzyme positive(CaMKⅡαcre/+),parvalbumin(PV)cre/+,somatostatin(SOM)cre/+or vasoactive intestinal peptide(VIP)cre/+mice to obtain 5-HT2A R conditional knockout(cKO)mice(5-HT2AΔCaMKⅡα,5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP).Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 15 mice in each group.The drugs of the corresponding groups were ip given before the HTR frequency of mice within 30 min was recorded.③ Each type of cKO mice was randomly divided into the normal control group and mescaline 12.5 mg·kg-1 group,with 12 mice in each group.After receiving the corresponding drug via ip,they were placed in a spontaneous activity test box for 30 minutes and their activity levels were recorded.RESULTS ① Compared with the normal control group,mescaline 3.125,6.25,12.5 and 25 mg·kg-1 significantly increased the HTRs of mice(P<0.05,P<0.01).② Among the different neuronal types of 5-HT2AR cKO mice,only 5-HT2A ΔCaMKⅡα mice had no difference in HTR frequency between the normal control group and the mescaline 12.5 mg·kg-1 group.In 5-HT2AΔPV,5-HT2AΔSOM and 5-HT2AΔVIP mice,the HTRs of mice in the mescaline 12.5 mg·kg-1 group were significantly increased(P<0.01)compared with the normal control group.③ There was no difference in spontaneous activity between the normal control group and the mescaline 12.5 mg·kg-1 group of all cKO mice.CONCLU-SION Pyramidal neurons are involved in mediating the induction of mescaline on HTRs in mice.

Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.

Objective To investigate the expression level of serum ubiquitin-conjugating enzyme 2C(UBE2C)and tripartite motif-containing protein 27(TRIM27)in patients with endometrial cancer(EC)and their correlation with pathological parameters.Methods A total of 96 EC patients from March 2020 to March 2023 were selected as EC group;65 patients with endometrial atypical hyperplasia(EAH)as EAH group,and 80 healthy subjects as the control group.Enzyme linked immunosorbent assay was applied to analyze the expression level of serum UBE2C and TRIM27.The relationship between serum UBE2C,TRIM27,and pathological data was analyzed;receiver operating characteristic was applied to evaluate the predictive value of serum UBE2C and TRIM27 level for EC.Results The level of serum UBE2C and TRIM27 of EC patients was obviously higher than that in healthy subjects(P<0.05),and was correlated with tumor diameter,tumor differentiation,lymph node metastasis,FIGO stage,muscle layer invasion depth,cervical involvement,estrogen receptor expression,and progestogen receptor expression(P<0.05).There was positive correlation between serum UBE2C and TRIM27(r=0.475,P<0.001);and the level of serum UBE2C and TRIM27 was positively correlated with tumor diameter,lymph node metastasis,FIGO stage,and depth of musclular invasion,but negatively with tumor differentiation,estrogen receptor expression,and progestogen receptor expression(P<0.05).The combination of UBE2C and TRIM27 had obviously higher AUC in evaluating EC than single detection(ZUBE2C-combination=3.406,P<0.001,ZTRIM27-combination=3.285,P=0.001).Conclusion The expression level of UBE2C and TRIM27 in serum of EC patients is up-regulated,which is closely related to pathological parameters.The level of serum UBE2C and TRIM27 can provide reference for early diagnosis of EC.

Bile reflux gastritis is a common and frequently occurring disease of the digestive system,and the pathology is diverse.Professor Zhou Xinyou emphasized that the disease primarily affects the gallbladder,liver and stomach,advocating for a comprehensive differentiation of its etiology and pathogenesis across three distinct stages.In the early stage,the gallbladder is dysfunctional,which then affects the stomach;In the intermediate stage,there is congestion in the liver and gallbladder,leading to excessive wood element suppressing the earth element;in the late stage,gastric collaterals damage,with qi deficiency and blood stasis.Professor Zhou Xinyou follows the diagnosis and treatment ideas of"multiple compound methods,comprehensive application,and overall adjustment".For typical clinical symptoms,he has formulated the treatment principles and treatment methods of pain separation,general use,oral bitterness and upset,purging heat and stomach,treating gallbladder and stomach,regulating qi and resolving depression,so as to achieve both symptoms and root causes of treatment,gallbladder and stomach regulation.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.

Objective: To analyze the status of childhood bullying bystander s behaviors among pupils and the correlation with family function,so as to provide empirical support for educational intervention in campus bullying. Methods: A questionnaire survey using the cluster random sampling method was administered to 1 145 pupils from a primary school in Wushan County within Chongqing City in November 2019, including Pupil Bullying Bystander Behavior Scale and Family Adaptability and Cohesion Evaluation Scale(FACES). The χ 2 test, Spearman related analysis and binary Logistic regression were used to determine the detection rate of different bullying bystander behaviors among pupils and the association with family function. Results: The proportion of bullying promoters, bullying protectors, and bystanders were 4.7%, 92.1%, and 42.1%, respectively. There were statistically significant differences in the three types of bullying bystander s behaviors among the different grades pupils( χ 2=21.45, 7.98, 27.48, P < 0.05 ). There were significant correlation between family function and its dimensions with different types of bullying bystander behavior ( | r |= 0.07-0.20, P <0.05). Binary Logistic regression analysis showed that pupils family function and grade had statistically significant impact on promoting bullying behavior, protecting victim behavior, and bystander behavior ( OR =0.98, 3.33; 1.02, 1.95 ; 0.99, 0.58, 0.41, 0.61, P <0.05). Conclusions The bullying bystanders behaviors of pupils are related to grade in school and family function. Schools should implement educational interventions for pupils of different grades and focus on improving pupils family function to effectively promote the occurrence of positive bystanders behaviors in pupils.

ObjectiveTo systematically review the studies about Yiqing Capsules in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat-toxin syndrome and clarify the advantages and therapeutic characteristics of Yiqing capsules， thus providing reference for the decision-making by relevant departments and clues for the clinical and basic research. MethodThe multi-criteria decision analysis （MCDA） model and CSC v2.0 were employed to comprehensively evaluate Yiqing capsules from multiple aspects. ResultThe serious adverse reactions in the spontaneous reporting system （SRS） monitoring data of Yiqing capsules included pruritus， rash， an ddiarrhea， all of which were relieved or cured， without aggravation or interhospital transfer for treatment. Literature data showed that the main clinical adverse reactions were abdominal pain， diarrhea， etc. Both acute toxicity and long-term toxicity tests showed good safety， and thus the safety of Yiqing capsules was rated as grade B. The results of Meta-analysis showed that Yiqing capsules used alone or in combination with other medicines outperformed Niuhuang Jiedu capsules or Western medicine in the treatment of pharyngitis， tonsillitis， gingivitis， and oral ulcers with heat toxin in terms of symptom alleviation， disappearance rate of main symptoms， and recurrence rate of aphtha. Pharmacological and pharmacodynamic studies showed that Yiqing capsules had antimicrobial， antiviral， and anti-inflammatory effects， with the effectiveness rated as grade B. The decision tree model was adopted to analyze the incremental cost-effectiveness ratio. With the threshold of 1 fold per capita GDP and the disappearing rate of pain in gingivitis as the indicator， Yiqing capsules had an economic advantage in the treatment of gingivitis due to heat-toxin compared with Niuhuang Jiedu capsules， and the incremental cost-effectiveness ratio was 0.39 yuan/%， which indicated acceptable cost， with the economy rated as grade B. Yiqing capsules can not only clear heat from Qi aspect but also purge blood fire， serving as the representative prescription of clearing and purging for heat-toxin syndrome. Considering the industrial service system and enterprise innovation， the comprehensive innovation of Yiqing capsules was rated as grade B. Generally， this product does not require personalized treatment plans and features convenient supply， storage， transportation， policy publicity， drug information standards， and easy operation for medical care and patients. The Chinese patent medicine information was complete and in line with national standards， and thus the suitability of Yiqing capsules was rated as grade A. With a low price and good availability and affordability， the accessibility of Yiqing capsules was rated as grade A. The Yiqing capsules prescription， Sanhuang Xiexin decoction， originated from ancient medical books， with rich real-world studies， and thus the traditional Chinese medicine characteristics of Yiqing capsules was rated as grade C. ConclusionThe clinical value of Yiqing capsules was rated as grade B from the "6+1" dimensions， suggesting that it could be conditionally converted into the relevant policy results of basic clinical drug management according to the procedure.

Objective To observe the effects of Gegen Qinlian Decoction on pancreatic endoplasmic reticulum stress in mice with type 2 diabetes mellitus(T2DM);To explore its mechanism of action in the treatment of T2DM.Methods Totally 75 SPF male db/db mice were randomly divided into model group,metformin group,and Gegen Qinlian Decoction high-,medium-,low-dosage groups,with 15 mice in each group.15 db/m mice were set as the blank group.The administration groups received corresponding medicine for gavage for 12 weeks.Body mass,fasting blood glucose(FBG)and glycated hemoglobin(HbA1c)in mice were detected,HE staining was used to observe the pathological changes of pancreatic tissue,the apoptosis of islet cells was determined by TUNEL staining,Western blot was used to detect pancreatic tissue glucose regulatory protein 78(GRP78),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,activated transcription factor 4(ATF4)and C/EBP homologous protein(CHOP)protein expression,RT-PCR was used to detect pancreatic tissue PERK,ATF4,CHOP mRNA expressions.Results Compared with the blank group,the body mass,FBG and HbA1c contents in the model group significantly increased(P<0.01);the pancreatic tissue structure was incomplete,with blurry boundaries and vacuoles inside,leading to a significant increase in pancreatic islet cells apoptosis(P<0.01);the expressions of GRP78,p-PERK,ATF4,and CHOP proteins in pancreatic tissue significantly increased(P<0.01),and the mRNA expressions of PERK,ATF4 and CHOP significantly increased(P<0.01).Compared with the model group,the body mass,FBG and HbA1c contents of mice in each administration group significantly decreased(P<0.05,P<0.01);pathological changes in pancreatic tissue was reduced,and islet cells apoptosis decreased to varying degrees(P<0.05,P<0.01);the expressions of GRP78,p-PERK,ATF4 and CHOP proteins in pancreatic tissue significantly decreased(P<0.01)in Gegen Qinlian Decoction high-and medium-dosage groups and the metformin group,and the expressions of PERK,ATF4 and CHOP mRNA significantly decreased(P<0.05,P<0.01).Conclusion Gegen Qinlian Decoction may decreased pancreatic islet cells apoptosis,protect pancreatic cell function,and delay the progression of T2DM by inhibiting the endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway,and down-regulating the expressions of related genes and proteins.