Colorectal inflammatory cancer transformation poses a major risk to patients with colitis. Patients with chronic intestinal inflammation have an approximately 2-3 folds increased risk of developing colorectal cancer (CRC). Unfortunately, there is currently no effective intervention available. Huangqin decoction (HQD), a well-known traditional Chinese medicine (TCM) formula, is frequently clinically prescribed for treating patients with colitis, and its active ingredients have effective antitumour efficacy. Nonetheless, the mechanism of HQD-mediated prevention of colorectal inflammatory cancer transformation remains unclear. A strategy integrating metagenomic, lipidomic, and messenger RNA (mRNA) sequencing analysis was used to investigate the regulatory effects of HQD on the gut microbiome, metabolism and potential mechanisms involved in colorectal inflammatory cancer transformation. Our study revealed that HQD suppressed colorectal inflammatory cancer transformation, which was associated with enhanced intestinal barrier function, decreased the inflammatory response, and regulation of the gut microbiome. Notably, cohousing experiments revealed that the transfer of the gut microbiome from HQD-treated mice largely inhibited the pathological transformation of colitis. Moreover, gut microbiome transfer from HQD-treated mice primarily resulted in the altered regulation of fatty acid metabolism, especially the remodeling of arachidonic acid metabolism, which was associated with the amelioration of pathological transformation. Arachidonic acid metabolism and the key metabolic enzyme arachidonic acid 12-lipoxygenase (ALOX12) were affected by HQD treatment, and no obvious protective effect of HQD was observed in Alox 12 ^-/- mice, which revealed that ALOX12 was a critical mediator of HQD protection against colorectal inflammatory cancer transformation. In summary, multiple omics analyses were applied to produce valuable data and theoretical support for the application of HQD as a promising intervention for the transformation of inflammatory CRC.

Noncarious lesions,a multifactorial condition encompassing tooth attrition,abrasion,and erosion,have a surge in prevalence and required increased attention in clinical practice.These nonbacterial-associated tooth de-fects can compromise aesthetics,phonetics,and mastica-tory functions.When providing full-arch fixed occlusal rehabilitation for such cases,the treatment strategy should extend beyond by restoring dentition morphology and aesthetics.This report details a complex case of erosive dental wear addressed through a fully digital,full-arch fixed occlusal rehabilitation.A 4D virtual patient was created using multiple digital data sources,including intraoral scanning,3D facial scanning,digital facebow registration,and mandibular movement tracing.With a comprehensive understanding of the masticatory system,various types of microinvasive prostheses were customized for each tooth,including labial ve-neers,buccal-occlusal veneers,occlusal veneers,overlays,inlays,and full crowns,were customized for each tooth.The reported digital workflow offered a predictable diagnostic and treatment strategy,which was facilitated by virtual visual-ization and comprehensive quality control throughout the process.

Objective: To explore the association between processed food consumption and anxiety symptoms among college students in Yunnan Province, so as to provide a reference for the prevention and treatment of anxiety symptoms in this population. Methods: A cluster random sample of 2 515 first year students from two universities in Yunnan Province was selected to carry out a longitudinal investigation which included a baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The food frequency questionnaire was administered to assess processed food consumption, and the Depression Anxiety Stress Scale-21 (DASS-21, Chinese version) was used to evaluate anxiety symptoms. A generalized estimation equation model was used to analyze the relationship between processed food consumption and anxiety symptoms. Results: The detection rates of T1-T4 anxiety symptoms among college students in Yunnan Province were 29.70%, 36.70%, 37.69% and 38.73 %, respectively, and the corresponding anxiety symptom scores were 4(0,8), 4(0,10), 4(0,12), 2(0,14). After controlling for demographic variables and confounding factors in the generalized estimation equation model, a statistically significant association was found between consumption of carbonated beverages ( β=0.06, 95%CI =0.03-0.08), and other processed snacks ( β= 0.04 , 95%CI =0.01-0.07) ( P <0.05). The stratified analysis by gender showed that the consumption of carbonated beverages ( β=0.08, 95%CI =0.05-0.12) and fast food ( β=0.03, 95%CI =0.00-0.06) was significantly associated with anxiety symptoms in female college students ( P <0.05). There was no significant association between processed food consumption and anxiety symptoms in male college students ( P >0.05). Conclusions Processed food consumption by college students in Yunnan Province may increase the risk of anxiety symptoms, particularly among female students. There is a need to strengthen guidance in respect to processed food consumption, so as to prevent and treat anxiety symptoms.

Objective:To analyze the clinical characteristics of hemodialysis patients with corona virus disease 2019(COVID-19)in a single-center from Beijing.Methods:Patients with COVID-19 who re-ceived regular hemodialysis at Peking University Third Hospital from November 30,2022 to January 4,2023 were selected as the study objects.Clinical symptoms,severity and duration of symptoms during the period of virus positive were investigated in the form of questionnaires,and the basic information of the patients,as well as the results of blood tests(routine blood and blood biochemistry,etc.)before and af-ter infection,dialysis treatment and the outcome of the disease were collected by consulting medical re-cords.Results:A total of 203 subjects were included in this study,including 148 mild cases(72.91％),23 medium cases(11.33％),32 severe and critical cases(15.76％),and 16(7.88％)deaths occured during the follow-up.Clinical symptoms mainly included respiratory symptoms(among which 81.77％had cough,68.97％had expectoration),fever(81.28％)and fatigue(65.52％),and fatigue and weakness had the longest duration[9(5,15)days]among all symptoms.Twenty-six patients(12.8％)reduced the dialysis sessions[1(1,2)times],25 patients(12.32％)had the behavior of early finishing dialysis(27 times),reducing the dialysis time by 30.0(20.0,30.5)minutes.Univa-riate analysis showed that the hemoglobin,creatinine,urea nitrogen and ultrafiltration decreased signi-ficantly after infection(P＜0.05).There were significant differences in age,albumin,hemoglobin,creatinine levels and vascular access types among the patients with different clinical subtypes,and the changes of dialysis sessions,fever,expectoration and fatigue degree were also different among the patients with different clinical subtypes(P＜0.05).Multivariate Logistic regression analysis showed that age(OR=1.051,95％CI:1.017-1.086,P=0.003)and albumin levels(OR=0.905,95％CI:0.803-1.019,P=0.098)corrected by fever,expectoration and fatigue levels were still associated with the oc-currence of pneumonia.Conclusion:The morbidity of pneumonia and the proportion of deaths in hemo-dialysis patients with COVID-19 were higher,and some clinical symptoms lasted for a longer time than the general population.During the infection period,the incidence of dialysis-related complications in-creased,hemoglobin and nutritional status decreased.Elderly patients and patients with low albumin level had a higher risk of developing pneumonia after infection.

Objective To investigate the role of homologous genes absent from the wings of drosophila melanogaster(Notch)signaling pathway in the imbalance of helper T cells 1(Th1)and helper T cells 2(Th2)and the intervention mechanism of Qizhi Zhoufei Granule in chronic obstructive pulmonary disease(COPD).Methods Ten of seventy Wistar rats were selected as the blank control group,and the other rats were established by cigarette smoking combined(CS)with tracheal infusion of lipopolysaccharide(LPS).The COPD model was established by randomly selecting 3 rats in the control group and the model group to verify the success of the model.At the end of modeling,gavage administration was performed.The rats in the model group were randomly divided into model control group,positive control group(67.5 μg·kg-1)and Qizhi Zhoufei Granule high,medium and low treatment group(3.24,1.62,0.81 g·kg-1).Each group was treated with normal saline,dexamethasone acetate suspension and Qizhi Zhoufei Granule suspension at high,medium and low doses.The rats in the blank control group were given the same volume of normal saline as the model control group.After modeling with 28 days and treatment with 28 days,peak inspiratory flow(PIF)and peak expiratory flow(PEF)were detected by the animal lung function test system.Rats were killed to extract lungs,spleen,serum and bronchoalveolar lavage fluid(BALF),hematoxylin-eosin(HE)staining was used to evaluate the pathological changes of lung tissues.The level of tumor necrosis factor-α(TNF-α)in serum and BALF was determined by enzyme-linked immunosorbent assay(ELISA).Flow cytometry was used to detect Th1/Th2 cells in spleen.Immunohistochemistry(IHC)and western blot were used to detect Notch1,Hes1 and Hey1 protein levels in lung tissues.Real-time fluorescence quantitative polymerase chain reaction(Real-Time PCR)was used to detect Notch1,Hes1 and Hey1 gene expression levels in lung tissues.Result Compared with the blank control group,the lung function of the model control group was significantly decreased(P<0.05),inflammatory cell infiltration and bronchial structure destruction occurred in the lung tissue,TNF-α content in serum and BALF increased significantly(P<0.05),the percentage of spleen Th1 cells was significantly decreased(P<0.05),and the percentage of Th2 cells was significantly increased(P<0.05),the protein and mRNA expressions of Notch1,Hes1 and Hey1 in lung tissues were significantly increased(P<0.05),the differences were statistically significant;Compared with the model control group,the lung function of rats in each administration group was significantly increased(P<0.05),the pathological injury of lung tissue was alleviated,TNF-α content in serum and BALF decreased significantly(P<0.05),the percentage of spleen Th1 cells was significantly increased(P<0.05),the percentage of Th2 cells was significantly decreased(P<0.05),the lung tissue of Notch1,Hes1,Hey1 protein and mRNA expression were significantly decreased(P<0.05),the differences were statistically significant.Conclusion Qizhi Zhoufei Granule regulate Th1/Th2 balance by inhibiting Notch signaling pathway,thereby improving pulmonary function and pathological injury,and affecting immune function in COPD rats.

OBJECTIVE To explore the distribution of airborne pollen in Cangzhou,to analyze the correlation between pollen characteristics,meteorological factors and the rate of allergic rhinitis visits,and to provide a reference basis for the precise prevention and treatment of allergic rhinitis in Cangzhou.METHODS The gravity deposition method was applied to collect daily airborne pollen from the monitoring sites in Cangzhou from March to October 2022 and record the pollen species and quantities.We also collected information on allergic rhinitis patients who visited the ENT Department of Cangzhou Central Hospital during the same period and meteorological data(daily maximum temperature,minimum temperature,maximum relative humidity,maximum precipitation,and maximum wind speed at ground level)during the same period,and analyzed the relationship between the number of AR patients'visits,the amount of pollen,and the meteorological factors.RESULTS 1.A total of 229 pollen exposures were collected from March to October 2022,totaling 19 368 pollen grains,of which 18 750 grains of pollen could be identified in 19 families and 618 grains were difficult to identify the families.2.There were two peaks of pollen during the period,in April and September respectively.Spring pollen to tree-based category,to the pine family,willow willow family,Xylariaceae(ash)most often;summer pollen volume has declined,but still tree-based category;fall pollen to herbaceous category,to the Asteraceae Artemisia,mulberry,Gramineae most often.3.The pollen concentration in Cangzhou City was negatively correlated with maximum humidity,maximum precipitation,maximum temperature,and minimum temperature.Maximum wind speed at ground level was positively correlated with pollen concentration.4.Pollen concentration was positively correlated with the number of visits.The correlation analysis between daily medical visits from June to October and air pollen concentration showed a significant positive correlation,while the results from March to May showed no significant correlation.CONCLUSION The peak of airborne pollen dispersal in April and September in Cangzhou.Spring and summer pollen is dominated by tree species,and the dominant pollen is Pinaceae,Willow genus of Populus,and Xylariaceae(ash genus);fall pollen is dominated by herbaceous species,and the dominant pollen is Artemisia,Asteraceae,Mulberry,and Gramineae.Meteorological factors are important factors affecting pollen concentration.Within a certain range,the lower the maximum humidity,the lowest maximum precipitation,the lower the highest or the lowest temperature,the higher the pollen concentration,and the pollen concentration is more affected by the lowest temperature.There is a correlation between pollen concentration and the number of AR patients'visits from June to October,which can be used as an environmental early warning indicator of the prevalence of AR.

The aim of this study is to explore the protective mechanism of Jiedu Tongluo Tiaogan decoction(JTTD)on islet cells of type 2 diabetic SD rats based on autophagy regulation.8-week-old SD male mice were fed with high-fat diet for 4 weeks and then induced with a single intraper-itoneal injection of streptozotocin 40 mg/kg.The Chinese medicine group was given the low(1.5 g·kg-1·d-1),medium(4.5 g·kg-1·d-1)and high(13.5 g·kg-1·d-1)doses of JTTD,and the western medicine group was given metformin hydrochloride(0.15 g·kg-1·d-1).Fasting blood glucose(FBG),glycated serum protein(GSP),triglycerides(TG),cholesterol(CHO),high-densi-ty lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),free fat(FFA)were measured.Moreover,the fasting serum insulin was determined by ELISA method and insulin resistance index(HOMA-IR)was calculated,glucose tolerance test was performed.The pancreatic tissues of SD mice were stained with HE,and the expression of Beclin-1 and LC3 were checked by immunohistochemistry,the expression of Beclin-1,LC3 and P62 was determined by Western blot,the expression of Beclin-1 and LC3RNA was determined by RT-PCR.The results showed that both the JTTD group and metformin hydrochloride group had better hypoglycemic and lipid-lowering effects(P＜0.05,P＜0.01).HE staining of pancreatic tissues showed that disorganized structure,unclear boundary,irregular arrangement,less cytoplasm,and lighter cytoplasmic staining or vacuo-lation in the islets in the JTTD group and metformin hydrochloride group were improved.In terms of autophagy regulation,immunohistochemistry,Western blot and RT-PCR,compared with the model group,the expression of Beclin-1 and LC3 mRNA was significantly increased(P＜0.01)and the level of p62 protein was decreased(P＜0.05,P＜0.01)in the JTTD group and metformin hydrochloride group.In conclusion,the JTTD can alleviate the trend of weight loss and improve ex-cessive drinking effectively in type 2 diabetic mellitus SD mice,as well as have better effects on im-proving glucose and lipid metabolism,moreover,it can alleviate the damage of pancreatic his-topathological structure and protect islet cells,which may be achieved by regulating the level of au-tophagy.

Objective To investigate the protective effect of sappanone A(SA)against high-fat diet-induced myocardial lipotoxicity through ferroptosis in rats.Methods Sixteen healthy male rats were equally divided into the normal diet(NCD)and model groups(n=8).Another 40 healthy male rats were equally divided into the high-fat diet(HFD),high-fat diet+normal saline(HFD+saline),high-fat diet+low-dose SA(HFD+10 mg/kg SA),high-fat diet+medium-dose SA(HFD+20 mg/kg SA),and high-fat diet+high-dose SA(HFD+40 mg/kg SA)groups(n=8).Ultrasonography detected the changes in cardiac systolic function in the rats.Changes of myocardial hypertrophy,myocardial fibrosis,and myocardial cell apoptosis were evaluated by HE,Masson,Sirius red,and TUNEL staining.Differen-tially expressed genes in the myocardium of the HFD+20 mg/kg SA and HFD groups were analyzed by transcriptome sequencing.The SA signaling pathway was analyzed using the Kyoto Encyclopedia of Genes and Genomes.Results Compared with the NCD group,the model group had significantly increased left ventricular wall thickness,cross-sectional area of the myocardium,percentage of myocardial fibrosis,myocardial collagen deposition,and apoptosis,and significantly reduced short-axis shortening rate(all P＜0.05).Compared with the HFD group,the SA treatment groups has significantly reduced left ventricular wall thickness,cross-sectional area of the myocardium,percentage of myocardial fibrosis,myocardial collagen deposition,and apoptosis,and significantly increased short-axis shortening rate(all P＜0.05).Transcriptome sequencing revealed that ferroptosis was the most abundant pathway.Conclusion High-fat diet can induce myocardial lipotoxicity,and SA has a protective effect against myocardial lipotoxicity through ferroptosis.

Objective:To evaluate the role of ubiquitin-specific peptidase 22 (USP22) in myocardial ischemia-reperfusion (I/R) injury in diabetic mice.Methods:Seventy-eight SPF male C57BL/6 mice, aged 6-8 weeks, were divided into 6 groups using a random number table method: sham operation group (Sham group, n=12), type 1 diabetes mellitus + sham operation group (T1D+ Sham group, n=12), myocardial I/R injury group (I/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury group (DI/R group, n=12), type 1 diabetes mellitus + myocardial I/R injury + empty vector group (DI/R+ V group, n=15), and type 1 diabetes mellitus + myocardial I/R injury + USP22 overexpression group (DI/R+ U group, n=15). Type 1 diabetes mellitus was induced by intraperitoneal injection of streptozotocin-citrate buffer. Myocardial I/R was induced by ligation of the left coronary artery. At 1 day before developing the myocardial I/R injury model, DI/R+ U group and DI/R+ V group received an intramyocardial injection of USP22 overexpression plasmid or empty vector plasmid, respectively. At 24 h of reperfusion, cardiac function was assessed using the echocardiography to measure the left ventricular ejection fraction and left ventricular fractional shortening. The mice were then sacrificed, and their hearts were harvested for measurement of the myocardial infarct size, for microscopic examination of pathological changes (using HE staining) and for determination of the apoptosis rate (TUNEL staining), reactive oxygen species(ROS) activity (DHE staining), and USP22 expression (by Western blot, immunofluorescence, and immunohistochemistry). Proteomic analysis was performed to identify downstream proteins regulated by USP22, and protein-protein interactions were investigated using co-immunoprecipitation. Results:Compared with Sham group, the cardiac function indices were significantly decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was down-regulated in I/R group ( P<0.05). Compared with I/R group, the percentage of myocardial infarct size was significantly increased, the cardiac function indices were decreased, the apoptosis rate of myocardial cells and ROS activity were increased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was aggravated in DI/R group. Compared with DI/R+ V group, the percentage of myocardial infarct size was significantly decreased, the cardiac function indices were increased, the apoptosis rate of myocardial cells and ROS activity were decreased, and USP22 expression in myocardial tissues was up-regulated ( P<0.05), and the pathological damage to myocardial tissues was alleviated in DI/R+ U group. The results of proteomics combined with co-immunoprecipitation experiments showed an interaction between calponin 1 and USP22. Conclusions:During myocardial I/R injury in diabetic mice, USP22 may act as an endogenous protective mechanism, and calponin 1 might be a downstream mechanism through which USP22 exerts its protective effects.

Abstract OBJECTIVE Oxcarbazepine(OXC) is an antiepileptic drug, which is metabolized to the active 10-monohydroxy derivative(MHD) after oral administration. The half-life period of MHD in children is significantly shorter than that in adults, and the clearance is increased by 30% to 160% compared with that in adults, which indicates that the pharmacokinetics(PK) of MHD in children is obviously different from that in adults, while adults and children exhibit different levels of expression of metabolism enzymes and transporter proteins with the same genotype. At present, there is no study describing the influence of genetic polymorphism of PK-related enzymes on MHD plasma concentrations in children with epilepsy. This study investigates whether the polymorphism of metabolic enzymes and transporter genes have significant effects on MHD plasma concentrations in children with epilepsy in China, so as to provide the reference for individualized application of OXC in pediatric patients. METHODS The plasma samples from pediatric patients with epilepsy aged 0-14 years old at the First Affiliated Hospital of Fujian Medical University who received OXC were prospective collected from June 2021 to June 2023. The MHD blood concentrations of the patients were measured using enzyme amplified immunoassay, and the metabolic enzyme genes UGT2B7 802T>C, UGT1A9 I399C>T, as well as the transporter genes ABCB1 3435C>T and ABCB2 1249G>A polymorphism were detected using dideoxy chain-termination method in epilepsy children. According to Hardy Weinberg's law of genetic balance, the theoretical values of genotype frequency of the patients were calculated, and a Chi-Square test method was used to compare whether there was a significant difference between the theoretical value and the measured value, to examine whether the genotype of the patients included in the study is accordance with the law of genetic balance. One-way ANOVA statistical method was used to analyze the correlation of the four single nucleotide polymorphisms, daily maintenance dosage of OXC, and MHD blood concentrations. Subsequently, Fisher's least significant difference(LSD) test was performed. LSD test is a pairwise comparison of the differences between the mean values of each group, calculated based on the standard error and degrees of freedom to obtain the minimum significant difference between each two groups, while P<0.05 indicated that the difference was significant. RESULTS In this study, 161 trough concentrations were collected from children with epilepsy. The genotype of the included population conformed to the genetic balance law, which indicated that the included patients were representative for the population. Unite analysis of variance showed a significant correlation between the transporter gene ABCB1 3435C>T and MHD blood drug concentration(P<0.05). Subsequently, Fisher's minimum significant difference test was conducted, and MHD plasma concentrations of patients carrying the ABCB1 3435C>T mutation allele were significantly higher than that of non-carriers. No significant association was found between the four single nucleotide polymorphisms and the daily maintenance dosage of OXC, and no significant impact of the other metabolic enzyme and transporter genetic polymorphisms on MHD plasma concentrations was found. CONCLUSION The results of research shows that the ABCB1 3435C>T polymorphism significantly affect the MHD blood concentration of pediatric patients with epilepsy, and the effects of UGT2B7 802T>C, UGT1A9 I399C>T and ABCB2 1249G>A genetic polymorphisms on MHD blood concentration and daily maintenance dosage of OXC are not found. The results suggest that MHD blood concentrations are significantly increased by affecting the expression of the encoded MDR1 transporter protein after ABCB1 3435C>T site mutation, which also may increase the risk of adverse reactions of OXC. The genetic polymorphisms of ABCB1 3435C>T can be detected in children with epilepsy when taking OXC, and the dosage can be adjusted appropriately for patients with genetic mutations. The results of this study can provide the reference for the individualized administration of OXC in clinic.