Objective To investigate the role of triggering receptor expressed on myeloid cells-1(TREM-1)in ath-erosclerosis induced by chronic intermittent hypoxia(CIH).Methods ApoE-/-mice were randomly divided into blank group,model group and experimental group.The mice in the model group and the experimental group were kept in a hypoxic environment and fed with a high-fat diet.After 4 weeks of high-fat feeding,mice in the experi-mental group were intraperitoneally injected with TREM-1 inhibitor LR12(5 mg/kg)for 8 weeks.After 12 weeks of feeding,the level of serum total cholesterol(TC),low density lipoprotein(LDL),triglyceride(TG),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and interleukin-10(IL-10)were detected.Histological analysis of aortic TREM-1 expression,plaque area and macrophage level were examined.Results Compared with blank group,the expression of TREM-1 in the aorta of the model group significantly increased(P＜0.05).Com-pared with model group,the aortic plaque,the level of lipids in serum(TC,LDL,TG)and inflammatory factors(TNF-α,IL-1β,IL-10),aortic plaque,the expression of TREM-1 and infiltrating macrophages in aortic plaque of the experimental group were all significantly reduced(P＜0.05).Conclusions TREM-1 is involved in the develop-ment of CIH-induced AS.Inhibition of TREM-1 can alleviate CIH-induced AS and its mechanism is related to the inhibition of macrophage activation.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

With the increasing proportion of human papilloma virus(HPV)infection in the pathogenic factors of oro-pharyngeal cancer,a series of changes have occurred in the surgical treatment.While the treatment mode has been im-proved,there are still many problems,including the inconsistency between diagnosis and treatment modes,the lack of popularization of reconstruction technology,the imperfect post-treatment rehabilitation system,and the lack of effective preventive measures.Especially in terms of treatment mode for early oropharyngeal cancer,there is no unified conclu-sion whether it is surgery alone or radiotherapy alone,and whether robotic minimally invasive surgery has better func-tional protection than radiotherapy.For advanced oropharyngeal cancer,there is greater controversy over the treatment mode.It is still unclear whether to adopt a non-surgical treatment mode of synchronous chemoradiotherapy or induction chemotherapy combined with synchronous chemoradiotherapy,or a treatment mode of surgery combined with postopera-tive chemoradiotherapy.In order to standardize the surgical treatment of oropharyngeal cancer in China and clarify the indications for surgical treatment of oropharyngeal cancer,this expert consensus,based on the characteristics and treat-ment status of oropharyngeal cancer in China and combined with the international latest theories and practices,forms consensus opinions in multiple aspects of preoperative evaluation,surgical indication determination,primary tumor re-section,neck lymph node dissection,postoperative defect repair,postoperative complication management prognosis and follow-up of oropharyngeal cancer patients.The key points include:① Before the treatment of oropharyngeal cancer,the expression of P16 protein should be detected to clarify HPV status;② Perform enhanced magnetic resonance imaging of the maxillofacial region before surgery to evaluate the invasion of oropharyngeal cancer and guide precise surgical resec-tion of oropharyngeal cancer.Evaluating mouth opening and airway status is crucial for surgical approach decisions and postoperative risk prediction;③ For oropharyngeal cancer patients who have to undergo major surgery and cannot eat for one to two months,it is recommended to undergo percutaneous endoscopic gastrostomy before surgery to effectively improve their nutritional intake during treatment;④ Early-stage oropharyngeal cancer patients may opt for either sur-gery alone or radiation therapy alone.For intermediate and advanced stages,HPV-related oropharyngeal cancer general-ly prioritizes radiation therapy,with concurrent chemotherapy considered based on tumor staging.Surgical treatment is recommended as the first choice for HPV unrelated oropharyngeal squamous cell carcinoma(including primary and re-current)and recurrent HPV related oropharyngeal squamous cell carcinoma after radiotherapy and chemotherapy;⑤ For primary exogenous T1-2 oropharyngeal cancer,direct surgery through the oral approach or da Vinci robotic sur-gery is preferred.For T3-4 patients with advanced oropharyngeal cancer,it is recommended to use temporary mandibu-lectomy approach and lateral pharyngotomy approach for surgery as appropriate;⑥ For cT1-2N0 oropharyngeal cancer patients with tumor invasion depth＞3 mm and cT3-4N0 HPV unrelated oropharyngeal cancer patients,selective neck dissection of levels ⅠB to Ⅳ is recommended.For cN+HPV unrelated oropharyngeal cancer patients,therapeutic neck dissection in regions Ⅰ-Ⅴ is advised;⑦ If PET-CT scan at 12 or more weeks after completion of radiation shows intense FDG uptake in any node,or imaging suggests continuous enlargement of lymph nodes,the patient should undergo neck dissection;⑧ For patients with suspected extracapsular invasion preoperatively,lymph node dissection should include removal of surrounding muscle and adipose connective tissue;⑨ The reconstruction of oropharyngeal cancer defects should follow the principle of reconstruction steps,with priority given to adjacent flaps,followed by distal pedicled flaps,and finally free flaps.The anterolateral thigh flap with abundant tissue can be used as the preferred flap for large-scale postoperative defects.

The National Medical Products Administration have become an official applicant of the Pharmaceutical Inspection Co-operation Scheme(PIC/S)in 2023,and the good manufacturing practice appendix and inspection memorandum are key documents of PIC/S.Based on the analysis of the history,framework and main contents of the appendix and inspection memorandum of PIC/S investigational medicinal products,this paper discusses the key contents of the appendix and inspection memorandum of PIC/S clinical trial drugs,and provides reference for the inspection work.

Objective To study chest computed tomography(CT)manifestations in neonates with chronic granulomatous disease(CGD)to provide clues for early diagnosis of this disease.Methods A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital.Results Nine neonates with CGD were included,with eight presenting respiratory symptoms as the initial sign.Chest CT findings included:consolidation in all 9 cases;nodules in all 9 cases,characterized by multiple,variably sized scattered nodules in both lungs;masses in 4 cases;cavities in 3 cases;abscesses in 6 cases;bronchial stenosis in 2 cases;pleural effusion,interstitial changes,and mediastinal lymphadenopathy each in 1 case.CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement;no signs of pulmonary emphysema,lung calcification,halo signs,crescent signs,bronchiectasis,or scar lesions were observed.There was no evidence of rib or vertebral bone destruction.Fungal infections were present in 8 of the 9 cases,including 6 with Aspergillus infections;three of these involved mixed infections with Aspergillus,with masses most commonly associated with mixed Aspergillus infections(3/4).Conclusions The primary manifestations of neonatal CGD on chest CT are consolidation,nodules,and/or masses,with Aspergillus as a common pathogen.These features can serve as early diagnostic clues for neonatal CGD.

Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.

Abstract: Objective To detect the polymorphisms of drug resistance-related genes pvcrt-o and pvmdr1 of Plasmodium vivax in lazan city in the China-Myanmar border, in order to guide the treatment plan of Plasmodium vivax. Methods A total of 48 Plasmodium vivax samples were collected from Lazan in the China-Myanmar border in 2007, and fragments of pvcrt-o and pvmdr1 genes were amplified by PCR and sequenced. The sequences were aligned with the Salvador I (Sal-I) strain reference genome sequences to determine the presence of SNPs. Results The target fragments of pvcrt-o gene were amplified from 39 Plasmodium vivax samples, while pvmdr1 genes were amplified from 40 samples. Amongst them, 25 samples had AAG insertion before the 10th amino acid (K10 insertion) of pvcrt-o gene, accounting for 64.1%. Non-synonymous mutations were detected at three loci of pvmdr1 gene (T958M, Y976F, and F1076L), the mutation rates were 100%, 22.5%, and 55.0%, respectively. There were three haplotypes of pvmdr1 gene, of which the triple mutant 958M/976F/1076L accounted for 22.5% (9/40), the double mutant 958M/Y976/1076L accounted for 32.5% (13/40), and the single mutant 958M/Y976/F1076 accounted for 45.0% (18/40). The proportion of strains with pvcrt-o and pvmdr1 gene mutation is 63.16%, which is significantly different from those only with pvmdr1 mutation. Conclusions The proportion of pvcrt-o and pvmdr1 gene mutation of 48 Plasmodium vivax isolates is high in the China-Myanmar border, and there is a certain degree of correlation between the two gene mutations. To assess changes in Plasmodium vivax drug resistance in this region, it is required to improve the surveillance of these two molecular markers.

Abstract: Objective　To evaluate the influence of coronavirus disease 2019 (COVID-19) prevention and control measures on the transmission and epidemic of influenza in Chongqing, so as to provide references for formulating targeted influenza prevention and control strategies. Methods　The influenza surveillance data, during the year 2018 to 2020, were collected through the "China Influenza Surveillance Information System", and the seasonal characteristics of influenza epidemic were analyzed. The percentage of influenza like cases (ILI%) and influenza virus positive rate between 2020 and 2018-2019 were compared, so as to evaluate the impact of COVID-19 prevention and control measures on influenza epidemic characteristics. Results　The annual proportions of ILI cases in Chongqing were respectively 3.53%, 2.23% and 1.2% from 2018 to 2020, while the positive rates of influenza virus were respectively 13.97%, 23.81% and 2.65%. The distribution trend of ILI% from 2018 to 2019 fluctuated were similar, but it continued to drop and remain at a low level since February 2020. The positive rate of influenza virus showed an epidemic peak from December to March in 2018-2019, also peaked from November 2019 to January 2020, but decreased to 0 in March. ILI% was positively correlated with the positive rate of influenza virus (r=0.404 8, P<0.05). In 2020, compared with the same period of 2018-2019, the growth rate of ILI% was -66.09% and -46.32%, respectively. The positive rate of influenza virus in 2020 decreased by 81.03% and 88.87% compared with the same period of 2018-2019, respectively. The growth rates of influenza virus positive rate in January 2020 were decreased with a small rate of about 39.87%, and with a significantly decline of more than 93.65% from February. No influenza epidemic was found after March. Conclusions　Since COVID-19 prevention and control measures were implemented in January 2020 in Chongqing, the ILI% and the positive rate of influenza virus in sentinel hospitals decreased significantly. In the season of high incidence of respiratory infectious diseases, personal protection and other measures can effectively reduce influenza virus infection.

OBJECTIVE: To predict the learning curve of tooth preparation for all ceramic crowns of maxillary central incisors on phantom head simulators for graduate students participating in standardized dental resident training based on the modified Wright learning curve model, then to analyze and applicate the learning curve. METHODS: Twelve graduate students participating in standardized dental resident training were selected to prepare the resin maxillary central incisors on phantom head simulators for all ceramic crowns 4 times. The results of preparation were evaluated by 3 prosthetic experts with at least 10 years' experience focusing on the reduction, contour, taper, shoulder, finish line, margin placement, adjacent tooth injury, and preparation time for tooth preparation. The learning rate of tooth preparation was calculated by scores of tooth preparation of 4 times. The learning curve of tooth preparation was predicted based on the modified Wright learning curve model. According to the criteria of standardized training skill examinations for dental residents in Beijing, 80 was taken as the qualified standard score. The minimum training times for tooth preparation to satisfy the qualified standard score (80) was calculated, to analyze the characteristics of learning curve and evaluate the effectiveness of tooth preparation. RESULTS: The scores of 4 tooth preparation were 64.03±7.80, 71.40±6.13, 74.33±5.96, and 75.98±4.52, respectively. The learning rate was (106±4)%, which showed the learning curve an upward trend. There were no significant differences between the qualified standard score and the predicted scores of tooth preparation from the 5^th preparation to the 13^th preparation (P > 0.05). The predicted score of the 14^th preparation was higher than the qualified standard score (P < 0.05). CONCLUSION The trend of the learning curve of tooth preparation for all ceramic crowns of maxillary central incisors on phantom head simulators for graduate students participating in standardized dental resident training is upward, which predicts the minimum training times higher than the qualified standard score is 14 times.
Humans ; Tooth Preparation, Prosthodontic/methods* ; Incisor ; Learning Curve ; Crowns ; Tooth Preparation ; Ceramics ; Dental Porcelain ; Dental Prosthesis Design

Objective:To construct a predict model based on ultrasomics parameters that can identify moderate acute hypoxemic respiratory failure patients at risk of non-invasive respiratory strategies(NIRS) failure and evaluate its value.Methods:This is a prospective observational trial.The patients with moderate acute respiratory failure (100 mmHg≤PaO 2/FiO 2≤200 mmHg) in intensive care unit(ICU) ,emergency and respiratory ward of Changshu Hospital Affiliated to Soochow University from Oct 2020 to Jan 2023 were included, NIRS failure is defined as death or intubation while on therapy.At admission time and 24 h after treatment vital signs,biological and ultrasound parameters were determined.The study subjects were randomly ( random number) divided into a development group (70%) and a validation group (30%).Univariate and multivariate logistic regression was performed.The treatment failure prediction models were constructed according to ultrasonic parameters combined with clinical parameters.The models were also validated by ROC curves, calibration curves, NRI index and decision curve analysis (DCA).The nomograms were drawn. Results:A total of 193 patients were included in the study, 137 were allocated to the development group, and 56 to the validation group, there was no statistically significant difference between the two groups. NIRS failed in 112 (58%) of 193 patients..Univariate analysis revealed that PaO 2/FiO 2, DE at the time of admission and 24 h in the failure group were found to be statistically lower than the success group, RV/LV was higher (all P<0.05). RR, LUS at 24 h in the failure group were higher and ROX index was lower (all P<0.01). In addition, more patients in the failure group received vasopressors ( P= 0.001). Use of vasopressors( OR=4.709, P=0.012), RR( OR=1.254, P=0.035), LUS( OR=1.250, P=0.037), RV/LV( OR=1.057, P=0.008), PaO 2/FiO 2 ( OR=0.950, P=0.001), DE ( OR=0.107, P=0.001) in the development group were independent risk factors for NIRS failure.ROC analysis revealed that model B achieved a larger area under curve (AUC) than model A in the development group, with their AUC values of 0.928 and 0.872 ( P=0.009), AUC of model A and model B in the validation group were 0.867 and 0.932 respectively ( P=0.07).Two prediction models showed a good degree of calibration (all P>0.05). NRI analysis showed significant improvement in the predictive power of model B ( P<0.01). DCA showed that the model B had a good net benefit between the threshold probabilities of 0-80%. Conclusions:Ultrasomics parameters combined with Clinical parameters can effectively predict NIRS failure in moderate acute hypoxemic respiratory failure patients.