[Research progress on global health competency and its models].

At present, the research on Global Health Competencies is mainly conducted in the field of the establishment of competency models and application of indicators. This review summarizes the research progress of the Global Health Competency and its models, and focuses on cutting-edge research from the aspects of target audience, purpose, content, classical model, methods and future development. The competency model is suggested to be adjusted and updated according to the practices of different countries and regions. The research and funding of the competency model in the field of public health is suggested to be strengthened, and the global health and diplomacy are suggested to be combined to enrich and improve the competency model. Finally, this review aims to promote Global Health Competencies research in China, especially to improve the global health talent training system and relevant policies in further research.

Effect of Sc contents on the mechanical properties and damping capacity of Al-Zn-Mg-Cu-Zr-Sc alloys with different grain structures.

Al-Zn-Mg-Cu-Zr-Sc alloys with different Sc contents were fabricated by casting, deformation, and T6 treatment. Deformation methods including rolling and friction-stir processing (FSP) were used to design their grain structure. A low additive amount (0.1) of Sc cannot refine the grains of the alloy with rolling and T6 treatment, and it instead coarsened the grains. The reason was the non-uniform distribution of nanosize Al3(Sc,Zr) phases that led to the occurrence of abnormal grain growth during homogenization. Meanwhile, the alloy with only 0.1Sc exhibited finer grains after FSP and T6 treatment than the alloys subjected to the same process but with higher Sc additive amount. Alloys with rolling-induced elongated grain structure exhibited better mechanical properties, and alloys with FSP-induced fine equiaxed grain structure exhibited higher high-strain and high-temperature internal friction values. These features are important performance parameters for applications in fields where vibration and noise are sensitive. The optimum additive amounts of Sc for alloys with elongated and fine equiaxed grain structures were 0.25 and 0.1, respectively.

The Double Antibody Drug Conjugate (DAD) phase I trial: sacituzumab govitecan plus enfortumab vedotin for metastatic urothelial carcinoma.

BACKGROUND: The antibody-drug conjugates sacituzumab govitecan (SG) and enfortumab vedotin (EV) are standard monotherapies for metastatic urothelial carcinoma (mUC). Given the different targets and payloads, we evaluated the safety and efficacy of SG + EV in a phase I trial in mUC (NCT04724018). PATIENTS AND METHODS: Patients with mUC and Eastern Cooperative Oncology Group performance status ≤1 who had progressed on platinum and/or immunotherapy were enrolled. SG + EV were administered on days 1 + 8 of a 21-day cycle until progression or unacceptable toxicity. Primary endpoint was the incidence of dose-limiting toxicities during cycle 1. The number of patients treated at each of four pre-specified dose levels (DLs) and the maximum tolerated doses in combination (MTD) were determined using a Bayesian Optimal Interval design. Objective response, progression-free survival, and overall survival were secondary endpoints. RESULTS: Between May 2021 and April 2023, 24 patients were enrolled; 1 patient never started therapy and was excluded from the analysis. Median age was 70 years (range 41-88 years); 11 patients received ≥3 lines of therapy. Seventy-eight percent (18/23) of patients experienced grade ≥3 adverse event (AE) regardless of attribution at any DL, with one grade 5 AE (pneumonitis possibly related to EV). The recommended phase II doses are SG 8 mg/kg with EV 1.25 mg/kg with granulocyte colony-stimulating factor support; MTDs are SG 10 mg/kg with EV 1.25 mg/kg. The objective response rate was 70% (16/23, 95% confidence interval 47% to 87%) with three complete responses; three patients had progressive disease as best response. With a median follow-up of 14 months, 9/23 patients have ongoing response including 6 responses lasting over 12 months. CONCLUSIONS: The combination of SG + EV was assessed at different DLs and a safe dose for phase II was identified. The combination had encouraging activity in patients with mUC with high response rates, including clinically significant complete responses. Additional study of this combination is warranted.

[Survey of Helicobacter pylori levofloxacin and clarithromycin resistance rates and drug resistance genes in Ningxia, 2020-2022].

Objective: To explore the rate of Helicobacter pylori (Hp) resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia, and to assess the concordance between phenotypic resistance and genotypic resistance. Methods: Cross-sectional study. Patients diagnosed with Hp infection in 14 hospitals in Ningxia region from February 2020 to May 2022 were retrospectively selected. Hp strains were isolated from gastric biopsy specimens of Hp-infected patients and subjected to phenotypic drug sensitivity testing and detection of resistance genes to analyze the rate of Hp resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia region; and the concordance rate and Kappa concordance test were used to assess the concordance between phenotypic resistance and genotypic resistance. Results: A total of 1 942 Hp strains were isolated and cultured, and among the infections, 1 069 cases (55.0%) were male and 873 cases (45.0%) were female, aged (50.0±12.5) years (15-86 years). The rates of Hp resistance to levofloxacin and clarithromycin in Ningxia were 42.1% (818/1 942) and 40.1% (779/1 942), respectively, and the rate of dual resistance to both was 22.8% (443/1 942). The rate of resistance to levofloxacin and clarithromycin of Hp strains from female patients was higher than in male patients (levofloxacin: 50.4%(440/873) vs 35.4%(378/1 069); clarithromycin: 44.4%(388/873) vs 36.6%(391/1 069), both P<0.001). Among the GyrA gene mutations associated with levofloxacin resistance, the differences in mutation rate of amino acid at positions 87 and 91 were statistically significant in both drug-resistant and sensitive strains(both P<0.001), except for Asn87Thr. Hp strains were statistically significant for levofloxacin (Kappa=0.834, P<0.001) and clarithromycin (Kappa=0.829, P<0.001) had good concordance in resistance at the phenotypic and genotypic levels. Conclusion: The resistance of Hp to levofloxacin and clarithromycin in Ningxia region is severe, and there is good consistency between genotypic and phenotypic resistance.

[Mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence].

Objective: To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence. Methods: After excluding individuals with missing educational levels and cancer information at baseline, 446 772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer. Results: During a median follow-up of 7.13 years, 1 994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer (HR=0.88, 95%CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self-report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95%CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with ß coefficients (95%CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score (ß=0.042, 95%CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95%CI: 31.802%-51.659%) and 1.784% (95%CI: 0.405%-3.713%), respectively. Conclusion: Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.

[Comparative analysis on prevalence of tobacco and e-cigarettes uses in junior middle school students in Shanghai, 2013 and 2019].

Objective: To examine the prevalence and trend of tobacco and e-cigarettes uses and identify the influencing factors for smoking behavior in junior middle school students in Shanghai, and provide data support and scientific basis for the development of tobacco control intervention strategy in adolescents. Methods: Multi-stage stratified random sampling method was used to select junior middle school students in 8 districts and 10 districts in Shanghai in 2013 and in 2019 respectively. Information about tobacco and e-cigarettes uses in the students were collected by using self-administrated questionnaire. The prevalence of tobacco and e-cigarettes uses were calculated, the difference between two years was compared with χ2 test. The influencing factors were identified by multivariate logistic regression analysis. Results: In 2019, the current smoking rate was 0.6% in junior middle school students in Shanghai, and the smoking attempt rate was 2.9%, both were lower than the levels in 2013 (0.7% and 6.9%). The current use rate of e-cigarettes was 0.6% in 2019,with no significant change compared with 2013 (0.6%). The proportion of the students who had heard of e-cigarettes in 2019 (78.4%) was higher than that in 2013 (47.2%). In 2019, the second-hand smoke (SHS) exposure rate at home, in both indoor and outdoor public places and on public transportations was 72.5%, which was slightly lower than the level in 2013 (73.0%), the differences were all significant (P<0.05). In 2019, the students seeing close friend smoking (OR=27.381, 95%CI: 12.037-62.287), seeing someone smoking in school (OR=2.477, 95%CI: 1.155-5.312), believing that SHS may not be harmful (OR=8.471, 95%CI: 1.464-49.005) had higher possibility of smoking. Being aged ≥15 years (compared with being aged ≤12 years, OR=8.688, 95%CI: 1.922-39.266), exposure to SHS in outdoor public place (OR=8.608, 95%CI: 1.048-70.692), close friend smoking (OR=8.115, 95%CI: 1.754-37.545) were positively associated with e-cigarettes use, and believing that smoking results in uncomfortable social contact [compared with believing that smoking results in comfortable social contact (OR=0.105,95%CI: 0.018-0.615)] were negatively associated with e-cigarettes use, the difference was significant (P<0.05). Conclusion: The prevalence of tobacco and e-cigarette uses in junior middle school students in Shanghai remained at a low level in recent years. The SHS exposure rate in junior middle school students is high. Smoking behavior of junior middle school students is closely related to personal attitude and awareness of tobacco, exposure to SHS, peer smoking and the situation of tobacco control in schools. Prevention and intervention should be carried out from multi-dimensions to effectively protect teenagers from tobacco hazards.

Enhanced corrosion resistance by engineering crystallography on metals.

Nanometer-thick passive films, which impart superior corrosion resistance to metals, are degraded in long-term service; they are also susceptible to chloride-induced localized attack. Here we show, by engineering crystallographic configurations upon metal matrices adjacent to their passive films, we obtain great enhancement of corrosion resistance of FeCr15Ni15 single crystal in sulphuric acid, with activation time up to two orders of magnitude longer than that of the non-engineered counterparts. Meanwhile, engineering crystallography decreases the passive current density and shifts the pitting potential to noble values. Applying anodic polarizations under a transpassivation potential, we make the metal matrices underneath the transpassive films highly uneven with {111}-terminated configurations, which is responsible for the enhancement of corrosion resistance. The transpassivation strategy also works in the commercial stainless steels where both grain interior and grain boundaries are rebuilt into the low-energy configurations. Our results demonstrate a technological implication in the pretreatment process of anti-corrosion engineering.

[Application of machine learning in orthodontics].

With the increasing integration of artificial intelligence (AI) with other fields, machine learning, one of the major methods in AI, has been extensively applied in dentistry in the stage of diagnosis, therapy and prognosis evaluation. Nowadays, numerous studies have reported the applications of machine learning in orthodontics in two major aspects, including image identification and clinical decision support system. Herein, we reviewed the application progress of machine learning in orthodontics in order to provide new insight for the future precision medicine.

[Alveolar echinococcosis metastatic to the brain: a case report].

This paper reports a case with alveolar echinococcosis metastatic to the brain. This case underwent 10-year antiechinococcosis treatment and operations of the liver, right kidney and brain. Following multiple operations and oral administration of albendazole, the case still had recurrence and distant metastasis of hepatic echinococcosis. It is suggested that early prevention, early diagnosis, early regular treatment and surgical radical treatment are critical to the treatment of alveolar echinococcosis.

[A comparative study of 3.0T (1)H-MRS for varying degrees of liver fibrosis in cynomolgus monkeys].

Objective: To investigate the changing rules with (1)H magnetic resonance spectroscopy ((1)H-MRS) in order to provide human research theoretical basis with varying degrees of liver fibrosis in cynomolgus monkeys. Methods: Liver fibrosis model in twenty-two cynomolgus monkey was successfully established with carbon tetrachloride (CCl(4)). Among them, fifteen cynomolgus monkey developed to early-stage liver cirrhosis (S4 stage). A comparative study was conducted in 15 cynomolgus monkeys that had fully developed liver fibrosis. The changing rules for varying degrees of liver fibrosis in cynomolgus monkeys were analyzed with (1)H-MRS. Supplementary methods: statistical analysis was performed using compatibility group design and analysis of variance for each research indicators. SNK-q test was used for pairwise comparison between the groups. The correlation between the 1H-MRS research indicators and the severity of liver fibrosis was analyzed by Spearman's rank correlation. Results: The Cho of (1)H-MRS was increased with the severity of liver fibrosis in cynomolgus monkeys. Moreover, there were statistically significant (P < 0.01) differences between liver fibrosis staging (S1 ~ S4) and normal liver tissue (S0 stage), severe liver fibrosis staging (S3 and S4) and mild to moderate liver fibrosis staging (S1 and S2). Compared with S0 stage, the peak value of lipid in S1 stage was significantly higher than that of S2 stage, and the peak value of lipid in S3 and S4 stage was significantly lower than that of S0 stage, and the differences between S1, S3, S4 and S0 stages were statistically significant (P < 0.01). The Cho/lipid ratio had gradually increased with the severity of liver fibrosis progression and the differences between groups were statistical significant (P < 0.01). Spearman's rank correlation coefficient between Cho / lipid ratio and pathological stage of liver fibrosis was 0.98 (P = 0.000). ROC curve analysis showed that Cho / lipid ratio was the most significant diagnostic indicator for liver fibrosis. The threshold values of CHO/lipid ratio were≥ 0.028, and≥ 0.131 (P < 0.01) for the diagnosis of liver fibrosis and early-stage cirrhosis. Conclusion: (1)H-MRS of the cynomolgus monkey liver fibrosis model changes rules regularly with the aggravation of severity of liver fibrosis. Among them, the Cho/lipid ratio is the most valuable indicator for the diagnosis of liver fibrosis staging, which may provide a theoretical basis for the study of human liver fibrosis.

[Research progress in psychological factors in the diagnosis and treatment of temporomandibular joint disorders].

Temporomandibular disorders (TMD) is one of the most common diseases in the orofacial region. The occurrence, development and outcome of TMD are affected by many factors. Among various risk factors, the psychological factors, especially anxiety, depression and somatic symptoms, are getting more and more attention in the etiology, diagnosis and treatment of TMD. Psychological factors are associated with the occurrence of TMD, and the accurate diagnostic criteria is conducive to the assessment of the patient's psychological state. If necessary, an appropriate psychological treatment according to a patient's psychological status can effectively improve the effect of clinical treatment. This article, based on domestic and international literatures, reviews the research progress of the correlation between the psychological factors and the etiology, diagnosis and treatment of TMD, in order to provide new ideas for clinicians to diagnose and treat TMD.

[Comparison of the registration methods for the three-dimensional facial scans applied to the design of full-arch implant supported restoration].

OBJECTIVE: To compare the registration accuracy of three-dimensional (3D) facial scans for the design of full-arch implant supported restoration by five methods and to explore the suitable registration method. METHODS: According to the criteria, ten patients with maxillary edentulous jaw or end-stage dentition requiring implant supported restorations were enrolled in this study. A special rim with individual feature marks reflected appropriate occlusal relationship and esthetic characteristics was made for each patient. Both 3D facial scan data of natural laughter and with opener traction to expose the teeth or occlusal rim of each patient were acquired by facial scan and input to the digital analysis software Geomagic Qualify 2012. The dataset was superimposed by five different methods: seven facial anatomical landmark points alignment, facial immobile area alignment (forehead and nasal area), facial anatomical landmark points and immobile area combining alignment, facial feature points alignment, facial and intraoral feature points alignment with the same local coordinate system. The three-dimensional deviation of the same selected area was calculated, the smaller the deviation, the higher the registration accuracy. The 3D deviation was compared among the three registration methods of facial anatomical landmark points, facial immobile area alignment and the combination of the above two methods. Friedman test was performed to analyze the difference among the three methods (α=0.05). The effect of the aid of the facial and intraoral feature points were evaluated. Paired t test were performed to analyze the difference (P<0.05). RESULTS: The average three-dimensional deviation of the selected area after alignment with the facial anatomical landmarks was (1.501 2±0.406 1) mm, significantly larger than that of the facial immobile area best-fit alignment [(0.629 1±0.150 6) mm] and the combination of the two methods[(0.629 1±0.150 6) mm] (P < 0.001). The aid of the facial feature points could significantly reduce the deviation (t=1.001 3, P < 0.001). There was no significant statistical difference in the remaining groups. CONCLUSION: The forehead area of the 3D facial scan can be exposed as much as possible. The establishment of facial characteristic landmark points and the use of the invariant area alignment can improve the accuracy of registration. It should be clinically feasible to apply three-dimensional facial scan to the design of full-arch implant supported restoration with the registration of the immobile area on the face especially the forehead area.

[Three-year clinical effects of a modified semi-fixed bridge on restoring a missing posterior tooth].

OBJECTIVE: To observe the effects of a modified semi-fixed bridge to restore a missing posterior tooth for three years. METHODS: In the study, 38 cases with a posterior tooth missed were chosen as experiment group. The inclusion criteria for these cases required that one abutment tooth be defected, and another abutment intact. The missed posterior tooth was restored with a modified semi-fixed bridge in which a metal wing retainer was applied to the intact abutment tooth and a full crown retainer was applied to the defected abutment tooth, and the non-rigid connector linked to the metal wing retainer and the pontic, while the rigid connector linked to the full crown retainer and the pontic. And 42 cases with same abutment conditions were chosen as control group. These control patients were treated with classical rigidly-fixed partial dentures. The clinical effects regarding the bridge survival, abutment conditions, and etc. were observed by examination. RESULTS: The average observation time for experiment group was 40.3 months (from 9 to 60 months). One case failed with loose crown retainer after 7 months' usage. Another failed case was the same performance after 20 months' wearing. The restorations were rebounded after the inner face of crowns was treated, and they were used normally. No loose abutment and retainer, no decayed abutment teeth were found, and the marginal adaptations between retainers and abutment teeth were good. The average observation time of control group was 44.7 months(from 22 to 50 months). No secondary decays and loose abutment teeth were detected and the marginal adaptation of the retainers was good. CONCLUSION: This modified semi-fixed bridge has similar survival rate and clinical effects to restore a missing posterior tooth when compared with the traditional rigidly-fixed partial dentures. But the long-term observation is required.

[Study on the immune functions of dendritic cells regulated by histone deacetylase inhibitor Belinostat].

Objective: To explore effects of histone deacetylase inhibitor Belinostat on the immunologic function of dendritic cells (DC) and its possible mechanism. Methods: Cultured mouse bone marrow-derived DC from C57BL/6 mouse in vitro. The experiments were divided into 0, 50, 100 nmol/L Belinostat + immature DC (imDC) group, and 0, 50, 100 nmol/L Belinostat mature DC (mDC). The changes of the ultrastructure of DC were observed by transmission electron microscope (TEM). Immunophenotype and CCR7 expression rate were detected by FCM, and the migration rate was observed by chemotaxis assay. The proliferation of lymphocytes stimulated by different DC was detected by mixed lymphocyte culture reaction. The cytokines in the culture supernatant, including TNF-α, IL-12 and IL-10, were examined by ELISA. RQ-PCR was used to examine the relative expression of mRNA in RelB. Results: Successful cultured and identified the qualified imDC and mDC. Belinostat decreased the expression of CCR7 on imDC [(25.82±7.25)% vs (50.44±5.61)% and (18.71±2.00)% vs (50.44±5.61)%], meanwhile increased the rate on mDC [(71.14±1.96)% vs (64.90±1.47)%]. Chemotaxis assay showed that the migration rate of Belinostat+imDC and Belinostat+mDC group were both decreased, but the difference in imDC was not significant. T lymphocyte proliferation rate stimulated by 100 nmol/L Belinostat+imDC group was lower than imDC group in condition irritation cell∶reaction cell=1∶2 [(227.09±13.49)% vs (309.49±53.69)%]. Belinostat significantly suppressed the secretion of cytokines TNF-α, IL-12 and IL-10 (all P<0.01). The relative expression of mRNA in RelB was slightly decreased in Belinostat+imDC and Belinostat+mDC group (all P<0.05). Conclusion: Belinostat could effectly suppress DC maturation and regulate immune tolerance of DC, which may be due to the down-regulation of mRNA level of RelB in DC.

Aerobic exercise blocks interleukin-6 levels and germ cell apoptosis in obese rats.

To investigate the effect of a high-fat diet and aerobic exercise intervention and its related mechanism on rat germ cell apoptosis. Forty male Sprague-Dawley rats were randomly divided into control group, high-fat diet group, control exercise group and high-fat exercise group. Rats were fed with high-fat diet or were given weight-free swimming. The levels of TG, TC, HDL, LDL and IL-6 in serum of rats were measured. The body weight, body length and inguinal fat weight were measured to calculate the Lee's index and lipid/body weight ratio. The expression of IL-6 mRNA in inguinal fat and IL-6R,Bcl-2 and Bax mRNA in testis was detected by RT-PCR. The morphological structure of testis was observed, and the Johnsen's ten-point score was calculated by HE staining, and the germ cell apoptosis was detected by TUNEL method. We got from the experimental results: a high-fat diet induces obesity and lipid metabolism disorder, alters testis morphological structure and increases germ cell apoptosis in rats. Aerobic exercise improves the lipid metabolism disorder and interferes with germ cell apoptosis by reducing interleukin-6 and interleukin-6 receptor expression.

[Ki-67 expression and its effect on response to neo-adjuvant chemotherapy in invasive breast cancer].

Objective: To investigate the response to neoadjuvant chemotherapy (NAC) among different molecular subtypes of breast cancers using molecular classification with Ki-67 (ER+ PR+ HER2+ Ki-67) or without Ki-67 (ER+ PR+ HER2). Methods: One hundred and twenty-seven cases of invasive breast cancer confirmed by core needle biopsy before NAC were collected from January 2007 to December 2009 and diagnosed at West China Hospital, Sichuan University. The cases were classified into different molecular subtypes using molecular classifications with or without Ki-67. Their clinical and pathological response to NAC was evaluated and compared. Results: The different subtypes using both molecular classifications showed significant difference in clinical response(with Ki-67: χ(2)=22.40, P<0.01; without Ki-67: χ(2)=9.202, P=0.027)but not pathological(P>0.05) response to NAC. By multivariate analysis, Ki-67 was predictive for a clinical complete response (P=0.041) and clinical overall response (P<0.01); also Ki-67 was the only clinicopathological factor predictive of pathological response(P=0.041). Conclusion: The molecular classification with Ki-67 is better to predict breast cancers responsiveness to NAC than the molecular classification without Ki-67.