Objective: To explore the treatment plan for severe papillary defects in the aesthetic zone caused by severe periodontitis, providing a reference for clinical practice. Methods : A patient with severe periodontitis leading to severe papillary defects in the upper anterior teeth from 12 to 23 was treated using interdental tunnel technique combined with personalized connective tissue grafting for periodontal plastic surgery, and stable soft tissue augmentation was achieved. Resin restoration was conducted to modify the crown shape of the aesthetic zone teeth, reconstruct white aesthetics, guide the shaping of the gingival papillae, reduce “black triangles,” and enhance the patient’s confidence in smiling. Results : The patient’s periodontal condition and the regeneration of soft tissues in the aesthetic zone were good, and the smile aesthetics were restored. After a 3-year follow-up, the gingival morphology, color, and texture were good, and the effect was stable. The literature review indicates that for papillary defects in the aesthetic zone, analysis should be conducted based on the following aspects: whether a defect is present in periodontal hard and soft tissues, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest. Based on the analysis of aesthetic defects and surgical indications, a personalized treatment plan should be designed. Conclusion For patients with obvious papillary defects in the aesthetic zone due to the reduction of periodontal support tissues caused by severe periodontitis, factors such as periodontal hard and soft tissue defects, crown shape, and the distance from the most apical part of the crown contact area to the top of the alveolar crest should be fully considered, and a personalized treatment plan should be formulated after multidisciplinary joint consultation.

Objective To analyze the value of serum C1q tumor necrosis factor related protein 12(CTRP12)in early pregnancy in predicting gestational diabetes(GDM).Methods 182 pregnant women who underwent prenatal examinations in our department from March 2020 to October 2022 were selected,serum CTRP12 levels were measured at 6～14 weeks of pregnancy.At 24～28 weeks of pregnancy,they were divided into normal glucose tolerance(n=152,NGT)group and GDM group(n=30,GDM)based on OGTT results.The serum CTRP12 levels of the two groups were compared and its predictive value for GDM was analyzed.Results The incidence rate of GDM was 16.48%.Compared with NGT group,the age,pre pregnancy BMI,FPG and family history of diabetes in GDM group were significantly higher,and the serum level of CTRP12 was significantly lower(P<0.05).BMI before pregnancy,family history of diabetes,FPG and serum CTRP12 were the influencing factors of GDM.Receiver operating characteristic analysis showed that the AUC of serum CTRP12 for predicting GDM was 0.822(95%CI 0.759～0.885),the optimal cut-off value was 5.66 ng/ml,with the sensitivity 68.2%and the specificity 90.3%,respectively.Compared with the high level group of CTRP12,the incidence rate of GDM in the low level group of CTRP12 was significantly higher(P<0.05).Conclusions The serum CTRP12 level in GDM patients decreases in the early pregnancy.CTRP12 as an influencing factor may have certain predictive value for GDM.

Objective:To construct the liver organoid infected with hepatitis D virus (HDV), and to investigate the role of the sodium taurocholate cotransporting polypeptide (NTCP) receptor inhibitor bulevirtide in inhibiting viral replication.Methods:Hepatocyte-like cells (HLC) differentiated from induced pluripotent stem cells (iPSC) were seeded onto inverted colloidal crystal polyethylene glycol scaffolds (ICC) to construct liver organoids. After transfecting human hepatocelluar carcinoma cells (HuH7 cells) with plasmids, HDV particles were harvested from the supernatant, while HBV particles were extracted from the HepG2.2.15 cell supernatant. The liver organoids were infected with both HBV and HDV particles, and the negative control group without HDV infection was set up. The microstructure of the liver organoid units and the expression of hepatitis D antigen (HDAg) and hepatitis B surface antigen (HBsAg) were observed under laser scanning confocal microscope by immunofluorescence method. The protein levels of NTCP and HDAg in the liver organoids were detected by Western blotting. Bulevirtide was added before HDV infection (bulevirtide pre group) and 24 hours after infection (bulevirtide post group), and interferon-alpha (IFN-α) was also added after 24 hours infection (IFN-α group), and a control group without drug treatment was set up. HDV replication was compared among the four groups after drug intervention. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to measure the relative mRNA expression levels of Nanog homeobox (NANOG), sex determining region Y-box (SOX)2, SOX17, forkhead box protein A2 (FOXA2), hepatocyte nuclear factor 4 alpha (HNF-4α), albumin (ALB), alpha-fetoprotein (AFP), NTCP during the differentiation of iPSC, and the mRNA expression of HDV after the drug intervention of the four groups. Statistical analysis was performed using two independent sample t tests. Results:Within 21 days of the differentiation of iPSC into HLC, the mRNA expression level of NANOG gradually decreased, while the expression levels of SOX17, FOXA2 initially increased then decreased, and the expression levels of the HNF-4α, ALB, AFP and NTCP progressively increased. The protein level of NTCP in iPSC (0.118±0.003) was lower than that in HLC (1.315±0.073), and the difference was statistically significant ( t=11.92, P<0.001).The protein level of HDAg in the liver organoids after HDV infection was higher than that in the negative control group without HDV infection (1.284±0.128 vs 0.157±0.040), and the difference was statistically significant ( t=23.27, P<0.001).Laser scanning confocal microscopy showed three-dimensional spheroid structures and high expressions of HDAg and HBsAg at the 14th day of infection.Compared with the control group (1.000±0.077), the HDV mRNA expressions in both IFN-α group (0.453±0.028) and bulevirtide pre group (0.136±0.012) decreased after three days of drug intervention. The differences were statistically significant ( t=19.95 and 33.15, respectively, both P<0.001). However, there was no significant difference in HDV mRNA expressions between the bulevirtide post group (0.968±0.069) and the control group ( t=0.94, P>0.05). Conclusions:The liver organoids constructed from iPSC-derived HLC and ICC can simulate human liver functions and successfully be infected by HDV particles. Early blockade with bulevirtide can effectively reduce the level of viral replication in the HDV-infected liver organoids.

OBJECTIVE To systematically review the pharmacoeconomic evaluation literature about proprotein convertase subtilisin/kexin type 9 （PCSK9） inhibitors for the prevention of cardiovascular disease in patients with hypercholesterolemia， and to provide a reference for clinical treatment， health decision-making and future follow-up research. METHODS Retrieved from English and Chinese databases such as PubMed and CNKI， the pharmacoeconomic literature about PCSK9 inhibitors （evolocumab and alirocumab） for the prevention of cardiovascular disease in patients with hypercholesterolemia was collected from the establishment of the database to October 8， 2023. The quality of the included literature was assessed with Consolidated Health Economic Evaluation Reporting Standards 2022 （CHEERS 2022） scale. The descriptive analysis was performed for basic information， model structure， related parameters， sensitivity analysis and the results of included studies. RESULTS & CONCLUSIONS A total of 29 literature were included， with overall good quality. The evaluation mainly adopted the Markov model from the healthcare system， payer and societal perspective. The effectiveness and utility data mainly came from the previous studies； the direct cost was mainly considered with a discount rate of 1.5%-5.0% per year， while the willingness-to-pay threshold was often set at 1-3 times the gross domestic product per capita. Most health output indicators were measured in life years and quality-adjusted life years. The sensitivity analysis of most studies demonstrated the robustness and the main influential factor was the drug cost. Most Chinese studies showed that PCSK9 inhibitor was not cost-effective for the prevention of cardiovascular disease in patients with acute coronary syndrome， myocardial infarction and atherosclerotic cardiovascular disease. It was cost-effective to use PCSK9 inhibitors for the prevention of cardiovascular disease only in specific groups， such as patients with triple vessel disease， patients with newly diagnosed acute coronary syndrome and low-density lipoprotein cholesterol≥100 mg/dL. Future research should refer to the CHEERS 2022 scale to improve the design， and strive to select large-scale， high-quality data to enhance the quality of reports and the transparency of health decisions， so as to more accurately assess the cost-effectiveness of PCSK9 inhibitors.

Objective To construct a stable synovial cell line MH7A from rheumatoid arthritis(RA)patients using lentiviral vectors that interfere with the expression of tumor necrosis factor receptor associated factor 2(TRAF2),and to study the role of TNF-α-TRAF2 signaling in MH7A abnormal proliferation.Methods Based on the design principles of human TRAF2 gene sequence and shRNA sequence,three pairs of TRAF2 shRNA interference se-quences were designed and synthesized.The primers were annealed by PCR,and a linear vector was obtained by double enzyme digestion PLKO.1-puro.The linearized vector was connected to the annealed primers through Solu-tion I,and the connected products were introduced into receptive cells.The plates were coated,and positive colo-nies were selected for sequencing.Three different recombinant plasmids of PLKO.1-TRAF2-shRNA lentivirus were constructed,and lentivirus packaging plasmids was used to package logarithmic growth phase HEK 293T cells.Vi-rus solution was collected to infect MH7A cells.At the same time,puromycin was used to screen MH7A stable transgenic strains with low TRAF2 expression.CCK-8 method,Western blot,and qPCR were used to detect the proliferation function of MH7A induced by TNF-α and low expression of TRAF2,as well as downstream signal TRAF2,P65 protein expression and mRNA levels.Results PLKO.1-TRAF2-shRNA(1),PLKO.1-TRAF2-shR-NA(2),and PLKO.1-TRAF2-shRNA(3)lentivirus vector plasmids and control group lentivirus vector plasmids PLKO.1-puro were successfully constructed.The three TRAF2-shRNA lentivirus vector plasmids and control group lentivirus vector plasmids PLKO.1-puro were respectively introduced into the lentivirus packaging plasmid of HEK 293T to obtain virus solution.After infecting MH7A cells with the virus solution,they were treated with puromycin(2.00 μ G/mL)screening and obtaining MH7A stable transgenic plants after 2 days.Through qPCR and Western blot results,it was found that the expression of TRAF2 mRNA and protein in PLKO.1-TRAF2-shRNA(1)MH7A stably transfected cells was significantly reduced compared to the negative control group.The results of CCK-8 and Western blot showed that after knocking down TRAF2 in MH7A,the proliferation of MH7A cells with low TRAF2 expression induced by TNF-α and the phosphorylation level of P65 were significantly reduced.Conclusion A sta-ble transgenic strain of PLKO.1-TRAF2-shRNA(1)MH7A cells was successfully constructed to investigate the role of TNF-α-TRAF2 signal activation in mediating abnormal proliferation of RA synovial cells.

In 2023，World Health Organization（WHO）announced that the pandemic of COVID-19 is over；while there was an epidemic of multi-pathogenic infections in the respiratory tract by the end of the year in China，indicating that high attention still need to be paid to infectious diseases. In the past one year，some breakthroughs for infectious diseases have been achieved.This article reviews the major events and research progress in the diagnosis，prevention and treatment of infectious diseases in 2023.

Objective:To summarize the main practices and experiences of the Centers for Medicare&Medicaid Services in the US.to pay for artificial intelligence(AI),which can provide references for the formulation of health insurance payment policies in China.Methods:Based on the literature study,it systematically analyzed the payment mechanism and typical cases of AI pay-ment in the US.Results:The US.has established four payment mechanisms for AI used in inpatient,outpatient and physician ser-vices,and set clear criteria for inclusion and payment,which has facilitated the clinical use of AI.Conclusion:It is suggested that China establish the payment mechanism for AI,focus on the clinical benefits of AI,and be alert of the overuse of AI.

Objective:To summarize the main practices and experiences of the Centers for Medicare&Medicaid Services in the US.to pay for artificial intelligence(AI),which can provide references for the formulation of health insurance payment policies in China.Methods:Based on the literature study,it systematically analyzed the payment mechanism and typical cases of AI pay-ment in the US.Results:The US.has established four payment mechanisms for AI used in inpatient,outpatient and physician ser-vices,and set clear criteria for inclusion and payment,which has facilitated the clinical use of AI.Conclusion:It is suggested that China establish the payment mechanism for AI,focus on the clinical benefits of AI,and be alert of the overuse of AI.

Objective:To summarize the main practices and experiences of the Centers for Medicare&Medicaid Services in the US.to pay for artificial intelligence(AI),which can provide references for the formulation of health insurance payment policies in China.Methods:Based on the literature study,it systematically analyzed the payment mechanism and typical cases of AI pay-ment in the US.Results:The US.has established four payment mechanisms for AI used in inpatient,outpatient and physician ser-vices,and set clear criteria for inclusion and payment,which has facilitated the clinical use of AI.Conclusion:It is suggested that China establish the payment mechanism for AI,focus on the clinical benefits of AI,and be alert of the overuse of AI.

Objective:To summarize the main practices and experiences of the Centers for Medicare&Medicaid Services in the US.to pay for artificial intelligence(AI),which can provide references for the formulation of health insurance payment policies in China.Methods:Based on the literature study,it systematically analyzed the payment mechanism and typical cases of AI pay-ment in the US.Results:The US.has established four payment mechanisms for AI used in inpatient,outpatient and physician ser-vices,and set clear criteria for inclusion and payment,which has facilitated the clinical use of AI.Conclusion:It is suggested that China establish the payment mechanism for AI,focus on the clinical benefits of AI,and be alert of the overuse of AI.