With the increasing use of nirmatrelvir-ritonavir in older COVID-19 patients, adverse drug reactions due to drug-drug interactions have become more frequent. This report describes a patient who experienced severe bradycardia and hypotension following the concurrent use of heart rate-control medications and nirmatrelvir-ritonavir during an active COVID-19 infection. This suggests that clinicians should be cautious when dealing with nirmatrelvir-ritonavir and try their best to avoid serious adverse reactions.

Objective:To explore the predictive value of atherogenic index of plasma(AIP)combined with neutro-phil/HDL-C ratio(NHR),lymphocyte/HDL-C ratio(LHR)and monocyte/HDL-C ratio(MHR)for major adverse cardiovascular events(MACE)in patients with acute coronary syndrome(ACS).Methods:This retrospec-tive study enrolled 320 patients underwent coronary angiography in Department of Cardiovascular Medicine,Harri-son International Peace Hospital between January 2021 and December 2022,including 215 ACS patients and 105 pa-tients without ACS;according to Gensini score,ACS patients were divided into low risk group(n=50),medium risk group(n=70)and high risk group(n=95).According to the presence of MACE within 1 year,patients were divided into MACE group(n=55)and no MACE group(n=160).After admission,blood routine,blood lipids,C-reactive protein(CRP)and endothelin-1(ET-1)levels were measured,then NHR,LHR,MHR and AIP were calculated.Spearman method was used to analyze the association of above-mentioned indexes with Gensini score;stepwise Logistic regression was used to analyze the influencing factors of MACE within 1 year in ACS patients;and ROC curve was used to analyze the predictive value of single and combined detection of above indexes for MACE within 1 year in ACS patients.Results:Compared to patients in no ACS group,those in ACS group had significantly higher BMI[(23.59±0.85)kg/m2 vs.(21.57±1.16)kg/m2],proportions of hypertension(57.67％vs.13.33％),diabetes(23.26％vs.8.57％),NHR[(12.09±3.46)vs.(3.81±1.29)],MHR[(0.70±0.18)vs.(0.33±0.10)],LHR[(0.79±0.21)vs.(0.40±0.09)],AIP[(0.21±0.06)vs.(0.11±0.02)],CRP[(9.82±3.09)mg/L vs.(2.20±0.58)mg/L],ET-1[(31.25±10.34)μg/L vs.(10.60±1.96)μg/L](P＜0.001 all).Compared to those in no MACE group,patients in MACE group had significantly higher NHR[(17.33±3.87)vs.(10.12±2.68)],MHR[(0.93±0.24)vs.(0.61±0.13)],LHR[(1.05±0.27)vs.(0.71±0.16)],AIP[(0.28±0.04)vs.(0.17±0.02)],CRP[(15.52±3.83)mg/L vs.(7.69±2.40)mg/L],ET-1[(46.68±9.51)μg/L vs.(25.47±4.66)μg/L]levels(P＜0.001 all).Spearman correlation analysis showed that NHR,MHR,LHR and AIP were significant positively correlated with Gensini score(r=0.837～0.868,P＜0.001 all).Stepwise Logistic regression analysis showed that NHR(OR=1.225,95％CI 1.016～1.550,P=0.035),AIP(OR=2.632,95％CI 1.055～6.566,P=0.038)were independent risk factors for MACE within 1 year in ACS patients.ROC curve shows that AUC of AIP combined with NHR,MHR and LHR predicting MACE within 1 year in ACS patients was 0.786(95％CI 0.725～0.839),which was significantly higher than those of NHR(AUC 0.768,95％CI 0.706～0.823),LHR(AUC 0.749,95％CI 0.686～0.806)and AIP(AUC 0.764,95％CI 0.701～0.819)alone(Z=2.597,2.687,1.965,P＜0.05 or＜0.01).Conclusion:AIP combined with NHR,MHR and LHR have certain predictive value for MACE within 1 year in ACS patients.

Objective:In order to effectively educate students on tooth defect diseases and restoration techniques, the teaching and research team at the School of Stomatology of Qingdao University developed an integrated course operative dentistry. This course is specifically designed to align with the undergraduate curriculum reform requirements of "Three Early, Two Multiple and One Integration".Methods:The teaching practice of operative dentistry was conducted with the stomatology undergraduates of grade 2020 and 2021. The course group redesigned the curriculum by reorganizing teaching content, rebuilding teaching resources, reconstructing teaching mode, and reshaping the evaluation system. Evaluation of the curriculum design included test scores, satisfaction questionnaires, and teacher self-evaluation. Statistical analysis was performed using SPSS 27.0 software, including independent sample t-tests for numerical variables and Fisher's exact test or Wilcoxon rank sum test for categorical variables. Results:Through the integrated course learning, 92.68% (38/41) of the students of grade 2020 and 97.44% (38/39) of the students of grade 2021 can basically or completely master various dental defect repair schemes and understand the importance of preserving natural tooth. 82.93% (34/41) of the students of grade 2020 and 100.00% (39/39) of the students of grade 2021 could basically or completely master the key points of various dental defect restorations.Conclusions:Through the practice of teaching, it has been confirmed that the integrated course of operative dentistry is beneficial to students' mastering the knowledge and skills of dental defect diseases and their restoration in a more comprehensive way, and is conducive to the cultivation of clinical thinking, hands-on ability and the patient-centered, comprehensive problem-solving thinking, which is in line with the guidance on the innovation and development of medical education.

Objective To investigate the effect of Pirfenidone(PFN)on respiratory syncytial virus(RSV)infection-induced damage to bronchial epithelial cells by regulating the high mobility group protein B1(HMGB1)/receptor for advanced glycation end products(RAGE)signaling pathway.Methods Human bronchial epithelial cells(HBE)were divided into Control group(cultured for 24 h under normal conditions),RSV group(inoculated with 4.65×106/mL RSV at 33℃for 2 h);low PFN(L-PFN)group(treated with 0.05 mg/mL PFN for 24 h),moderate PFN(M-PFN)group(treated with 0.10 mg/mL PFN for 24 h),high PFN(H-PFN)group(treated with 0.20 mg/mL PFN for 24 h)and recombinant HMGB1(rHMGB1)group(treated with 1 μg/mL rHMGB1+0.20 mg/mL PFN for 24 h).EdU method was applied to detect the proliferation rate of cells in each group,Hochest33258 staining method was applied to detect apoptosis status of cells in each group,and the migration of cells in each group was evaluated by the scratch experiment.Enzyme linked immunosorbent assay(ELISA)was applied to measure the levels of interferon(IFN)-α,IFN-γ,tumor necrosis factor-α(TNF-α),interleukin(IL)-1α,IL-6 and IL-4 in each group of cells,and Western blot was applied to detect the protein expression of HMGB1,RAGE,B lymphoblastoma-2-associated X protein(Bax),cysteine aspartic protease-3(Caspase-3),and B lymphoblastoma-2(Bcl-2).Results Compared with the RSV group,the cell proliferation rate,scratch closure rate,IL-4 levels,and expression of Bcl-2 in L-,M-,and H-PFN groups increased,while the apoptosis rate,the levels of IFN-α,IFN-γ,TNF-α,IL-1α,IL-6,and the expression of HMGB1,RAGE,Bax,and Caspase-3 reduced(P<0.05);rHMGB1 weakened the effect of H-PFN on the above-mentioned indicators(P<0.05).Conclusion PFN may suppress the apoptosis and inflammatory damage of RSV-infected bronchial epithelial cells by inhibiting the HMGB1/RAGE pathway.Conclusion PFN may suppress the apoptosis and inflammatory damage of RSV-infected bronchial epithelial cells by inhibiting the HMGB1/RAGE pathway.

Objective:To evaluate the relevant factors to optimize the learning curve and the impact of the basic skills of endoscopic technology on the learning curve of gasless transaxillary posterior endoscopic thyroidectomy.Methods:A retrospective analysis was performed to evaluate the clinical outcomes of 50 patients who underwent Glandular Ultrasound-Assisted (GUA) thyroid surgery by a surgeon with a background in endoscopic thyroid surgery via the thoracic-areolar approach, and 50 patients operated on by a surgeon without such experience at the Thyroid Surgery Department of Jilin University China-Japan Union Hospital from Apr. to Dec. 2023. The patients were divided into two groups: the Endoscopic Experience Group and the Non-Endoscopic Experience Group. The Cumulative Sum Control Chart (CUSUM) was applied to construct learning curves for both groups, dividing the technical exploration period from the mastery period. The analysis compared the surgical time, postoperative first-day drainage volume, number of central lymph nodes dissected rates, and postoperative complications between the two groups and across the two phases.Results:The analysis of the learning curve revealed that the inflection point of the Endoscopic Experience Group was 15, while of the Non-Endoscopic Experience Group was 18. The learning curve was divided into the technical exploration stage and the proficient mastery stage. The operative time of technical exploration stagde was significantly longer than of proficient mastery stage of both group (183.46±36.13min vs.144.40±26.14min, P<0.001; 186.89±48.91min vs.131.59±22.90min; P<0.001) . The operative time in the proficient mastery stage of the Endoscopic Experience Group was longer than that of the Non-Endoscopic Experience Group (144.40±26.15min vs. 131.59±22.90min, P<0.05) . The postoperative drainage volume in the Endoscopic Experience Group was lower than that in Non-Endoscopic Experience Group in both stages (65.40±32.48mL vs.93.22±30.67mL, 57.40±15.35mL vs.78.50±28.30mL, P<0.05) , and the postoperative drainage volume in the proficient mastery stage of the Non-Endoscopic Experience Group was significantly lower than in the technical exploration stage (93.22±30.67mL vs.78.50±28.30mL, P<0.05) .No significant differences in central lymph node dissection numbers or postoperative complications were observed between the groups at both stages. Conclusions:There is a specific learning curve in the early stage of gasless transaxillary posterior endoscopic thyroidectomy. After crossing the learning curve, the operation time is obviously shortened with the improvement of the operator's surgical technique.Having a basic understanding of endoscopic technology in the early stage can reduce the occurrence of postoperative drainage, but has a minimal impact on the learning curve.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.

Xeroderma pigmentosum(XP)is a rare autosomal recessive disorder related to XP gene variation,often causing secondary malignant tumors.This article reports a case of a young child with secondary squamous cell carcinoma of the lower lip caused by xero-derma pigmentosum.Through a review of relevant literature,the clinical characteristics,pathogenesis,clinical pathological manifesta-tions,and prognosis of XP are discussed.

Objective:Currently, there is a lack of targeted training programs for resident physicians in cardiopulmonary resuscitation (CPR) in China. This study aims to establish a stratified training indicator system for resident physicians in CPR that is in line with the medical realities in China.Methods:Expert consultation questionnaires were designed through literature review, group discussions, and surveys. Two rounds of expert consultation were conducted using the modified Delphi method to develop the stratified training indicator system for resident physicians in CPR. Statistical analysis was performed using SPSS 26.0 software and Kendall's coefficient of concordance was used to assess the consistency of expert opinions.Results:A total of 15 experts participated in two rounds of questionnaire consultation, with a positive coefficient of 100.00% and an authority coefficient of 0.91, indicating high expert engagement and authority, thus ensuring the credibility of the results. The coefficient of variation for expert ratings in the first round of questionnaire consultation ranged from 0 to 0.40, with a concordance coefficient of 0.22 ( P<0.001). In the second round of questionnaire consultation, the coefficient of variation for expert ratings ranged from 0 to 0.24, with a concordance coefficient of 0.25 ( P<0.001). The Kendall's coefficient of concordance for expert opinions showed statistically significant differences in both rounds of questionnaire consultation, indicating consensus among experts and reliable results. This system consisted of 6 primary indicators and 32 secondary indicators. Conclusions:Based on the modified Delphi method, this study established a stratified training indicator system for resident physicians in CPR. In the future, based on the research findings, CPR training programs adapted to the medical realities in China will be developed and promoted to validate their scientific and practical value.

Objective:To explore the predictive value of atherogenic index of plasma(AIP)combined with neutro-phil/HDL-C ratio(NHR),lymphocyte/HDL-C ratio(LHR)and monocyte/HDL-C ratio(MHR)for major adverse cardiovascular events(MACE)in patients with acute coronary syndrome(ACS).Methods:This retrospec-tive study enrolled 320 patients underwent coronary angiography in Department of Cardiovascular Medicine,Harri-son International Peace Hospital between January 2021 and December 2022,including 215 ACS patients and 105 pa-tients without ACS;according to Gensini score,ACS patients were divided into low risk group(n=50),medium risk group(n=70)and high risk group(n=95).According to the presence of MACE within 1 year,patients were divided into MACE group(n=55)and no MACE group(n=160).After admission,blood routine,blood lipids,C-reactive protein(CRP)and endothelin-1(ET-1)levels were measured,then NHR,LHR,MHR and AIP were calculated.Spearman method was used to analyze the association of above-mentioned indexes with Gensini score;stepwise Logistic regression was used to analyze the influencing factors of MACE within 1 year in ACS patients;and ROC curve was used to analyze the predictive value of single and combined detection of above indexes for MACE within 1 year in ACS patients.Results:Compared to patients in no ACS group,those in ACS group had significantly higher BMI[(23.59±0.85)kg/m2 vs.(21.57±1.16)kg/m2],proportions of hypertension(57.67％vs.13.33％),diabetes(23.26％vs.8.57％),NHR[(12.09±3.46)vs.(3.81±1.29)],MHR[(0.70±0.18)vs.(0.33±0.10)],LHR[(0.79±0.21)vs.(0.40±0.09)],AIP[(0.21±0.06)vs.(0.11±0.02)],CRP[(9.82±3.09)mg/L vs.(2.20±0.58)mg/L],ET-1[(31.25±10.34)μg/L vs.(10.60±1.96)μg/L](P＜0.001 all).Compared to those in no MACE group,patients in MACE group had significantly higher NHR[(17.33±3.87)vs.(10.12±2.68)],MHR[(0.93±0.24)vs.(0.61±0.13)],LHR[(1.05±0.27)vs.(0.71±0.16)],AIP[(0.28±0.04)vs.(0.17±0.02)],CRP[(15.52±3.83)mg/L vs.(7.69±2.40)mg/L],ET-1[(46.68±9.51)μg/L vs.(25.47±4.66)μg/L]levels(P＜0.001 all).Spearman correlation analysis showed that NHR,MHR,LHR and AIP were significant positively correlated with Gensini score(r=0.837～0.868,P＜0.001 all).Stepwise Logistic regression analysis showed that NHR(OR=1.225,95％CI 1.016～1.550,P=0.035),AIP(OR=2.632,95％CI 1.055～6.566,P=0.038)were independent risk factors for MACE within 1 year in ACS patients.ROC curve shows that AUC of AIP combined with NHR,MHR and LHR predicting MACE within 1 year in ACS patients was 0.786(95％CI 0.725～0.839),which was significantly higher than those of NHR(AUC 0.768,95％CI 0.706～0.823),LHR(AUC 0.749,95％CI 0.686～0.806)and AIP(AUC 0.764,95％CI 0.701～0.819)alone(Z=2.597,2.687,1.965,P＜0.05 or＜0.01).Conclusion:AIP combined with NHR,MHR and LHR have certain predictive value for MACE within 1 year in ACS patients.

Objective:To explore the safety and efficacy of intraosseous regional administration (IORA) of vancomycin for preventing infection in primary total knee arthroplasty (TKA).Methods:A total of 124 patients with knee osteoarthritis undergoing TKA between February 2024 and May 2024 at nine hospitals were enrolled. Preoperative infection prophylaxis involved either IORA (0.5 g vancomycin administered via intraosseous regional infusion before incision) or intravenous infusion (1 g vancomycin via peripheral vein). The IORA group included 15 males and 47 females with a median age of 66.5 years (range, 60.0-70.0 years), while the intravenous group included 14 males and 48 females with a median age of 66.0 years (range, 61.8-70.3 years) years. Intraoperative samples were collected including fat and synovium tissues after incision, before prosthesis placement, and after tourniquet release; distal femoral cancellous bone during femoral osteotomy; proximal tibial cancellous bone during tibial osteotomy; proximal intercondylar cancellous bone before prosthesis placement; and peripheral blood from non-infused arms at surgery initiation and after tourniquet release. Vancomycin concentrations were measured using liquid chromatography-tandem mass spectrometry. Vital sign changes were recorded from admission to 5~10 minutes post-IORA (IORA group) or post-incision (intravenous group). Follow-ups were conducted on postoperative day 1 and 3, and at 1 and 3 months, to document complications including IORA-related adverse events, periprosthetic joint infections, surgical site infections, red man syndrome, acute kidney injury, deep vein thrombosis and so on.Results:Vancomycin concentrations in bone, fat, and synovial tissue samples were significantly higher in the IORA group than in the intravenous group ( P<0.05), while vancomycin concentrations in blood samples were significantly lower in the IORA group than in the intravenous group ( P<0.05). Only 7.3%(41/558) of tissue samples in the IORA group had vancomycin concentrations below 2.0 μg/g (the minimum inhibitory concentration of vancomycin against coagulase-negative staphylococcus), compared to 59.3%(331/558) in the intravenous group (χ 2=11.285, P<0.001). In the intravenous group, 16.9%(21/124) of blood samples had vancomycin concentrations exceeding 15.0 mg/L (the threshold associated with a significantly increased risk of nephrotoxicity), while all concentrations in the IORA group were below this threshold, the difference was statistically significant (χ 2=22.943, P<0.001). There were no statistically significant difference ( P>0.05) in vital signs changes before and after vancomycin administration between the two groups. Two patients in the intravenous group experienced incision exudate, while no other related complications occurred in either group. Conclusions:Compared to the traditional intravenous infusion of 1 g vancomycin, intraosseous injection of a low dose (0.5 g) of vancomycin achieves higher local tissue concentrations in the knee joint with a lower incidence of adverse reactions and is safe for infection prophylaxis. Despite guidelines not recommending the routine use of vancomycin for preventing infection after primary TKA, intraosseous injection of 0.5 g vancomycin may be considered intraoperatively for primary TKA in the following scenarios: patients in medical institutions with a high prevalence of methicillin-resistant staphylococcus aureus (MRSA) infections, patients with potential preoperative MRSA colonization, or patients with cephalosporin allergy.