BACKGROUND:For teeth with normal dental crown height,pulp cavity retention crown restoration with different depths of the pulp cavity and different repair materials affects the stress and flexural strength of tooth tissue.For short crown molar defects,the research on pulp cavity repair mainly focuses on clinical observation and in vitro flexural strength experiments. OBJECTIVE:To establish a three-dimensional finite element model for short crown molar restored by the endocrown after root canal treatment to analyze the effects of different pulp cavity retention depths and different repair materials on the distribution and size of dentin equivalent stress. METHODS:Based on establishing the complete model of the short crown mandible first molar,a three-dimensional finite element model was established for repairing the distal adjacent defect of the short crown molar with different pulp cavity retention depths(h=2,3,4 mm)and different repair materials(zirconia,lithium disilicate).Under the oblique loading,the equivalent stress distribution was observed.The peak value of dentin equivalent stress and the mean value of equivalent stress near the bottom of the mesial pulp cavity wall were calculated. RESULTS AND CONCLUSION:(1)Equivalent stress concentration areas:The stress of complete short crown molar and restored models mainly concentrated in the mesial root mesial neck and mesial root lingual neck.The stress concentration area was found in the mesial pulp cavity wall corresponding to the bottom layer of restored models,and the stress concentration was obvious in the 4 mm retention depth group.(2)Under the same repair material,the peak value of dentin equivalent stress was the lowest at 3 mm for all models after repair.The average value of equivalent stress near the bottom of the mesial pulp cavity wall was lowest at 3 mm.(3)Under the same retention depth,there was no significant difference between the two materials in the dentin equivalent stress peak and the mean value near the bottom of the mesial pulp cavity.(4)The results showed that under the conditions of this experiment,the endocrown was used to repair the defect of the short crown molar and the retention depth was 3 mm,which was more beneficial to protect the remaining dental tissue.The selection of zirconia or lithium disilicate as the repair material had little effect on the dentin stress.

ObjectiveTo observe the inhibitory effect of sinomenine on human glioblastoma and its pharmacokinetic characteristics in glioblastoma. MethodA human glioblastoma U87 cell line stably expressing luciferase was constructed， and a mouse glioma model was established for use in both pharmacodynamic and pharmacokinetic studies. Pharmacodynamics： Model mice were randomly divided into model group and sinomenine low-， medium-， and high-dose groups （50， 100， 150 mg·kg^-1）. Sinomenine was administered intraperitoneally for 14 days. The fluorescence value of brain tumors was observed to analyze its inhibitory effect on glioblastoma proliferation. Brain tumors and the surrounding brain tissue were collected， and the expression levels of vascular endothelial growth factor A （VEGFA）， P-glycoprotein （P-gp）， breast cancer resistance protein （BCRP）， and Occludin were detected by Western blot. Pharmacokinetics： Mice were divided into a normal group （50 mg·kg^-1） and model groups （50， 100， 150 mg·kg^-1）. After a single intraperitoneal injection of sinomenine， extracellular fluid from brain tumors was collected in vivo by microdialysis every 15 min for 6 h. Sinomenine concentrations in the dialysate were detected by HPLC-MS/MS， and pharmacokinetic parameters were calculated to analyze pharmacokinetic characteristics of sinomenine in the brain and glioblastoma. ResultCompared with model group， after 14 days of sinomenine administration， the fluorescence value of brain tumors significantly decreased （P<0.05） in a dose-dependent manner. Sinomenine inhibited the increase in VEGF and the degradation of Occludin in the tissue surrounding the tumor and inhibited the expression of VEGF， P-gp， and BCRP in glioblastoma. After a single administration， sinomenine was detected in brain and tumor tissues within 7.5 min. Compared with normal group， the C_max and AUC in the tumor significantly increased， T_max shortened （from 1.63 h to 0.71 h）， and CLz/F decreased. In the dose range of 50-150 mg·kg^-1， sinomenine exhibited a linear pharmacokinetic process in glioblastoma. ConclusionSinomenine has a significant inhibitory effect on glioblastoma， which can inhibit VEGF elevation and drug transporter efflux， reduce tumor invasion， and maintain the integrity of the blood-brain barrier. Sinomenine can rapidly cross the blood-tumor barrier， reach peak concentration， and exhibit linear pharmacokinetic characteristics in the tumor.

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Objective:To investigate the effect of sodium tanshinone ⅡA sulfonate (STS) on pyroptosis of human umbilical vein endothelial cells (HUVECs) induced by H 2O 2 and its possible mechanism. Methods:From November 2021 to September 2022, HUVECs were used as the research subjects at Wuxi Ninth People’s Hospital. The experiment was divided into four groups: the blank control group (normal condition), blank + STS group, H 2O 2 group and H 2O 2 + STS group. When the cells reached 80% fusion, 500.00 μmol/L of H 2O 2 was added to H 2O 2 group and H 2O 2 + STS group for 3 hours, and then the medium containing 500.00 μmol/L H 2O 2 was removed. After that, the blank+ STS group and the H 2O 2+ STS group were each supplemented with 5.00 μg/ml of STS and co-cultured with HUVECs for 24 hours. CCK-8 was used to assess the impact of STS at various concentrations (0.00, 0.05, 0.50, 5.00, 50.00, 500.00 μg/ml) on the proliferation of HUVECs. DNA damage-positive cells were detected with TUNEL staining. The expression of NOD-like receptor protein 3 (NLRP3) was detected using real-time PCR (RT-PCR) to investigate the optimal concentration of pyroptosis induced by H 2O 2. A detection kit was used to measure the expression of reactive oxygen species (ROS) induced by H 2O 2. The effect of STS on the migration and tube formation of HUVECs during pyroptosis was examined using a cell scratch test and a matrix gel tube formation test. The expressions of NLRP3, caspase-1, interleukin-18, and interleukin-1β were detected using RT-PCR and Western blotting. Repeated measures ANOVA was used to compare the concentrations at different time points, t-tests were used to compare data between two groups, and one-way ANOVA was used to compare data between multiple groups. P<0.05 was considered statistically significant. Results:STS below 50.00 μg/ml had no effect on the proliferation of HUVECs, while 500.00 μmol/L H 2O 2 had the most significant effect on inducing pyroptosis in HUVECs. TUNEL staining showed that compared with the control group, the number of TUNEL-positive cells in H 2O 2 group was significantly increased, and the difference was statistically significant ( P<0.01). However, there was no significant difference in the number of TUNEL-positive cells in the H 2O 2+ STS group ( P>0.05). The results of ROS detection showed that compared with the H 2O 2 group, intracellular ROS levels in the H 2O 2+ STS group was significantly decreased, and the difference was statistically significant ( P<0.01). Cell scratch and tube formation in vitro experiments showed that compared with the control group, cell mobility and tube formation ability were significantly decreased in the H 2O 2 group (all P<0.01), and there was no statistical significance in the H 2O 2+ STS group (all P>0.05). RT-PCR and Western blotting results showed that, compared with the H 2O 2 group, the expression of pyroptosis-related factors in the H 2O 2+ STS group was significantly decreased (all P<0.05). Conclusion:STS can inhibit the excessive production of ROS, promote the cell migration and tubular formation of HUVECs after pyroptosis induction, and alleviate H 2O 2-induced pyroptosis of HUVECs, thereby promoting angiogenesis.

Objective:The effect of bone marrow soluble B cell maturation antigen (sBCMA) expression on the efficacy and side effects of chimeric antigen receptor (CAR) -modified T-cell-targeting B cell maturation antigen (BCMA) in patients with multiple myeloma (MM) .Methods:This study involved 29 patients with relapsed or refractory MM (RRMM) who received humanized anti-BCMA CAR-T cell clinical trials from January 2018 to December 2021. The expression of sBCMA in bone marrow before and after anti-BCMA CAR-T cell treatment was detected by flow cytometry and compared.Results:①Two months after BCMA CAR-T cell treatment, 20 patients (68.97%) achieved an overall response (OR), whereas nine patients had stable disease (SD) or miner emission (MR). ②The expression of sBCMA in the bone marrow of 20 patients with OR was higher before treatment than after [26 926 (18 215, 32 488) ng/L vs 9 968 (6 634, 11 459) ng/L; P<0.001]; no significant difference was observed in patients with MR and SD [41 187 (33 816, 47 046) ng/L vs. 33 954 (31 569, 36 256) ng/L; P=0.145]; sBCMA expression in patients with OR before CAR-T cell treatment was lower than in patients with MR and SD ( P=0.005). ③No significant linear correlation was found between the peak value of CAR-T cells and sBCMA expression in the bone marrow of all 29 patients with RRMM ( R2=0.035, P=0.330). ④No significant difference in sBCMA expression was found between grades 0-1 CRS group (13 patients) and grades 2-4 CRS group [16 patients; 32 045 (18 742, 40 801) ng/L vs 29 102 (24 679, 38 776) ng/L, P=0.879], nor between grade 0 ICANS group (22 patients) and grade 1-3 ICANS group [seven patients; 30 073 (19 375, 40 065) ng/L vs 33 816 (22 933, 43 459) ng/L, P=0.763]. Conclusion:sBCMA expression in the bone marrow is related to the efficacy of BCMA CAR-T cell therapy in patients with RRMM, but is not significantly correlated with the severity of adverse events. It may serve as a predictive biomarker for the efficacy of BCMA CAR-T cell therapy in these patients.

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

Objective:To analyze the changes in the management methods of large medical equipment in China, evaluate the equity of large medical equipment allocation planning from the 13th Five-Year Plan to the 14th Five-Year Plan.Methods:The literature research was used to sort out the characteristics and changes of the management of large medical equipment in China. The database was established to quantitatively analyze the existing number of large medical equipment at the end of the 13th Five-Year Plan and the planned number of large medical equipment at the end of the 14th Five-Year Plan, and then the fairness evaluation was carried out based on the Lorenz curve and Gini coefficient.Results:Since the 1980s, the management measures of large-scale medical equipment in China have been introduced and updated iteratively to meet the needs of social development and medical services. In addition to conventional radiotherapy equipment, the number of large medical equipment per million population in China at the end of the 14th Five-Year Plan at least doubled compared with the end of the 13th Five-Year Plan, among which the heavy ion radiotherapy system and the laparoscopic surgery system increased by more than two times. Lorenz curve analysis showed that the fairness of large medical equipment based on population distribution at the end of the 14th Five-Year Plan was better than that at the end of the 13th Five-Year Plan, especially for heavy ion proton radiotherapy system, high-end radiotherapy equipment and PET/MR. The Gini coefficient of large medical equipment planning based on population distribution during the 14th Five-Year Plan was generally smaller than that of the 13th Five-Year Plan. Except for the heavy ion proton radiotherapy system and PET/MR in North China, the Gini coefficient of the planned number of all kinds of equipment in the six regions of the country during the 14th Five-Year Plan was less than 0.4 based on population distribution, which was in a relatively fair state.Conclusions:The management of large medical equipment in China keeps pace with the times and constantly adapts to the new development stage of health care. The fairness of large medical equipment allocation planning based on population distribution in six regions of China has been steadily improved, and it is suggested that the fairness based on population distribution and the clinical application of existing equipment should be taken into account in the allocation planning.

Objective:To evaluate the efficacy and safety of endoscopic retrograde cholangiopancreatography (ERCP) after pancreaticoduodenectomy and endoscopic selection strategies.Methods:Clinical data of 34 patients treated with ERCP after pancreaticoduodenectomy at the Endoscopic Center of the First Affiliated Hospital of Air Force Medical University from January 2013 to December 2021 were retrospectively analyzed. The success rates of endoscopic insertion, diagnosis, treatment and ERCP, and the incidence of adverse events were analyzed.Results:Fifty ERCP treatments were performed in 34 patients. The success rates of endoscopic insertion, diagnosis, treatment, and ERCP after pancreaticoduodenectomy were 92.0% (46/50), 93.5% (43/46), 88.4% (38/43) and 76.0% (38/50), respectively. The success rates of ERCP assisted with colonoscope and balloon-assisted enterosocpe were 76.0% (19/25) and 75.0% (18/24), respectively. There were 3 adverse events, including 1 case of anastomotic mucosa tear during surgery, 1 case of cardiopulmonary arrest and 1 case of postoperative cholangitis.Conclusion:ERCP is effective and safe after pancreaticoduodenectomy in general. ERCP assisted with colonoscope and balloon-assisted colonoscope shows similar success rate after pancreaticoduodenectomy.

Objective:To investigate the efficacy of autologous fat grafting in the treatment of stable linear scleroderma.Methods:A retrospective analysis was performed on 40 patients with stable linear scleroderma who received autologous fat grafting from October 2017 to November 2020 in the Department of Dermatology, Xijing Hospital, Air Force Medical University. There were 22 males and 18 females, aged 12 - 36 (18.2 ± 4.82) years. Skin lesions involved the forehead in 16 cases, the perioral area in 4, the lower jaw in 2, the cheek in 9, the trunk in 5, and the lower limb in 4, and the size of depressed skin defects was 3 - 24 cm 3. The patients′ subjective satisfaction rate, the decrease in the size of depressed skin defects, and the incidence of adverse reactions after autologous fat grafting were analyzed during the follow-up. Results:Six months after the grafting, 40 patients were followed up and evaluated, and the size of depressed skin defects markedly decreased. The satisfaction rate for appearance improvement after the first grafting was 60% (24/40) ; 35 patients received the second grafting, with a satisfaction rate of 88.6% (31/35) ; 17 received the third grafting, with a satisfaction rate of 94.1% (16/17) ; the total satisfaction rate was 87.5% (35/40). After the grafting, local skin unevenness was observed in the grafting area in 3 patients, and in the liposuction area in 2. The incidence rate of postoperative adverse reactions was 12.5% (5/40) .Conclusion:Autologous fat grafting was markedly effective in the treatment of stable linear scleroderma.

Objective:To analyze postoperative adverse reactions in patients with acne scars treated with punch elevation.Methods:Totally, 27 patients with moderate or severe acne scars, who were treated with punch elevation, were collected from the Department of Dermatology, Xijing Hospital, Air Force Medical University from June 2020 to March 2021. The patients received local infiltration anesthesia during the operation, and were cared for with tensile adhesive plaster bandaging, cold compresses, and waterproofing after the operation; telephone and face-to-face follow-up visits were conducted immediately, 3, 7, 14, 21, 30, and 60 days after the operation, and numerical rating scale (NRS) of intraoperative pain, postoperative swelling duration, postoperative erythema duration, and the incidence of post-inflammatory hyperpigmentation were recorded.Results:Among the 27 patients, the severity score of acne scars was 77.76 ± 43.76 points. The intraoperative pain NRS score was 3.75 ± 2.95 points after local infiltration anesthesia, the postoperative swelling lasted 3.42 ± 2.43 days, postoperative erythema lasted 4.74 ± 3.25 weeks, and the duration of postoperative erythema was not significantly correlated with the severity score of acne scars ( r = -0.13, P = 0.449). After the operation, post-inflammatory hyperpigmentation occurred in 2 patients, and no local infections or fulminant acne was observed. The patient satisfaction rate was 100% (27/27) . Conclusion:The main adverse reactions to punch elevation for acne scars were postoperative swelling and erythema, which subsided spontaneously about 1 month after the operation.