Endodontic microsurgery (EMS) is an oral surgical procedure that utilizes the magnification and illumination provided by a microscope. Fine instruments are used to remove periapical diseased tissues, resect the root apex, and tightly seal the root canal system, aiming to promote the healing of periapical tissues and retain the affected tooth whenever possible. Precise localization and resection of the root apex have always been challenging in EMS. The application of digital technology in EMS can address many issues in traditional endodontic microsurgery. Digital technology offers advantages such as optimizing surgical planning, providing precise positioning guidance, and enhancing operational accuracy. Currently, the commonly used digital technologies in EMS include static and dynamic navigation technologies and oral surgical robots. Static navigation technology enhances surgical predictability through precise preoperative planning and guided fabrication, yet is constrained by its inability to adjust during surgery. Dynamic navigation technology excels in real-time tracking and intraoperative flexibility but demands high hand-eye coordination from surgeons and may be hindered by bulky handheld devices. Oral surgical robots reduce hand tremors and human error in surgery with their high precision, stability, and ability to adjust in real time, but their clinical applicability is limited and their cost is high. In clinical practice, tailored combinations of these technologies can be applied based on case complexity. For simple cases with well-defined anatomy, static navigation alone may suffice. For complex anatomical cases, static navigation can provide initial planning, supplemented by dynamic navigation for real-time guidance or robotic systems for high-precision execution. This paper discusses the workflow, clinical application status and advantages and limitations of these three digital technologies in EMS. The continuous development of digital technology is expected to simplify the operation process, improve the navigation accuracy, and reduce the operation cost. It is believed that with continuous improvement and optimization, these technologies will effectively break through the current bottleneck of the cost of equipment, operation complexity, and accuracy enhancement. These technologies are also expected to further expand the application boundaries, providing more minimally invasive, precise, and time-saving personalized treatment solutions for endodontic diseases.

OBJECTIVE: To investigate the effect and mechanism of Hyssopus cuspidatus Boriss. extract (HCE) in ovalbumin (OVA)-induced allergic asthma. METHODS: Components identification of HCE was conducted using ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry. Mice were sensitized with OVA to establish asthmatic model, and dexamethasone was used as positive control. Respiratory reactivity, white cells counting in bronchoalveolar lavage fluid and peripheral blood, cytokine level measurement in serum and lung tissue, and histologic examination were performed to evaluate the therapeutic effect of HCE on asthma. Network pharmacology approach was used for mechanism prediction. Western blotting and untargeted lipidomics method were applied for mechanism validation. RESULTS: Fifty-two compounds were identified in HCE, predominantly terpenoids and flavonoids. HCE markedly reduced airway resistance, the eosinophil infiltration in lung tissues, and the levels of immunoglobulin E, interleukin-4, interleukin-5, and interleukin-13. Network pharmacology analysis suggested phosphatidylinositol 3-kinases (PI3K), c-Jun N-terminal kinase (JNK), and p38 Mitogen-activated protein kinase (p38 MAPK) may be key proteins of HCE in the treatment of allergic asthma. Western blot results indicated that the levels of phosphorylated PI3K, JNK, and P38 were downregulated in HCE-treated group. Moreover, HCE significantly upregulated the levels of ceramide and sphingomyelin and downregulated the level of phosphatidylcholine. CONCLUSION HCE inhibited allergic asthma via PI3K/JNK/P38 signaling pathway and lipid homeostasis regulation.

Multiple sclerosis (MS) is a neuroinflammatory demyelinating disease, mediated by pathogenic T helper 17 (Th17) cells. However, the therapeutic effect is accompanied by the fluctuation of the proportion and function of Th17 cells, which prompted us to find the key regulator of Th17 differentiation in MS. Here, we demonstrated that the triggering receptor expressed on myeloid cells 2 (TREM-2), a modulator of pattern recognition receptors on innate immune cells, was highly expressed on pathogenic CD4-positive T lymphocyte (CD4⁺ T) cells in both patients with MS and experimental autoimmune encephalomyelitis (EAE) mouse models. Conditional knockout of Trem-2 in CD4⁺ T cells significantly alleviated the disease activity and reduced Th17 cell infiltration, activation, differentiation, and inflammatory cytokine production and secretion in EAE mice. Furthermore, with Trem-2 knockout in vivo experiments and in vitro inhibitor assays, the TREM-2/zeta-chain associated protein kinase 70 (ZAP70)/signal transducer and activator of transcription 3 (STAT3) signal axis was essential for Th17 activation and differentiation in EAE progression. In conclusion, TREM-2 is a key regulator of pathogenic Th17 in EAE mice, and this sheds new light on the potential of this therapeutic target for MS.
Animals ; Humans ; Mice ; CD4-Positive T-Lymphocytes/pathology* ; Cell Differentiation ; Encephalomyelitis, Autoimmune, Experimental/metabolism* ; Mice, Inbred C57BL ; Multiple Sclerosis ; Th1 Cells/pathology*

OBJECTIVE To prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets by stereolithography （SLA） 3D printing technology， and to conduct its quality evaluation and in vitro release investigation. METHODS Using venlafaxine hydrochloride/fluoxetine hydrochloride， photopolymerization monomer PEGDA 400， porogen PEG 300， photoinitiator TPO and light absorber citrine as formulation， SLA 3D printer technology was employed to prepare venlafaxine hydrochloride and fluoxetine hydrochloride multiplayer tablets， with outer diameter of 10 mm， inner diameter of 5 mm， and thickness of 6 mm. Moreover， the tablets’ appearance， three-dimensional dimensions， weight uniformity， drug content， internal structural characteristics and in vitro release characteristics were all investigated. RESULTS The multilayer tablets had good printing formability， smooth and round edges， and uniform size and thickness； the outer diameter， inner diameter and thickness were （10.06±0.26）， （4.94±0.06）， （5.80±0.12） mm （RSD＝2.58%， 1.21%， 2.07%，n＝20）， and the weight difference all met the requirements. The contents of venlafaxine hydrochloride and fluoxetine hydrochloride were （7.96±0.09） and （11.26±0.46） mg/tablet， respectively. The results of X-ray diffraction and scanning electron microscopy characterization showed that the two drug molecules in the multilayer film existed in an amorphous structure； after the dissolution of the venlafaxine hydrochloride layer， a clear pore structure was formed， while the fluoxetine hydrochloride layer did not show any pore structure. According to the release curve， 24 h accumulative release rates of venlafaxine hydrochloride layer and fluoxetine hydrochloride layer were（91.88±0.94）% and （106.25±1.28）%， which were in line with Rigter-Peppas release model. CONCLUSIONS This study successfully prepared venlafaxine hydrochloride and fluoxetine hydrochloride multilayer tablets using SLA 3D printing technology； the multilayer tablets have the advantages of excellent printing formability， which are in line with Rigter-Peppas release model.

Objective:To analyze and summarize the clinical, genotypic and pathological characteristics of children with PAX2 gene mutation in China, and to provide information for the monitoring, treatment and prognosis of the disease. Methods:It was a case series analysis study. The clinical data of children with PAX2 gene mutation in Pediatric Nephrology Department, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from January 2014 to December 2022 were collected, and peripheral blood gene DNA was extracted and sequenced for whole exome sequencing. The clinical, pathological and genotypic characteristics of PAX2 gene variation of children in China were summarized by searching PubMed, Medline, China National Knowledge Infrastructure and Wanfang database and compared with the cases in this single center. Results:Among the 13 children with PAX2 gene mutation, there were 9 males and 4 females, 12 patients with abnormal urine tests, 7 patients with small kidney volume by imaging examination, and 5 patients with renal cysts. The clinical phenotypes were congenital renal and urinary tract malformations in 8 cases, renal coloboma syndrome in 1 case, and hematuria or proteinuria in 3 cases. Five patients underwent renal biopsies, showing focal segmental glomerulosclerosis and C3 glomerulopathy in 1 case, focal segmental glomerulosclerosis in 1 case, thin basement membrane lesion in 1 case, and IgA nephropathy in 2 cases. The genetic testing in 13 children showed 9 de novo mutations and 4 new mutations of c.321G>A, c.213-8C>G, c.63C>A and c.449C>T. There were 2 cases of 76dupG (p.V26Gfs*28) mutant. A total of 51 Chinese children with PAX2 gene mutation were found in the literature search. There were 32 males and 19 females, 8 cases with small kidney volume and 12 cases with renal cysts. The clinical phenotypes were congenital anomalies of kidney and urinary tract in 28 cases, renal coloboma syndrome in 17 cases, and hematuria or proteinuria in 6 cases. Seven patients underwent renal biopsies, including 2 cases with focal segmental glomerulosclerosis, 1 case with minimal lesion, 1 case with mesangial proliferative glomerulonephritis, 1 case with IgA nephropathy, 1 case with membranous nephropathy and a case with focal proliferative sclerosing purpura nephritis combined with glomerular hypertrophy. Thirty-four cases were de novo mutations, and 12 mutations were from the father or mother. The father or mother of 5 children had no clinical manifestations, with normal renal function. There were 11 cases of 76dupG (p.V26Gfs*28) mutant. Conclusions:The clinical phenotypes and genotypes of PAX2 gene variation in Chinese children are diverse. The most common clinical phenotype of PAX2 gene variation is congenital anomalies of kidney and urinary tract. c.76dupG (p.V26Gfs*28) is the most common of PAX2 gene variant.

Objective To establish a risk prediction model for type 2 diabetes mellitus(T2DM)related overactive bladder(OAB),and to verify the diagnostic efficacy and clinical application value of the model.Methods The clinical data of 298 patients with diabetes who underwent urodynamic examination in The First Affiliated Hospital of Wannan Medical College from January 2020 to October 2023 were analyzed retrospectively.According to the results of urodynamics,all the patients were divided into T2DM group(T2DM,n=218)and OAB group(OAB,n=80).The risk factors of OAB were analyzed by logistic regression,and the prediction model was established according to the risk factors.Receiver operating characteristic(ROC)curve,calibration diagram and decision curve analysis(DCA)were used to analyze and evaluate the diagnostic efficiency of the model.Results Logistic regression analysis results showed that age,DM duration,BMI,HbA1c,DPN and OAB score(OABSS),were independent predictors for OAB.The nomogram model built based on the above risk factors had good predictive ability,and its area under ROC curve was 0.937.The correction curve showed that the predicted probability of OAB in patients with type 2 diabetes mellitus was basically parallel to the actual probability of urodynamic detection.The results of DCA show that the model has high clinical value.Conclusions The nomogram model built by age,DM duration,OABSS,BMI,HbA1c,DPN has high predictive efficacy for OAB in patients with T2DM.

Objective:To determine a relationship between ultrasound shear wave elastography (SWE) and pathological lessions of renal tissues in children with chronic kidney disease (CKD).Methods:It was a cross-sectional observational study, involving children admitted to the Department of Pediatrics of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2021 with definite pathological diagnosis through kidney biopsy. The SWE was used to determine the Young's modulus (elastic modulus) of the cortex and medulla of the upper, middle, and lower poles of the kidney. The renal histopathology was classified or graded. The statistical method was used to analyze the relationship between Young's modulus of the inferior polar cortex (YM cor) and medulla (YM med) of the right kidney and renal pathology. Results:The study included 110 children with definite pathological diagnosis through renal biopsy, aged (10.1±3.4) years old (2-17 years old), with 55 males (50.0%). The body mass index was (20.6±2.4) kg/m 2, and mean arterial pressure was (95±24) mmHg. There were 94 patients (85.4%) with CKD stage 1, 8 patients (7.3%) with CKD stage 2, and 8 patients (7.3%) with CKD stage 3. There was no significant difference of YM cor and YM med in the upper and middle poles of the right kidneys, and YM med in the lower poles of right kidneys in CKD patients with different stages (all P>0.05). Both YM cor [(15.75±3.36) kPa] and YM med [(13.50±2.43) kPa] of CKD stage 3 patients were significantly higher than those of CKD stage 1 patients [(12.94±2.45) kPa, (11.88±2.23) kPa](both P<0.05). There was no significant difference of YM cor and YM med in the lower poles of right kidneys between stage 1 and stage 2 CKD patients (both P>0.05). YM cor[(17.93±3.23) kPa] and YM med [(15.50±1.48) kPa] in patients with crescentic glomerulonephritis were higher than those in patients with focal segmental glomerulosclerosis [(12.71±2.42) kPa, (11.57±2.63) kPa] and mesangial proliferative glomerulonephritis [(12.73±2.04) kPa, (11.48±2.10) kPa](all P<0.05). There was no significant difference of YM cor and YM med between focal segmental glomerulosclerosis and mesangial proliferative glomerulonephritis (both P>0.05). YM cor [(16.30±2.63) kPa] and YM med [(15.54±1.59) kPa] of Lee's Ⅳ grade of IgA nephropathy were higher than those of Lee's Ⅲ grade [(13.32±2.70) kPa, (12.57±2.50) kPa](both P<0.05), while the International Study of Kidney Disease in Children grade of purpura nephritis had no significant correlation with YM cor and YM med (both P>0.05). YM cor [(15.41±2.37) kPa] and YM med [(13.82±2.59) kPa] of interstitial fibrosis/tubular atrophy (T1/T2) group of IgA nephropathy mixed with purpura nephritis were significantly higher than those of T0 group's [(12.99±2.40) kPa, (11.79±2.05) kPa] (both P<0.05). Moreover, crescent formation (C1) group had a higher YM cor [(14.21±2.77) kPa] and YM med [(12.80±2.47) kPa] than those in C0 group [(12.73±2.15) kPa, (11.59±1.97) kPa] (both P<0.05), while YM cor and YM med were unrelated to the mesangial hypercellularity (M), endocapillary cellularity (E), segmental sclerosis or adhesion (S) indicators (all P>0.05). In lupus nephritis patients, YM cor ( r=0.744, P=0.035) and YM med ( r=0.728, P=0.009) were favorably linked with the chronic index, but not with the activity index (both P>0.05). Conclusions:Renal interstitial fibrosis/tubular atrophy and crescentic development are connected with YM cor and YM med at the lower pole of the kidney as measured by SWE. SWE can be used to assess the chronic renal lesions in children with CKD in the early and middle stages. It may develop into a new noninvasive way to assess renal pathology.

Objective To observe the metabolomic changes of amniotic fluid in control group and administration group,and to explore the toxicity of aqueous extract of rhubarb on reproduction and embryonic development of pregnant rats.Methods Pregnant rats in teratogenic sensitive period were given rhubarb aqueous extract by gavage for 10 days.The toxicity of rhubarb to maternal rats and the abnormal conditions of dead fetus and absorbed fetus were observed.The amniotic fluid samples were detected by liquid chromatography-mass spectrometry(LC-MS),the amniotic fluid metabolic profiles were compared by principal component analysis(PCA)and partial least squares(OPLS-DA),and the differential lipids were analyzed by metaboanalyst 5.0.Results Rhubarb administration in the teratogenic sensitive period can significantly reduce the number of live fetuses,and lead to adverse phenomena such as absorption of fetuses and premature death of fetuses.The preliminary results of lipomics showed that rhubarb could cause the metabolic disorder of amniotic fluid in pregnant rats,and there were metabolic abnormalities in lipids in amniotic fluid such as PI,PC and LPC.Conclusion Under the equivalent dose of the maximum dose recommended by the clinic,the aqueous extract of rhubarb has certain reproductive and embryonic toxicity to rats;Rhubarb may affect the normal development of rat embryos by causing the disorder of lipid metabolism in amniotic fluid.

Objective To investigate the clinical efficacy of peripheral blood stem cell transplantation from haploidentical and matched sibling donors for treatment of high-risk and refractory/relapsed acute myeloid leukemia (AML). Methods Data on the efficacy of haploidentical peripheral blood stem cell transplantation (Haplo-HSCT) with myeloablative conditioning regimen were retrospectively analyzed and compared with that of matched sibling donors' peripheral blood stem cell transplantation (MSD-HSCT) for treatment of high-risk refractory/relapsed AML in our center from January 1st, 2010 to June 30th, 2020. Results A total of 98 patients were enrolled, including 62 patients in the Haplo-HSCT group and 36 patients in MSD-HSCT group. The median age, conditioning regimen, and infusion doses of MNC and CD34+ cells were significantly different between the two groups, but no significant differences in other baseline parameters were found. Transplantation-related infectious complications and the incidence of acute and chronic graft-versus-host disease (GVHD) were also not significantly different between the two groups. The 3-year cumulative relapse in the Haplo-HSCT group was significantly lower than that in the MSD-HSCT group (16.2% vs. 41.1%, P=0.036). The 3-year DFS of the Haplo-HSCT and MSD-HSCT groups were 66.98% and 41.8%, respectively (P=0.140), and their OS were 73.37% and 51.41%, respectively (P=0.105). Conclusion The clinical efficacy of Haplo-HSCT for the treatment of high-risk and refractory/relapsed AML is similar to that of MSD-HSCT, and Haplo-HSCT may have better GVL effect.

Objective:To analyze the online learning behaviors and learning results of students under different teaching modes with different learning motivations, and to provide a reference for optimizing the development of online teaching.Methods:Samples of students taking the physiology small private online course (SPOC) in 2019 and 2020, and students taking the massive open online courses (MOOC) in the same year were selected in the study to discuss the differences in learning behaviors of students under different teaching modes and learning effects on students with different learning motivations. The online learning behaviors of students were analyzed based on their learning engagement, interactive behavior and learning motivation. SPSS 25.0 was used to analyze the data with statistical methods such as function calculation, frequency statistics, regression analysis, rank sum test, correlation test and chi-square test.Results:The learning participation level ( z=14.36, P<0.001), and the human-machine and interpersonal learning interaction level ( z=-11.70, -16.18, both P<0.001) of SPOC learners in 2020 were higher than those in 2019. The overall interactive level was moderately correlated with performances of students ( r=0.42, 0.52, both P<0.001), and the correlation between interpersonal behavior and grades was much more stronger ( r=0.60, 0.55, both P<0.001). The performance composition of SPOC and MOOC learners in 2019 was completely different ( χ2=857.45, P<0.001). The learning effect of externally motivated students was significantly better than that of internally motivated students ( z=-28.42, P<0.001). Conclusion:The teaching mode adopted by the school can affect the learning effect by influencing the students' online learning engagement and interactive behavior. Besides, students' own learning motivation also plays a key role in their academic performance.