Objective:To explore the force distribution on the maxillary dentition when the first and second molars distalized simultaneously with different step sizes using clear aligners in vitro in order to provide a theoretical basis for the rational design of molar distalization. Methods:Clear aligners were designed to simultaneously distalize the maxillary first and second molars bilaterally, with rectangular attachments placed on the buccal surfaces of the first and second premolars, as well as the second molars. Based on different step sizes, the aligners were divided into three groups: Group A (0.15 mm per step), Group B (0.20 mm per step), and Group C (0.25 mm per step). Ten aligners were fabricated for each group using 0.76 mm thick polyethylene terephthalate glycol (PET-G) sheets. A three-dimensional force measurement system was used to measure the forces exerted on each tooth by the aligners, the first and second molars served as the target teeth and the remaining teeth as anchorage teeth. The three-dimensional force data were compared among the three groups.Results:In the mesiodistal direction, the forces on the central and lateral incisors were relatively small among all three groups, with no statistically significant differences ( P>0.05). However, significant differences were observed in the forces on the canines, first premolars, second premolars, first molars, and second molars ( P<0.05). The distal forces on the second molars in Groups B and C were (6.13±1.45) N and (6.83±1.58) N, respectively, significantly higher than that in Group A [(3.51±1.01) N] ( P<0.05). The distal force on the first molars in Group C [(6.62±0.89) N] was significantly higher than that in Groups A and B ( P<0.05). The mesial reactive forces on the first and second premolars in Groups B and C were significantly higher than those in Group A ( P<0.05). The mesial reactive force on the canines in Group C [(-2.98±1.33) N] was significantly higher than that in Group A [(-1.69±0.68) N] ( P<0.05), while there were no significant differences between Groups B and C in the forces on the canines, first premolars, and second premolars ( P>0.05). In the buccolingual direction, there were no statistically significant differences in the forces on the central and lateral incisors among three groups ( P>0.05), but significant differences were observed in the forces on the canines, second premolars, and second molars ( P<0.05). The buccolingual forces on the canines, second premolars, and second molars in Group B were (-0.56±0.54), (-2.07±0.95), (1.13±0.55) N, respectively, significantly higher than those in Group A ( P<0.05), but there were no significant differences compared to Group C ( P>0.05). Compared to the mesiodistal and buccolingual forces, the vertical forces on the target and anchorage teeth were relatively small in all three groups. Conclusions:When using 0.76 mm thick PET-G sheets to fabricate clear aligners for simultaneous molar distalization, a step size of 0.20 mm per step is recommended. To prevent buccal tipping of the molars during distalization, it is advisable to design lingual displacement for the molars and buccal displacement for the adjacent anchorage teeth to counteract the unfavorable forces, with attachments placed on the primary anchorage teeth.

In traditional clinical teaching of impacted tooth extraction, there are problems including limited observation fields for students, insufficient doctor-patient communication training, inadequate clinical thinking development, and low levels of clinical participation. Based on the core elements of visualizing jaw structure with perspective, formulating clinical strategy, immersing in clinical participation, and cultivating the spirit of caregiving, we developed a virtual reality simulation teaching platform for the clinical decision analysis of impacted tooth extraction. The virtual simulation-based platform can create three different impacted tooth scenarios in 3D, which demonstrates the process of clinical decision analysis of impacted tooth extraction through virtuality-reality interaction, allowing students to immerse in the discovery, analysis, and resolution of the medical and humanistic problems in the process of impacted tooth extraction. The questionnaire survey showed that 81.36% (48/59) of the students believed that the software could improve their clinical thinking ability; 76.27% (45/59) of the students believed that it could help them master the basic process of impacted tooth extraction; and 62.71% (37/59) of the students believed that it could improve their skills of impacted tooth extraction. By providing immersive learning experience, constructive teaching design, and multi-dimensional teaching evaluation, the software achieved the goals of cultivating students' clinical thinking ability and professional literacy in oral and maxillofacial surgery.

Mitochondrial dysfunction after spinal cord injury (SCI) is recognized as a crucial pathological mechanism for secondary SCI. Studies have indicated that mitochondrial transfer plays a significant role in the process of neural regeneration following injury. After mitochondria migrating to injured neurons, they mainly function via enhancing the energy metabolism level of damaged neurons and reducing oxidative stress. In this article, we present an exhaustive overview on mechanism of mitochondrial transfer, and impact on neural regeneration after mitochondrial transfer so as to provide valuable insights for further exploring the role of mitochondrial transfer in SCI progression and offer innovative perspective on potential therapeutic strategies for SCI.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

Objective:To investigate the efficacy and related influencing factors of autologous hematopoietic stem cell transplantation(auto-HSCT)as first-line consolidation therapy for newly diagnosed elderly patients with diffuse large B cell lymphoma(DLBCL).Methods:Retrospective study of clinical characteristics, therapeutic effect, and prognostic factors of newly diagnosed DLBCL elderly patients with an International Prognostic Index(IPI)score≥3 who underwent auto-HSCT in the Affiliated People's Hospital of Ningbo University from January 2015 to August 2020.Results:Among the 31 patients, 18 were males and 13 were females, with a median age of 65(60-75)years.The 13 cases(41.9%)were involved in 2 sites outside lymph nodes, and 13 cases(41.9%)were involved in bone marrow.IPI medium and high risk(IPI=3 points)was found in 21 cases(67.7%), high risk(≥4 points)in 10 cases(32.2%). Before transplantation, 21(67.7%)patients achieved complete remission(CR), and the other 10(32.3%)patients were in the partial remission(PR). All patients after transplantation achieved hematopoietic reconstitution.The median time for neutrophil and platelet engraftment were 10(9-16)days and 12(8-58)days respectively.During a median follow-up of 20.9(3.1 to 73.0)months after transplantation, transplant-related mortality within 100 days was 3.2%(1/31). The 2-year overall survival(OS)and progression-free survival(PFS)were(77.2±8.4)% and(72.7±8.3)%, respectively.Multivariate Cox analysis showed that the achieved partial remission status before auto-hematopoietic stem cell transplantation[OS( HR=30.064, 95% CI: 2.231-405.209, P=0.010), PFS( HR=9.165, 95% CI: 1.926-43.606, P=0.005)], and CD34 + cell count in graft <3×10 6/kg[OS( HR=12.004, 95% CI: 1.234-116.807, P=0.032), PFS( HR=6.115, 95% CI: 1.325-28.221, P=0.020)]were the independent poor prognostic factor affecting both OS and PFS in elderly lymphoma patients. Conclusions:Auto-HSCT may improve the survival rate of carefully selected elderly patients with DLBCL.Pretransplant disease status and the number of CD34 + cells in the graft are important factors to predict the efficiency of auto-HSCT of the patients.

Objective:To evaluate the efficacy and safety of intravitreal ranibizumab combined with laser (IVR+ Laser) and the intravitreal ranibizumab (IVR) monotherapy for the treatment of diabetic macular edema (DME).Methods:A meta-analysis was conducted on randomized controlled trial (RCT) literature related to IVR+ Laser therapy and IVR alone for DME.Databases including Cochrane Library, PubMed, EMbase, Web of Science, SinoMed, CNKI, VIP and WanFang Data were searched from their inception to April 2022.Literature screening, data extraction, quality evaluation and cross-checking were conducted independently by two researchers according to inclusion and exclusion criteria.Then a meta-analysis was conducted using RevMan 5.4.1 software.The two therapies were compared in terms of best corrected visual acuity (BCVA), central macular thickness (CMT), mean number of injections and adverse events.Results:Twelve RCTs involving 1 695 eyes were included in the study.Meta-analysis showed that at the end of follow-up, IVR+ Laser demonstrated better improvement in BCVA and CMT than IVR alone, and there were significant differences in the changes in BCVA and CMT between the two groups (weighted mean difference[WMD]=-0.66, 95% confidence interval[ CI]: -1.11--0.21, P<0.01; WMD=-5.05, 95% CI: -9.21--0.89, P=0.02).IVR+ Laser required significantly fewer injections than IVR alone (WMD=-1.16, 95% CI: -2.07--0.25, P=0.01).There were no significant differences in the adverse events incidence between the two therapies (all at P>0.05). Conclusions:The safety of IVR+ Laser is comparable to IVR alone, and it requires fewer injections for the treatment of DME.

Objective:To explore the effect of repetitive transcranial magnetic stimulation (rTMS) combined with cognitive behavioral therapies (CBT) on the cognitive function and alcohol craving in patients with alcohol dependence.Methods:From March 2019 to September 2021, a total of 150 patients with alcohol dependence were enrolled and randomly divided into rTMS treatment group (rTMS+ sham CBT, n=41), CBT treatment group (CBT+ sham rTMS, n=34), rTMS+ CBT treatment group( n=36) and control group (sham rTMS+ sham CBT, n=39). At baseline (before treatment), 2nd week, 8th week, 12th week and 24th week, alcohol dependence scale (ADS) was used to evaluate the degree of alcohol dependence, the obsessive compulsive drinking scale (OCDS) was used to assess patients' drinking craving, and Montreal cognitive assessment scale (MoCA) was used to assess the overall cognitive level of patients.SPSS 23.0 statistical software was used to compare the differences of ADS, OCDS and MoCA scale scores of the four groups by repeated measure ANOVA and simple effect analysis. Results:(1)The patients in the four groups were evaluated with ADS scale at baseline, 12th week and 24th week respectively.The interaction of group×time( F=1.279, P=0.279) and the main effect of group were not significant ( F=0.882, P=0.454), and the main effect of time was significant ( F=12.925, P<0.001) .Further simple effect analysis showed that the ADS score of rTMS+ CBT group was lower than that of baseline(14.48±5.70, 10.00±6.51) ( P=0.01) at 24th week.(2)Patients in the four groups were assessed with OCDs scale at baseline, 2nd week, 8th week, 12th week and 24th week, and the interaction of group×time was significant ( F=2.015, P=0.042). Further simple effect analysis showed that the OCDs scores of rTMS group and rTMS+ CBT group at each follow-up time node were lower than those at baseline period (all P<0.05). (3)Patients in the four groups were assessed with MoCA scale at baseline, 8th week, 12th week and 24th week, and the interaction of group×time was not significant ( F=1.660, P=0.106), and the main effect of group and the main effect of time were significant ( F=2.964, P=0.038; F=14.239, P<0.001). Further simple effect analysis showed that the score of MoCA scale in CBT group at the 24th week was higher than that at baseline (21.73±5.81, 24.60±3.98)( P=0.029), the score of MoCA scale in rTMS+ CBT group at the 24th week was higher than that at the 8th week (23.50±6.01, 25.95±2.87) ( P=0.006), and the score of MoCA scale in rTMS group at the 12th week was higher than that in control group (22.08±6.64, 26.64±2.46)( P=0.009). Conclusion:rTMS combined with CBT can be effective in improving alcohol craving and cognitive function in patients with alcohol dependence, and has a good long-term effect.

Objective:To compare the clinical manifestations of ocular toxoplasmosis (OT) in adult and children, and to preliminarily explore the role of intraocular fluid detection in the early diagnosis of OT.Methods:A retrospective study. From January 2018 to October 2019, 60 cases of OT patients with 60 eyes diagnosed in the Department of Ophthalmology of Beijing Chaoyang Hospital Affiliated of Capital Medical University were included in the study. The medical history information of patients was collected in parallel with slit-lamp microscopy, indirect ophthalmoscope examination, and canine toxoplasma antibody detection in aqueous or vitreous fluid. Fifty-eight cases underwent visual inspection; 2 cases did not underwent visual inspection, who were children. The visual acuity examination was carried out using the new version of the standard logarithmic visual acuity chart, which was converted into the logarithmic minimum angle of resolution(logMAR) visual acuity during statistics. According to age, the patients were divided into adult group and child group, with 12 eyes in 12 cases and 48 eyes in 48 cases, respectively. The clinical characteristics and main points of diagnosis and treatment of the two groups of patients were compared and observed. The comparison among the measurement data groups conforming and the normal distribution was performed by the independent t test. The comparison between the measurement data groups of the skewed distribution was performed by the Kruskal- Wallis test. The qualitative data were compared with χ 2 test. Results:Among the adult group and the child group, 7 (58.3%, 7/12) and 34 (70.8%, 34/48) patients with a clear history of contact with dogs and cats were in the adult group and the child group, respectively. The adult group was significantly lower than the child group, however, there was no different statistical significance ( χ 2=0.236, P=0.627). At the first visit, the self-reported blurred vision of the adult group and the child group was 10 (83.3%, 10/12) and 22 (45.8%, 22/48) cases, respectively. In the adult group and the child group, 3 (25.0%, 3/12) and 20 (43.5%, 20/46) eyes with logMAR visual acuity greater than 1.85, 8 (66.7%, 8/12) and 22 (45.8%, 22/46) eyes with logMAR visual acuity less than 0.3. The visual acuity of the adult group was better than that of the child group, and the difference was statistically significant ( Z=2.162, P=0.031). There was no statistically significant difference in the composition ratio of different clinical types of the two groups of eyes ( χ 2=1.908, P=0.385). The incidence of inflammation in the anterior segment of the eye in the adult group and the child group were 25.0% (3/12) and 56.3% (27/48), respectively; there was no statistically significant difference between the two groups ( χ 2=3.750, P=0.053). The concentration of antibodies in the vitreous humor of the affected eye in the adult group and the child group was greater than that of aqueous humor. The antibody concentrations of vitreous humor and aqueous humor were 36.51 (22.58) and 19.94 (21.78) U/ml in the children group; 45.95 (56.44) and 32.20 (38.64) U/ml in the adult group. Comparison of antibody concentrations in the vitreous humor and aqueous humor of the affected eyes in the child group showed statistically significant differences ( Z=-1.984, P=0.047). Conclusions:Compared with children with OT, adult patients with OT have better vision and mild inflammation or hyperplasia of the vitreous cavity. The detection of antibodies related to toxoplasma in the intraocular fluid is helpful for early diagnosis.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.