Objective: This study aims to explore the influencing factors, formation mechanisms, and treatment methods of labial protuberance in the anterior maxilla during orthodontic treatment, providing a reference for clinical practice. Method: This study reports a case where the absence of upper anterior teeth 11 and 21, and the retraction tilting movement of teeth 12 and 22, resulted in labial protuberance and gingival hyperplasia. Alveolar osteoplasty and gingivoplasty were performed. The specific changes in the alveolar bone during the retraction of the anterior teeth and the characteristics of its remodeling were analyzed. Combined with relevant literature, the factors influencing the formation of labial protuberance in orthodontic patients, mechanisms, and methods for prevention and treatment were summarized. Results: After periodental surgery follow-up for 6 months, the gingival color and shape of teeth 12 and 22 were good, the labial alveolar bone was normal, and the overall condition was stable. A review of the literature showed that labial protuberance is more common in adult orthodontic patients, and the distance (>4 mm) and speed of retraction of anterior teeth are related to its formation, with the main mechanism likely being differential remodeling of the alveolar bone. In adult patients, the number of active osteoblasts and osteoclasts in the alveolar bone decreases, along with a reduction in metabolic activity and overall cellular activity, which diminishes the reactivity of the alveolar bone. After treatment of anterior teeth retraction, there is insufficient labial bone resorption. Moreover, the lack of mechanical stress-mediated periodontal ligament in the interdental space leads to reduced bone remodeling stimulation in this area, resulting in thickening of the labial alveolar bone of the upper anterior teeth. The remodeling rates of cortical and trabecular bone differ, with active trabecular bone proliferation near the tooth root surface and slow cortical bone resorption near the outer surface, which ultimately results in increased bone thickness at the labial cervical region. Specific case analysis indicates that the retraction distance of the upper anterior teeth in this case was about 6 mm. The alveolar bone at the missing sites of teeth 11 and 21, lacking periodontal ligament stimulation, showed less remodeling and absorption, likely appearing as hyperplasia. The prevention of labial bone protrusion mainly involves controlling the speed and distance of retraction of anterior teeth. Smaller labial protuberances generally do not require treatment, but those affecting function and aesthetics can be addressed with periodontal alveolar osteoplasty. Conclusion After the retraction of anterior teeth in orthodontics, a prominent, hard bone protuberance on the labial side can sometimes occur, which may be due to differential remodeling efficiency in different regions of the alveolar bone. For bone protuberance that influences aesthetics or function, periodontal alveolar osteoplasty can be a reliable option.

OBJECTIVE: To evaluate the feasibility and short-term effectiveness of three-dimensional (3D)-printed customized porous acetabular components for reconstruction of extensive acetabular bone defects during primary total hip arthroplasty (THA). METHODS: The clinical data of 8 patients with extensive acetabular bone defects, who were treated with 3D-printed individualized porous acetabular components between July 2018 and January 2022, were retrospectively analyzed. The cohort comprised 4 males and 4 females with an average age of 48 years ranging from 34 to 56 years. Acetabular bone defects were classified as Paprosky type ⅢA in 3 cases and type ⅢB in 5 cases. The causes of acetabular destruction were hip tuberculosis (5 cases), pigmented villonodular synovitis (2 cases), and syphilitic arthritis (1 case). Visual analogue scale (VAS) score and Harris hip score (HHS) were used to evaluate the pain relief and hip function before and after operation. Reconstruction outcomes were further assessed by imaging results [X-ray film and Tomosynthesis Shimadzumetal artefact reduction technology (T-SMART)], and the mechanical properties were evaluated by finite element analysis. RESULTS: The operation time ranged from 174 to 195 minutes (mean, 187 minutes), and intraoperative blood loss ranged from 390 to 530 mL (mean, 465 mL). All 8 patients were follow-up 26-74 months (mean, 44 months). Among the 5 patients with tuberculosis, none experienced postoperative recurrence. At last follow-up, the VAS score was 0.3±0.5 and the HHS score was 87.9±3.7, both significantly improved compared to preoperative values ( t=25.170, P<0.001; t=-28.322, P<0.001). X-ray films at 2 years after operation demonstrated satisfactory matching between the 3D-printed customized acetabular component and the acetabulum. The postoperative center of rotation of the operated hip was shifted by (2.1±0.5) mm horizontally and (2.0±0.7) mm vertically relative to the contralateral side, with both offsets showing significant differences compared to preoperative values ( t=24.700, P<0.001; t=55.230, P<0.001). T-SMART imaging showed satisfactory osseointegration at the implant-host bone interface. No complications such as aseptic loosening or screw breakage was observed during follow-up. Finite element analysis showed that the acetabular component had good mechanical properties. CONCLUSION The application of 3D-printed individualized porous acetabular components in the reconstruction of extensive acetabular bone defects demonstrated precise anatomical reconstruction, stable mechanical support, and good functional performance in short-term follow-up, offering a potential alternative for acetabular defect reconstruction in primary THA.
Humans ; Middle Aged ; Male ; Female ; Printing, Three-Dimensional ; Arthroplasty, Replacement, Hip/instrumentation* ; Acetabulum/diagnostic imaging* ; Adult ; Follow-Up Studies ; Retrospective Studies ; Hip Prosthesis ; Prosthesis Design ; Porosity ; Treatment Outcome ; Plastic Surgery Procedures/methods*

In protein engineering, while computational models are increasingly used to predict mutation effects, their evaluations primarily rely on high-throughput deep mutational scanning (DMS) experiments that use surrogate readouts, which may not adequately capture the complex biochemical properties of interest. Many proteins and their functions cannot be assessed through high-throughput methods due to technical limitations or the nature of the desired properties, and this is particularly true for the real industrial application scenario. Therefore, the desired testing datasets, will be small-size (∼10-100) experimental data for each protein, and involve as many proteins as possible and as many properties as possible, which is, however, lacking. Here, we present VenusMutHub, a comprehensive benchmark study using 905 small-scale experimental datasets curated from published literature and public databases, spanning 527 proteins across diverse functional properties including stability, activity, binding affinity, and selectivity. These datasets feature direct biochemical measurements rather than surrogate readouts, providing a more rigorous assessment of model performance in predicting mutations that affect specific molecular functions. We evaluate 23 computational models across various methodological paradigms, such as sequence-based, structure-informed and evolutionary approaches. This benchmark provides practical guidance for selecting appropriate prediction methods in protein engineering applications where accurate prediction of specific functional properties is crucial.

This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL^-1) were used to induce fibrotic model, and high glucose (30 mmol·L^-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.

Objective:To investigate the effect of preoperative old muscular calf vein thrombosis on the safety and efficacy of total knee arthroplasty (TKA).Methods:A total of 411 patients with end-stage knee osteoarthritis who underwent primary TKA in the First Affiliated Hospital of Nanjing Medical University from September 2021 to March 2023 were retrospectively analyzed. There were 89 males and 322 females, aged 68.05±5.91 years (range, 50-82 years). The body mass index was 26.8±3.7 kg/m 2 (range, 17.4-39.8 kg/m 2). The group was divided into a preoperative thrombosis group (47 cases) and a preoperative none-thrombosis group (364 cases) according to whether or not there was a combination of old muscular calf vein thrombosis before TKA. The clinical characteristics (location and size) and lower limb swelling were observed, and the American Knee Society (AKS) score, visual analogue scale (VAS) and Villalta score were recorded to compare the differences between the two groups. Results:All patients successfully completed the operation and were followed up for 7.4±1.1 months (range, 6-9 months). Postoperative deep venous thrombosis (DVT) occurred in 96% (45/47) of the patients in the preoperative thrombus group, which was greater than the 38.5% (140/364) in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=55.184, P<0.001). 29% (13/45) of the patients who developed DVT postoperatively in the preoperative thrombus group had DVT located in the main vein, which was greater than the 9% (12/140) in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=12.028, P<0.001). 51% (23/45) of patients with DVT after operation had thrombosis ≥6 mm, which was higher than 34% (47/140) of patients in the preoperative none-thrombus group, and the difference was statistically significant (χ 2=4.454, P=0.035). The rate of thigh swelling on postoperative day 3 was 8.42%±3.50% in the group with preoperative thrombus and 7.80%±4.12% in the preoperative none-thrombus group, and the differences were not statistically significant ( t=-0.995, P=0.320). The rate of calf swelling on postoperative day 3 was 8.14%±3.40% in the preoperative thrombus group, which was greater than the 5.51%±3.45% in the preoperative none-thrombus group, and the difference was statistically significant ( t=-4.923, P<0.001). Postoperative AKS scores were elevated in both groups and were greater than preoperative scores at 3 and 6 months postoperatively, with statistically significant differences ( P<0.05). There was no significant difference in AKS score between the two groups before operation ( P>0.05), and the AKS scores in the preoperative thrombus group were smaller than those in the preoperative none-thrombus group at 3 and 6 months postoperatively, with a statistically significant difference ( P<0.05). Postoperative VAS scores were reduced in both groups and were smaller than preoperative scores at 3 and 6 months postoperatively, with statistically significant differences ( P<0.05). There was no significant difference in preoperative VAS scores between the two groups ( P<0.05), and the VAS scores in the preoperative thrombus group were greater than those in the preoperative none-thrombus group at 3 and 6 months postoperatively, with a statistically significant difference ( P<0.05). The Villalta score of patients with DVT after operation in the preoperative thrombus group was 4.47±2.47 at the last follow-up, which was greater than that of the preoperative none-thrombus group, which was 2.90±1.92, and the difference was statistically significant ( t=-4.395, P<0.001). Conclusion:Preoperative combined old muscular calf vein thrombosis increases the incidence of postoperative DVT and the dangerousness of DVT is higher.

Objective:To evaluate the value of 18F-FDG PET/CT for preoperative localization of epileptogenic foci in refractory epilepsy patients with negative MRI. Methods:Clinical data (550 lobes) of 55 epilepsy patients (38 males, 17 females, age (20.0±8.1) years) with negative MRI who underwent preoperative 18F-FDG PET/CT-MRI between January 2014 and June 2020 at the First Affiliated Hospital of Jinan University were retrospectively analyzed. The sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) of 18F-FDG PET/CT, video electroencephalogram (VEEG), PET/CT+ VEEG and PET/CT-VEEG for localizing epileptogenic foci were calculated using stereoelectroencephalography (SEEG) and the outcomes of at least 1 year of postoperative follow-up as reference standards. χ2 test was used to compare the efficiencies of different examination modalities for unilobar, multilobar and all patients. Results:The correct lateralization rate of epileptogenic foci was 92.6%(25/27) using PET/CT. The sensitivity, specificity, accuracy, PPV and NPV of PET/CT for localization of epileptogenic foci were 65.1%(54/83), 77.9%(364/467), 76.0%(418/550), 34.4%(54/157) and 92.6%(364/393), respectively. The sensitivities of PET/CT-VEEG for localization of epileptogenic foci in all patients and patients with multilobar epilepsy were higher than those of VEEG alone (75.9%(63/83) vs 45.8%(38/83), 68.6%(35/51) vs 31.4%(16/51); χ2 values: 15.80, 14.16, both P<0.001). The specificities of PET/CT+ VEEG for localization of epileptogenic foci in all patients and patients with unilobar epilepsy were higher than those of VEEG alone (97.6%(456/467) vs 94.6%(442/467), 97.9%(282/288) vs 94.1%(271/288); χ2 values: 5.66, 5.48; P values: 0.017, 0.019). The sensitivity of PET/CT-VEEG (PET/CT and VEEG concordance) for localization of epileptogenic foci was higher than that of PET/CT+ VEEG (PET/CT and VEEG discordance) (8/9 vs 28.4%(21/74); χ2=10.40, P=0.001), and its specificity and accuracy were higher than those of PET/CT-VEEG (PET/CT and VEEG discordance) (93.4%(57/61) vs 71.7%(291/406), 92.9%(65/70) vs 72.1%(346/480); χ2 values: 13.23, 13.96; both P<0.001). Conclusions:18F-FDG PET/CT can localize and lateralize epileptogenic foci in patients with negative MRI. The combination of 18F-FDG PET/CT and VEEG improves the sensitivity, specificity, and accuracy for epileptogenic foci detection. 18F-FDG PET/CT is more accurate in detecting epileptogenic foci when it is concordant with VEEG.

Objective To compare the effects of erector spinae plane block (ESPB) and serratus anteri-or plane block (SAPB) on postoperative analgesia and recovery time in the patients with thoracic surgery by the meta analysis.Methods The databases of Pubmed,Embase,Cochrane Library,Web of Science,CNKI, Wanfang and VIP were systematically retrieved by computer.The studies on the effect of ESPB and SAPB for postoperative analgesia in the patients with thoracic surgery published from January 1,2013 to now were col-lected.The RevMan5.4 software was used to conduct the summary analysis.Results A total of 13 random-ized controlled trials (RCT) involving 929 patients were included,including 464 cases in the ESPB group and 465 cases in the SAPB group.There was no statistically significant difference in the VAS pain scores at rest at postoperative 1,2,6,8,12,24,48 h and during activity at postoperative 2,4,8,12 h between the two groups (P>0.05).The rest VAS score at postoperative 4 h had statistical difference between the ESPB group and SAPB group (MD=-0.15,95％CI:-0.24 to -0.06,P<0.01).The activity VAS scores at postoperative 24 h had statistical difference between the ESPB group and SAPB group(MD=0.74,95％CI:0.01-1.48, P=0.05).There was statistically significant difference in the effective pressing times of analgesic pump at postoperative 48 h between the two groups (MD=-0.19,95％CI:-0.36-0.02,P=0.03).There was no statistically significant difference in the use amount of opioids drugs at postoperative 48 h between the two groups (MD=-5.32,95％CI:-11.76-1.13,P=0.11).There was no statistically significant difference in the incidence rates of postoperative analgesia-related adverse events,nausea and vomiting and skin pruritus between the two groups (MD=1.07,95％CI:0.85-1.34,P=0.58;MD=0.86,95％CI:0.53-1.40,P=0.56).The first time out of bed after surgery (MD=-0.01,95％CI:-0.04-0.05,P=0.81),postoperative eating time (MD=-0.22,95％CI:-0.84-0.40,P=0.49) and postoperative hospitalization stay duration (MD=-0.07,95％CI:-0.64-0.51,P=0.82) had no statistical differences between the two groups.Con-clusion SAPB and ESPB as postoperative analgesic methods all could provide good analgesic effect in the pa-tients with thoracic surgery.ESPB is recommended to use it first for postoperative analgesia in the patients with thoracic surgery

Objective:To investigate the effect of preoperative patellar tilt angle on postoperative outcome of total knee arthroplasty (TKA).Methods:A total of 277 patients with knee osteoarthritis who underwent TKA without patellar replacement in the First Affiliated Hospital of Nanjing Medical University from October 2020 to September 2022 were retrospectively analyzed. There were 72 males and 205 females, aged 69.16±6.77 years (range, 52-87 years), body mass index 27.01±3.81 kg/m 2 (range 18.14-39.01 kg/m 2). The patients were divided into three groups according to the preoperative tilt angle of the patella: tilt angle<5° for mild tilt group, 5°≤tilt angle<10° for moderate tilt group, and tilt angle≥10° for severe tilt group. There were 103 cases in the mild group, 137 cases in the moderate group, and 37 cases in the severe group. The preoperative and postoperative visual analogue scale (VAS), Hospital for Special Surgery (HSS) score and Feller's score of patella were compared. Results:All patients were followed up for 15.73±3.06 months (range, 12-22 months). The patellar tilt angle was 6.86°±3.55° preoperatively and 3.63°±2.61° postoperatively ( t=19.086, P<0.001). The patellar tilt angle of mild group, moderate group and severe group decreased after operation, and the difference was statistically significant compared with that before operation ( P<0.05). The anterior knee VAS of the three groups decreased after operation, and the differences were statistically significant compared with those before operation. The anterior knee VAS at 3, 6, and 12 months after operation were lower than those before operation. The differences between groups at 6 and 12 months postoperatively were statistically significant ( P<0.05), with anterior knee VAS scores of 2.59±0.55 and 2.03±0.55 in the severe group being greater than those of 2.15±0.38 and 1.57±0.50 in the mild group and 2.19±0.49 and 1.67± 0.61 in the moderate group. The HSS score of the three groups was increased after operation, and the difference was statistically significant compared with that before operation ( P<0.05), and the HSS scores at 3, 6 and 12 months after operation were higher than those before operation. There were significant differences at 6 and 12 months after operation ( P<0.05), the HSS scores of the severe group were 86.27±2.04 and 87.73±2.28, which were lower than those of the mild group 89.02±2.33 and 89.83±1.48, and the moderate group 88.77±2.83 and 89.52±1.95. Postoperative patellar Feller score increased in all three groups, and the difference was statistically significant compared with that before operation ( P<0.05), the patellar Feller score at 3, 6 and 12 months after operation was higher than that before operation. There were significant differences at 6 and 12 months after operation ( P<0.05), the patellar Feller scores in the severe group were 18.32±1.99 and 20.32±1.60, which were lower than those in the mild group 20.92±1.01 and 23.07±1.39 and the moderate group 20.91±1.95 and 22.69±1.59. Conclusion:In TKA patients without patella replacement, the increase of patellar tilt angle before operation can lead to anterior knee pain and reduced knee function.

Objective·To develope an auditory brainstem implant(ABI)vocoder based on cochlear implant(CI)vocoder characteristics and ABI electrode array topology,and to verify its reliability.Methods·An"n-of-m"coding strategy CI/ABI vocoder was constructed based on MATLAB.Within each frame,only the envelopes of the n channels with the highest energy were selected.The interaction coefficient(IC)(range:1?3),channel numbers(range:5?22),and electrode array topology(CI/ABI)were adjustable parameters,allowing for the synthesis of simulated speech.Psychoacoustic evaluation was employed,recruiting normal hearing subjects to perform closed-set simulated phoneme perception.The phoneme recognition accuracy(20 vowel questions/condition,11 consonant questions/condition)was compared with the corresponding conditions of CI and ABI from reference literature to determine the IC value of the vocoder and verify its reliability.Results·The vocoder successfully synthesized all test stimuli.In the closed-set CI-simulated speech recognition,the simulated vowel and consonant recognition accuracy for IC2 and IC3 conditions showed no significant difference compared to the accuracy reported in the CI reference literature(P＞0.05).The difference in vowel and consonant accuracy between IC2 and the literature was smaller than that between IC3 and the literature(vowel|d|=1.6%vs.20%,consonant|d|=8.4%vs.9.9%),thus determining the optimal interaction coefficient of this model as 2.Subsequently,when modifying the electrode array topology to ABI,it was found that the simulated phoneme recognition accuracy for a 16-channel ABI was significantly lower than that for the 16-channel CI group,consistent with the reported literature.The simulated vowel and consonant accuracy within the 5?8 channel range for ABI showed no significant difference(P＞0.05),also aligning with the trend reported in the literature.Conclusion·A CI/ABI vocoder based on"n-of-m"coding strategy is established and the optimal IC is determined.The established ABI encoder has been evaluated for high reliability through psychoacoustic experiments.It provides suitable technical means for validating ABI-specific coding strategies.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*