Loss-of-function variants of low-density lipoprotein receptor-related protein 5 (LRP5) can lead to reduced bone formation, culminating in diminished bone mass. Our previous study reported transcription factor osterix (SP7)‍-binding sites on the LRP5 promoter and its pivotal role in upregulating LRP5 expression during implant osseointegration. However, the potential role of SP7 in ameliorating LRP5-dependent osteoporosis remained unknown. In this study, we used mice with a conditional knockout (cKO) of LRP5 in mature osteoblasts, which presented decreased osteogenesis. The in vitro experimental results showed that SP7 could promote LRP5 expression, thereby upregulating the osteogenic markers such as alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and β‍-catenin (P<0.05). For the in vivo experiment, the SP7 overexpression virus was injected into a bone defect model of LRP5 cKO mice, resulting in increased bone mineral density (BMD) (P<0.001) and volumetric density (bone volume (BV)/total volume (TV)) (P<0.001), and decreased trabecular separation (Tb.‍Sp) (P<0.05). These data suggested that SP7 could ameliorate bone defect healing in LRP5 cKO mice. Our study provides new insights into potential therapeutic opportunities for ameliorating LRP5-dependent osteoporosis.
Animals ; Low Density Lipoprotein Receptor-Related Protein-5/metabolism* ; Osteoporosis/genetics* ; Mice ; Mice, Knockout ; Sp7 Transcription Factor/physiology* ; Osteogenesis ; Bone Density ; Osteoblasts/metabolism* ; Core Binding Factor Alpha 1 Subunit/metabolism* ; Mice, Inbred C57BL ; beta Catenin/metabolism*

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective:To analyze the effect of continuous positive airway pressure (CPAP) on maternal and neonatal outcomes in pregnant women with obstructive sleep apnea syndrome (OSAS), especially on the incidence of hypertensive disorder in pregnancy (HDP) in women with moderate to severe OSAS.Methods:A total of 180 pregnant women with OSAS who were diagnosed through sleep monitoring during pregnancy due to high-risk factors of OSAS and registered in Peking University People′s Hospital from January 2021 to May 2024 were selected as the study subjects. Clinical data were collected from medical records for retrospective analysis. According to whether they received standardized treatment with CPAP, they were divided into the CPAP treatment group (42 cases) and the control group (138 cases). The CPAP treatment group consisted of 9 pregnant women with moderate to severe OSAS, while the control group consisted of 34 pregnant women with moderate to severe OSAS. The maternal and neonatal outcomes, the incidence of HDP, placental weight after delivery and placental weight/neonatal birth weight ratio were compared between the two groups.Results:(1) The average gestational age of pregnant women in the CPAP treatment group was higher than that in the control group [(38.7±1.0) vs (38.0±1.4) weeks], the proportion of infants small for gestational age (SGA) in the CPAP treatment group was lower [0 (0/42) vs 12.3% (17/138)], and the birth weight of infants in the CPAP treatment group was bigger [(3 396±475) vs (3 082±710) g); the differences between the two groups were statistically significant (all P<0.05). There were no significant differences between the CPAP treatment group and the control group in terms of delivery mode, rates of postpartum hemorrhage and preterm birth, umbilical artery blood gas analysis pH<7.1, lactate≥6.0 mmol/L, base excess<-12.0 mmol/L and the incidence of gestational diabetes mellitus and HDP (all P>0.05). (2) The placental weight of the CPAP treatment group was significantly lower than that of the control group [(554.0±70.6) vs (615.7±119.1) g], the placental weight/newborn birth weight ratio of the CPAP treatment group was significantly lower than that of the control group (median: 0.17 vs 0.19), and the differences were statistically significant (all P<0.05). (3) The incidence of HDP in pregnant women with moderate to severe OSAS in the CPAP treatment group was lower than that in the control group [1/9 vs 61.8% (21/34)], and the difference was statistically significant ( P<0.05). Conclusions:CPAP treatment could prolong the gestational age in pregnant women with OSAS, reduce the incidence of SGA, increase the birth weight of infants, and reduce the incidence of HDP in pregnant women with moderate to severe OSAS, and is worth promoting in clinical practice. The improvement of neonatal outcomes by CPAP treatment is closely related to the placenta, which is worthy of further exploration.

Objective:To analyze the clinical characteristics and treatment of patients with acute Q fever in Dali Bai Autonomous Prefecture, Yunnan Province.Methods:A total of 26 patients with acute Q fever admitted to People′s Hospital of Yunnan Dali Bai Autonomous Prefecture from October 2022 to December 2023 were enrolled. A retrospective cross-sectional study analysis was performed to analyze the demographic characteristics, epidemiology, clinical manifestations, laboratory tests and pathogen detection of these patients.Results:Of the 26 patients, 25 were male and one was female. The age ranged from 18 to 82 years with an average age of (45.6±17.2) years. All of them were sporadic cases. The neighbors of eight patients had sheep and cattle, 11 cases had a history of field work, and four cases had a history of field trip. Coxiella burnetii was detected in 26 patients by different molecular diagnostic techniques, including 21 cases by blood quantitative polymerase chain reaction (qPCR), three cases by sputum multi-pathogen targeted next-generation sequencing (tNGS), one case by alveolar lavage fluid tNGS, and one case by cerebrospinal fluid metagenomic next-generation sequencing (mNGS). Routine blood cultures of 19 cases were negative. All 26 patients presented with chills and fever, 21 cases (80.8%) with headache, 19 cases (73.1%) with fatigue, 14 cases (53.8%) with generalized aches and pains, 12 cases (46.2%) with poor appetite, and 14 cases (53.8%) with cough. Twenty-four cases had concurrent hepatitis, 12 cases had pneumonia, one had encephalitis, and 19 cases had myocardial damage. The laboratory tests showed that 23 cases (88.5%) had normal white blood cell count, eight cases (30.8%) had decreased platelet count, 25 cases (96.2%) had C-reactive protein elevated, 24 cases (92.3%) had procalcitonin elevated, 14 out of 17 cases had elevated erythrocyte sedimentation rate, and 19 cases had elevated D-dimer levels. Liver function tests showed that alanine aminotransferase increased in 24 cases (92.3%) (all less than 10 times of upper limit of normal (ULN)), aspartate aminotransferase increased in 23 cases (88.5%) (all less than 10 times of ULN), alkaline phosphatase increased in 10 cases (38.5%)(all less than two times of ULN), and γ-glutamyl transpeptidase increased in 19 cases (73.1%), which were all less than 10 times of ULN. Myocardial enzymes were detected in 21 cases, of which seven cases (33.3%) had elevated lactate dehydrogenase and 12 cases (57.1%) had elevated hydroxybutyrate dehydrogenase (all less than three times of ULN). In terms of treatment, 16 cases were treated with doxycycline alone, and nine cases were treated with doxycycline combined with azithromycin or quinolones or rifampicin, and one with tigecycline. After treatment, the conditions of patients improved. The overall length of hospital stay was (7.7±5.0) d, and that of eight patients treated with doxycycline combined with quinolones or azithromycin was 4.8 to 6.0 days. Conclusions:Acute Q fever often has no clear epidemiological history, and the clinical manifestations and laboratory tests are lack of specificity. qPCR, tNGS, mNGS can provide pathogenic diagnostic evidence for suspected cases. In terms of treatment, doxycycline is the first choice for treatment of acute Q fever, and combined treatment with azithromycin or quinolones could result in a shorter hospital stay.

Objective:To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate(ThuFLEP)in the treatment of oversized(＞200 mL)prostate.Methods:Clinical data of 475 benign prostatic hyperplasia(BPH)patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed,all of whom were treated with thu-lium fiber laser,and the patients were divided into three groups according to the total volume of the pros-tate(TPV):group A(TPV＜100 mL),group B(100 mL≤TPV＜200 mL),and group C(TPV ≥200 mL).The age of the patients in the three groups[(69.38±7.79)years,(69.64±8.69)years,(70.32±7.44)years],International Prostate Symptom Score(IPSS)[(22.7±1.9),(22.8±2.7),(25.8±3.7)],and the maximum urinary flow rate(Qmax)[(7.9±2.7)mL/s,(9.3±4.3)mL/s,(9.9±3.3)mL/s]were not statistically significant(P＞0.05).The prostate volume in the three groups[(103.49±46.19)mL,(75.73±30.69)mL,(273.49±49.19)mL]and prostate specific antigen(PSA)[3.52(1.05,8.76)μg/L,6.78(1.61,7.45)μg/L,8.52(5.05,12.76)μg/L]were statistically significant(P＜0.05).Results:All surgeries were successfully completed.The dif-ferences in enucleation time[30.0(21.2,44.5)min,41.6(31.2,52.5)min,45.1(35.2,50.0)min]and hospitalization time[(6.06±1.21)d,(6.15±1.50)d,(7.71±1.74)d]among the three groups were not statistically significant(P＞0.05);and the differences in the postoperative in-dwelling catheter time[(4.0±1.4)d,(4.0±1.3)d,(6.6±1.1)d],operative time[61(42,89)min,82(62,105)min,115(96,142)min],enucleation efficiency[1.29(0.71,1.56)g/min,1.67(1.23,2.15)g/min,2.74(2.20,3.34)g/min],and hemoglobin drop values[12(7,19)g/L,17(11,24)g/L,27(19,35)g/L]were statistically different(P＜0.05).Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight(r=0.880,P＜0.001),and the enucleation efficiency increased with the increase of prostate volume.The differences in IPSS[(6.6±1.7),(6.2±1.4),(4.6±1.1)]and Qmax[(18.9±3.1)mL/s,(16.8±3.8)mL/s,(22.9±7.1)mL/s]were not statistically significant among the three groups(P＞0.05),and the differences in IPSS and Qmax were statistically significant compared with those before surgery.The differences were statistically significant in preoperative comparisons,but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax(P＜0.05).The patients in the three groups were followed up for 3 months,and post-operative complications were categorized into Clavien-Dindo Ⅰ(urinary retention,persistent hematu-ria),Clavien-Dindo Ⅱ(glandular remnants,urinary tract infection,blood transfusion)and Clavien-Dindo Ⅲ(urethral stenosis,contracture of the bladder neck,and reoperation for hemorrhage)based on the Clavien-Dindo Complications System score,the incidence of Clavien-Dindo in the three groups was 5.2％(13 cases),6.7％(12 cases)and 12.1％(7 cases),respectively,with statistically significant differences(P＜0.05);among them,there were statistically significant differences in urinary infection,blood transfusion and bleeding reoperation(P＜0.05),and there was no statistically significant difference in the remaining complications(P＞0.05).Conclusion:The risk of blood transfusion and re-hemostasis increases with larger prostate volume,the efficiency of enucleation increases with the increase of prostate vo-lume,and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.

Aim To investigate the predictive value of the Murray law-based quantitative flow ratio(μQFR)after target vessel pretreatment for vascular-related adverse events in patients with de novo coronary lesions treated with drug-coated balloon.Methods This retrospective study included 223 lesions from 223 patients who underwent drug-coated balloon-only strategy and completed 2-year clinical follow-up.Coronary angiographic images of target vessels pre-procedure,post-balloon and post-procedure were collected,and analyzed using a novel Murray's law-based algorithm.The μQFR analysis of each target vessel included not only the μQFR value of the target vessel,but also the length of the target vessel,the degree of vessel diameter stenosis,the reference lumen diameter,the minimum lumen diameter and blood flow velocity.The primary endpoint was defined as the postoperative vessel-oriented composite endpoint(VOCE).Results During the2-year clinical follow-up period,a total of 25 patients(11.2%)experienced VOCE events.Com-pared with the control group,patients with VOCE events after pretreatment showed a decrease in μQFR(P<0.001).Multivariate Logistic analysis showed that a lower target vessel μQFR after pretreatment(OR=0.931,95%CI:0.894～0.969,P<0.001)was an independent predictor of VOCE events.ROC curve analysis showed that the cut-off value for predicting 2-year VOCE events using preprocessed μQFR was 0.83(95%CI:0.727～0.840),with a sensitivity of 72.7%and a specificity of 84.0%(AUC=0.773,95%CI:0.676～0.870,P<0.001).Survival analysis showed that compared with patients with μQFR>0.83,patients with μQFR≤0.83 had a significantly higher incidence of VOCE events at 1 and 2 years,increasing to 3.909 times(16.9%vs.4.6%,HR=3.909,95%CI:1.539～9.930,P=0.004)and 2.867 times(19.7%vs.7.2%,HR=2.867,95%CI:1.301～6.316,P=0.009).After adjusting for potential con-founds,patients with pretreated μQFR≤0.83 had a 2.567 times in 2-year incidence of VOCE events(HR=2.567,95%CI:1.151～5.727,P=0.021)and a 3.712 times in 1-year incidence of VOCE events(HR=3.712,95%CI:1.478～9.810,P=0.006)compared to patients with good pretreatment.Conclusions For patients with in situ coronary artery disease,a lower μQFR after pretreatment increases the risk of postoperative adverse clinical events.μQFR≤0.83 may be used to evaluate the effectiveness of lesion pretreatment.

Objective To investigate the impact of enterovirus 71(EV71)on skeletal muscle injury and explore its mechanism in relation to the caspase-1/interleukin(IL)-1 β signaling pathway in EV71-induced skeletal muscle damage.Methods One-day-old BALB/c suckling mice were divided randomly into three groups:normal control(NC)(n=60),EV71 infection model(n=60),and caspase-1 inhibitor(EV71+VX765)(n=15)groups.The NC and EV71 model groups were further subdivided into four subgroups(5,7,10,and 14 days)(n=5 mice per group).An EV71-infected model was established by intraperitoneal injection of 25 × 103 μL/kg EV71 viral solution for 3 consecutive days.Mice in the caspase-1 inhibitor group received VX765(20 mg/kg)intraperitoneally 6 hours post-viral inoculation,continued daily for 10 days until sample collection.Mice in the NC group received an equivalent volume of saline containing 5％dimethylsulfoxide and 10％PEG300,followed by 2％cell maintenance solution after 6 hours.Post-modeling body weight and clinical disease scores were recorded.Pathological skeletal muscle damage was observed by hematoxylin-eosin(HE)staining,and expression levels of EV71 VP-1(viral capsid protein),pro-caspase-1,cleaved-caspase-1,IL-1 β,α-smooth muscle actin(SMA),and Collagen Ⅰ were detected by Western blot and immunofluorescence.Results Compared with the NC group at the same time points,mice in the EV71 model group exhibited reduced body weight,elevated disease scores,and skeletal muscle pathology characterized by inflammatory cell infiltration,myofiber dissolution,and decreased cross-sectional area(HE staining).Western blot showed significantly increased levels of EV71 VP-1,IL-1β,α-SMA,and Collagen Ⅰ in skeletal muscle homogenate from EV71 mice at 5,7,and 10 days post-infection(P＜0.001).In contrast,mice in the VX765 group showed improved body weight,reduced clinical scores(P＜0.01),and significant downregulation of EV71 VP-1(P＜0.01),pro-caspase-1,cleaved-caspase-1,IL-1β,and Collagen Ⅰ compared with the EV71 model group(P＜0.01).These findings were confirmed by immunofluorescence,indicating that inhibition of caspase-1 alleviated EV71-induced skeletal muscle injury.Conclusions EV71 may induce skeletal muscle injury by activating the caspase-1/IL-1β signaling pathway.

[Objective]To clearly identify the difference between rescue injuries and agonal injuries and to avoid duplicate identifications and misidentifications.[Methods]Based on the forensic pathological data of 5 923 cases of death cause identification from 2013 to 2022 in Sun Yat-sen University Forensic Identification Center and Guangzhou Tianhe District Branch of Guangzhou Public Security Bureau,this study retrospectively studied the characteristics of rescue injuries and agonal injuries seen in cause of death identification and their influence on cause of death identification.[Results]Among all the 5 923 cases,640 cases were found to have rescue injuries or agonal injuries,and 624 cases received treatment,of which 609 cases were found to have rescue injuries(97.60%),44 cases were found to have agonal injuries,and 13 cases were found to have both types of injuries.Among the 640 cases,441 were male and 199 were female.The age of death was discontinuously distributed from 0 to 95 years old.The leading cause of death was disease,followed by mechanical injury and asphyxia.The main manifestations of rescue injuries were rib and sternum fractures,soft tissue injuries in the prechest area or face,and pericardial rupture.The most common injuries in agonal stage were falling after unconsciousness,inhalation of foreign body in respiratory tract or multiple violent injuries.Among the 640 cases,19 cases were repeatedly identified,including 15 cases of rescue injuries,6 cases of agonal injuries,and 2 cases of both types of injuries.Compared with the cases where neither type of injuries was detected,the repeated identification rate of treatment injuries and agonal injuries was significantly increased(χ2=4.04,P=0.044;χ2=43.49,P<0.001).Among the 640 cases,11 cases(1.72%)were misidentified as the initial injuries in the first identification,and 13 cases had combined rescue injuries or agonal injuries that were involved in death.[Conclusions]By elucidating the epidemiological characteristics of the two types of injuries,this study proved that the two types of injuries were associated with higher rates of repeated identification and misidentification,which provided a reference for reducing repeated identification and misidentification and improving the accuracy of cause of death identification.

Objectives:To investigate the predictive value of Murray's law-based quantitative flow ratio(μQFR)in side branches for long-term clinical prognosis in patients with non-left main bifurcation lesions who underwent simple main branch stenting,and to provide a potential functional assessment standard for intervention decision-making on coronary bifurcation lesions.Methods:A retrospective analysis was conducted in 408 patients with non-left main bifurcation lesions who underwent simple main branch stenting at Lianyungang First People's Hospital and Nanjing First Hospital between July 2018 and January 2021.The study utilized third-generation QFR software to analyze pre-and post-procedure anatomical and functional parameters of the target lesion's main branch and key branches.The primary endpoint was target vessel failure(TVF)events during the 3-year follow-up.Patients were stratified into TVF and non-TVF groups.Baseline characteristics,procedural data,and pre-/post-procedural parameters of target vessels were compared between groups.Multivariable Cox regression was performed to identify predictors of TVF.Diagnostic efficacy of predictors was evaluated using area under the receiver operating characteristic(ROC)curve(AUC)with DeLong's method for comparison.Patients were dichotomized based on the optimal cutoffof post-procedural side branch μQFR,with TVF incidence rates compared via Cox regression and Kaplan-Meier analysis.Results:During 3-year follow-up,54 patients(13.2%)experienced TVF(TVF group),data were compared with 354 patients(86.76%)without TVF(non-TVF group).The TVF group showed higher post-procedural side branch diameter stenosis([32.93±17.80]%vs.[22.62±11.96]%,P<0.001)and lower μQFR(0.80±0.10 vs.0.89±0.07,P<0.001).Multivariate Cox regression identified higher post-procedural side branch μQFR as an independent protective factor against 3-year TVF(per 0.01 increase:HR=0.903,95%CI:0.850-0.959,P<0.001).ROC curves indicated that post-procedural side branch μQFR had moderate diagnostic efficacy for predicting 3-year TVF(AUC=0.769,95%CI:0.678-0.861,P<0.001),with a significantly higher AUC value than post-operative side branch area stenosis and minimal lumen diameter(both P<0.001),the optimal cutoffvalue was 0.84.Multivariate Cox regression and Kaplan-Meier survival analysis revealed markedly higher 3-year TVF rates in patients with μQFR≤0.84 compared to patients with μQFR>0.84(HR=4.007,95%CI:2.342-6.855,P<0.001;28.3%vs.7.9%,log-rank P<0.001).Conclusions:For patients with bifurcation lesions not involving the left main,the immediate post-procedural side branch μQFR could better predict 3-year TVF than anatomical indices.Maintaining post-stenting side branch μQFR>0.84 may optimize clinical outcomes when using a single-stent strategy.

Objective:To evaluate the effectiveness and safety of thulium fiber laser enucleation of the prostate(ThuFLEP)in the treatment of oversized(＞200 mL)prostate.Methods:Clinical data of 475 benign prostatic hyperplasia(BPH)patients operated by the same urologist at Peking University First Hospital from January 2022 to May 2024 were retrospectively analyzed,all of whom were treated with thu-lium fiber laser,and the patients were divided into three groups according to the total volume of the pros-tate(TPV):group A(TPV＜100 mL),group B(100 mL≤TPV＜200 mL),and group C(TPV ≥200 mL).The age of the patients in the three groups[(69.38±7.79)years,(69.64±8.69)years,(70.32±7.44)years],International Prostate Symptom Score(IPSS)[(22.7±1.9),(22.8±2.7),(25.8±3.7)],and the maximum urinary flow rate(Qmax)[(7.9±2.7)mL/s,(9.3±4.3)mL/s,(9.9±3.3)mL/s]were not statistically significant(P＞0.05).The prostate volume in the three groups[(103.49±46.19)mL,(75.73±30.69)mL,(273.49±49.19)mL]and prostate specific antigen(PSA)[3.52(1.05,8.76)μg/L,6.78(1.61,7.45)μg/L,8.52(5.05,12.76)μg/L]were statistically significant(P＜0.05).Results:All surgeries were successfully completed.The dif-ferences in enucleation time[30.0(21.2,44.5)min,41.6(31.2,52.5)min,45.1(35.2,50.0)min]and hospitalization time[(6.06±1.21)d,(6.15±1.50)d,(7.71±1.74)d]among the three groups were not statistically significant(P＞0.05);and the differences in the postoperative in-dwelling catheter time[(4.0±1.4)d,(4.0±1.3)d,(6.6±1.1)d],operative time[61(42,89)min,82(62,105)min,115(96,142)min],enucleation efficiency[1.29(0.71,1.56)g/min,1.67(1.23,2.15)g/min,2.74(2.20,3.34)g/min],and hemoglobin drop values[12(7,19)g/L,17(11,24)g/L,27(19,35)g/L]were statistically different(P＜0.05).Linear regression ana-lysis was used to show a strong positive linear correlation between enucleation efficiency and enucleation weight(r=0.880,P＜0.001),and the enucleation efficiency increased with the increase of prostate volume.The differences in IPSS[(6.6±1.7),(6.2±1.4),(4.6±1.1)]and Qmax[(18.9±3.1)mL/s,(16.8±3.8)mL/s,(22.9±7.1)mL/s]were not statistically significant among the three groups(P＞0.05),and the differences in IPSS and Qmax were statistically significant compared with those before surgery.The differences were statistically significant in preoperative comparisons,but the postoperative urinary flow rate of group C increased significantly more than the remaining two groups in terms of Qmax(P＜0.05).The patients in the three groups were followed up for 3 months,and post-operative complications were categorized into Clavien-Dindo Ⅰ(urinary retention,persistent hematu-ria),Clavien-Dindo Ⅱ(glandular remnants,urinary tract infection,blood transfusion)and Clavien-Dindo Ⅲ(urethral stenosis,contracture of the bladder neck,and reoperation for hemorrhage)based on the Clavien-Dindo Complications System score,the incidence of Clavien-Dindo in the three groups was 5.2％(13 cases),6.7％(12 cases)and 12.1％(7 cases),respectively,with statistically significant differences(P＜0.05);among them,there were statistically significant differences in urinary infection,blood transfusion and bleeding reoperation(P＜0.05),and there was no statistically significant difference in the remaining complications(P＞0.05).Conclusion:The risk of blood transfusion and re-hemostasis increases with larger prostate volume,the efficiency of enucleation increases with the increase of prostate vo-lume,and thulium fiber laser prostate enucleation is safe and effective in the treatment of large-volume BPH.