Insufficient alveolar bone thickness increases the risk of periodontal dehiscence and fenestration, especially in orthodontic tooth movement. Abaloparatide (ABL), a synthetic analog of human PTHrP (1-34) and a clinical medication for treating osteoporosis, has recently demonstrated its potential in enhancing craniofacial bone formation. Herein, we show that intraoral submucosal injection of ABL, when combined with mechanical force, promotes in situ alveolar bone thickening. The newly formed bone is primarily located outside the original compact bone, implying its origin from the periosteum. RNA sequencing of the alveolar bone tissue revealed that the focal adhesion (FA) pathway potentially mediates this bioprocess. Local injection of ABL alone enhances cell proliferation, collagen synthesis, and phosphorylation of focal adhesion kinase (FAK) in the alveolar periosteum; when ABL is combined with mechanical force, the FAK expression is upregulated, in line with the accomplishment of the ossification. In vitro, ABL enhances proliferation, migration, and FAK phosphorylation in periosteal stem cells. Furthermore, the pro-osteogenic effects of ABL on alveolar bone are entirely blocked when FAK activity is inhibited by a specific inhibitor. In summary, abaloparatide combined with mechanical force promotes alveolar bone formation via FAK-mediated periosteal osteogenesis. Thus, we have introduced a promising therapeutic approach for drug-induced in situ alveolar bone augmentation, which may prevent or repair the detrimental periodontal dehiscence, holding significant potential in dentistry.
Osteogenesis/drug effects* ; Periosteum/cytology* ; Parathyroid Hormone-Related Protein/administration & dosage* ; Animals ; Focal Adhesion Protein-Tyrosine Kinases/metabolism* ; Alveolar Process/drug effects* ; Cell Proliferation/drug effects* ; Phosphorylation ; Rats ; Male ; Humans ; Focal Adhesion Kinase 1/metabolism* ; Cell Movement/drug effects*

Comfortable diagnosis and treatment aims to ensure that patients can receive medical exami-nations and treatments safely and comfortably.The traditional anesthesia plan often relies on opioid,but the latter is prone to cause risks such as respiratory depression,hypotension,and hypoxemia.Opioid-free anesthe-sia(OFA),as a multimodal strategy,significantly reduces opioid-related adverse reactions by combining non-opioid drugs(such as esketamine,dexmedetomidine,lidocaine)and techniques(such as surface anesthesia,re-gional block).This article systematically reviews the application progress of OFA in comfortable diagnosis and treatment such as painless gastroscopy and colonoscopy,endoscopic retrograde cholangiopancreatography,bronchoscopy and induced abortion.

Objective To investigate the differences and the immunocompatibility of wild-type (WT), four-gene modified (TKO/hCD55) and six-gene modified (TKO/hCD55/hCD46/hTBM) pig erythrocytes with human serum. Methods The blood samples were collected from 20 volunteers with different blood groups. WT, TKO/hCD55, TKO/hCD55/hCD46/hTBM pig erythrocytes, ABO-compatible (ABO-C) and ABO-incompatible (ABO-I) human erythrocytes were exposed to human serum of different blood groups, respectively. The blood agglutination and antigen-antibody binding levels (IgG, IgM) and complement-dependent cytotoxicity were detected. The immunocompatibility of two types of genetically modified pig erythrocytes with human serum was evaluated. Results No significant blood agglutination was observed in the ABO-C group. The blood agglutination levels in the WT and ABO-I groups were higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (all P<0.001). The level of erythrocyte lysis in the WT group was higher than those in the ABO-C, TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups. The level of erythrocyte lysis in the ABO-I group was higher than those in the TKO/hCD55 and TKO/hCD55/hCD46/hTBM groups (both P<0.01). The pig erythrocyte binding level with IgM and IgG in the TKO/hCD55 group was lower than those in the WT and ABO-I groups. The pig erythrocyte binding level with IgG and IgM in the TKO/hCD55/hCD46/hTBM group was lower than that in the WT group and pig erythrocyte binding level with IgG was lower than that in the ABO-I group (all P<0.05). Conclusions The immunocompatibility of genetically modified pig erythrocytes is better than that of wild-type pigs and close to that of ABO-C pigs. Humanized pig erythrocytes may be considered as a blood source when blood sources are extremely scarce.

Inflammatory bowel disease(IBD)is a serious disorder,and exploration of active compounds to treat it is necessary.An acidic polysaccharide named SUSP-4 was purified from Selaginella uncinata(Desv.)Spring,which contained galacturonic acid,galactose,xylose,arabinose,and rhamnose with the main chain structure of →4)-α-D-GalAp-(1 → and →6)-β-D-Galp-(1 → and the branched structure of →5)-α-L-Araf-(1 →.Animal experiments showed that compared with Model group,SUSP-4 significantly improved body weight status,disease activity index(DAI),colonic shortening,and histopathological damage,and elevated occludin and zonula occludens protein 1(ZO-1)expression in mice induced by dextran sulfate sodium salt(DSS).16S ribosomal RNA(rRNA)sequencing indicated that SUSP-4 markedly downregulated the level of Akkermansia and Alistipes.Metabolomics results confirmed that SUSP-4 obviously elevated thiamine levels compared with Model mice by adjusting thiamine metabolism,which was further confirmed by a targeted metabolism study.Fecal transplantation experiments showed that SUSP-4 exerted an anti-IBD effect by altering the intestinal flora in mice.A mechanistic study showed that SUSP-4 markedly inhibited macrophage activation by decreasing the levels of phospho-nuclear factor kappa-B(p-NF-κB)and cyclooxygenase-2(COX-2)and elevating NF-E2-related factor 2(Nrf2)levels compared with Model group.In conclusion,SUSP-4 affected thiamine metabolism by regulating Akker-mania and inhibited macrophage activation to adjust NF-κB/Nrf2/COX-2-mediated inflammation and oxidative stress against IBD.This is the first time that plant polysaccharides have been shown to affect thiamine metabolism against IBD,showing great potential for in-depth research and development applications.

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth,known as taurodontism;thus,indicating the critical role of Wnt10a in tooth root morphogenesis.However,the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath(HERS)cellular behaviors and contributes to root furcation patterning remains unclear.In this study,we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/flmice from post-natal day 0.5(PN0.5)to PN4.5.EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial(IEE)cells of HERS in K14-Cre;Wnt10afl/flmice at PN2.5 and PN3.5.Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane,which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/flmice.RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice.Furthermore,after activation of Notch signaling in K14-Cre;Wnt10afl/flmolars by Notch2 adenovirus and kidney capsule grafts,the root furcation defect was partially rescued.Taken together,our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

Although blood banks based on human blood can provide blood transfusions for the wounded timely and effec-tively,scientific research has never given up on finding new blood sources due to the restrictions of human blood sources.With the application of transgenic technology and the successful breeding of gene-edited pigs,gene-edited pig blood as a po-tential source of clinical transfusion has attracted wide attention.Now there are preclinical studies showing the feasibility of transfusing gene-edited pig red blood cells into primates.This paper discusses the related research and future development of xenogeneic transfusion of porcine red blood cells by gene editing.

Objective To observe the efficacy and safety of percutaneous transhepatic cholangial drainage(PTCD)for treating isolated bilioenteric anastomotic stenosis(BAS)after liver transplantation in children.Methods Totally 31 children with BAS after liver transplantation were retrospectively enrolled.PTCD was performed,and the drainage tubes were placed into bilioenteric anastomosis of the second and the third biliary tract for long-term support.Complications after PTCD,success rate of extubation,serum total bilirubin after PTCD and performance of the secondary liver transplantation or not were recorded.Results All 31 cases were successfully treated with PTCD.Delayed recovery after general anesthesia occurred in 1 case after PTCD,which was considered as anesthesia related complication and relieved after symptomatic treatments.No PTCD related complication,such as hemorrhage,infection and biliary fistula occurred.The serum total bilirubin before PTCD was(64.09±24.40)μmol/L,which returned to normal at the first reexamined after treatment with an average of(19.98±3.99)μmol/L.The drainage tubes were successfully extubated in 27 cases,with the success rate of 87.10%(27/31)and the mean drainage time of(7.0±3.7)months.Among the rest 4 cases,further observation was necessary in 2 cases due to intermittent fever,while severe obstruction of bilioenteric anastomosis was found during PTCD,the drainage tube of non-obstruction segment was removed but of obstruction segment was retained in the other 2 cases.No secondary liver transplantation was performed.Conclusion PTCD was effective and safe for treating BAS after liver transplantation in children.

Objective To explore the effects of relaxation therapy combined with music intervention on pain degree and mental state of patients with impacted tooth extraction.Methods A total of 76 patients who were diagnosed with low impacted mandibular third molar and confirmed to be in need of extraction in The Second Affiliated Hospital of Naval Medical University from January 2022 to March 2023 were selected as research objects.The patients were randomly divided into observation group and control group by random number table method,with 38 cases in each group.All the surgeries were operated by the same deputy chief physician.The same anesthesia and operation methods were used.The control group received routine nursing,and the observation group received routine nursing,relaxation therapy and music intervention.The pain degree,mental state(Hamilton anxiety scale[HAMA]and Hamilton depression scale[HAMD]),heart rate,systolic blood pressure and diastolic blood pressure were compared between the two groups.Results Postoperative pain in the observation group was significantly less than that in the control group(P<0.05).The HAMA and HAMD scores in the observation group were significantly lower than those in the control group after surgery(P<0.05).Intraoperative heart rate,systolic blood pressure and diastolic blood pressure in the observation group were significantly lower than those in the control group(P<0.05).Conclusion This intervention method can obtain good outcomes in patients with impacted tooth extraction.It can not only alleviate the pain of patients to a large extent,but also significantly reduce the negative emotions of patients.It can also have good effects on the blood pressure and heart rate of patients,and is worthy of clinical application.

Objective To investigate the oral health of officers and soldiers in a navy unit.Methods From September to December 2022,a questionnaire survey and oral examination were conducted in 1 923 officers and soldiers of a navy unit.The incidence of caries,periodontal problem,the third molar impaction,and dental deficiency and defect were analyzed.Results Among the interviewees,51.79%took up smoking,79.88%brushed their teeth daily≥2 times,64.01%brushed their teeth≥3 min,32.97%used cleaning tools other than toothbrushes.The incidence of caries was 23.40%,the incidence of gingivitis and periodontitis was 28.97%,the detection rate of dental calculus was 64.33%,and the total detection rate of pigment teeth was 46.33%.The defect of dental body,residual roots,temporomandibular joint disorders,defect of dentition,and molar impaction accounted for 4.32%,2.81%,11.6%,40.72%,and 68.28%,respectively.Conclusion The oral health status of the shipboard personnel is still poor,so it should be targeted to further strengthen oral health care and popular science propaganda.

The incidence of breast cancer has jumped to the first place in malignant tumors, posing a severe threat to women's health. Different from oxidative phosphorylation metabolism of normal cells, breast cancer cells often undergo metabolic reediting characterized by aerobic glycolysis. In the process of initiating aerobic glycolysis, phosphofructokinase-2/fructose bisphosphatase-2 (PFK-2/FBPase-2) family isozymes PFKFB3 and PFKFB4 play key roles and are involved in the growth and proliferation, invasion and migration, autophagy, and drug resistance of breast cancer. This review summarizes the correlation of PFKFB3 and PFKFB4 with breast cancer, aiming to provide a reference for future breast cancer-related research and clinical translation.