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*

Objective To investigate the effect of manual therapy based on surface electromyography on knee osteoarthritis(KOA)in the older people. Methods A total of 106 outpatient with unilateral KOA were selected from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,from August,2023 to June,2024,and were randomly divided into control group(n=53)and experimental group(n=53).The control group accepted routine manual therapy,and the experimental group accepted manual therapy based on the analysis of average electromyography(AEMG).They were assessed with Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),Visual An-alogue Scale(VAS)for pain,Tinetti Balance and Gait Score,and 6-minute walk test(6-MWT)distances before and after treatment. Results One case dropped down in each group.Before treatment,AEMG decreased in the rectus femoris,medial femoris and medial head of gastrocnemius on the affected side in the experimental group(|Z|>8.647,P<0.001),and it increased in the lateral femoris,semitendinosus and biceps femoris(|Z|>4.808,P<0.001).The scores of WOMAC,VAS,Tinetti Balance and Gait Score,and distances of 6-MWT improved in both groups after treat-ment(|t|>3.987,P<0.001),and improved more in the experimental group than in the control group,except the VAS score(|t|>2.213,P<0.05). Conclusion Manual therapy focusing on activation of rectus femoris,medial femoris and medial head of gastrocnemius,inhibition of the lateral femoris,semitendinosus and biceps femoris,and releasing the tension of the medial and lateral collateral ligaments,according to the results of surface electromyography,can alleviate the pain of the KOA in the older people and improve the mobility of the knee.

Objective:To document any effect of a pulsed electromagnetic field (PEMF) on the regulation of neuropeptide Y (NPY) in nucleus pulposus (NP) tissue, NP cell apoptosis and matrix degradation using rats with intervertebral disc degeneration (IDD).Methods:Eighteen Sprague-Dawley rats were randomly divided into a control group, an IDD model group (the model group), and a PEMF group. IDD was induced in both the model and PEMF groups. Right after the modeling, the PEMF group received 14 days of PEMF treatment, while the control group and model group were given no special treatment. Meanwhile, the primary rat nucleus pulposus cells (NPCs) were cultured using Dulbecco′s Modified Eagle Medium at 37℃ and 5% CO 2. When the fusion rate reached 90% after passage, the NPCs were divided into a control group, a TNF-α model group (referred to as model group) and TNF-α + PEMF group (referred to as PEMF group) and treated accordingly. Eight weeks after the modeling, safranin-o/fast green staining was used to assess any pathological morphology changes. The expression of NPY, neuropeptide Y receptor Y2 (NPY2R), bcl-2-associated X protein (Bax), B-cell lymphoma 2 (Bcl-2), collagen type II (Col-II) and matrix metalloproteinase-3 (MMP3) in the intervertebral disc and the cultivated nucleus pulposus cells of the 3 groups were determined. Results:The intervertebral disc cells in the model group were ruptured and folded, with significantly increased polysaccharide and protein components, and significantly increased bone fibers. In the PEMF group the cell boundaries were clearer, with less fibrin fracture and increased cartilage tissue. NPY was expressed in the fibrous annulus and the nucleus pulposus of the intervertebral disc in the model group. The average expression levels of NPY and NPY2R were significantly higher than in the control group and the model group. Compared with the control group, there was a significant increase in the level of Bax and a significant decrease in the expression of Bcl-2 in the model group, and there was a significant decrease in the level of Bax in the PEMF group. Compared with the control group, there was a significant decrease in the Col-II level but a significant increase in the MMP3 protein expression in the model group. The average Col-II mRNA expression was significantly higher in the PEMF group compared with the model group, but the average MMP3 protein expression was significantly less. Those results are consistent with observations in vivo.Conclusion:PEMF may reverse the imbalance of ECM metabolism and delay IDD degeneration by up-regulating the expression of NPY and Bcl-2, as well as blocking the Bax/Bcl-2 signaling pathway to inhibit apoptosis of nucleus pulposus cells.

Osteoarthritis (OA) is a type of highly prevalent heterogeneous degenerative disease that leads to joint pain, deformity, the destruction of articular cartilage, and eventual disability. The current treatment strategies for OA often suffer from systemic side effects, poor anti-inflammatory efficacy, and persistent pain. To address these issues, we develop light-inducible nanomedicine that enables the co-delivery of anti-inflammatory drug (diacerein, DIA) and small interfering RNA (siRNA) targeting nerve growth factor (NGF) for pain relief to enhance the therapeutic efficacy of OA. The nanomedicine is based on poly(β-amino-ester)-coated gold nanocages (AuNCs), which is further incorporated with the phase-change material (lauric acid/stearic acid, LA/SA). Following intra-articular (IA) injection in vivo, the nanomedicine displays high degree of drug accumulation and retention in the joint lesion of OA mouse models. The photothermal effect, induced by AuNCs, not only promotes DIA and siRNA release, but also upregulates the expression of heat shock protein 70 (HSP-70) to resist the apoptosis of chondrocytes in the inflammatory condition. The internalization of both DIA and siRNA results in strong anti-inflammatory and pain-relieving effects, which greatly contribute to the joint repair of OA mice. This study offers a promising combination strategy for OA treatment.

Single chain antibody fragment (scFv) is a small molecule composed of a variable region of heavy chain (VH) and a variable region of light chain (VL) of an antibody, and these two chains are connected by a flexible short peptide. scFv is the smallest functional fragment with complete antigen-binding activity, which contains both the antibody-recognizing site and the antigen-binding site. Compared with other antibodies, scFv has the advantages of small molecular weight, strong penetration, low immunogenicity, and easy expression. Currently, the most commonly used display systems for scFv mainly include the phage display system, ribosome display system, mRNA display system, yeast cell surface display system and mammalian cell display system. In recent years, with the development of scFv in the field of medicine, biology, and food safety, they have also attracted much attention in the sectors of biosynthesis and applied research. This review summarizes the advances of scFv display systems in recent years in order to facilitate scFv screening and application.
Animals ; Immunoglobulin Variable Region/genetics* ; Immunoglobulin Fragments/metabolism* ; Single-Chain Antibodies/metabolism* ; Peptide Library ; Mammals/genetics*

Objective: To analyze the epidemiological characteristics and genetic characteristics of sapovirus (SaV) in a cluster of schools in Changzhou, so as to provide a reference for the treatment of clustered vomiting and diarrhea events in schools. Methods: The epidemiological data and laboratory test data of sapovirus clusters in Changzhou from 2019 to 2022 were collected and analyzed. Partial VP1 genes of SaV positive samples were amplified and sequenced for phylogenetic analysis. Results: A total of 8 cases of clusters of SaV epidemics were reported in Changzhou City from 2019 to 2022, with 118 reported cases. The total attack rate was 1.47%, and the median of the attack number was 15. There were 6 outbreaks in kindergartens and 2 outbreaks in primary schools, which were reported in the epidemic period from September to December. The main clinical manifestations were vomiting (113 cases, 95.76 %), abdominal pain (39 cases, 33.05%), and diarrhea (16 cases, 13.56%). Among the 8 outbreaks, 17 sample strains were successfully sequenced. 5 outbreaks were GII.3 , and the other 3 outbreaks were GI.1, GI .3 and GII.2. GI and GII were the main genotypes in this area, and GII .3 was the predominant strain. Conclusion SaV is an important pathogen in the clusters of vomiting and diarrhea in schools after the transmission of norovirus. Continuous surveillance of SaV should be carried out to further understand its epidemiological characteristics and genotype distribution, so as to provide scientific basis for the prevention and control of the epidemic in schools.

Objective     To investigate the effect and prognosis of patients with ventricular septal rupture after myocardial infarction treated by surgical repair combining an occluder and a patch. Methods     Clinical data of 42 patients with myocardial infarction complicated with ventricular septal rupture admitted to the First Affiliated Hospital of Zhengzhou University from January 2010 to September 2021 were retrospectively analyzed. According to the surgical methods, 27 patients were divided into a traditional group, including 17 males and 10 females, with an average age of 62.81±6.81 years, who were repaired by patch only, and 15 patients were divided into a modified group, including 11 males and 4 females, with an average age of 64.27±9.24 years, who were repaired by surgery combining an occluder and a patch. Perioperative and follow-up data of the two groups were compared and analyzed. Results     There were statistical differences between the two groups in preoperative Killip grading, rate of intra-aortic balloon pump use, interval from myocardial infarction to operation, and the number of culprit artery (P<0.05). There was no statistical difference in other preoperative data, the cardiopulmonary bypass time, aortic cross-clamping time, postoperative hospital stay or in-hospital death rate between the two groups (P>0.05). No residual shunt occurred in the modified group, and the difference was statistically significant compared with the traditional group (P=0.038). There was no statistical difference in other complications between the two groups (P>0.05). The median follow-up time was 4 years. Two patients in the traditional group and one in the modified group died during follow-up. The follow-up cardiac function grading of patients in the modified group was statistically different from that in the traditional group (P=0.023). Conclusion     The perioperative  mortality of ventricular septal rupture after myocardial infarction is high, but the long-term effect is satisfactory. Surgical repair combining an occluder and a patch is a safe and effective treatment for ventricular septal rupture, which can effectively reduce postoperative residual shunt.

【Objective】 To investigate the effect of total flavone of oldenlandia diffusa(FOD) on the stemness, proliferation and apoptosis of breast cancer(BC) stem cells sorted from MDA-MB-231. 【Methods】 Human BC cell lines MDA-MB-231 was cultured in vitro; MDA-MB-231 was stimulated by different concentrations(0 μg/mL, 100 μg/mL, 200 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h and 72 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on MDA-MB-231 proliferation; CD44⁺/CD24^-MDA-MB-231 cell line were tested by flow cytometry and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting; Annexin V-PE/7-AAD was used to detect the effect of FOD on MDA-MB-231 apoptosis and Bcl2, cleaved-caspase3 and Bax were tested by Western blotting. 【Results】 Cell proliferation of MDA-MB-231 was significantly inhibited by FOD, with the significant suppression at concentrations of 400 μg/mL for 72 h compared with negative control group(P<0.05). The apoptosis rate was significantly upregulated than the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and cleaved-caspae3 increased, and stemness markers such as Nanog, Sox2 and Oct4 decreased in FOD-treated cells. Moverover, Akt-GSK3β-β-catenin axis was inhibited in FOD-treated cells. 【Conclusion】 FOD could significantly inhibit the stemness and proliferation and promote the apoptosis of MDA-MB-231.

【Objective】 To investigate the effects of total flavone of oldenlandia diffusa (FOD) on the proliferation and apoptosis of hepatocellular carcinoma (HCC) stem cells sorted from Huh7. 【Methods】 Human HCC cell lines Huh7 was cultured in vitro; CD133 positive (CD133⁺) stem cells in Huh7 cell line were sorted by flow cytometry, and stem cell markers such as Nanog, Oct4 and Sox2 were tested by Western blotting. CD133⁺-Huh7 was stimulated by different concentrations (0 μg/mL, 50 μg/mL, 100 μg/mL and 400 μg/mL) of FOD for different time (24 h, 48 h, 72 h and 96 h). CCK8 and plate cell cloning assay were used to detect the effect of FOD on CD133⁺-Huh7 proliferation while Annexin V-PE/7-AAD was used to detect the effect of FOD on CD133⁺-Huh7 apoptosis. Western blotting was used to detect the protein expressions of protein 53 (P53), factor associated suicide-Fas-associating protein with a novel death domain (Fas-FADD), B-cell lymphoma-2 (Bcl-2), Cleaved-Caspase3, and Bcl-2 associated X protein (Bax). 【Results】 More than 95% of stem cells were purified for further experiments. Cell proliferation of CD133⁺-Huh7 was significantly inhibited by FOD, with the significant suppression at the concentration of 100 μg/mL for 72 h compared with negative control group (P<0.05). The apoptosis rate was significantly upregulated than that in the negative control group (P<0.05). The protein expression of Bcl2 decreased while Bax and Cleaved-Caspae3 increased via FAS/FADDD and P53 axis. 【Conclusion】 FOD can significantly inhibit the proliferation and promote the apoptosis of CD133⁺-Huh7.

Conversion therapy has become the core in the treatment of borderline resectable or unresectable liver cancer, which provides resectable opportunities for more advanced liver cancer patients. In accordance with the first-choice treatment regimen recommended by the guidelines, the authors reported a successful case of Atezolizumab and Bevacizumab (T+A regimen) conversion therapy. The patient with initially borderline resectable advanced liver cancer was performed liver segment resection sucessfully after conversion therapy, and non-tumor recurrence was observed at postoperative 9 months. Postoperative pathological examination showed combined hepatocellular-cholangiocarcinoma, which also indicated the important value of T+A regimen in the conversion therapy of combined hepatocellular-cholangiocarcinoma.