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*

Autoimmune diseases, cancers, and viral infections pose significant global health threats, characterized by chronic pathology, unregulated cellular proliferation, and rapid transmission, respectively, requiring urgent early warning and treatment strategies. Antibodies, primarily classified into autoantibodies and therapeutic antibodies based on their clinical roles, provide essential information and show considerable value in the precise diagnosis and treatment of these serious diseases. Among the technologies utilized in bioanalysis, electrochemical biosensors, with their unique advantages of rapid response, high sensitivity, miniaturization, cost-effectiveness and user-friendly operation, have been developed as a trending technology for precise diagnostic and therapeutic drug monitoring. This review systematically summarizes the relationships and roles of clinically relevant antibodies in autoimmune diseases, cancers, and viral infections, while detailing the composition, strategies, development, and application trends of relevant electrochemical biosensors. Furthermore, it highlights the remaining challenges and opportunities for the advancement and prospects of electrochemical sensors in the context of clinically relevant antibodies.

Objective:To explore potential risk factors for central lymph node metastasis (CLNM) in papillary thyroid microcarcinoma (PTMC).Methods:The clinicopathological data of 304 PTMC patients admitted to Baotou Cancer Hospital from Oct 2021 to Mar 2023 were retrospectively analyzed. The risk factors of CLNM were analyzed using unifactorial and multifactorial regression.Results:The rate of central regional lymph node metastasis in 304 patients with PTMC was 46.7% (142/304). Univariate analysis showed that male, age <45 years, maximum cancerous lesion diameter ≥5 mm, total cancerous lesion diameter ≥9.5 mm, anterior-posterior lesion diameter ≥5 mm, anterior-posterior lesion diameter ratio of cancerous lesions ≥0.48, breaching of thyroid capsule, number of lymph nodes on the side of cancerous lesions ≥5, and antithyroid peroxidase antibody ≤34 IU/ml were associated with CLNM (all P<0.05); Logistic multivariate regression analysis showed that. male, age <45 years, total diameter of cancer foci ≥9.5 mm ( OR=2.052, 95% CI: 1.176-3.581, P=0.011), anteroposterior diameter ratio of cancer foci ≥0.48 ( OR=2.076, 95% CI: 1.161-3.711, P=0.014), number of lymph nodes on the side of cancer foci ≥5, and anti-thyroid peroxidase antibody ≤34 IU/ml were independent risk factors for CLNM. Conclusion:Male, age ,total diameter of cancer foci, anterior-posterior diameter ratio of cancer foci, number of lymph nodes on the side of cancer foci, and anti-thyroid peroxidase antibody level are all independent risk factors for CLNM in patients with PTMC.

Objective:To investigate risk factors for permanent hypoparathyroidism (PHPP) after total thyroidectomy in patients with differentiated thyroid carcinoma (DTC).Methods:The clinical data of 316 DTC patients who underwent total thyroidectomy at our hospital from Jan 2020 to Jan 2023 were retrospectively analyzed. Patients were divided into normal parathyroid function group (284 cases) and hypoparathyroidism group (32 cases) according to whether parathyroid function was decreased. The clinical examination, intraoperative conditions and postoperative pathological data of the two groups were statistically analyzed.Results:Logistic regression analysis showed that: serum calcium on the first postoperative day ( OR=0.163, P<0.05), parathyroid hormon (PTH) on the first postoperative day ( OR=0.958, P<0.05), bilateral lymph node dissection ( OR=3.138, P<0.05), accidental resection of parathyroid (PG) ( OR=2.614, P<0.05), posterior capsule tumor invasion ( OR=3.336, P<0.05) and multiple cancer foci ( OR=2.664, P<0.05) were independent risk factors for PHPP after total thyroidectomy. Conclusion:Postoperative day 1 serum calcium, postoperative day 1 PTH, bilateral lymph node dissection, accidental resection of PG, posterior capsule invasion and multiple cancer foci are independent risk factors for PHPP after total thyroidectomy.

Objective:To investigate the factors influencing the metastasis of right-sided lymph nodes posterior to right recurrent laryngeal nerve (LN-prRLN) in patients with papillary thyroid microcarcinoma (PTMC) at cN 0 stage, to construct a nomogram prediction model for metastasis of right-sided LN-prRLN in patients with PTMC at cN 0 stage and to provide the decision reference for the dissection of right-sided LN-prRLN. Methods:A retrospective case-controlled study was conducted. The clinical data of patients receiving right-sided LN-prRLN dissection in Baoding No.1 Central Hospital between January 2023 and June 2024 were collected. All patients were divided into the metastatic group and the normal group according to whether metastasis of right-sided LN-prRLN would happen after the postoperative pathological examination. The differences in the clinicopathological characteristics between the 2 groups were compared, and multivariate logistic regression model was used to screen out the independent risk factors influencing right-sided LN-prRLN. A nomogram prediction model for metastasis of right-sided LN-prRLN based on independent risk factors was built; taking the postoperative pathological examination results as the gold standard, the receiver operating characteristic (ROC) curve was used to evaluate the efficacy of the model in determining the metastasis of right-sided LN-prRLN. Bootstrap internal validation method was used for random sampling to calculate the consistency index (CI) of the model. The calibration curves and clinical decision curves were drawn to respectively verify the calibration degree of the model and the clinical application ability of the model.Results:All 235 patients included 57 males (24.3%) and 178 females (75.7%). The age was (39±13) years old and 47 cases (20.0%) out of 235 patients had the metastasis of right-sided LN-prRLN. The proportion of patients characterized by male, right-sided tumors, tumor diameter > 0.5 cm, extrathyroidal invasion, metastasis of right-sided lymph nodes anterior to right recurrent laryngeal nerve (LN-arRLN) in the metastatic group was higher than that in the normal group, and the differences were statistically significant (all P < 0.05). Multivariate logistic regression analysis showed that male ( OR = 3.705, 95% CI: 1.133-12.116, P = 0.030), right-sided tumors ( OR = 5.610, 95% CI: 1.811-17.381, P = 0.003), the increased tumor diameter ( OR = 3.504, 95% CI: 1.169-10.507, P = 0.025), extrathyroidal invasion ( OR = 2.812, 95% CI: 1.026-7.708, P = 0.044) and right-sided LN-arRLN metastasis ( OR = 10.522, 95% CI: 3.237-34.199, P < 0.001) were independent risk factors of the metastasis of LN-prRLN in PTMC patients at cN 0 stage; based on the above independent risk factors, a nomogram prediction model was established. The ROC curve showed that the area under the curve of the nomogram prediction model for determining the metastasis of right-sided LN-prRLN in PTMC patients at cN 0 stage was 0.864 (95% CI: 0.794-0.935), Youden index was 0.735, the optimal cut-off value was 4.562, the corresponding sensitivity was 87.0%, and the corresponding specificity was 86.5%, which indicated a high predictive value of the nomogram model. Bootstrap test internal validation showed that the CI was 0.810 (95% CI: 0.763-0.917). Calibration curves showed that bias-corrected line was close to the ideal line, indicating a good consistency ( P = 0.347). Decision curve showed a good clinical efficacy. Conclusions:Male, right-sided tumors, the increased tumor diameter, extrathyroidal invasion and right-sided LN-arRLN metastasis are independent risk factors for right-sided LN-prRLN metastases in patients with PTMC at cN 0 stage. The nomogram prediction model based on the above factors has a good predictive performance, which is helpful for surgeons to make clinical decisions.

OBJECTIVE: To observe the effect of electroacupuncture combined with enhanced recovery after surgery (ERAS) protocol on promoting intestinal function in patients after gastric cancer surgery. METHODS: Forty-four patients who underwent radical gastrectomy for gastric cancer were randomly divided into an experimental group (22 cases, 3 cases were excluded) and a control group (22 cases, 4 cases were excluded). Both groups received treatment under ERAS protocol, the experimental group was given electroacupuncture at bilateral Neiguan (PC6), Hegu (LI4), Zusanli (ST36) and Quchi (LI11), disperse-dense wave was selected, with frequency of 2 Hz/100 Hz. The control group received placebo electroacupuncture intervention, with the same acupoints as the experimental group, electrode pads were placed on the acupoints without electrical stimulation. Each session lasted 30 min, starting from 1 h after surgery, once every 24 h, until the patient resumed anal flatus. The intestinal sound rate of both groups was observed 24 h before surgery and 24, 48 h after surgery. The bowel sound recovery time (BSRT), time to first anal flatus, time to first defecation, and tolerance to oral enteral nutrition suspension were compared between the two groups. The levels of serum C-reactive protein (CRP), interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, IL-17, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were measured 24 h before surgery and 24 h after surgery in both groups. RESULTS: The intestinal sound rate 24 h after surgery was decreased compared with that 24 h before surgery in the two groups (P<0.05), the intestinal sound rate 24, 48 h after surgery in the experimental group was higher than that in the control group (P<0.05). The BSRT in the experimental group was earlier than that in the control group (P<0.05) .The levels of serum CRP, IL-6, IL-10 24 h after surgery in the experimental group were higher than those 24 h before surgery (P<0.05), while the levels of serum CRP, IL-4, IL-6, IL-10, IFN-γ in the control group were higher than those 24 h before surgery (P<0.05); the levels of serum CRP、IL-4、IFN-γ 24 h after surgery in the experimental group were lower than those in the control group (P<0.05) .The tolerance rate of oral enteral nutrition suspension in the experimental group was 84.2% (16/19), which was higher than 50.0% (9/18) in the control group (P<0.05). CONCLUSION Electroacupuncture combined with ERAS protocol can improve the intestinal motility, shorten the BSRT, enhance the tolerance of oral intake, and reduce inflammatory response in patients after gastric cancer surgery.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Acupuncture Points ; C-Reactive Protein/metabolism* ; Electroacupuncture ; Gastrectomy ; Interleukin-10 ; Interleukin-6 ; Intestines/physiopathology* ; Stomach Neoplasms/therapy*

Objective To investigate the association between serum magnesium levels,serum phosphorus concentrations,vascular calcification,and cardiovascular disease mortality in maintenance hemodialysis patients.Methods This study enrolled 200 hemodialysis patients admitted to Nanjing Drum Tower Hospital from May 2020 to May 2022 as subjects,with an additional 200 healthy individuals from the same period selected as a control group.The biochemical indicators between the two groups were compared;their correlations were analyzed.Binary logistic regression was used to investigate the independent factors of serum magnesium and phosphorus levels in relation to vascular calcification and cardiovascular events in maintenance hemodialysis patients.ROC curve analysis was employed to assess the predictive value of serum magnesium and phosphorus for vascular calcification and cardiovascular events.Results The research group's patients exhibited significantly elevated levels of blood phosphorus,calcium-phosphorus product,iPTH,AACS,and 25-(OH)-VitD compared to the control group.In contrast,their blood magnesium and BMP-7 levels were notably lower than those of the control group,with statistical significance(P<0.05).Pearson correlation showed positive correlations between serum magnesium and serum calcium,phosphorus,calcium-phosphorus product,25-(OH)-VitD3,and BMP-7(r=0.385,0.183,0.141,0.131,0.458,P<0.05);between serum calcium and serum phosphorus,calcium-phosphorus product,iPTH,AACS,25-(OH)-VitD3,and BMP-7(r=0.318),correlation(r=0.318,0.311,0.098,0.170,0.277,0.485,P<0.05);between serum phosphorus and calcium-phosphorus product,iPTH,AACS,25-(OH)-VitD3(r=0.362,0.506,0.367,0.461,P<0.05);between calcium-phosphorus product and iPTH,AACS,25-(OH)-VitD3(r=0.542,0.373,0.434,P<0.05);between iPTH and AACS,25-(OH)-VitD3 showing positive correlations(r=0.553,0.616,P<0.05)and a negative correlation with BMP-7(r=-0.373,P<0.05);between AACS and 25-(OH)-VitD3 showing a positive correlation(r=0.402,P<0.05),and a negative correlation with BMP-7(r=-0.155,P<0.05),with statistically significant differences(P<0.05).Statistically significant differences were noted between the two groups in age,diabetes,serum magnesium,serum calcium,serum phosphorus,calcium-phosphorus product,25-(OH)-VitD3,and hs-CRP(P<0.05).Logistic regression analysis showed that age,serum magnesium,serum calcium,serum phosphorus,calcium phosphate product,25-(OH)-vitamin I were all risk factors for cardiovascular disease(CVD)mortality in maintenance hemodialysis(MHD)patients(P<0.05).ROC curve analysis showed that serum magnesium,serum calcium,and serum phosphorus had predictive areas under the curve(AUC)of 0.895,0.802,and 0.851 for CVD mortality in MHD patients,with sensitivities and specificities of 87.5%/98.7%,66.7%/90.8%,and 72.9%/100%,respectively.The combined prediction for CVD mortality in MHD patients showed an AUC of 0.921,with a sensitivity of 81.3%and specificity of 93.4%.Conclusion MHD patients exhibit low blood magnesium levels,elevated serum phosphorus concentrations,and increased calcium-phosphorus product,with complex correlations among these biomarkers.Age,magnesium,calcium,and phosphorus levels were all associated with CVD mortality.ROC curve analysis demonstrates that magnesium,calcium,and phosphorus,both individually and in combination,have high predictive value for CVD mortality risk.

Objective To examine the role and mechanism of clopidogrel in the development of salt-sensitive hypertension.Methods 8-week-old Dahl salt-sensitive(Dahl SS)rats and control salt-resistant(SS13BN)rats were divided randomly into six groups and fed for 8 weeks with normal salt(0.4％NaCl,NS),high salt(8％NaCl,HS),or high salt combined with clopidogrel gavage(8％NaCl+10 mg/(kg·d))clopidogrel,HS+CLO).Arterial systolic blood pressure was measured continuously over 8 weeks by the tail-cuff method,and systolic blood pressure was measured by carotid cannulation after 8 weeks(56 days).Renal histopathology was observed by hematoxylin and eosin staining,and renal inflammatory cell infiltration was detected by immunohistochemistry.Peripheral blood platelet activation and platelet-leukocyte aggregation were analyzed by flow cytometry,and the renal inflammation-related proteins tumor necrosis factor-α,interleukin(IL)-1β,IL-6,and key proteins in the p38MAPK/nuclear factor(NF)-κB signaling pathway were detected by Western blot.Results Compared with the NS group,Dahl SS HS rats had significantly increased blood pressure(P＜0.05),aggravated renal tissue damage,increased inflammatory cell infiltration,increased expression of inflammatory cytokines(P＜0.05),elevated peripheral blood platelet activation(P＜0.05)and platelet-leukocyte aggregation(P＜0.05),and increased expression of p38MAPK/NF-κB signaling pathway proteins(P＜0.05).Clopidogrel effectively alleviated these phenotypes induced by high salt in Dahl SS rats.Conclusions Clopidogrel alleviated high-salt-induced salt-sensitive hypertension and decreased renal inflammatory responses and dysfunction in Dahl SS rats by inhibiting platelet activation and the p38MAPK/NF-κB signaling pathway.

In order to delve into the molecular mechanism underlying the increased pathogenicity of the recombinant Muscovy duck parvovirus(rMDPV)towards Muscovy ducklings,two sub-genom-ic fragments of the rMDPV strain ZW were cloned into the plasmid pBluescript Ⅱ(SK)to gener-ate the recombinant plasmid pZW.A single nucleotide mutation was engineered in the VP3 gene of pZW to discriminate from the parental strain ZW.pZW plasmid-lipid complex was transfected into the chorioallantoic membrane of 11-day-old embryonated Muscovy duck embryos,resulting in res-cue of infectious virus,rZW,carrying the genetic marker.The rescued virus was passaged in 12-day-old embryonated Muscovy duck embryos and exhibited the similar medium embryo lethal dose(ELD50)value and growth curve compared to the parental strain ZW.Both rZW and strain ZW led to 100％mortality in the infection tests performed with 3-day-old Muscovy duckling.Postmortem necropsy revealed a characteristic intestine embolism formed in the rZW-infected ducklings.Taken together,the generation of the infectious clone pZW lays a solid foundation for deciphering the pathogenesis of rMDPV.