Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

Objectives: . This study aimed to investigate the regulatory functions of gamma-aminobutyric acid (GABA)ergic neural circuits from the inferior colliculus (IC) to the medial geniculate body (MGB) in salicylate-induced tinnitus. Methods: . Mice were treated with salicylate to induce tinnitus, and tinnitus-like behaviors were evaluated via gap prepulse inhibition of acoustic startle. Using combined viral tracing methodologies, we identified and mapped the pathways and connections from the IC to the MGB. Furthermore, we employed Gq-coupled human M3 designer receptors exclusively activated by designer drugs (DREADDs) and Gi-coupled human M4 DREADDs to achieve targeted excitation or suppression of GABAergic neurons in the IC and MGB. Following the administration of clozapine N-oxide, which binds to these receptors, we modulated these neural circuits to assess their impact on tinnitus severity in a mouse model. Results: . Our findings demonstrated that mice exposed to salicylate exhibited tinnitus-like behaviors. GABAergic neurons projecting retrogradely from the MGB to the IC were primarily concentrated in the external nucleus of the IC. After clozapine N-oxide administration, chemogenetic activation of IC-MGB GABAergic neurons aggravated salicylate-induced tinnitus. Additionally, activation of GABAergic neurons between the IC and MGB induced the perception of tinnitus even without salicylate. However, chemogenetic inhibition of the IC-MGB GABAergic circuit did not reverse salicylate-induced tinnitus. Conclusion . These findings suggest that activation of the IC-MGB GABAergic neural circuit may contribute to tinnitus generation through a mechanism distinct from that of salicylate-induced tinnitus. This study provides novel insights into the mechanisms underlying tinnitus.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Enamel demineralization, the formation of white spot lesions, is a common issue in clinical orthodontic treatment. The appearance of white spot lesions not only affects the texture and health of dental hard tissues but also impacts the health and aesthetics of teeth after orthodontic treatment. The prevention, diagnosis, and treatment of white spot lesions that occur throughout the orthodontic treatment process involve multiple dental specialties. This expert consensus will focus on providing guiding opinions on the management and prevention of white spot lesions during orthodontic treatment, advocating for proactive prevention, early detection, timely treatment, scientific follow-up, and multidisciplinary management of white spot lesions throughout the orthodontic process, thereby maintaining the dental health of patients during orthodontic treatment.
Humans ; Consensus ; Dental Caries/etiology* ; Dental Enamel/pathology* ; Tooth Demineralization/etiology* ; Tooth Remineralization

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objective To evaluate the prognosis and safety of patients with advanced pancreatic ductal adenocarcinoma(PDAC)who received I-125 seed implantation in treatment with anti-PD-1 monoclonal antibody+chemotherapy.Methods A retrospective analysis was conducted on patients with stage Ⅳ metastatic PDAC who received anti-PD-1 combined chemotherapy treatment at Yixing Hospital,Jiangsu University from Jan 2021 to Jun 2023.Patients were divided into two groups based on whether they received I-125 seed implantation:the I-125 seed implantation+anti-PD-1 monoclonal antibody+Chemotherapy group(IPC group)and the anti-PD-1 monoclonal antibody+chemotherapy group(PC group).The follow-up period ranged from 2 to 24 months,with a median follow-up time of 9 months.The prognosis of patients was analysed in combination with peripheral blood biomarkers.The peripheral lymphocyte subsets of patients in different treatment groups were preliminarily analysed by flow cytometry.Results A total of 13 patients were included,with 5 in the IPC group and 8 in the PC group.Progression-free survival(PFS)and overall survival(OS)in the IPC group were significantly longer than those in the PC group.The treatment in the IPC group was relatively safe,adverse reactions were controllable.The neutrophil-lymphocyte ratio(NLR)and CD4/CD8 ratio indicated that the prognosis of the IPC patients was better.The levels of regulatory T cells(Treg)and active regulatory T cells(aTreg)cells in the IPC patients were reduced after treatment compared with those of the PC patients.Conclusion The addition of I-125 seed implantation can improve the prognosis of patients with advanced PDAC who receive anti-PD-1 monoclonal antibody+chemotherapy,the post-treatment levels of patients'circulating aTreg cells are reduced,and the combination therapy has good safety.

AIM:To investigate whether casein kinase 2(CK2)/calmodulin(CaM)/small-conductance Ca2+-activated K+channel type 2(SK2)signaling pathway mediates autophagy-induced sympathoexcitation in the paraventricu-lar nucleus(PVN)of rats with chronic heart failure(CHF).METHODS:We randomly divided 180 Wistar rats,aged 6 to 8 weeks,into 10 groups:sham+dimethyl sulfoxide(DMSO),sham+artificial cerebrospinal(aCSF),CHF+DMSO,CHF+aCSF,CHF+rapamycin(RAPA),CHF+3-methyladenine(3-MA),CHF+5,6-dichlorobenzimidazole riboside(DRB),CHF+calmidazolium chloride(CMDZ),CHF+N-cyclohexyl-N-[2-(3,5-dimethyl-1H-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine(CyPPA),and CHF+apamin groups.We measured cardiac function,hemodynamic parameters,anatomic indicators,and sympathetic drive indicators(n=18).Western blot was used to examine the protein levels of mi-crotubule-associated protein 1 light chain 3-II(LC3-II)/LC3-I,beclin-1,P62,CK2α,SK2,and phosphorylated CaM.The number of SK2-positive neurons was measured using immunofluorescence staining.The NG108 cells were randomly divided into 6 groups:DMSO,aCSF,RAPA,3-MA,RAPA+DRB,and RAPA+CMDZ groups.Radioisotope 32P-ATP pro-tein kinase activity assays were used to detect CK2 activity in cultured NG108 cells.We used Western blot to examine the protein levels of CK2α,SK2,and phosphorylated CaM.RESULTS:Compared with CHF rats treated with vehicle,CHF rats treated with RAPA or apamin exhibited increased sympathetic drive indicators,but decreased left ventricular ejection fraction and fractional shortening(P<0.01).However,CHF symptoms,including sympathoexcitation,were attenuated by 3-MA,DRB,CMDZ or CyPPA infusion into the PVN(P<0.01).In CHF rats,RAPA infusion into the PVN induced CK2 activity,up-regulated LC3-II/LC3-I,beclin-1,CK2α,and phosphorylated CaM levels,but down-regulated P62 and SK2 expression,as well as the number of SK2-positive neurons(P<0.05 or P<0.01).In CHF rats,infusion of 3-MA or DRB into the PVN decreased CK2 activity,and down-regulated phosphorylated CaM level(P<0.01).Infusion of 3-MA,DRB or CMDZ into the PVN up-regulated SK2 expression and the number of SK2-positive neurons(P<0.01).In cultured NG108 cells,RAPA induced CK2 activation and up-regulated the expression of CK2α and the phosphorylation of CaM,but down-regulated SK2 expression(P<0.01).Treatment with RAPA increased the level of phosphorylated CaM and down-regulated SK2 expression in cultured NG108 cells(P<0.01),which was inhibited by DRB and CMDZ(P<0.05 or P<0.01).CONCLUSION:In rats with CHF,the CK2/CaM/SK2 signaling pathway in the PVN contributes to autophagy-induced sympathoexcitation.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.