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.

Aim To explore the effect of C1q/tumor necrosis factor-related protein 6(CTRP6)on cardio-myocyte pyroptosis in rats with acute myocardial infarc-tion(AMI)inhibited by quercetin(Que)and the un-derlying mechanism.Methods A rat model of AMI was established by ligation of the left anterior descend-ing coronary artery.Firstly,the rats were divided into the sham operation group(Sham),AMI group,low-dose quercetin group(Que-L,25 mg·kg-1),high-dose quercetin group(Que-H,100 mg·kg-1),fosino-pril sodium tablet group(fosinopril,4 mg·kg-1),with 10 rats in each group.Each group was orally ad-ministered with the corresponding drug dose or physio-logical saline once a day for 14 consecutive days.Doppler ultrasonography was used to detect the changes of cardiac function,the pathological changes of rat myo-cardial tissue were observed,and Western blot was used to detect the myocardial tissue pyroptosis-related proteins and CTRP6 expression.The optimal dosage of Que was determined through the screening of the above experimental indicators.Subsequently,the experiment was divided into the Sham,AMI,Que(100 mg·kg-1),Que+si-NC group,Que+si-CTRP6,with 10 rats in each group.After 14 days of intervention,myo-cardial infarction,myocardial injury indicators,pyropto-sis,CTRP6,and PI3K/Akt pathway protein expression were detected.Results Compared with the Sham group,the LVEDV and LVESV significantly increased,the EF and FS significantly decreased(P＜0.05),the myocardial tissue had obvious pathological damage,the degree of fibrosis increased,the myocardial infarction area,LDH,CK-MB,cTnI levels,TUNEL positive cell ratio increased,NLRP3,cleaved caspase-1,GSDMD-N,IL-1 β,IL-18 expression increased,and CTRP6 expres-sion,p-PI3K/PI3K,p-Akt/Akt ratio decreased in the AMI group(P＜0.05).Compared with the AMI group,Que-L and Que-H rats showed reduced cardiac function indicators and pathological damage to myocar-dial tissue,decreased myocardial infarction area,LDH,CK-MB,cTnI levels,decreased TUNEL positivity rate(P＜0.05),decreased expression of pyroptosis related proteins,and increased expression of CTRP6 and PI3K/Akt pathway proteins(P＜0.05),all of which were dose-dependent.Compared with the Que group,the changes in the above indicators in the Que+si-CTRP6 group rats were significantly reversed.Conclu-sions Que can inhibit cardiomyocyte pyroptosis and improve myocardial infarction in AMI rats,and its mechanism is related to up-regulating CTRP6 expres-sion and promoting the activation of PI3 K/Akt signa-ling pathway.

This study was aimed at preliminarily investigating the genetic and antimicrobial resistance characteristics of Salmonella Alachua isolates through whole-genome analyses.Five Salmonella Alachua isolates from various sources(both hu-man and non-human)were collected and identified.Phenotype and serotype verification,antimicrobial susceptibility testing,and whole-genome sequencing were performed.Virulence genes,antimicrobial resistance genes,and plasmid replicons were predicted according to globally available Salmonella Alachua genomic data.A phylogenetic tree was constructed to explore the genetic background.The first report of Salmonella Alachua in China emerged in Shanghai in 2015,and patients presented pri-marily with diarrhea.The isolates have been found predominantly in the eastern and southern coastal regions.Among the five i-solates analyzed,four belonged to sequence type(ST)2061,and one belonged to ST1298.All isolates were susceptible to most commonly used clinical antibiotics.Whole-genome analyses revealed that two ST2061 strains carried the blaKPC-2 gene,and one ST1298 strain carried the fosA7 gene.Phylogenetic analysis of global Salmonella Alachua populations indicated that the ST2061 clone belonged to the C1 clade,which was closely related to strains from the UK,whereas the ST1298 clone was found in the C4 clade,a globally disseminated fosA 7-positive lineage.This study provides initial insights into the genetic and antimi-crobial resistance characteristics of Salmonella Alachua in China,highlighting the presence of strains carrying blaKPC-2 and fo-sA7 genes.These findings may provide a reference for future large-scale molecular epidemiological surveillance and source-trac-ing efforts,and they underscore the importance of enhanced resistance monitoring for Salmonella Alachua.

Aim To explore the effect of C1q/tumor necrosis factor-related protein 6(CTRP6)on cardio-myocyte pyroptosis in rats with acute myocardial infarc-tion(AMI)inhibited by quercetin(Que)and the un-derlying mechanism.Methods A rat model of AMI was established by ligation of the left anterior descend-ing coronary artery.Firstly,the rats were divided into the sham operation group(Sham),AMI group,low-dose quercetin group(Que-L,25 mg·kg-1),high-dose quercetin group(Que-H,100 mg·kg-1),fosino-pril sodium tablet group(fosinopril,4 mg·kg-1),with 10 rats in each group.Each group was orally ad-ministered with the corresponding drug dose or physio-logical saline once a day for 14 consecutive days.Doppler ultrasonography was used to detect the changes of cardiac function,the pathological changes of rat myo-cardial tissue were observed,and Western blot was used to detect the myocardial tissue pyroptosis-related proteins and CTRP6 expression.The optimal dosage of Que was determined through the screening of the above experimental indicators.Subsequently,the experiment was divided into the Sham,AMI,Que(100 mg·kg-1),Que+si-NC group,Que+si-CTRP6,with 10 rats in each group.After 14 days of intervention,myo-cardial infarction,myocardial injury indicators,pyropto-sis,CTRP6,and PI3K/Akt pathway protein expression were detected.Results Compared with the Sham group,the LVEDV and LVESV significantly increased,the EF and FS significantly decreased(P＜0.05),the myocardial tissue had obvious pathological damage,the degree of fibrosis increased,the myocardial infarction area,LDH,CK-MB,cTnI levels,TUNEL positive cell ratio increased,NLRP3,cleaved caspase-1,GSDMD-N,IL-1 β,IL-18 expression increased,and CTRP6 expres-sion,p-PI3K/PI3K,p-Akt/Akt ratio decreased in the AMI group(P＜0.05).Compared with the AMI group,Que-L and Que-H rats showed reduced cardiac function indicators and pathological damage to myocar-dial tissue,decreased myocardial infarction area,LDH,CK-MB,cTnI levels,decreased TUNEL positivity rate(P＜0.05),decreased expression of pyroptosis related proteins,and increased expression of CTRP6 and PI3K/Akt pathway proteins(P＜0.05),all of which were dose-dependent.Compared with the Que group,the changes in the above indicators in the Que+si-CTRP6 group rats were significantly reversed.Conclu-sions Que can inhibit cardiomyocyte pyroptosis and improve myocardial infarction in AMI rats,and its mechanism is related to up-regulating CTRP6 expres-sion and promoting the activation of PI3 K/Akt signa-ling pathway.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

Objective:To investigate the impact of vitamin D deficiency on the outcomes of in vitro fertilization and embryo transfer (IVF-ET) in women with polycystic ovary syndrome (PCOS) and normal ovarian reserve (NOR). Methods:A retrospective cohort study was conducted on infertile women undergoing their first IVF-ET cycle in the Department of Reproductive Genetics, Zhengzhou Maternity and Child Health Care Hospital from January 2018 to December 2023, including 318 PCOS patients (group P) and 528 NOR patients (group N). Each group was divided into three subgroups according to serum 25-hydroxyvitamin D [25(OH)D] levels: severe deficiency [25(OH)D<12 μg/L], deficiency [12 μg/L≤25(OH)D<20 μg/L], and non-deficiency [25(OH)D≥20 μg/L]. The impact of vitamin D deficiency on pregnancy outcomes was analyzed in each group. 1∶1 propensity score matching was applied to match the baseline characteristics between group P and group N , resulting in 158 matched cases of PCOS (group P) and NOR (group N). Pregnancy outcomes were compared between the two groups under the same vitamin D status.Results:1) Among PCOS patients, there were no significant differences in general characteristics and pregnancy outcomes among the three subgroups (all P>0.05). The two pronuclei (2PN) rate in the severe deficiency subgroup [59.93% (721/1 203)] was significantly lower than that in the deficiency subgroup [63.70% (1 032/1 620)], with a statistically significant difference ( P=0.045), and both were lower than that in the non-deficiency subgroup [68.06% (554/814)], with a statistically significant difference ( P<0.001, P=0.037). There were no statistically significant differences in the number of oocytes retrieved and MⅡ oocytes, MⅡ oocyte rate, 2PN number, 2PN rate, cleavage number, cleavage rate, number of available embryos on day 3 (day 3, D3), number of high-quality embryos on D3, D3 high-quality embryo rate, clinical pregnancy rate, embryo implantation rate, early miscarriage rate, live birth rate, and premature birth rate among subgroups (all P>0.05). Female age ( OR=0.930, 95% CI: 0.871-0.992, P=0.028), endometrial thickness on the day of transfer ( OR=0.877, 95% CI: 0.791-0.971, P=0.012), number of D3 high-quality embryos ( OR=1.135, 95% CI: 1.050-1.228, P=0.001), and ovulation stimulating protocol ( OR=2.230, 95% CI: 1.153-4.314, P=0.017) were independent factors influencing clinical pregnancy. 2) Among NOR patients, there were no significant differences in general characteristics, pregnancy outcomes, laboratory parameters, or other outcome-related indices among the three subgroups (all P>0.05). Female age ( OR=0.944, 95% CI: 0.900-0.990, P=0.018), number of D3 high-quality embryos ( OR=1.070, 95% CI: 1.004-2.597, P=0.037), and number of transferred embryos ( OR=1.753, 95% CI: 1.184-2.597, P=0.005) were independent factors influencing clinical pregnancy. 3) After matching, there were no significant differences in baseline characteristics and pregnancy outcomes between group P and group N (all P>0.05). In the severe vitamin D deficiency state, group P had significantly lower MⅡ oocyte rate [76.64% (525/685)], 2PN rate [59.69% (345/578)], embryo implantation rate [35.71% (30/84)], and live birth rate [34.00% (17/50)] compared with group N [81.58% (465/570), P=0.033; 67.00% (335/500), P=0.013; 51.28% (40/78), P=0.046; 55.32% (26/47), P=0.035]. In the vitamin D deficiency state, the 2PN rate in group P [66.50% (532/800)] was significantly lower than that in group N [72.00% (725/1 007), P=0.012]. Conclusion:Vitamin D deficiency may adversely affect IVF-ET outcomes in patients with PCOS, with more pronounced effects in cases of severe deficiency. However, it has no impact on the assisted reproductive outcomes in NOR patients.

Aim To explore the in vitro anti-human triple-negative breast cancer(TNBC)effect and mech-anism of Austocystin R.Methods MTT assay was used to evaluate the anti-tumor potential of Austocystin R for various human tumor cells and normal cells.Flow cytometry was employed to evaluate the influence on cell cycle progression.mRFP-GFP-LC3 adenovirus transfection was used to evaluate the autophagic flux process.Western blot assay was used to verify the effect of Austocystin R on the expression of related pro-teins.Results The results showed that Austocystin R significantly inhibited the proliferation of multiple tumor cells in a dose-dependent manner,especially for the MDA-MB-231 cells with an IC50 of 1.45μmol·L-1.In addition,Austocystin R increased the protein expression of PTEN,p53,p-p53,p27,p21,and down-regulated the expression of p-PI3K,p-AKT and p-mTOR.Austocystin R can significantly increase the proportion of S-phase MDA-MB-231 cells,inhibit the expression of Cyclin D1,CDK4,CDK6,Rb,Cyclin B1 and CDK1,and promote the expression of Cyclin E1 and CDK2.Austocystin R can promote the autophagic flux process of MDA-MB-231 cells,promote the expres-sion of LC3 Ⅰ/Ⅱ,p-Beclin-1,p-ULK1,HMGB-1 and Atg 14 proteins,and inhibit the expression of Beclin-1,ULK1,p62,ATG 3,ATG 4B,ATG 5,ATG 7,ATG 12,ATG 13 and ATG 16L1 proteins.Conclusion Austo-cystin R can exhibit its anti-TNBC activity by inhibi-ting the PI3K/AKT/mTOR signaling pathway,blocking the cell cycle at the S phase and inducing autophagic cell death.

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.

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

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.