Objective:To observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP).Methods:A retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants.Results:The two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. Conclusions:BBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.

Objective:The aim of this study is to explain the key role of chondrocyte ferroptosis in TMJ OA and demonstrate that abnormal occlusion stimulation is an important causative factor of ferroptosis.Methods:We observed the morphological changes of mouse condylar cartilage in unilateral anterior crossbite(UAC,an abnormal occlusion stimulation)and bilateral anterior elevation(BAE,a proliferation occlusion stimulation)mice by HE and SO staining,and analyzed the expression of intracellular GPX4 by im-munofluorescence staining,and analyzed the changes in the content of mitochondria and reactive oxygen species by JC-1 and ROS staining.Results:The UAC caused degeneration of condylar cartilage and ferroptosis of chondrocytes in mice.The accumulation of iron ions and the dysfunction of mitochondria in chondrocytes significantly upregulated.The expression of GPX4,which is a key reg-ulator in the regulation of ferroptosis was lowered in UAC mice condyle cartilage.Moreover,in BAE model the condylar cartilage hy-perplasia was observed,but not the ferroptosis of chondrocytes.Conclusion:This study revealed that the abnormal biological force caused by abnormal occlusion could induce ferroptosis of chondrocytes,and ferroptosis is one of the main factors leading to the de-generation and thinning of condylar cartilage.GPX4 could regulate the ferroptosis of chondrocytes.

Objective:The aim of this study is to explain the key role of chondrocyte ferroptosis in TMJ OA and demonstrate that abnormal occlusion stimulation is an important causative factor of ferroptosis.Methods:We observed the morphological changes of mouse condylar cartilage in unilateral anterior crossbite(UAC,an abnormal occlusion stimulation)and bilateral anterior elevation(BAE,a proliferation occlusion stimulation)mice by HE and SO staining,and analyzed the expression of intracellular GPX4 by im-munofluorescence staining,and analyzed the changes in the content of mitochondria and reactive oxygen species by JC-1 and ROS staining.Results:The UAC caused degeneration of condylar cartilage and ferroptosis of chondrocytes in mice.The accumulation of iron ions and the dysfunction of mitochondria in chondrocytes significantly upregulated.The expression of GPX4,which is a key reg-ulator in the regulation of ferroptosis was lowered in UAC mice condyle cartilage.Moreover,in BAE model the condylar cartilage hy-perplasia was observed,but not the ferroptosis of chondrocytes.Conclusion:This study revealed that the abnormal biological force caused by abnormal occlusion could induce ferroptosis of chondrocytes,and ferroptosis is one of the main factors leading to the de-generation and thinning of condylar cartilage.GPX4 could regulate the ferroptosis of chondrocytes.

Objective:To observe and analyze the pathogenic genes and clinical phenotype characteristics of retinitis pigmentosa sinepigmento(RPSP).Methods:A retrospective clinical study. Two patients (proband) and five family members from two RPSP families admitted to Xiamen Eye Center of Xiamen University in December 2022 and Shenzhen Eye Hospital in July 2023 were included in the study. Two families have no blood relationship and were both Han Chinese. Detailed ocular and systemic medical history and specialized examinations were performed for all members, including color fundus photography, fundus autofluorescence (FAF), and full field electroretinogram (ff-ERG) examination. The peripheral venous blood of all members was collected, and genomic DNA was extracted. Pathogenic genes and their loci were screened using whole exome high-throughput sequencing technology. Sanger sequencing was used to verify the pathogenic genes in the two pedigrees. The pathogenicity of candidate variants was evaluated according to the American Society for American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants.Results:The two probands were male, aged 9 and 7 years, respectively. The main complaint was poor binocular vision for 6 and 3 years and poor treatment effect of amblyopia. The proband (Ⅱ2) in family 1 had a pale red color on the optic disc, with leopard-like changes in the posterior pole and thinner retinal arteries. FAF showed mottled fluorescence attenuation outside the macular vascular arch. There was no significant waveform in both bright and dark visual responses of ff-ERG. He also had 6-toed deformity of both feet, renal cysts, and a slightly overweight body. The clinical diagnosis was non-pigmentary retinitis pigmentosa. The proband of family 2 (Ⅱ1) had poor binocular vision in a dark environment and had atrophy lesions on the nasal side of the optic disc and leopard print like changes in the fundus. FAF showed uneven enhancement in the fovea. ff-ERG showed severe abnormalities in dark and light response, with significant decrease and delay in b-wave amplitude and latency. He had no other systemic abnormalities. The clinical diagnosis was binocular RPSP. There were no abnormal ocular and systemic manifestations in the two family members. Gene sequencing revealed a homozygous mutation (c.534+1G>T) of BBS2 gene, which was inherited from the mother and father respectively. Based on clinical manifestations and genetic testing results, the final diagnosis was Bardet Biedl syndrome. The genetic sequencing results confirmed a novel compound heterozygous mutation (c.950T>G: p. Leu317Arg missense mutation and c.849+1G>C splicing mutation) of BBS7 gene. His father (Ⅰ1) and mother (Ⅰ2) carried M1 heterozygous variants. Combined with the clinical manifestations and genetic testing results, the final diagnosis was Bardet-Biedl syndrome (BBS). Family 2 proband (Ⅱ1) carried the BBS7 gene C.950T>G (p.Leu317Arg) (M2) missense variation and C.849 +1G>C (M3) splice site variation. His father (Ⅰ1) and mother (Ⅰ2) carried M3 shear site variation and M2 missense variation, respectively. The two families all fit the autosomal recessive inheritance pattern, and the genotype and clinical phenotype were coseparated. According to ACMG guidelines, M1, M2 and M3 were all identified as possible pathogenic variants. Conclusions:BBS2 gene M1 homozygous variation and BBS7 gene M2, M3 complex heterozygous variation are the possible pathogenic genes in family 1 and family 2, respectively. Two families are affected by BBS and RPSP, respectively.

Background and aims:Kehuang(KH)capsule is an herbal medical product approved for the treatment of liver diseases,including liver injury,in China.However,the mechanism is still unclear.This study aimed to elucidate the protective effects of KH capsule against carbon tetrachloride(CCl4)-induced acute liver injury(ALI)in a murine model.Methods:Mice were randomly divided into control,model(CCl4),CCl4+KH_Low and CCl4+KH_High group.Liver enzyme levels and histological changes were assessed to evaluate liver injury.Oxidative stress markers and inflammatory cell infiltration in liver tissues were measured.Additionally,network pharmacology was employed to explore the potential mechanisms of KH capsule.Results:KH capsule significantly reduced serum alanine aminotransferase(ALT)and aspartate amino-transferase(AST)levels,as well as the necrotic area in liver tissue.KH capsule also decreased the infil-tration of macrophages and neutrophils,thereby inhibiting the expression of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β).Furthermore,KH capsule decreased liver malondialdehyde(MDA)levels and increased superoxide dismutase(SOD)activity.The number of ter-minal deoxynucleotidyl transferase(TdT)-mediated dUTP nick-end labeling(TUNEL)-positive cells in liver tissue was also reduced.The expression of nuclear factor erythroid 2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)proteins was significantly elevated,while the protein expression of cyto-chrome P450 2E1(CYP2E1)was significantly reduced.Mass spectrometry identified genistein,galangin,wogonin,skullcapflavone Ⅱ,and hispidulin as potential active ingredients of KH capsule.Network pharmacology analysis revealed enrichment in the mitogen-activated protein kinase(MAPK)and phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)signaling pathways.Western blot analysis confirmed that KH capsule suppressed AKT,extracellular signal-regulated kinase(ERK),and p38 signaling.Conclusions:These findings suggest that KH capsule could exert protective effects against CCl4-induced ALI,with the inhibition of MAPK and PI3K-AKT signaling pathways playing a crucial role in its mecha-nism of action.

Objective To analyze the relationship of serum S100 calcium binding protein A4(S100A4)and pentraxin-3(PTX3)levels with left atrial appendage thrombosis in patients with NVAF.Methods A total of 120 elderly NVAF patients treated in our hospital from March 2020 to March 2023 were enrolled in this study.According to their echocardiograms,they were divided into a left atrial appendage thrombosis group(40 cases)and a non-thrombosis group(80 cases).Serum S100A4 and PTX3 levels were detected.Spearman correlation analysis was applied to ana-lyze the relationship between serum S100A4 and PTX3 levels and left atrial appendage thrombo-sis.Logistic regression analysis was conducted to analyze the factors affecting left atrial appendage thrombosis.Results The serum levels of S100A4 and PTX3 were higher in the thrombosis group than the non-thrombosis group(P＜0.01).The serum levels of S100A4 and PTX3 were positively correlated with left atrial appendage thrombosis(r=0.497,P=0.000;r=0.555,P=0.000).Heart failure,CHA2DS2-VASc score,B-type natriuretic peptide,uric acid,S100A4 and PTX3 were risk factors for left atrial appendage thrombosis in NVAF patients(P＜0.05,P＜0.01).Combination of serum S100A4 and PTX3 in predicting left atrial appendage thrombosis formation in NVAF patients had an AUC value of of 0.949(95％CI:0.893-0.981).Conclusion Serum S100A4 and PTX3 levels are increased in NVAF patients,they are related to left atrial appendage thrombosis,and their serum levels have certain predictive value for left atrial appendage thrombosis.

OBJECTIVE:To observe the effect of rosuvastatin on prognostic of patients with paroxysmal atrial fibrillation (AF) after circumferential pulmonary vein ablation. METHODS:75 patients with paroxysmal AF were divided into observa-tion group(n=39)and control group(n=36)according to the admission single. All patients underwent circumferential pulmo-nary vein ablation antiarrhythmic treatment. Control group orally received warfarin sodium,amiodarone,metoprolol,and sub-cutaneous injected low molecular weight heparin. Observation group additionally received 10 mg Rosuvastatin tablet,qd on the basic of contol group. Changes of cardiac function,inflammatory factors,lipid levels in 2 groups before and after treat-ment were observed,and follow-up results were compared. RESULTS:There was no significant difference in left atrial diame-ter and left ventricular ejection fraction in 2 groups before and after treatment (P>0.05);atrial effective refractory periods (AERP)in 2 groups significantly prolorged,and observation group prolorged more significantly than control group,the differ-ence was statistically significant(P<0.05). Serum high sensitivity C-reactive protein,interleukin-6 48 h and 1 month after op-eration in 2 groups significantly increased,and control group was significantly higher than observation group,the difference was statistically significant (P<0.05);before operation and after 3 months of operation,there was no significant difference in inflammatory cytokine levels(P>0.05). Triglyceride and low density lipoprotein cholesterol in observation group 1 month after operation significantly decreased, HDL-C significantly increased, there were significant differences (P<0.05). Fol-low-up time was (23.91 ± 5.28) months,AF recurrence was 7.8%,which was significantly lower than control group (13.9%),the difference was statistically significant (P<0.05);and there were no significant differences in ablation-related atrial tachycardia (ATa) and the incidence of adverse reactions between 2 groups (P>0.05). CONCLUSIONS:Rosuvastatin can effectively inhibit the inflammatory reaction and prolong the AERP,thereby reducing the recurrence rate of AF,with good efficacy and safety.

Objective To investigate the role of eNOS/NO signaling pathway in peritubular capillary lesions of mouse renal interstitial fibrosis with unilateral ureteral obstruction ( UUC) and the potential mechanism .Methods Sixty-four healthy male KM mice were randomly divided into sham operated group ( n=32 ) and unilateral ureteral obstruction group (n =32).At each week, serum BUN, Scr and NO were determined and the percentages of CD 133 +/VEGFR+en-dothelial progenitor cells in peripheral blood mononuclear cells were detected by flow cytometry .Morphological changes of the renal tissue were observed using Masson staining .The expression of CD34 +cells in the renal interstitium was analyzed by immunohistochemistry to calculate the peritubular capillary density .The expressions of eNos and VEGF mRNA were de-termined by real-time PCR.Results The expression of blood NO , the percentages of endothelial progenitor cells , peritu-bular capillaries, eNOS mRNA, and VEGF mRNA in the UUO group were significantly decreased compared with those of the sham group at 2, 3, and 4 weeks (P<0.05).NO was positively correlated with peritubular capillaries (r =0.715, P<0.05), eNOS mRNA was positively correlated with peritubular capillaries (r =0.624, P<0.05), endothelial progeni-tor cells (r =0.375, P<0.05), and VEGF mRNA (r =0.351, P<0.05).Conclusions eNOS/NO signaling path-way participates in regulation of peritubular capillary lesions in renal interstitial fibrosis of UUO mice .The mechanism may be partly related to the regulation of vasomotor reflex , the expression of VEGF mRNA and mobilization of endothelial pro-genitor cells.

Objective To compare the results of Danielson procedure with and without prosthetic valve ring in treating Ebstein anomaly and to define the effect of prosthetic valve ring on the procedure.Methods From January 2006 to December 2009,31 cases of Ebstein anomaly over 10 years old were classified as type A or type B according the Carpentier＇s classification scheme.Patients were treated by Danielson procedure or Danielson procedure plus prosthetic valve ring at Anzhen hospital.They were retrospectively classified as Danielson procedure group (group A,n =19) and Danielson procedure plus prosthetic valve ring group (group B,n =12 ).Results There was 1 early in-hospital death due to lung infection and hypoxemia in group A,and no early death in group B ( Fisher exact test,P =0.51 ).The mean follow-up time was ( 23.0 ± 18.5 ) months (5 -41 months).The cumulative follow-up time was 59.42 patient-years.There was one late death in group A due to the redo tricuspid valve plastic procedure because of severe tricuspid regurgitation,and no late death in group B.With echocardiography inspection,11 patients had mild and 7 had moderate to severe tricuspid regurgitation in group A,and only 2 mild tricuspid regurgitation in group B.The tricuspid valve competence after surgery in group B was better than in group A ( Fisher exact test,P=0.024).The 6-minute walk distance test (6MWD) in group B was significantly better than in group A(415 ±41 )m vs ( 382 ± 46 ) m( t test,P =0.047 ).The New York heart functional class in group B was statistically better than in Group A ( P =0.024).Conclusion Although there was no significant difference in the early and late mortality rate between the two groups after surgery,Danielson procedure plus prosthetic valve ring was better than pure Danielson procedure in prevention of late tricuspid regurgitation recurrence,heart function and 6MWD test during follow-up.

Objective To evaluate the safety and rationality of total/near total bilateral thyroidectomy(TBT) for patients with bilateral multinodular goiter(BMG). Methods From January 2003 to December 2006,311 BMG cases were preoperatively divided into two groups, 130 cases in group A underwent TBT, and 181 cases in group B were treated with subtotal/partial bilateral thyroidectomy. Results There were 6 and 2 eases in group A and group B respectively diagnosed by intraoperative frozen biopsy as BMG, but identified as papillary carcinoma by final pathology. Hence the 6 cases in group A avoided reoporation, while the 2 cases in group B underwent a resection of the remnant gland. Transient hoarseness developed in 3 (2.42%, 3/124) and 3 (1.68%, 3/179) eases in group A and group B respectively (P =0.48). Transient hypocalcemia developed in 11 (8.87% ,11/124) and 9(5.03% ,9/179) cases in group A and group B respectively(P =0.16). There was no postoperative goiter recurrence in group A, but recurrence developed in 12 cases (6.70%,12/179) in group B(P=0.02). Conclusions Total bilateral thyroidectomy is safe and rational for the management of bilateral thyroid goiter.