Objective:To synthesize 18F labeled PET imaging probe based on giredestrant (GDC-9545), an estrogen receptor α (ERα) degrader and antagonist, and evaluate its ERα-targeting properties. Methods:The precursor-GDC (PGDC), GDC and 18F-GDC were synthesized. The radiochemical yields, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-GDC were determined. Cellular uptake and blocking assays of 18F-GDC were performed using ERα high-expressing MCF-7 cells and ERα low-expressing MDA-MB-231 cells. MCF-7 and MDA-MB-231 tumor-bearing mice were constructed and microPET imaging was performed. The biodistribution of 18F-GDC in MCF-7 tumor-bearing mice was studied. Data were analyzed by using two-way repeated measures analysis of variance and Bonferroni correction method. Results:PGDC and GDC were successfully prepared with the purity more than 95%. 18F-GDC was successfully synthesized with the labeling yield of (11.25±3.18)%, radiochemical purity more than 98%, specific activity of (140.66±17.20)GBq/μmol and lipid water partition coefficient log P of 2.12±0.13. 18F-GDC was stable in PBS or mouse serum, with the radiochemical purity still more than 98% after 2 h of incubation. After incubation for 60 and 120min, the uptakes of 18F-GDC in MCF-7 cells were significantly higher than those in MDA-MB-231 cells ( F values: 113.78, 369.70, P values: 0.002, 0.001 (Bonferroni correction method)), and could be blocked by GDC. 18F-GDC had a high uptake in MCF-7 tumors and could be blocked by GDC. Tumor uptake at 60 min post-injection was (7.23±0.74) percentage activity of injection dose per gram of tissue (%ID/g) and the tumor/muscle uptake ratio was 2.83±0.29 in MCF-7 tumors, while 18F-GDC had a lower uptake in MDA-MB-231 tumors, with (2.01±0.46)%ID/g at 60min post-injection, and a tumor/muscle uptake ratio of 0.96±0.22 ( F values: 77.28, 55.44, P values: 0.002, 0.006 (Bonferroni correction method)). 18F-GDC was mainly distributed in MCF-7 tumors and organs including heart, liver, spleen, kidney, stomach and intestines. Conclusions:18F-GDC is successfully synthesized, with high radiochemical purity and stability, and can concentrate in the ERα-overexpressing cancer cells and lesion area of xenograft tumor mouse. It presents good image contrast in PET imaging, indicating excellent diagnostic performance.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective Through molecular genetics analysis of a calculi family lineage,this study aims to explore its pathogenesis and the association between genotypes and phenotypes.Methods A retrospective analysis was conducted on a calculi family lineage admitted to Tongji Hospital,affiliated with Tongji Medical College,Huazhong University of Science and Technology.Clinical data and peripheral blood samples of the affected children and some family members were collected.Whole exome sequencing was performed,followed by Sanger sequencing to validate the candidate variants.Results Among the 38 family members across four generations,10 members were diagnosed with calculi disease.The second generation,member 2(Ⅱ-2),third generation,member 2(Ⅲ-2),and third generation,member 4(Ⅲ-4)suffered from recurrent multiple kidney stones and gallstones.The second generation,member 6(Ⅱ-6),second generation,member 13(Ⅱ-13),and third generation,member 5(Ⅲ-5)had recurrent multiple kidney stones alone,while first generation,member 2(Ⅰ-2),second generation,member 4(Ⅱ-4),second generation,member 8(Ⅱ-8),and second generation,member 11(Ⅱ-11)only had gallstones.No other family members exhibited any signs of kidney or gallbladder involvement.Ⅱ-2 was diagnosed in 2018 with end-stage renal disease stage 5,grade 3 hypertension and gallstones,urinary amino acid high-performance liquid chromatography analysis indicated elevated urinary cystine.This member had a history of recurrent multiple kidney stones and recurrent urinary tract infections for over 30 years,with multiple histories of ureteroscopic stone removal.Genetic analysis revealed that Ⅱ-2,Ⅲ-2,Ⅲ-4,Ⅲ-5 and Ⅳ-1 all carry a heterozygous mutation in exon 10 of the solute carrier family 3 member 1(SLC3A1)gene,c.1889G＞A(p.Gly630Asp).The third generation,member 1(Ⅲ-1),and fourth generation,member 2(Ⅳ-2),are wild type.This mutation shows a phenomenon of family co-segregation.Conclusions The heterozygous mutation of SLC3A1 gene,c.1889G＞A,may be the genetic cause of calculi disease in multiple members of this family lineage.Recurrent multiple kidney stones and/or gallstones require high attention to genetic etiology.It is recommended to perform genetic analysis on calculi family lineages and patients with early-onset calculi disease.

Objective Through molecular genetics analysis of a calculi family lineage,this study aims to explore its pathogenesis and the association between genotypes and phenotypes.Methods A retrospective analysis was conducted on a calculi family lineage admitted to Tongji Hospital,affiliated with Tongji Medical College,Huazhong University of Science and Technology.Clinical data and peripheral blood samples of the affected children and some family members were collected.Whole exome sequencing was performed,followed by Sanger sequencing to validate the candidate variants.Results Among the 38 family members across four generations,10 members were diagnosed with calculi disease.The second generation,member 2(Ⅱ-2),third generation,member 2(Ⅲ-2),and third generation,member 4(Ⅲ-4)suffered from recurrent multiple kidney stones and gallstones.The second generation,member 6(Ⅱ-6),second generation,member 13(Ⅱ-13),and third generation,member 5(Ⅲ-5)had recurrent multiple kidney stones alone,while first generation,member 2(Ⅰ-2),second generation,member 4(Ⅱ-4),second generation,member 8(Ⅱ-8),and second generation,member 11(Ⅱ-11)only had gallstones.No other family members exhibited any signs of kidney or gallbladder involvement.Ⅱ-2 was diagnosed in 2018 with end-stage renal disease stage 5,grade 3 hypertension and gallstones,urinary amino acid high-performance liquid chromatography analysis indicated elevated urinary cystine.This member had a history of recurrent multiple kidney stones and recurrent urinary tract infections for over 30 years,with multiple histories of ureteroscopic stone removal.Genetic analysis revealed that Ⅱ-2,Ⅲ-2,Ⅲ-4,Ⅲ-5 and Ⅳ-1 all carry a heterozygous mutation in exon 10 of the solute carrier family 3 member 1(SLC3A1)gene,c.1889G＞A(p.Gly630Asp).The third generation,member 1(Ⅲ-1),and fourth generation,member 2(Ⅳ-2),are wild type.This mutation shows a phenomenon of family co-segregation.Conclusions The heterozygous mutation of SLC3A1 gene,c.1889G＞A,may be the genetic cause of calculi disease in multiple members of this family lineage.Recurrent multiple kidney stones and/or gallstones require high attention to genetic etiology.It is recommended to perform genetic analysis on calculi family lineages and patients with early-onset calculi disease.

To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.

Objective:To synthesize 18F labeled PET imaging probe based on giredestrant (GDC-9545), an estrogen receptor α (ERα) degrader and antagonist, and evaluate its ERα-targeting properties. Methods:The precursor-GDC (PGDC), GDC and 18F-GDC were synthesized. The radiochemical yields, radiochemical purity, specific activity, lipid water partition coefficient log P, and stability of 18F-GDC were determined. Cellular uptake and blocking assays of 18F-GDC were performed using ERα high-expressing MCF-7 cells and ERα low-expressing MDA-MB-231 cells. MCF-7 and MDA-MB-231 tumor-bearing mice were constructed and microPET imaging was performed. The biodistribution of 18F-GDC in MCF-7 tumor-bearing mice was studied. Data were analyzed by using two-way repeated measures analysis of variance and Bonferroni correction method. Results:PGDC and GDC were successfully prepared with the purity more than 95%. 18F-GDC was successfully synthesized with the labeling yield of (11.25±3.18)%, radiochemical purity more than 98%, specific activity of (140.66±17.20)GBq/μmol and lipid water partition coefficient log P of 2.12±0.13. 18F-GDC was stable in PBS or mouse serum, with the radiochemical purity still more than 98% after 2 h of incubation. After incubation for 60 and 120min, the uptakes of 18F-GDC in MCF-7 cells were significantly higher than those in MDA-MB-231 cells ( F values: 113.78, 369.70, P values: 0.002, 0.001 (Bonferroni correction method)), and could be blocked by GDC. 18F-GDC had a high uptake in MCF-7 tumors and could be blocked by GDC. Tumor uptake at 60 min post-injection was (7.23±0.74) percentage activity of injection dose per gram of tissue (%ID/g) and the tumor/muscle uptake ratio was 2.83±0.29 in MCF-7 tumors, while 18F-GDC had a lower uptake in MDA-MB-231 tumors, with (2.01±0.46)%ID/g at 60min post-injection, and a tumor/muscle uptake ratio of 0.96±0.22 ( F values: 77.28, 55.44, P values: 0.002, 0.006 (Bonferroni correction method)). 18F-GDC was mainly distributed in MCF-7 tumors and organs including heart, liver, spleen, kidney, stomach and intestines. Conclusions:18F-GDC is successfully synthesized, with high radiochemical purity and stability, and can concentrate in the ERα-overexpressing cancer cells and lesion area of xenograft tumor mouse. It presents good image contrast in PET imaging, indicating excellent diagnostic performance.

Lecanemab is a new drug used to treat early Alzheimer's disease (AD) with mild cognitive impairment or mild dementia. It is a human anti-Aβ fibril monoclonal IgG1 antibody, which is injected intravenously into the patient, through the blood-brain barrier into the brain, clearing amyloid plaque, thereby slowing the rate of cognitive decline in patients and delaying disease progression. This article reviews the pharmacological studies, clinical studies, safety and limitations of lecanemab, in order to help clinical understand the current research status and existing achievements of this drug.

Objective:To investigate the prognosis and risk factors of IgA vasculitis nephritis (IgAVN) in children.Methods:A retrospective cohort study was conducted. Clinical data were collected from 264 children who were pathologically diagnosed with IgAVN at Department of Pediatric Nephrology, Tongji Hospital, affiliated with Tongji Medical College, Huazhong University of Science and Technology, between January 2011 and December 2017. All patients had a follow-up period of more than 3 years. Clinical characteristics, renal pathology, 3-year and 5-year prognosis were analyzed. The patients were grouped based on gender, age of onset (≤6 years, >6-9 years, and >9 years), pathological classification (≤Ⅲ and>Ⅲ),whether the prognosis was complete remission at 3 and 5 years. Independent sample t-tests, ANOVA or chi-squared test were used for intergroup comparisons. Spearman correlation analysis was applied for ordinal data, and multivariate Logistic regression was used to analyze factors affecting the prognosis. Receiver operating characteristic (ROC) curve was utilized to evaluate the predictive value of these factors. Results:Of the 264 children with IgAVN, 153 were male and 111 were female, the age of onset was 8.3 (6.7, 10.3) years, 118 patients (45%) with onset age >6-9 years accounted for the highest proportion. All patients presented with skin purpura and renal involvement, primarily manifesting as hematuria and/or proteinuria. Microscopic hematuria was observed in 253 patients (95.8%), while 246 patients (93.2%) showed proteinuria. In 256 patients (97.0%), hematuria or proteinuria urinalysis was detected within 6 months of skin purpura onset, and 243 patients (92.0%) underwent renal biopsy within 6 months of renal involvement. The most common clinical subtype in 264 IgAVN children was hematuria and proteinuria (204 cases, 77.3%), with grade Ⅲ being the predominant pathological classification (181 cases, 68.6%). Among children ≤6 years old, the 3-year complete remission rate was higher in males than in females (83.9% (26/31) vs. 7/16, χ2=8.12, P=0.012). Factors independently associated with poor 5-year prognosis included time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission 3 years post-biopsy ( OR=5.41, 1.39, 6.02, 95% CI 1.40-20.86, 1.04-1.84, 2.61-13.88, all P<0.05). The serum cholesterol has a predictive value for 5-year prognosis ( P=0.020, AUC=0.62, 95% CI 0.52-0.71, Youden index=0.27, cutoff=4.37). Conclusions:For children with IgAVN aged≤6 years, the 3-year prognosis is better in males than in females. Time from hematuria or proteinuria urinalysis to renal biopsy >6 months, elevated serum cholesterol levels, and incomplete remission at 3 years post-biopsy may be independent risk factors for poor 5-year prognosis in children with IgAVN.

Tafamidis is a selective stabilizer for transthyretin （TTR）， used for the treatment of transthyretin amyloidosis with cardiomyopathy （ATTR-CM） and transthyretin amyloidosis with polyneuropathy （ATTR-PN）. This article provides a review of the basic information and clinical studies on the efficacy and safety of tafamidis. It is found that tafamidis slows down or prevents the progression of TTR amyloidosis by inhibiting the dissociation of TTR tetramers. Multiple clinical studies have shown that tafamidis has good efficacy and safety， significantly reducing all-cause mortality and cardiovascular-related hospitalization rates in patients with amyloidosis， and delaying disease progression. Although tafamidis treatment may have certain limitations， it is still a key drug for the treatment of TTR amyloidosis， and the first drug approved for the treatment of ATTR-CM.

Immunoglobulin A nephropathy is a common autoimmune nephropathy.A growing body of research suggests that immunoglobulin A nephropathy may be associated with dysfunction of the mucosal immune system.Immunoglobulin A nephropathy is characterized by thylakoid deposi-tion of galactose-deficient IgA1 immune complex-es,which are thought to originate from mucosal B-cells,which are abundantly present in the distal ile-um,which is rich in Pyle's collecting lymph nodes.A novel targeted release formulation of budesonide has been shown to deliver the drug to the distal ileum with the aim of minimizing adverse events in patients with immunoglobulin A nephrop-athy.This article reviews the mechanism of action,dosage form characteristics,clinical studies,drug interactions and adverse events,and limitations of budesonide extended-release capsules.