OBJECTIVE: To explore the prenatal and postnatal phenotypes of 22q11.2 microdeletion syndrome (22q11.2DS) and enhance clinical understanding of this condition. METHODS: Data were collected from 86 fetuses diagnosed with 22q11.2DS at four prenatal diagnostic centers across China between January 2014 and August 2025. Prenatal imaging findings, pregnancy outcomes, and postnatal conditions were analyzed. RESULTS: Among the 86 fetuses, complete ultrasound data were available for 65 cases. Cardiovascular abnormalities were observed in 42 cases, thymic hypoplasia or aplasia in 7 cases, urinary system anomalies in 6 cases, nuchal translucency (NT) thickening in 7 cases, butterfly vertebrae, clubfoot, omphalocele and diaphragmatic hernia in 1 case each, cleft lip and palate in 2 cases, and ultrasound soft markers in 13 cases. The parents of 9 fetuses opted to continue with the pregnancy. Among these, 6 showed no significant ultrasound abnormalities and no related phenotypes postnatally, while the remaining 3 exhibited ultrasound anomalies with postnatal manifestations including developmental delay, immunodeficiency, and cardiac defects. CONCLUSION Fetuses with 22q11.2DS may exhibit various ultrasound abnormalities in multiple systems before and after birth. In addition to cardiovascular anomalies, they may also present with thymic hypoplasia or aplasia, thickened NT, and urinary abnormalities. Fetuses with thickened NT or thymic anomalies should be closely monitored, and thymic assessment should be included in routine prenatal imaging evaluations. For fetuses with 22q11.2DS who show no ultrasound abnormalities, the risk of developing severe phenotypes after birth is relatively low, but occult palate clefts and psychiatric disorders cannot be ruled out. Due to limitations in sample size and follow-up duration, above conclusions require further validation through large-scale prospective studies.
Humans ; Female ; Pregnancy ; Ultrasonography, Prenatal ; DiGeorge Syndrome/genetics* ; Adult ; Male ; Follow-Up Studies ; Fetus/diagnostic imaging* ; Phenotype ; Infant, Newborn

ObjectiveTo prepare a recombinant PETase with a dual-catalytic-triad and to evaluate its efficiency in the biodegradation of polyethylene terephthalate （PET）. MethodsBased on the crystal structure of wild-type PETase， point mutations （T88H/L117D） were introduced via site-directed mutagenesis. The recombinant protein was prepared using prokaryotic expression and chromatography purification techniques. The enzymatic hydrolysis of the mutant PETase was assessed by relatively quantifying the products mono （2-hydroxyethyl） terephthalate （MHET） and terephthalic acid （TPA）. ResultsBoth wild-type and mutant PETases accumulated as inclusion bodies， accounting for approximately 20% of the total bacterial protein. After solubilization in urea， the proteins were eluted at 300 mmol/L imidazole during affinity chromatography purification， with concentrations of 1.824 and 1.833 mg/mL and purities of 83.11% and 84.32%， respectively. Subsequent anion-exchange chromatography yielded highly pure enzymes in the 200 mmol/L NaCl fraction： 2.776 mg/mL （96.86% purity） for the wild type and 1.967 mg/mL （95.13% purity） for the mutant. Following refolding， the final concentrations were 0.484 mg/mL for the wild type and 0.991 mg/mL for the mutant. Hydrolysis assays revealed that the mutant released MHET and TPA at （237.67±17.00）% and （197.33±12.01）% of the wild-type levels， respectively. ConclusionThe T88H/L117D dual-catalytic-triad PETase is successfully prepared and it significantly enhanced PET-degrading activity， thus， it′s a promising biocatalyst for PET bioremediation.

Objective: Scutellarin in Shuganning injection has potential allergenicity and is prone to causing anaphylactoid reactions. There is an urgent need to establish a simple and rapid chromatographic quantitative method to achieve the limit control of scutellarin in Shuganning injection.
Methods: For scutellarin, HPLC method was used in the quantitative analysis using a Shim-pack GIS C₁₈ (2.1 mm×150 mm, 5 μm) column. The mobile phase was a blend of 0.1% trifluoroacetic acid in water and acetonitrile, and gradient elution progress was applied for the whole process. The flow rate was 0.3 mL·min^-1 and the column temperature was maintained at 37 ℃. The detecting wavelength was 320 nm.
Results: The linear regression equation was y=51 456x-27 352, the correlation coefficient r=0.999 8, namely the calibration curve was linear in the range of 1.02-102.00 μg·mL^-1; the average recovery was 103.76%; the detection and quantification limit for determining scutellarin was 0.16 μg·mL^-1 and 0.57 μg·mL^-1, respectively; the injection sample was stable at room temperature for 48 h.
Conclusion: This method is easy to operate, reproducible and has high accuracy, thus can be used for quality control of Shuganning injection.

Background: and Purpose Vertebrobasilar fusiform aneurysms (VBFAs) carry substantial morbidity and mortality, but optimal management for unruptured VBFAs remains unclear. We compared the safety and efficacy of conservative management (CM), stent-assisted coiling (SAC), and flow diverters (FDs) in patients with unruptured VBFAs, focusing on long-term prognosis. Methods: This study included data from a nationwide Chinese cohort of patients with vertebrobasilar dissecting aneurysms. Inverse probability of treatment weighting (IPTW) balanced confounders across groups. The primary outcome was poor prognosis (modified Rankin Scale score >2). Secondary outcomes included aneurysm rupture, ischemic stroke, compression symptoms, and VBFA-related deaths. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were performed. Results: Among 1,115 patients with unruptured VBFAs, 838 (median age, 54 years; 655 men) were included. After IPTW, baseline characteristics were balanced. Median follow-up was 54 months. FD was associated with a lower risk of poor prognosis than CM (OR, 0.48 [95% CI, 0.30 to 0.77]; p=0.002), with no difference between CM and SAC. FD also reduced aneurysm rupture (OR, 0.20 [95% CI, 0.07 to 0.60]; p=0.004) and compression symptoms (OR, 0.30 [95% CI, 0.13 to 0.68]; p=0.004) versus CM. Time-to-event analyses further revealed significant differences in vertebral artery lesions and Type I–II VBFAs, whereas no significant differences were observed in basilar or vertebrobasilar junction lesions or in Type III–IV VBFAs. Conclusions Compared with CM, FD was associated with improved long-term outcomes in unruptured VBFAs, particularly in vertebral artery lesions and Type I–II VBFAs, although residual confounding cannot be excluded.

Objective To explore the effect of young plasma intraperitoneal injection on the fertility and ovarian function of aging mice and analyze its potential molecular mechanism.Methods Fifty-four-week-old female C57BL/6 mice and 8-week-old male C57BL/6 mice were selected.Among them,the female mice were randomly divided into three groups:the young plasma group,the aging plasma group and the normal saline group.The young plasma group and the aging plasma group received intraperitoneal injection of plasma from young(25-29 years old)and elderly(45-49 years old)female donors,respectively.Each injection was 500 μL,administered every other day for 2 weeks.The saline group received an equal volume of saline.After the last injection,mating experiments were conducted to evaluate fertility.Ovarian histopathological changes were observed by HE staining.Oocytes and fertilized eggs were collected after superovulation and cultured in vitro to assess oocyte quality and embryo developmental potential.Transcriptomic analysis of ovarian tissue was performed,followed by KEGG and GO enrichment analysis.Results Compared with the normal saline group and the aging plasma group,the number of offspring increased in the young plasma group,which reflected higher extrusion rate of first polar body(PB1),decreased fragmentation rate of oocytes and increased conversion rate of two-cell embryos and increased formation rate of blastocysts.There were no significant differences in these indicators between the aging plasma group and the normal saline group.Transcriptomic sequencing revealed that the differentially expressed genes in ovarian tissue of the young plasma group were mainly involved in steroid biosynthesis and metabolic pathways.Among them,the expression level of steroid sulfatase protein was significantly upregulated.Conclusion Systemic infusion of young plasma enhances the reproductive potential of aging ovaries in elderly mice.The sulfated steroid metabolites in plasma may be key substances in restoring ovarian function and delaying the process of ovarian aging.

Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

OBJECTIVES: To investigate the association of serum albumin level after human albumin infusion with 28-day mortality in critically ill patients with acute kidney injury (AKI) and its impact on 90-day outcomes of the patients. METHODS: We conducted a retrospective cohort study based on the MIMIC IV database (2008-2019), including 5918 AKI patients treated with albumin in the ICU. Based on serum albumin levels within 72 h after albumin infusion, the patients were divided into low (<30 g/L), medium (30-35 g/L), and high albumin (>35 g/L) groups. Restricted cubic spline regression and multivariate logistic regression were used to analyze the association of albumin levels with patient mortality, and the results were verified in a external validation cohort consisting of 110 sepsis-induced AKI patients treated in Nanfang Hospital between 2017 and 2022 using survival analysis and multivariate adjustment. RESULTS: In the MIMIC training cohort, multivariate logistic regression showed no significant differences in 28-day mortality of the patients with different albumin levels (P>0.05). However, restricted cubic spline analysis indicated a non-linear dose-response relationship between albumin levels and 28-day mortality (threshold effect: risk increased when albumin levels >3.6 g/dL). Secondary endpoint analysis revealed that the patients with high albumin levels had a shorter duration of mechanical ventilation (P<0.001) but a longer ICU stay (P<0.001). In the validation cohort, albumin levels ≥30 g/L were significantly associated with a reduced 28-day mortality rate (P<0.05). CONCLUSIONS The association between increased serum albumin levels following albumin infusion and 28-day mortality of critically ill patients with AKI exhibits a cohort dependency and can be influenced by multiple factors including disease type and severity, infusion strategies, and statistical methods.
Humans ; Acute Kidney Injury/therapy* ; Critical Illness/mortality* ; Retrospective Studies ; Serum Albumin/analysis* ; Male ; Female ; Intensive Care Units ; Middle Aged ; Logistic Models ; Aged

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

Objective To investigate the effects of different cultivation method and harvest periods on chromatic characteristics and the primary bioactive components of Dendrobium officinale.Methods Fifteen batches of three-year-old Dendrobium officinale were categorized into five cultivation groups:DP-ZP,YB-ZP,HS-ZP,SP-ZP,and ZJ-ZP,with three batches per group.Thirty-six batches of Dendrobium officinale samples were categorized into twelve harvest groups according to different harvest periods and growth years:the T1 to T6 groups were three-year-old samples,and the F1 to F6 groups were four-year-old samples.Chromaticity values of Dendrobium officinale under different cultivation methods and harvest periods were measured using colorimetry.Polysaccharide content under different cultivation method and harvest periods was quantified via ultraviolet spectrophotometry.Mannose,glucose,flavonoids,and phenolic acids(rutin,quercetin,naringenin,and syringic acid)were analyzed in each group under different cultivation methods and harvest periods using HPLC.The total amount of mannose and glucose,the peak area ratio of mannose to glucose,and the total amount of flavonoids and phenolic acids were calculated.The entropy weight-TOPSIS method was applied to assign objective weights to indicators,followed by the calculation of relative closeness(C)for comprehensive quality assessment of medicinal materials.Results Under different cultivation methods,compared with the DP-ZP group,the b? value of the ZJ-ZP and YB-ZP groups decreased,whereas that of the SP-ZP group increased.The L? value and polysaccharide,syringic acid,naringenin,and quercetin contents decreased,whereas the a? value increased in the YB-ZP,SP-ZP,HS-ZP,and ZJ-ZP groups.The mannose contents decreased in the HS-ZP and SP-ZP groups and increased in the ZJ-ZP group(P<0.05).The glucose content in the ZJ-ZP and SP-ZP groups decreased,the peak area ratio of mannose to glucose increased(P<0.05).Compared with the SP-ZP group,the mannose and glucose contents and the total amount of mannose and glucose were significantly increased,and the peak area ratio of mannose to glucose was decreased in the DP-ZP,YB-ZP,HS-ZP,and ZJ-ZP groups(P<0.01).Compared with the ZJ-ZP group,the rutin contents and the total amount of flavonoids and phenolic acids were decreased in the SP-ZP,HS-ZP,DP-ZP,and YB-ZP groups(P<0.05).Compared with the T3 group,the L? value of the T1,T2,T5,and T6 groups decreased,whereas the b? value increased.The a? value and the peak area ratio of mannose to glucose increased in the T1,T2,and T4 to T6 groups,whereas the polysaccharide and glucose contents and the total amount of mannose and glucose decreased(P<0.05).Compared with the T5 group,the mannose content in the T1 to T4 and T6 groups decreased,whereas the rutin content increased in the T1 to T4 groups(P<0.05).Compared with the T6 group,the syringic acid and quercetin contents increased in the T1 to T5 groups,and the total amount of flavonoids and phenolic acids increased in the T1 to T4 group(P<0.05).Compared with the F1 group,the syringic acid content in the F2 to F6 group increased,the quercetin content decreased(P<0.01).Compared with the F2 group,the glucose and rutin content and the total amount of flavonoids and phenolic acids decreased in the F1 and F3 to F6 groups(P<0.01).Compared with the F3 group,the L? value decreased,the b? value increased,mannose content and the total amount of mannose and glucose decreased in the F1,F2,and F4 to F6 groups.Polysaccharide content in the F1 and F4 to F6 groups decreased(P<0.05).Compared with the F6 group,the peak area ratio of mannose to glucose was significantly decreased in the F1 to F4 groups(P<0.01).Entropy weight-TOPSIS analysis showed that the C of chromatic characteristics and primary bioactive components in DP-ZP(C=0.661 1)and F5(C=0.538 9)groups were the highest.Conclusion Dendrobium officinale cultivated under greenhouse conditions and four-year-old Dendrobium officinale harvested in February exhibit optimal overall quality.These findings provide an experimental basis for the selection of cultivation method and the optimal harvest period of high-quality Dendrobium officinale.