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

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*

Objective:To investigate the epidemic characteristics of imported malaria in Dezhou City, Shandong Province.Methods:The epidemic data of imported malaria in Dezhou City from January 2014 to December 2024 reported by the China Disease Prevention and Control Information System and the Parasitic Disease Prevention and Control Information Management System were collected, and the sources of infection and epidemiological characteristics of the cases were analyzed. Meanwhile, the surveillance data of malaria vector populations in Dezhou City reported by the China Disease Control and Prevention Information System during the same period were collected, and the types of mosquito populations were analyzed.Results:From 2014 to 2024, a total of 100 cases of imported malaria were reported in Dezhou City, all of which were laboratory-confirmed cases, mainly falciparum malaria, accounting for 61.0% (61/100). The cases came from 21 countries, mainly imported from Africa, accounting for 99.0% (99/100). The cases were mainly male, accounting for 99.0% (99/100). The age range was mainly between 21 and 50 years old, accounting for 88.0% (88/100). The occupations were mainly construction industry workers and catering industry personnel, accounting for 41.0% (41/100) and 27.0% (27/100), respectively. The median time interval between the entry of the case and the onset of the disease was 8 days, and the median time interval between the onset of the disease and diagnosis was 6 days. From 2014 to 2024, a total of 16 803 mosquitoes were captured in Dezhou City, with the dominant mosquito species being Culex pipiens pallens, accounting for 89.1% (14 979/16 803). Conclusion:The imported malaria in Dezhou City is mainly falciparum malaria imported from Africa, and the cases are mainly male, young and middle-aged people and construction industry workers.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

Objective:To investigate the epidemic characteristics of imported malaria in Dezhou City, Shandong Province.Methods:The epidemic data of imported malaria in Dezhou City from January 2014 to December 2024 reported by the China Disease Prevention and Control Information System and the Parasitic Disease Prevention and Control Information Management System were collected, and the sources of infection and epidemiological characteristics of the cases were analyzed. Meanwhile, the surveillance data of malaria vector populations in Dezhou City reported by the China Disease Control and Prevention Information System during the same period were collected, and the types of mosquito populations were analyzed.Results:From 2014 to 2024, a total of 100 cases of imported malaria were reported in Dezhou City, all of which were laboratory-confirmed cases, mainly falciparum malaria, accounting for 61.0% (61/100). The cases came from 21 countries, mainly imported from Africa, accounting for 99.0% (99/100). The cases were mainly male, accounting for 99.0% (99/100). The age range was mainly between 21 and 50 years old, accounting for 88.0% (88/100). The occupations were mainly construction industry workers and catering industry personnel, accounting for 41.0% (41/100) and 27.0% (27/100), respectively. The median time interval between the entry of the case and the onset of the disease was 8 days, and the median time interval between the onset of the disease and diagnosis was 6 days. From 2014 to 2024, a total of 16 803 mosquitoes were captured in Dezhou City, with the dominant mosquito species being Culex pipiens pallens, accounting for 89.1% (14 979/16 803). Conclusion:The imported malaria in Dezhou City is mainly falciparum malaria imported from Africa, and the cases are mainly male, young and middle-aged people and construction industry workers.

Objective To investigate the pharmacokinetic characteristics of asparaginase-loaded sulfobutyl ether-β-cyclodextrin supramolecule lipidic nanoparticles (ASLN) in rats and its inhibitory effect on the proliferation of small cell lung cancer cells. Methods ASLN were prepared by a reverse phase evaporation method,and their physicochemical properties,including morphology,particle size,zeta potential,and drug entrapment efficiency,were characterized. Twelve male Sprague-Dawley rats were randomly divided into 2 groups,with 6 rats in each group. After intravenous injection of ASLN and free asparaginase (Aase) 2 kU/kg,the activity of Aase in plasma samples was measured at different time points in 48 h,and the activity-time curve was drawn. The pharmacokinetic parameters were calculated by software DAS 2.1.1. The cytotoxicity of ASLN on H446 cells was explored by the MTT method. Results ASLN showed a spherical shape with a mean particle size of (321.27±1.42) nm,zeta potential of (-9.31±0.42) mV,and entrapment efficiency of (66.46±1.57)％. Pharmacokinetic parameters of ASLN and Aase were as follows:the area under curve (AUC(0-48 h)) (199.48±2.18) U·mL-1·h,(57.63±3.89) U·mL-1·h;the mean residence time (MRT(0-48 h)) (4.40±0.05) h,(2.09±0.07) h;and the peak concentration (Cmax) (35.49±1.11) U/mL,(27.58±1.28) U/mL. The relative bioavailability of ASLN to Aase was 325.96％. The cytotoxicity results indicated that ASLN had a proliferation inhibitory effect on H446 cells,and there was a positive correlation between the inhibition rate and the dose. Conclusion ASLN can improve the pharmacokinetics of Aase,enhance the bioavailability of Aase,and inhibit the proliferation of small cell lung cancer cells.

OBJECTIVE: The present study aimed to evaluate the immunogenicity of BA.2 variant receptor binding domain (RBD) recombinant protein formulated with CpG 1826 plus alum dual adjuvant. METHODS: The BA.2 variant RBD (residues 308-548) fusing TT-P ₂ epitope was obtained from prokaryotic expression system, purification technology and dialysis renaturation, which was designated as Sot protein. The soluble Sot protein formulated with CpG 1826 plus alum dual adjuvant was designated as Sot/CA subunit vaccine and then the BALB/c mice were intramuscularly administrated with two doses of the Sot/CA subunit vaccine at 14-day interval (day 0 and 14). On day 28, the number of effector T lymphocytes secreting IFN-γ and IL-4 in mice spleen were determined by enzyme-linked immunospot (ELISpot) assay. The serum IgG, IgG1 and IgG2a antibodies were examined by enzyme-linked immunosorbent assay (ELISA). In addition, the level of neutralizing antibodies (NAbs) induced by Sot/CA subunit vaccine was also evaluated by the microneutralization assay. RESULTS: The high-purity soluble Sot protein with antigenicity was successfully obtained by the prokaryotic expression, protein purification and dialysis renaturation. The Sot/CA subunit vaccine induced a high level of IgG antibodies and NAbs, which were of cross-neutralizing activity against SARS-CoV-2 BA.2 and XBB.1.5 variants. Meanwhile, Sot/CA subunit vaccine also induced a high level of effector T lymphocytes secreting IFN-γ (635.00 ± 17.62) and IL-4 (279.20 ± 13.10), respectively. Combined with a decreased IgG1/IgG2a ratio in the serum, which indicating Sot/CA subunit vaccine induced a Th1-type predominant immune response. CONCLUSION The Sot protein formulated with CpG 1826 plus alum dual adjuvant showed that the excellent cellular and humoral immunogenicity, which provided a scientific basis for the development of BA.2 variant subunit vaccines and references for the adjuvant application of subunit vaccines.
Animals ; COVID-19 Vaccines/immunology* ; Alum Compounds/pharmacology* ; Mice, Inbred BALB C ; Vaccines, Subunit/immunology* ; Mice ; SARS-CoV-2/immunology* ; Oligodeoxyribonucleotides/administration & dosage* ; Female ; Adjuvants, Immunologic ; COVID-19/immunology* ; Antibodies, Viral/blood* ; Immunogenicity, Vaccine ; Spike Glycoprotein, Coronavirus/immunology* ; Antibodies, Neutralizing/blood* ; Adjuvants, Vaccine ; Immunoglobulin G/blood*

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.