[Objective] To analyze the serological characteristics and molecular biology results for a P^k phenotype. [Methods] One patient with P^k phenotype upon unexpected antibodies at Jining Blood Center in July 2022 was selected as the study subject. The blood groups and unexpected antibodies of the proband and his second son were identified using serological methods. The sequences of 3-β-N-acetylgalactosaminyltransferase gene (B3GALNT1) and the coding region of α-1,4-galactosyltransferase gene (A4GALT) were amplified and analyzed by PCR direct sequencing, and haploid sequence analysis was carried out on the variant sites of the B3GALNT1 gene. PROVEAN, SIFT, PolyPhen2 and Mutation Taster were used to analyze the effect of mutations on the protein. [Results] Serological test results suggested that the proband was a P2^k type, including anti-P antibody in his serum, and his son was the P2 phenotype. Sequencing analysis revealed that the proband had a compound heterozygous variants of the B3GALNT1 in c. 239T>A (p. Leu80Gln) and c. 433C>T (p. Arg145Ter). Further haploid analysis showed that the c. 239T>A had occurred in one haploid while c. 433C>T was present in the other haploid, and his son carried a heterozygous variant of c. 433C>T (p. Arg145Ter); the proband and his son all have homozygous mutation variants of the A4GALT in c. 903C>G. Bioinformatic analysis also predicted that the mutations were harmful to the protein function. [Conclusion] The compound heterozygous variants c. 239T>A (p. Leu80Gln) and c. 433C>T (p. Arg145Ter) in the B3GALNT1 gene may contribute to the P^k phenotype, of which the c. 239T>A variant has not been reported.

Objective:To investigate the arsenic metabolism pattern and possible influencing factors in the population in drinking-water-borne endemic arsenic poisoning (drinking-water-borne arsenic poisoning for short) areas.Methods:In December 2004, a cluster sampling method was used to select arsenic poisoning population (arsenic poisoning group) and healthy population (control group) in drinking-water-borne arsenic poisoning area of Bayannur City, Inner Mongolia Autonomous Region as the survey subjects. A questionnaire survey was conducted. Arsenic content in drinking water at home of survey subjects, the levels of urinary arsenic and its metabolites, including [trivalent arsenic (As Ⅲ), inorganic arsenic (iAs), monomethylarsenic acid (pentavalent, MMA V), dimethylarsenic acid (pentavalent, DMA V), total arsenic (tAs), percentage of inorganic arsenic (iAs%), percentage of monomethylarsenic acid (MMA%), percentage of dimethylarsenic acid (DMA%), primary methylation index (PMI), secondary methylation index (SMI)] were tested using high performance liquid chromatography-inductively coupled plasma mass spectrometry; nail arsenic and nail selenium levels were tested using atomic fluorescence spectrometer. The influencing factors of arsenic metabolism pattern were analyzed by multiple linear regression. Results:A total of 536 survey subjects were included, including 155 individuals in the arsenic poisoning group and 381 in the control group. The water arsenic level ranged from 0.0 to 825.7 μg/L. Compared with the control group, there was no significant difference in the distribution of gender, education level and dental fluorosis in the arsenic poisoning group ( P > 0.05), but there were significant differences in the distribution of age, marital status, smoking, drinking and water arsenic ( P < 0.05). Compared with the control group, the levels of urinary As Ⅲ, iAs, MMA V, DMA V, tAs, MMA%, MMA/DMA and nail arsenic in the arsenic poisoning group were higher ( P < 0.05), while the levels of urinary DMA%, SMI and nail selenium were lower ( P < 0.05); but there was no statistically significant difference in the levels of urinary iAs% and PMI ( P > 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary As Ⅲ (β = - 19.82, - 23.83, 0.61, 0.21, 7.26, 2.98, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary tAs (β = 3.18, 3.25, 1.31, 15.59, P < 0.05). Gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic were the influencing factors of urinary iAs (β = - 20.47, - 25.90, 0.64, 0.25, 7.87, 3.11, P < 0.05). Age, gender, education level, water arsenic and nail arsenic were the influencing factors of urinary MMA V (β = 0.52, - 17.07, - 21.84, 0.22, 2.77, P < 0.05). Age, depth of wells, water arsenic and nail arsenic were the influencing factors of urinary DMA V (β = 2.35, 2.47, 0.85, 9.22, P < 0.05). Conclusions:Compared with healthy individuals, there are differences in arsenic metabolism pattern among individuals with drinking-water-borne arsenic poisoning. Age, gender, education level, depth of wells, water arsenic, total number of wells and nail arsenic may be influencing factors of different arsenic metabolism patterns.

Objective:To investigate the relationship between the outcome of skin injury and urinary arsenic methylation metabolism levels in people exposed to arsenic through drinking water.Methods:Using cluster sampling method, permanent residents from drinking-water-borne endemic arsenic poisoning areas in Bayannur City, Inner Mongolia Autonomous Region were selected as survey subjects in 2004 (before water improvement). In 2017 (after water improvement), 74 survey subjects from 2004 were tracked and followed up. Urine samples were collected from survey subjects and high-performance liquid chromatography inductively coupled plasma mass spectrometry was used to detect the levels of arsenic methylation metabolites in urine. According to the "Diagnosis of Endemic Arsenic Poisoning" (WS/T 211-2015), the clinical grading (normal, suspicious, mild, moderate and severe) of skin injury of the survey subjects and the outcome of 2017 (improved, unchanged, aggravated) were assessed. A database was established and SPSS 25.0 software was used for statistical analysis.Results:The clinical grading ratios of skin injuries among survey subjects in 2004 and 2017 were compared, the differences were statistically significant (normal, suspicious, mild, moderate and severe: 38, 18, 4, 14 cases in 2004 and 27, 31, 3, 13 cases in 2017, χ 2 = 53.02, P < 0.001). Compared with 2004, in 2017, the levels of total arsenic (tAs), inorganic arsenic (iAs), monomethylarsenic (MMA), dimethylarsenic (DMA), percentage of inorganic arsenic (iAs%), and ratio of monomethylarsenic to dimethylarsenic (MMA/DMA) in the urine of survey subjects were low, and the differences were statistically significant ( Z = - 8.24, - 9.07, - 7.81, - 8.04, - 8.24, - 3.56, P < 0.001). The levels of dimethylarsenic percentage (DMA%), monomethylation rate (PMI) and dimethylation rate (SMI) were higher, and the differences were statistically significant ( Z = - 6.39, - 8.24, - 3.52, P < 0.001). In 2004, patients with different clinical grading of skin injuries had different outcomes in 2017 (χ 2 = 30.80, P < 0.001). There were statistically significant differences in tAs, iAs, MMA and DMA variation in urine among skin injury patients with different outcomes ( H = 10.62, 9.35, 8.80, 9.13, P < 0.05). Conclusions:Improving water can significantly reduce the levels of tAs, iAs, MMA, and DMA in the urine of arsenic exposed individuals. The outcome of skin injury in individuals exposed to arsenic through drinking water is related to the variation of urinary arsenic methylation metabolites tAs, iAs, MMA, and DMA.

CRISPR-Associated Protein 9 ; Gene Editing ; CRISPR-Cas Systems/genetics*

Objective:To evaluate the effect of wrist-ankle acupuncture on the pharmacodynamics of remimazolam for loss of consciousness in the patients of different genders and ages undergoing painless gastroscopy.Methods:American Society of Anesthesiologists Physical Status classificationⅠor Ⅱ patients, undergoing elective painless gastroscopy, were divided into 4 groups according to gender and age: agedmale (age≥65 yr) group (group AM), agedfemale (age≥65 yr) group (group AF), young male (18 yr≤age <65 yr) group (group YM), and young female (18 yr≤age <65 yr) group (group YF). After 10 min of wrist-ankle acupuncture on 1st and 2nd areas of the bilateralupper limbs of the patient, modified Dixon′s up-and-down sequential experiment was used for the test.The initial dose of intravenous remimazolam was 0.20 mg/kg. Each time the dose increased/decreased by 0.05 mg/kg. If the patient lost consciousness, the next patient received a lower dose of remimazolam, otherwise a higher dose was given in the next patient. Loss of consciousness was defined as MOAA/S score was 0 or 1, and the process was repeated until 7 turning points appeared.The median effective dose (ED 50)and 95% confidence interval of remimazolam were calculated by probit method. Results:The ED 50 and 95% confidence interval of remimazolam were 0.296(0.233-0.376), 0.319(0.262-0.388), 0.323(0.278-0.375) and 0.344(0.285-0.415)mg/kg in AM, AF, YM and YF groups, respectively. There was no significant difference in ED 50 among the four groups ( P>0.05). Conclusions:Under the action of wrist-ankle acupuncture, the pharmacodynamics of remazolam is comparable when used for the patients of different genders and ages undergoing painless gastroscopy.

To explore the composition and diversity of the intestinal microflora of Leopoldamys edwardsi in Hainan Island. In November 2019, DNA was extracted from fecal samples of 25 adult Leopoldamys edwardsi (14 males and 11 females) in Hainan Island at the Joint Laboratory of tropical infectious diseases of Hainan Medical College and Hong Kong University. Based on the IonS5TMXL sequencing platform, single-end sequencing (Single-End) was used to construct a small fragment library for single-end sequencing. Based on Reads shear filtration and OTUs clustering. The species annotation and abundance analysis of OTUs were carried out by using mothur method and SSUrRNA database, and further conducted α diversity and β diversity analysis. A total of 1481842 high quality sequences, belonging to 14 Phyla, 85 families and 186 Genera, were obtained from 25 intestinal excrement samples of Leopoldamys edwardsi. At the level of phyla classification, the main core biota of the Leopoldamys edwardsi contained Firmicutes (46.04%),Bacteroidetes (25.34%), Proteobacteria (17.09%), Tenericutes (7.38%) and Actinobacteria (1.67%), these five phyla account for 97.52% of all phyla. The ratio of Helicobacter which occupied the largest proportion at the genus level was 12.44%, followed by Lactobacillus (11.39%), Clostridium (6.19%),Mycoplasma (4.23%) and Flavonifractor (3.52%). High throughput sequencing analysis showed that the intestinal flora of Leopoldamys edwardsi in Hainan Island was complex and diverse, which had the significance of further research.
Adult ; Animals ; Bacteria/genetics* ; Feces/microbiology* ; Female ; Gastrointestinal Microbiome/genetics* ; High-Throughput Nucleotide Sequencing ; Humans ; Intestines ; Male ; Murinae/genetics*

Objective: To explore the types and clinical characteristics of chronic rhinosinusitis with nasal polyps (CRSwNP) based on artificial intelligence and whole-slide imaging (WSI), and to explore the consistency of the diagnostic criteria of the Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis (JESREC) in Chinese CRSwNP patients. Methods: The data of 136 patients with CRSwNP (101 males and 35 females, aging 14 to 70 years) who underwent endoscopic sinus surgery from 2018 to 2019 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analysed retrospectively. The preoperative clinical characteristics of patients were collected, such as visual analogue scale (VAS) of nasal symptoms, peripheral blood inflammatory cell count, total immunoglobulin E (IgE), Lund-Kennedy score and Lund-Mackay score. The proportion of inflammatory cells such as eosinophils, lymphocytes, plasma cells and neutrophils were calculated on the WSI of each patient through artificial intelligence chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0), and the specific type of nasal polyps was then obtained as eosinophilic CRSwNP (eCRSwNP) or non-eosinophilic CRSwNP (non-eCRSwNP). In addition, the JESREC diagnostic criteria was used to classify the nasal polyps, and the classification results were compared with the current gold standard for nasal polyps diagnosis (pathological diagnosis based on WSI). The accuracy, sensitivity and specificity of the diagnostic criteria of JESREC were evaluated. The data were expressed in M (Q₁, Q₃) and statistically analyzed by SPSS 17.0. Results: There was no significant difference between eCRSwNP and non-eCRSwNP in age distribution, gender, time of onset, total VAS score, Lund-Kennedy score or Lund-Mackay score. However, there was a significant difference in the ratio of nasal polyp inflammatory cells (eosinophils 40.5% (22.8%, 54.7%) vs 2.5% (1.0%, 5.3%), neutrophils 0.3% (0.1%, 0.7%) vs 1.3% (0.5%, 3.6%), lymphocytes 49.9% (39.3%, 65.9%) vs 82.0% (72.8%, 87.5%), plasma cells 5.1% (3.6%, 10.5%) vs 13.0% (7.4%, 16.3%), χ² value was 9.91, 4.66, 8.28, 5.06, respectively, all P<0.05). In addition, eCRSwNP had a significantly higher level of proportion of allergic symptoms (nasal itching and sneezing), asthma, peripheral blood eosinophil and total IgE (all P<0.05). The overall accuracy, sensitivity and specificity of the JESREC diagnostic criteria was 74.3%, 81.3% and 64.3%, respectively. Conclusions: The eCRSwNP based on artificial intelligence and WSI has significant high level of allergic symptoms, asthma, peripheral blood eosinophils and total IgE, and the percentages of inflammatory cells in nasal polyps are different from that of non-eCRSwNP. The JESREC diagnostic criteria has good consistency in our research.
Artificial Intelligence ; Chronic Disease ; Eosinophils/metabolism* ; Female ; Humans ; Male ; Nasal Polyps/pathology* ; Retrospective Studies ; Rhinitis/pathology* ; Sinusitis/pathology*

Looking retrospectively at the development of humanity, vaccination is an unprecedented medical landmark that saves lives by harnessing the human immune system. During the ongoing coronavirus disease 2019 (COVID-19) pandemic, vaccination is still the most effective defense modality. The successful clinical application of the lipid nanoparticle-based Pfizer/BioNTech and Moderna mRNA COVID-19 vaccines highlights promising future of nanotechnology in vaccine development. Compared with conventional vaccines, nanovaccines are supposed to have advantages in lymph node accumulation, antigen assembly, and antigen presentation; they also have, unique pathogen biomimicry properties because of well-organized combination of multiple immune factors. Beyond infectious diseases, vaccine nanotechnology also exhibits considerable potential for cancer treatment. The ultimate goal of cancer vaccines is to fully mobilize the potency of the immune system as a living therapeutic to recognize tumor antigens and eliminate tumor cells, and nanotechnologies have the requisite properties to realize this goal. In this review, we summarize the recent advances in vaccine nanotechnology from infectious disease prevention to cancer immunotherapy and highlight the different types of materials, mechanisms, administration methods, as well as future perspectives.

Pro-gastrin-releasing peptide (ProGRP) is a specific marker of small cell lung cancer.

Objective:To study the effect of water improvement on urinary arsenic methylation metabolism in population exposed to arsenic through drinking water.Methods:A cluster sampling method was used to select drinking water type arsenism areas in Bayannur City, Inner Mongolia Autonomous Region. Permanent residents lived in the arsenism areas for more than 10 years were selected as the survey subjects. Urine samples ( n = 874, 111, 145) were collected in 2004 (before water improvement), 2014 (4 years after water improvement) and 2017 (7 years after water improvement), respectively, and some subjects were followed up in 2014 and 2017. High performance liquid chromatography-inductively coupled plasma mass spectrometry (HPLC-ICP-MS) was used to detect different forms of arsenic metabolites in urine [inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsenic acid (DMA)], and total arsenic (tAs), the iAs percentage (iAs%), MMA percentage (MMA%), DMA percentage (DMA%), monomethylation rate (PMI), dimethylation rate (SMI), and the ratio of MMA to DMA (MMA/DMA) were calculated. The content and distribution of urinary arsenic metabolites in people exposed to arsenic before and after water improvement were compared and analyzed. Results:Compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine of arsenic exposed population in 2014 were lower ( Z =-14.12,-12.79,-14.27,-14.21,-6.90, P < 0.001), the levels of MMA%, DMA% and PMI were higher ( Z =-3.22,-2.91,-6.90, P < 0.05); in the same drinking water arsenic exposed population, compared with 2004, the levels of iAs, MMA, DMA, tAs and iAs% in urine ( n = 48) were lower ( Z =-5.57,-5.53,-5.54,-5.55,-2.86, P < 0.05) in 2014, and PMI level was higher ( Z =-2.86, P = 0.004). Compared with 2014, the levels of iAs% and MMA/DMA in urine of arsenic exposed population in 2017 were lower ( Z =-4.97,-2.25, P < 0.05), the levels of MMA, DMA, tAs, DMA%, PMI and SMI were higher ( Z =-4.01,-5.39,-4.77,-4.61,-4.97,-2.25, P < 0.05); in the same drinking water arsenic exposed population, compared with 2014, the level of iAs% in urine ( n = 28) was lower ( Z =-2.87, P = 0.004) in 2017, the levels of DMA% and PMI were higher ( Z =-2.32,-2.87, P < 0.05). Conclusion:Water improvement could significantly reduce the levels of urinary arsenic metabolites iAs, MMA, DMA and tAs and increase the level of DMA% in arsenic exposed population.