[Analysis of the efficacy and safety of hepatic arterial infusion chemotherapy for unresectable hepatitis B-related intrahepatic cholangiocarcinoma].

Objective: To explore the efficacy and safety of hepatic arterial infusion chemotherapy(HAIC) for unresectable hepatitis B-related intrahepatic cholangiocarcinoma(ICC). Methods: This is a retrospective controlled study. Data from 140 unresectable ICC patients who received HAIC treatment at Sun Yat-sen University Cancer Center from March 2015 to June 2023 were retrospectively collected, including 72 patients in the hepatitis B surface antigen(HBsAg)negative group (43 males and 29 females, aged (59.6±9.5)years(range: 34 to 81 years)), 68 cases in the HBsAg-positive group (48 males, 20 females, aged (53.4±11.4)years(range: 29 to 82 years)). HAIC treatment used the FOLFOX regimen combined with oxaliplatin, leucovorin,and fluorouracil. The differences in effects, prognosis,and adverse reactions between the two groups of patients after HAIC treatment were analyzed. All variables were expressed as categorical data. The χ2 test or Fisher's exact probability method was used to compare between groups. The Kaplan-Meier method was used to draw survival curves. The difference of survival curve between groups were compared through the Log-rank test. Results: According to the Response Evaluation Criteria in Solid Tumors(RECIST) version 1.1,the objective response rate(ORR) of the HBsAg-negative group was 23.2%(16/69),and the ORR of the HBsAg-positive group was 40.3%(25/62). The difference in ORR between the two groups was statistically significant(χ2=4.459,P=0.035). According to the modified RECIST(mRECIST) criteria,the ORR of the HBsAg-negative group was 27.5%(19/69), and the ORR of the HBsAg-positive group was 45.2%(28/62). The difference in ORR between the two groups was statistically significant(χ2=4.410,P=0.036). The median progression-free survival(PFS) of the HBsAg-negative group and the positive group were 7.1 months(95%CI: 5.8 to 13.2 months) and 7.3 months (95%CI: 5.7 to 10.3 months), respectively, and the median overall survival(OS) were 16.3 months (95%CI: 12.5 to 33.9 months) and 15.9 months (95%CI: 9.2 to 20.7 months) respectively. There were no statistically significant differences in PFS and OS between the two groups (both P>0.05). The main serious adverse reactions of the two groups of patients included increased AST, increased ALT, thrombocytopenia,and neutropenia. There were no statistically significant differences in various adverse reactions between the two groups after HAIC treatment (all P>0.05). Conclusion: Patients with HBsAg-positive unresectable ICC are more likely to benefit from HAIC treatment.

First molecular identification and phylogenetic illustration of Sarcocystis species infection in Red Sea shortfin mako shark (Isurus oxyrinchus Rafinesque, 1810).

BACKGROUND: members of the genus Sarcocystis are intracellular obligate protozoan parasites classified within the phylum Apicomplexa and have an obligate heteroxenous life cycle involving two hosts. A more comprehensive understanding of the prevalence and geographic range of different Sarcocystis species in marine ecosystems is needed globally and nationally. Hence, the objective of this study was to document the incidence of Sarcocystis infection in sharks within the aquarium ecosystem of Egypt and to identify the species through the characterization of the SSU rDNA gene. METHODS: All organs of the mako shark specimen underwent macroscopic screening to detect the existence of a Sarcocystis cyst. Ten cysts were collected from the intestine and processed separately to extract the genomic DNA. The polymerase chain reaction (PCR) was accomplished by amplifying a specific 18S ribosomal RNA (rRNA) gene fragment. Subsequently, the resulting amplicons were subjected to purification and sequencing processes. RESULTS: Macroscopic examination of the mako shark intestinal wall sample revealed the presence of Sarcocystis cysts of various sizes and shapes, and sequencing of the amplicons from Sarcocystis DNA revealed a 100% nucleotide identity with the sequence of Sarcocystis tenella recorded from sheep in Iran; The mako shark sequence has been deposited in the GeneBank with the accession number OQ721979. This study presents the first scientific evidence demonstrating the presence of the Sarcocystis parasite in sharks, thereby documenting this specific marine species as a novel intermediate host in the Sarcocystis life cycle. CONCLUSIONS: This is the first identification of Sarcocystis infection in sharks, and we anticipate it will be an essential study for future screenings and establishing effective management measures for this disease in aquatic ecosystems.

Acromegaly presented with acne vulgaris: a retrospective study with 123 cases.

BACKGROUND: Acne vulgaris is a prevalent skin condition. We have found that some acromegaly patients have acne. However, no study has examined the relationship between acromegaly and acne. OBJECTIVE: To explore prevalence and correlation of adult acne in patients with acromegaly. METHODS: For this cross-sectional study, we collected questionnaires, clinical information, and laboratory test results of acromegaly patients from January 2022 to December 2022 at Huashan Hospital. Of the 133 questionnaires returned, 123 had valid responses. RESULTS: Of the 123 patients with acromegaly enrolled in this study, 54.5% had adult acne. No statistically significant difference was found in prevalence between male and female patients. 61.2% of adult acne patients reported late-onset acne. Late-onset acne patients first developed acne years before acromegaly diagnosis (mean of 5.6 years for male and 4.5 years for female patients). Some acne patients have received traditional anti-acne treatment. Moreover, 31% of the patients reported no improvement, and only 3.5% of patients claimed complete resolution of acne after treatment. Before acromegaly treatment, the prevalence of adult acne was 51.2%, with mild acne accounting for 73.0%, moderate acne accounting for 23.8%, and severe acne accounting for 3.2%. After acromegaly treatment, the prevalence of adult acne was significantly decreased to 37.4% (P = 0.007). An overall decrease in acne severity was noted, with 93.5%, 6.5%, and 0% having mild, moderate, and severe acne, respectively. A total of 83.6% of the patients had self-assessed acne remission, and 33.3% of the patients reported complete acne resolution. However, 9.0% of patients reported that their condition had worsened after acromegaly treatment. After treatment, GH, IGF-1, IGF-1 index, insulin levels, and HOMA-IR decreased significantly in all patients with acromegaly (P < 0.05). Acne remission correlated positively with IGF-1 levels, but not with GH levels. The relationship between acromegaly and acne remains to be elucidated. CONCLUSIONS: Our findings provide preliminary evidence of the high prevalence of adult acne in acromegaly patients, and a high rate of late-onset acne as well. Traditional anti-acne treatments are less effective. Acne could be considerably relieved by treating acromegaly. Acne remission positively correlated with IGF-1 decline as well, which revealed the correlation between acne and IGF-1.

Correlation study between bone metabolic markers, bone mineral density, and sarcopenia.

OBJECTIVE: To investigate the correlation between bone metabolism markers, bone mineral density (BMD), and sarcopenia. METHODS: A total of 331 consecutive patients aged ≥ 60 years who were hospitalized between November 2020 and December 2021 were enrolled. Participants were divided into sarcopenia and non-sarcopenia groups according to the Asian Working Group on Sarcopenia criteria (AWGS, 2019). The clinical data, bone metabolism markers (ß-CTX, N-MID, and TP1NP), and BMD were compared between the two groups. RESULTS: Age, ß-CTX, and N-MID of the sarcopenia group were higher than those of the non-sarcopenia group (P < 0.05), but the BMD T values were lower than those of the non-sarcopenia group (P < 0.05). Binary logistic regression analysis showed that increased femoral neck BMD (FNBMD) was a protective factor for sarcopenia, while increased ß-CTX was a risk factor. Pearson/Spearman correlation analysis showed that the diagnostic indices of sarcopenia were positively correlated with FNBMD and negatively correlated with ß-CTX and N-MID. Multiple linear regression analysis revealed that BMI and FNBMD significantly positively affected muscle strength and appendicular skeletal muscle mass (ASM). The FNBMD significantly positively affected physical performance, while ß-CTX significantly negatively affected muscle strength, ASM, and physical performance. CONCLUSION: Increased FNBMD may be a protective factor against sarcopenia, and increased ß-CTX may be a risk factor. The FNBMD significantly positively affected the diagnostic indices of sarcopenia, while ß-CTX significantly negatively affected them. BMD and bone metabolism marker levels may be considered in early screening for sarcopenia.

Application of optimized LSTM in prediction of the cumulative confirmed cases of COVID-19.

This paper proposes an optimized Long Short-Term Memory (LSTM+) model for predicting cumulative confirmed cases of COVID-19 in Germany, the UK, Italy, and Japan. The LSTM+ model incorporates two key optimizations: (1) fine-adjustment of parameters and (2) a 're-prediction' process that utilizes the latest prediction results from the previous iteration. The performance of the LSTM+ model is evaluated and compared with that of Backpropagation (BP) and traditional LSTM models. The results demonstrate that the LSTM+ model significantly outperforms both BP and LSTM models, achieving a Mean Absolute Percentage Error (MAPE) of less than 0.6%. Additionally, two illustrative examples employing the LSTM+ model further validate its general applicability and practical performance for predicting cumulative confirmed COVID-19 cases.

[Traditional Chinese medicine may reduce the risk of readmission in patients with rheumatoid arthritis complicated with elevated platelet count: a matched cohort study].

OBJECTIVE: To evaluate the association of traditional Chinese medicine (TCM) treatment with the risk of readmission in patients with rheumatoid arthritis (RA) complicated with elevated platelet count. METHODS: We retrospectively collected the data of inpatients diagnosed with RA in our hospital from 2013 to 2021. The patients with elevated platelet count receiving TCM treatment were matched to those without TCM treatment using propensity score matching at the 1∶1 ratio, and the confounding factors were adjusted including gender, age, Chinese patent medicine, and external application. A Cox proportional hazard model was used to evaluate the hazard ratio (HR) of the risk of readmission, and a Kaplan-Meier curve was generated to assess the incidence of readmission in these patients. RESULTS: A total of 1176 RA patients with elevated platelet count were included in this study, including 842 patients in the TCM group and 334 patients in the non-TCM group, and after 1∶1 propensity score matching, 334 patients were included in each group. The Cox proportional hazards model showed that the readmission rate was significantly lower in TCM group than in non-TCM group (HR=0.59, 95% CI: 0.48-0.73, P<0.001), and TCM was a protective factor against readmission in RA patients with elevated platelet count. Kaplan-Meier curves demonstrated that long-term use of TCM helped to decrease the risk of readmission (Log-rank P<0.001). Association rules showed that the use of several Chinese herbal medicines and the Chinese patent medicine Xinfeng Capsule had a strong correlation with improvement of such clinical indicators as rheumatoid factor, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSION: In RA patients with elevated platelet count, the use of TCM, as a protective factor against readmission, is strongly associated with a lowered risk of readmission with a long-term association.

Hyperbaric oxygen ameliorates neuronal injury and neurological function recovery in rats with intracerebral hemorrhage by silencing microRNA-204-5p-targeted chloride channel protein 3.

Hyperbaric oxygen (HBO) therapy is of clinical utility in patients with transient cerebral ischemia. The investigatory study was to identify the potential regulatory mechanism of HBO treatment on neuronal injury and neurological function recovery in rats with intracerebral hemorrhage (ICH). Firstly, the rat model of ICH was established by collagenase, and the experimental rats were treated with HBO at 2.5 absolute atmospheres for 60 min each time. Next, lentivirus interfering with microRNA (miR)-204-5p or chloride channel protein 3 (CLCN3) expression was injected via the tail vein. Afterward, neurological function assessment was conducted, serum S100ß and NSE contents were detected by enzymer-linked immunosorbent assay, and pathological conditions of brain tissue were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining was used to detect neuronal apoptosis. The results showed that HBO alleviated neuronal injury and neurological function recovery in ICH rats and reduced serum S100ß and NSE content (all P<0.05). At the same time, overexpressing miR-204-5p or depleting CLCN3 further promoted the therapeutic effect of HBO on ICH rats (all P<0.05), while silencing miR-204-5p or elevating CLCN3 did oppositely (all P<0.05). In conclusion, HBO alleviates neuronal injury and neurological function recovery in ICH rats by silencing miR-204-5p-targeted CLCN3.

[Epidemiological trend of early-onset gastric cancer and late-onset gastric cancer in China from 2000 to 2019].

Objective: In order to understand the changing trends of gastric cancer incidence and mortality in early-onset and late-onset in China from 2000 to 2019. Methods: The Global Burden of Disease research data was collected, and Excel and R 4.2.1 softwares were used to examine the incidence rate, mortality rate, and disability-adjusted life years (DALY) of Chinese people from 2000 to 2019, with a focus on gender, age, and year. Results: In 2019, the crude incidence rates were 7.06/100 000 (95%UI: 6.63/100 000-7.59/100 000) and 114.52/100 000 (95%UI: 108.79/100 000-121.63/100 000) for early- and late-onset gastric cancer, respectively. The crude mortality rate for early-onset gastric cancer was 3.29/100 000 (95%UI: 3.11/100 000- 3.50/100 000), while the crude mortality rate for late-onset gastric cancer was 81.88/100 000 (95%UI: 78.15/100 000-86.04/100 000). Additionally, the crude DALY rates for these two types of gastric cancer were 156.48/100 000 (95%UI: 148.82/100 000-165.84/100 000) and 1 750.13/100 000 (95%UI: 1 661.21/100 000-1 852.99/100 000). The standardized incidence of early-onset gastric cancer decreased from 5.49/100 000 in 2000 to 4.76/100 000 in 2019, and that of late-onset gastric cancer decreased from 143.45/100 000 in 2000 to 123.02/100 000 in 2019.The standardized mortality rate of early-onset gastric cancer decreased from 4.16/100 000 in 2000 to 2.18/100 000 in 2019, and that of late-onset gastric cancer decreased from 140.82/100 000 in 2000 to 91.49/100 000 in 2019. The standardized DALY rate for early-onset gastric cancer in 2019 was 105.87/100 000 (95%UI: 87.98/100 000 -125.60/100 000), lower than 198.84/100 000 (95%UI: 179.47/100 000- 219.83/100 000) in 2000. The standardized DALY rate for late onset gastric cancer in 2019 was 1 821.11/100 000 (95%UI: 1 509.42/100 000-2 158.53/100 000), lower than 2 932.52/100 000 (95%UI: 2 665.92/100 000-3 252.60/100 000) in 2000. Conclusions: The standardized mortality rate of early-onset gastric cancer in China showed a decreasing trend from 2000 to 2019. The standardized mortality rate of late onset gastric cancer showed a trend of first increasing and then decreasing. Notably, the incidence, mortality, and DALY of late-onset gastric cancer were significantly higher than those of early-onset gastric cancer during this period. Additionally, male incidence, mortality, and crude DALY rates were higher than female.

[Effects of macrophage glycolytic reprogramming on tuberculosis granuloma formation].

The formation of granulomatous lesions is a typical pathological feature of tuberculosis, and infection with Mycobacterium tuberculosis is the main cause. Although the mechanism underlying granuloma formation remains unclear, increasing evidence suggests that immune metabolism plays an important role. In this review, we summarized the latest advances in macrophage glycolytic reprogramming in tuberculosis granuloma formation to discover new methods for early diagnosis and provided new ideas for tuberculosis therapeutics based on the regulation of immune metabolism.

[Expert consensus on the biobank development of oral genetic diseases and rare diseases and storage codes of related biological samples from craniofacial and oral region].

The biological samples of oral genetic diseases and rare diseases are extremely precious. Collecting and preserving these biological samples are helpful to elucidate the mechanisms and improve the level of diagnose and treatment of oral genetic diseases and rare diseases. The standardized construction of biobanks for oral genetic diseases and rare diseases is important for achieving these goals. At present, there is very little information on the construction of these biobanks, and the standards or suggestions for the classification and coding of biological samples from oral and maxillofacial sources, and this is not conducive to the standardization and information construction of biobanks for special oral diseases. This consensus summarizes the background, necessity, principles, and key points of constructing the biobank for oral genetic diseases and rare diseases. On the base of the group standard "Classification and Coding for Human Biomaterial" (GB/T 39768-2021) issued by the National Technical Committee for Standardization of Biological Samples, we suggest 76 new coding numbers for different of biological samples from oral and maxillofacial sources. We hope the consensus may promote the standardization, and smartization on the biobank construction as well as the overall research level of oral genetic diseases and rare diseases in China.

[Two novel and de novo KMT2D mutations on the same allele cause Kabuki syndrome].

Objective: To screen the candidate genes in a patient with Kabuki syndrome (KS), providing basis for genetic counseling, prenatal screening, prenatal diagnosis and facilitating early treatment. Methods: This study included a 16-year-old female KS patient born of non-consanguineous Chinese parents who presented to Department of Orthognathic & Cleft Lip and Palate Plastic Surgery, School and Hospital of Stomatology, Wuhan University. Genomic DNA was extracted from the peripheral blood of the subjects and analyzed by whole-exome sequencing (WES). Sanger sequencing was performed to validate the mutation in the candidate gene. The conformational and physicochemical changes of the mutant were analyzed by Alphafold2, Antheprot and DOG.2.0.1, respectively. Distribution of KMT2D mutations in patients with KS was analyzed based on the Human Gene Mutation Database Results: The proband manifested a typical KS facial gestalt, congenital cleft palate, fifth finger deformity, hypodontia, renal hypoplasia and hydronephrosis. Two de novo mutations c.[1166A>C; 1167dupC] (NM_003482) in cis on the same allele in the KMT2D gene were identified by WES and confirmed by allele-specific PCR. Bioinformatics analysis showed that three more α-helixes were added, and a (ß-) turn and a (ß-) sheet were reduced in KMT2D p. Y389S, p.V390Rfs*26 compared with the wild type. Meanwhile, the interceptive mutant-KMT2D protein p.V390Rfs*26 lost all four domains (FYRN domain, FYRC domain, SET domain, and PostSET domain), which may cause functional disabilities. Conclusions: Our study is the first to identify two novel and de novo KMT2D mutations in cis on the same allele in a KS patient and extends the KMT2D mutation spectrum of KS, providing evidence for genetic susceptibility counseling, prenatal screening and diagnosis, and early treatment of KS.

[Pathological significance of plasma cell infiltration in diagnosing lymph node diseases].

Objective: To investigate the value of plasma cells for diagnosing lymph node diseases. Methods: Common lymphadenopathy (except plasma cell neoplasms) diagnosed from September 2012 to August 2022 were selected from the pathological records of Changhai Hospital, Shanghai, China. Morphological and immunohistochemical features were analyzed to examine the infiltration pattern, clonality, and IgG and IgG4 expression of plasma cells in these lymphadenopathies, and to summarize the differential diagnoses of plasma cell infiltration in common lymphadenopathies. Results: A total of 236 cases of lymphadenopathies with various degrees of plasma cell infiltration were included in the study. There were 58 cases of Castleman's disease, 55 cases of IgG4-related lymphadenopathy, 14 cases of syphilitic lymphadenitis, 2 cases of rheumatoid lymphadenitis, 18 cases of Rosai-Dorfman disease, 23 cases of Kimura's disease, 13 cases of dermal lymphadenitis and 53 cases of angioimmunoblastic T-cell lymphoma (AITL). The main features of these lymphadenopathies were lymph node enlargement with various degrees of plasm cell infiltration. A panel of immunohistochemical antibodies were used to examine the distribution of plasma cells and the expression of IgG and IgG4. The presence of lymph node architecture could help determine benign and malignant lesions. The preliminary classification of these lymphadenopathies was based on the infiltration features of plasma cells. The evaluation of IgG and IgG4 as a routine means could exclude the lymph nodes involvement of IgG4-related dieases (IgG4-RD), and whether it was accompanied by autoimmune diseases or multiple-organ diseases, which were of critical evidence for the differential diagnosis. For common lesions of lymphadenopathies, such as Castleman's disease, Kimura's disease, Rosai-Dorfman's disease and dermal lymphadenitis, the expression ratio of IgG4/IgG (>40%) as detected using immunhistochemistry and serum IgG4 levels should be considered as a standard for the possibility of IgG4-RD. The differential diagnosis of multicentric Castleman's diseases and IgG4-RD should be also considered. Conclusions: Infiltration of plasma cells and IgG4-positive plasma cells may be detected in some types of lymphadenopathies and lymphomas in clinicopathological daily practice, but not all of them are related to IgG4-RD. It should be emphasized that the characteristics of plasma cell infiltration and the ratio of IgG4/IgG (>40%) should be considered for further differential diagnosis and avoiding misclassification of lymphadenopathies.

[The influencing factors of functional somatic discomfort in clinical nurses].

Objective: To investigate the functional somatic discomfort status, and to analyze the effect of job stress, hostile attribution bias and ego depletion on functional somatic discomfort in clinical nurses. Methods: In May 2019, 10 cities in Henan Province and Fujian Province were randomly selected as sampling cities. Using the stratified cluster sampling method, nurses of clinical nursing posts in 22 third class hospitals and 23 second class hospitals were selected as the research objects. The general information, job stress, hostile attribution bias, ego depletion and functional somatic discomfort of clinical nurses were investigated by self-designed general information questionnaire, Perceived Stress Scale, Social Information Processing-attribution Bias Questionnaire, Self-regulatory Fatigue Scale, Patient Health Questionnaire-15. 1200 clinical nurses included, and a total of 1159 valid questionnaires were collected, the effective rate of questionnaire collection was 96.6%. The t test was used to compare the difference of the functional somatic discomfort scores of clinical nurses with different demographic characteristicst. The influence of job stress, hostile attribution bias and ego depletion on functional somatic discomfort of clinical nurses were analyzed with Bootstrap. Results: The functional somatic discomfort score of clinical nurses was (8.95±4.38), of which 859 (74.12%) had functional somatic discomfort symptom. The functional somatic discomfort score of clinical nurses aged 36-50 years old was higher than that of 19-35 years old, the functional somatic discomfort score of clinical nurses with service age ≥5 years was higher than that of <5 years, the functional somatic discomfort score of non-permanent clinical nurses was higher than that of permanent clinical nurses, the functional somatic discomfort score of clinical nurses in tertiary hospitals was higher than that of secondary hospitals, the functional somatic discomfort score of clinical nurses in surgical departments were higher than those in non-surgical departments, and the differences were statistically significant (P<0.05). Job stress affected functional somatic discomfort through the single mediating role of hostile attribution bias, the single mediating role of ego depletion, and the chain mediating role of hostile attribution bias and ego depletion (ß=0.17, 95%CI: 0.10-0.20; ß=0.16, 95%CI: 0.10-0.20; ß=0.07, 95%CI: 0.03-0.10; P<0.05) . Conclusion: The functional somatic discomfort symptoms of clinical nurses are significant and varied among different age, working age, employment form, hospital grade and department groups. They are affected by work stress directly and through the separate mediating effect of hostile attribution bias and ego depletion, and the chain mediating effect of hostile attribution bias and ego depletion.

Improved Measurement of the Evolution of the Reactor Antineutrino Flux and Spectrum at Daya Bay.

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

[The analysis of a pedigree with hereditary coagulation factor â ¤ deficiency caused by compound heterozygous variation of F5 gene].

Objective: To analyze the gene variation of a genetic coagulation factor Ⅴ (FⅤ) deficiency pedigree and explore the molecular pathogenesis. Methods: The proband was a 32 years old female. The patient was prone to nose bleeding since childhood which was usually self-healed. On March 10, 2021, the proband went to the First Affiliated Hospital of Air Force Medical University for treatment of knee hematoma caused by a fall. None of the family members reported any history of bleeding. The prothrombin time (PT), activated partial thromboplastin time (APTT) and FⅤ activity (FⅤ: C) were detected by clotting method and the FⅤ antigen (FⅤ: Ag) was tested with enzyme-linked immunosorbent assay (ELISA). All exons and flanks of F5 gene were determined by Sanger sequencing. Clustalx-2.1-win, PolyPhen-2 and Swiss-PDBViewer software were used to analyze the conservatism of missense variation sites, whether the variations were harmful and their influences on protein structure and function. MutationTaster and NetGene2 software were used to analyze whether the splice site variation was harmful and its effect on the splice site. Results: The PT and APTT of the proband prolonged to 24.0 s and 69.8 s, respectively. The FⅤ: C and FⅤ: Ag decreased to 6% and 9%, respectively. There were compound heterozygous variations in F5 gene, which included c.911G>A heterozygous missense variation in exon 6 leading to p.Gly276Glu variation and c.5208+1G>A heterozygous missense variation in intron 15. The father and daughter had the p.Gly276Glu heterozygous variation. Her mother and son had the c.5208+1G>A heterozygous variation. Software analysis results of p.Gly276Glu heterozygous variation showed that Gly276 was conserved among homologous species, the variation was harmful, and it could affect the local structure and function of the protein. The c.5208+1G>A heterozygous variation was deleterious and resulted in the disappearance of the splice site, thereby affecting the protein function. Conclusion: The p.Gly276Glu and c.5208+1G>A compound heterozygous variants are deleterious variants associated with the patient's disease and may be the molecular pathogenesis of inherited FⅤ deficiency in this family.

Precision Measurement of Reactor Antineutrino Oscillation at Kilometer-Scale Baselines by Daya Bay.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3} eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3} eV^{2} for the inverted mass ordering.

[Current practices in the harmonisation of autoantibodies test].

Standardisation and harmonisation of the detection of autoantibodies is important for the clinical application of autoantibodies. However, achieving complete standardisation is difficult and involves several challenges due to the complexity and particularity of autoantibody detection. Harmonisation is feasible and valued, but it involves all aspects and processes of autoantibody detection. Based on the consensus and practice of the clinical application of autoantibody detection in recent years, we discuss harmonisation in this review.