[Analysis of efficacy and prognosis of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation for the treatment of combined immunodeficiency (CID) and explore prognostic risk factors. Methods: In this retrospective cohort study, clinical characteristics, laboratory tests and prognosis of 73 CID children who underwent allogeneic hematopoietic stem cell transplantation from February 2014 to April 2022 in the Children's Hospital of Fudan University were analyzed. Based on the subtypes of diseases, all patients were divided into severe combined immunodeficiency disease (SCID) group and other CID group. Based on the types of donors, all patients were divided into matched sibling donor group, matched unrelated donor group, unrelated cord blood group, and haploidentical donor group. Kaplan-Meier method and Log-Rank test were used to analyze the survival data. Cox regression was used to analyze prognostic factors. Results: Among the 73 patients, there were 61 (84%) males and 12 (16%) females. Fifty-five (75%) patients were SCID, and 18 (25%) patients were other CID. Donor source included 2 (3%) matched sibling donors (MSD), 3 (4%) matched unrelated donors (MUD), 64 (88%) unrelated cord blood (UCB), and 4 (5%) haploidentical donors. The age at transplant was 10.7 (5.9, 27.5) months, and the follow-up time was 36.2 (2.5, 62.9) months. The 3-year overall survival rate of 73 patients with CID was (67±6) %. No significant difference was found in the 3-year overall survival rates between patients with SCID (55 cases) and other CID (18 cases) ((64±7) % vs. (78±10) %, χ2=1.31, P=0.252). And no significant difference was found in the 3-year overall survival rates among patients who received MSD or MUD (5 cases), UCB (64 cases), and haploidentical donor (4 cases) transplant (100% (66±6)% vs. (50±25) %, χ2=2.30, P=0.317). Cox regression analysis showed that the medical history of sepsis (HR=2.55, 95%CI 1.05-6.20, P=0.039) and hypoalbuminemia at transplant (HR=2.96, 95%CI 1.14-7.68, P=0.026) were independent risk factors for the prognosis of allogeneic hematopoietic stem cell transplantation in pediatric patients with CID. Conclusions: Allogeneic hematopoietic stem cell transplantation is an effective treatment for CID. The medical history of sepsis and hypoalbuminemia at transplant were risk factors for prognosis. Enhancing infection prevention and nutritional intervention before transplant can improve patient prognosis.

[Characteristics of baseline viral load before antiretroviral therapy in newly reported HIV-infected patients in Tianjin, 2019-2022].

Objective: To understand the baseline viral load (VL) of newly reported HIV- infected patients before antiretroviral therapy and related factors in Tianjin. Methods: Data were obtained from the China Disease Control and Prevention Information System, and the study subjects were HIV-infected patients before the first antiretroviral therapy in Tianjin from 2019 to 2022, and the information about their socio-demographic characteristics, baseline CD4+T lymphocyte (CD4) counts before antiretroviral therapy and baseline VL test results were collected, the baseline high VL was defined as ≥100 000 copies/ml. The effect of different factors on viral load were analyzed. Software SPSS 24.0 was used for statistical analysis. Results: A total of 1 296 newly reported HIV-infected patients were included in the study, in whom 15.89% (206/1 296) had high baseline VL, and multifactorial logistic regression analysis showed that those with history of STD (aOR=1.45, 95%CI:1.00-2.08) were more likely to have high baseline VL. Compared with those with baseline CD4 counts <200 cells/µl, those with baseline CD4 counts 200-350 cells/µl (aOR=0.40, 95%CI: 0.27-0.57), 351-500 cells/µl (aOR=0.32, 95%CI: 0.20-0.49), and >500 cells/µl (aOR=0.30, 95%CI: 0.18-0.49) were less likely to have high baseline VL. Conclusions: The proportion of HIV-infected patients with high baseline VL before antiretroviral therapy was low in Tianjin during 2019-2022. History of STD and baseline CD4 counts <200 cells/µl were associated with high baseline VL in HIV-infected patients, to which close attention needs to be paid in AIDS prevention and control.

[Preliminary study on the effect of Echinococcus multilocaris on phenotypic transformations of glucose metabolism and polarization types in macrophages].

OBJECTIVE: To investigate the effects of Echinococcus multilocularis on the phenotypic transformations of glucose metabolism, polarization types and inflammatory responses in macrophages, so as to provide insights into elucidation of echinococcosis pathogenesis. METHODS: Bone marrow cells were isolated from C57BL/6J mice at ages of 6 to 8 weeks, and induced into bone marrow-derived macrophages (BMDMs) with mouse macrophage colony-stimulating factor (M-CSF), which served as controls (BMDMs-M0). BMDMs-M0 induced M2 macrophages by interleukin-4 for 24 hours served as the IL-4 induction group, and BMDMs-M0 co-cultured with 2.4 ng/mL E. multilocularis cystic fluid (CF) served as the BMDM-CF co-culture group, while BMDMs-M0 co-cultured with E. multilocularis protoscolex (PSC) at a ratio of 500:1 served as the BMDM-PSC co-culture group. The types of polarization of BMDMs co-cultured with E. multilocularis CF and PSC were analyzed using flow cytometry, and the expression of macrophage markers, inflammatory factors, and glucose metabolism-related enzymes was quantified using fluorescent quantitative real-time PCR (qPCR) and Western blotting assays. RESULTS: There were significant differences among the four groups in terms of Arginase-1 (Arg1) (F = 1 457.00, P < 0.000 1), macrophages-derived C-C motif chemokine 22 (Ccl22) (F = 22 203.00, P < 0.000 1), resistin-like α (Retnla) (F = 151.90, P < 0.000 1), inducible nitric oxide synthase (iNOS) (F = 107.80, P < 0.001), hexokinase (HK) (F = 9 389.00, P < 0.000 1), pyruvate kinase (PK) (F = 641.40, P < 0.001), phosphofructokinase 1 (PFK1) (F = 43.97, P < 0.01), glucokinase (GK) (F = 432.50, P < 0.000 1), pyruvate dehydrogenase kinases1 (PDK1) (F = 737.30, P < 0.000 1), lactic dehydrogenase (LDH) (F = 3 632.00, P < 0.000 1), glucose transporter 1 (GLUT1) (F = 532.40, P < 0.000 1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (F = 460.00, P < 0.000 1), citrate synthase (CS) (F = 5 642.00, P < 0.01), glycogen synthase1 (GYS1) (F = 273.30, P < 0.000 1), IL-6 (F = 1 823.00, P < 0.000 1), IL-10 (F = 291.70, P < 0.000 1), IL-1ß (F = 986.60, P < 0.000 1), and tumor necrosis factor (TNF)-α (F = 334.80, P < 0.000 1) and transforming growth factor (TGF)-ß mRNA expression (F = 163.30, P < 0.001). The proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-PSC co-culture group [(22.87% ±1.48%) vs. (1.70% ±0.17%); t = 24.61, P < 0.001], and the proportion of M2 macrophages was significantly higher than that of M1 macrophages in the BMDM-CF co-culture group [(20.07% ±0.64%) vs. (1.93% ±0.25%); t = 45.73, P < 0.001]. The mRNA expression of M2 macrophages markers Arg1, Ccl22 and Retnla was significantly higher in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01), and no significant difference was seen in the mRNA expression of the M1 macrophage marker iNOS among the three groups (P > 0.05), while qPCR assay quantified higher mRNA expression of key glycolytic enzymes HK, PK and PFK, as well as inflammatory factors IL-10, IL-1ß, TNF-α and TGF-ß in the BMDM-CF and BMDM-PSC co-culture groups than in the control group (all P values < 0.01). Western blotting assay determined higher HK, PK and PFK protein expression in the BMDM-PSC co-culture group than in the control group (all P values < 0.05), and qPCR quantified higher GLUT1, GAPDH and IL-6 mRNA expression in the BMDM-CF co-culture group than in the control group (all P values < 0.05), while higher HK, PK and PFK protein and mRNA expression (all P values < 0.01), as well as lower IL-6 and TNF-α and higher TGF-ß mRNA expression (both P values < 0.05) was detected in the IL-4 induction group than in the control group. Glycolytic stress test showed no significant difference in the extracellular acidification rate (ECAR) of mouse BMDM among the control group, IL-4 induction group and BMDM-PSC co-culture group (F = 124.4, P < 0.05), and a higher ECAR was seen in the BMDM-PSC co-culture group and a lower ECAR was found in the IL-4 induction group than in the control group (both P values < 0.05). CONCLUSIONS: Treatment of E. multilocularis CF or PSC mainly causes polarization of BMDM into M2 macrophages, and phenotypic transformation of glucose metabolism into high-energy and high-glycolytic metabolism, and affects inflammatory responses in BMDM.

In ovo injection of AZD6244 suppresses feather follicle development by the inhibition of ERK and Wnt/ß-catenin pathways in goose embryos (Anser cygnoides).

1. Feathers are an important product from poultry, and the state of feather growth and development plays an important role in their economic value.2. In total, 120 eggs were selected for immunoblotting and immunolocalisation experiments of ERK and ß-catenin proteins in different developmental stages of goose embryos. The ERK protein was highly expressed in the early stage of goose embryo development, while ß-catenin protein was highly expressed in the middle stage of embryo development.3. The 120 eggs were divided into four treatment groups, including an uninjected group (BLANK), a group injected with 100 µl of cosolvent (CK), a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 5 mg/kg AZD6244 containing cosolvent (AZD5) and a group injected with 100 µl of AZD6244 containing cosolvent in a dose of 15 mg/kg AZD6244 containing cosolvent (AZD15). The eggs were injected on the ninth day of embryonic development (E9). Samples were collected at E21.5 to observe feather width, feather follicle diameter, ERK and Wnt/ß-catenin pathway protein expression.4. The AZD5 and AZD15 doses were within the embryonic safety range compared to the BLANK and CK groups and had no significant effect on the survival rate and weight at the inflection point, but significantly reduced the feather width and feather follicle diameter (p < 0.05). The AZD6244 treatment inhibited ERK protein phosphorylation levels and blocked the Wnt/ß-catenin pathway, which in turn significantly down-regulated the expression levels of FZD4, ß-catenin, TCF4 and LEF1 (p < 0.05), with an inhibitory effect in the AZD15 group being more significant. The immunohistochemical results of ß-catenin and p-ERK were consistent with Western blot results.5. The small molecule inhibitor AZD6244 regulated the growth and development of feather follicles in goose embryos by the ERK and Wnt/ß-catenin pathways.

Relationships of Hypnotics with Incident Dementia and Alzheimer's Disease: A Longitudinal Study and Meta-Analysis.

BACKGROUND: Evidence describing the association between hypnotics use and dementia risk is conflicting. It is unknown if the controversy is related to the type or dose of hypnotics or if hypnotics affect different populations. OBJECTIVES: We sought to derive lessons learned and future projections based on evidence from longitudinal studies. MEASUREMENTS: In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, 1,543 older adults without dementia (mean age = 73.3 years, female = 45%) were followed for four years. The association between hypnotics and the risk of Alzheimer's disease (AD) was investigated using Cox proportional hazards regressions. Next, electronic databases were searched until March 2022 to conduct the evidence synthesis of the associations of hypnotics with incident risk of dementia. RESULTS: In the ADNI cohort, ever use of hypnotics was associated with an increased risk of AD (hazard ratio = 1.96, 95% confidence intervals = 1.23-3.11, p < 0.01). This association was significant for benzodiazepines and Z-drugs but not for melatonin. The association was stronger in long-term (more than one year) users and those with high cumulative doses. A meta-analysis of 26 longitudinal studies with 3,942,018 participants revealed a correlation between the use of hypnotics and the risk of dementia (relative risk = 1.23, 95% confidence intervals = 1.13-1.33, p < 0.001, median risk difference = 4%). It is a linear dose-response relationship, if a person takes the daily recommended dose for 100 days, their risk of developing dementia increases by 5% relative to non-users. According to subgroup analyses, neither association was significant among patients with a history of insomnia. CONCLUSIONS: Individuals who use hypnotics, especially high-dose or long-term users, are at a higher risk of dementia and AD. The main issue with conclusion credibility is heterogeneity.

Local heating and Raman thermometry in a single molecule.

Because of the nonequilibrium nature of thermal effects at the nanoscale, the characterization of local thermal effects within a single molecule is highly challenging. Here, we demonstrate a way to characterize the local thermal properties of a single fullerene (C60) molecule during current-induced heating processes through tip-enhanced anti-Stokes Raman spectroscopy. Although the measured vibron populations are far from equilibrium with the environment, we can still define an "effective temperature (Teff)" statistically via a Bose-Einstein distribution, suggesting a local equilibrium within the molecule. With increased current heating, Teff is found to rise up to about 1150 K until the C60 cage is decomposed. Such a decomposition temperature is similar to that reported for ensemble C60 samples, thus justifying the validity of our methodology. Moreover, the possible reaction pathway and product can be identified because of the chemical sensitivity of Raman spectroscopy. Our findings provide a practical method for noninvasively detecting the local heating effect inside a single molecule under nonequilibrium conditions.

Pressure-induced linear enhancement of the superconducting transition in Nd0.8Sr0.2NiO2thin films.

We report the pressure (P) effect on the superconducting transition temperatureTcand the upper critical fieldµ0Hc2of infinite-layer Nd0.8Sr0.2NiO2thin films by measuring the electrical transport properties under various hydrostatic pressures to 4.6 GPa. At ambient pressure, it shows the clear superconducting transition withTc∼ 10 K. Based on the evolution of resistanceR(T), we found that theTcis monotonically enhanced to ∼14 K upon increasing pressure to 2.9 GPa. The constructed temperature-pressure phase diagram indicates that the calculated slope dTc/dPis about 1.14 K GPa-1and the superconductingTcshows no signatures of saturation with pressure. It thus gives the possibility to further enhanceTcby employing higher pressures or heterostructure engineering. In addition, the normalized slope of upper critical fieldµ0Hc2(0) implies that the electron correlations are gradually decreasing with pressure, which exhibits an opposite evolution with superconductingTc. Our work further confirms the positive pressure effects in nickelate superconductors and gives more insight to further enhance its superconducting transition temperature.

[Fuzheng Huayu capsules reducing development of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B based on the ratio of neutrophils/lymphocytes].

Objective: To explore the advantage of Fuzheng Huayu capsule in patients with hepatitis B cirrhosis based on neutrophil/lymphocyte ratio (NLR) risk stratification in reducing the incidence of hepatocellular carcinoma (HCC). Methods: 916 cases diagnosed with hepatitis B cirrhosis and followed up for five years from January 2011 to January 2016 at Beijing Ditan Hospital Affiliated with Capital Medical University were included, and clinical data were collected. Patients were divided into a combination group and an antiviral group according to whether they were treated with anti-fibrosis for≥6 months. The antiviral group was treated with entecavir or tenofovir disoproxil, while the combination group was treated with Fuzheng Huayu capsules based on the antiviral therapy. The incidence of HCC was compared between the two groups of patients within five years. The advantaged groups treated with Fuzheng Huayu capsule were explored based on NLR risk stratification. The independent sample t-test and Mann-Whitney U test were used to compare measurement data between two groups. Categorical variable data were compared using either the χ(2) test or Fisher's exact probability method. The incidence of HCC in the two groups of patients was analyzed through the Kalplan-Merier curve and compared using the log-rank method. Results: There were 299 (32.6%) and 617 (67.4%) cases in the combined group and the antiviral group, respectively. A total of 154 (16.8%) patients developed HCC during the follow-up period. The five-year cumulative incidence of HCC in the combination group was lower than that in the antiviral group (10.7% vs. 19.8%, χ(2) = 11.848, P = 0.000 4). Patients with baseline NLR>3 had an increased risk of HCC. According to NLR risk stratification, there were 191 cases in the low-risk group (NLR<1.4), 462 cases in the medium-risk group (NLR1.4 ~ 3.0), and 263 cases in the high-risk group (NLR>3). Among medium to high-risk patients, the incidence of HCC was significantly reduced in the combination group (11.5% vs. 19.4%, χ(2) = 4.519, P = 0.029; 13.2% vs. 26.2%, χ(2) = 5.258, P = 0.019), while there was no statistically significant difference in the incidence of HCC among the low-risk group (P = 0.38). Conclusion: Compared with antiviral treatment alone, Fuzheng Huayu capsules combined with antiviral treatment can better reduce the five-year HCC incidence rate in patients with hepatitis B cirrhosis. Medium-and high-risk patients with NLR stratification are the most advantageous population to be treated with Fuzheng Huayu capsules.

Species-wide quantitative transcriptomes and proteomes reveal distinct genetic control of gene expression variation in yeast.

Gene expression varies between individuals and corresponds to a key step linking genotypes to phenotypes. However, our knowledge regarding the species-wide genetic control of protein abundance, including its dependency on transcript levels, is very limited. Here, we have determined quantitative proteomes of a large population of 942 diverse natural Saccharomyces cerevisiae yeast isolates. We found that mRNA and protein abundances are weakly correlated at the population gene level. While the protein co-expression network recapitulates major biological functions, differential expression patterns reveal proteomic signatures related to specific populations. Comprehensive genetic association analyses highlight that genetic variants associated with variation in protein (pQTL) and transcript (eQTL) levels poorly overlap (3.6%). Our results demonstrate that transcriptome and proteome are governed by distinct genetic bases, likely explained by protein turnover. It also highlights the importance of integrating these different levels of gene expression to better understand the genotype-phenotype relationship. Highlights: At the level of individual genes, the abundance of transcripts and proteins is weakly correlated within a species ( ρ = 0.165). While the proteome is not imprinted by population structure, co-expression patterns recapitulate the cellular functional landscapeWild populations exhibit a higher abundance of respiration-related proteins compared to domesticated populationsLoci that influence protein abundance differ from those that impact transcript levels, likely because of protein turnover.

[Clinical and radiographic effect of simultaneously labial and lingual augmented corticotomy: a prospective case series study].

Objective: To investigate soft-and hard-tissue changes after simultaneously labial and lingual augmented corticotomy in patients with insufficient alveolar bone thickness of lower anterior teeth both in labial and lingual side during orthodontic treatment. Methods: From January 2021 to June 2022, 10 patients [2 males and 8 females, (26.2±3.1) years old] who received orthodontic and orthognathic combined treatment from the Fourth Clinical Division, Peking University School and Hospital of Stomatology were selected. The alveolar bone thickness of lower anterior teeth both in labial and lingual side in these patients was less than 0.5 mm according to cone-beam CT examination before or during treatment, and 60 lower anterior teeth were included. The 10 patients were treated with simultaneously labial and lingual augmented corticotomy. The differences in gingival recession, papilla index and the differences in labial and lingual alveolar bone thickness of lower anterior teeth were compared. Results: Six months after surgery, the alveolar bone thicknesses at the 4 mm under cemento-enamel junction (CEJ), 8 mm under CEJ and at the apical level [labial side: (1.02±0.39), (2.22±0.89) and (4.87±1.35) mm; lingual side: (1.07±0.46), (2.31±1.04) and (3.91±1.29) mm] were significantly higher than that before surgery [labial side: (0.02±0.09), (0.06±0.21) and (2.71±1.33) mm]; lingual side: (0.14±0.29), (0.40±0.52) and (2.13±1.02) mm] (P<0.001), respectively. The increases in alveolar bone thickness of central incisors [apical level on labial side: (2.53±1.20) mm, 8 mm under CEJ on lingual side: (2.27±1.24) mm, apical level on lingual side: (2.66±1.49) mm] and lateral incisors [apical level on labial side: (2.42±1.30) mm, 8 mm under CEJ on lingual side: (2.28±0.92) mm, apical level on lingual side: (1.94±1.15) mm] were significantly higher than that of canines [apical level on labial side: (1.52±1.47) mm, 8 mm under CEJ on lingual side: (1.17±1.09) mm,apical level on lingual side: (0.74±1.37) mm] (P<0.01). There were no significant differences in the degree of gingival recession [labial side before surgery: (0.72±0.88) mm, lingual side before surgery: (0.80±1.09) mm; labial side 6 months after surgery: (0.72±0.81) mm,lingual side 6 months after surgery: (0.89±0.21) mm] and gingival papilla index [before surgery: 1.00(0.75, 2.00); 6 months after surgery: 1.00(1.00, 2.00) ] between pre-operation and 6 months after surgery (P>0.05). No serious complications occurred. Conclusions: The method used in this article for simultaneously labial and lingual augmented corticotomy was safe and feasible. This surgery has positive clinical significance for the stability of the periodontal tissue in orthodontic treatment for patients with alveolar bone thickness less than 0.5 mm of lower anterior teeth both in labial and lingual side.

[Ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China: a CR-HepB-based real-world study].

Objective: To understand ten-year changes in clinical characteristics and antiviral treatment patterns of chronic hepatitis B in China. Methods: Patients with chronic HBV infection:demographic, virologic, hematologic, blood biochemistry, and antiviral treatment data were extracted from the China Registry of Hepatitis B (CR-HepB) database between 2012 and 2022 for descriptive statistics and change trend analysis. Multiple group comparisons were conducted using the Kruskal Wallis H test, while counting data was compared between groups using χ (2) test. Results: A total of 180 012 patients with chronic HBV infection were included, with a median age of 40 years old, and a male proportion accounting for 60.2%. The HBeAg positive rate was 43.3%. Over time, the median age of new patients each year increased from 39 to 47 years, while the HBeAg positive rate decreased from 51.3% to 32.8%. The initial diagnosis of patients was mainly CHB (71.4%), followed by hepatitis B cirrhosis (11.8%), inactive HBsAg carrier status (10.6%), and chronic HBV carrier status (6.2%). Among the newly registered patients every year from 2012 to 2022, the proportion of hepatitis B cirrhosis remained stable, but after 2019, the proportion of CHB increased and the proportion of other diagnoses decreased. The proportion of patients with cirrhosis increased with age in different age groups, with 3.5%, 19.3%, and 30.4% in the < 40, 40-69, and≥70 age groups, respectively. The proportion of women in patients with cirrhosis also increased with age, from 16.1% in those < 30 years old to 44.3% in those≥80 years old. From 2012 to 2022, the proportion of patients receiving first-line nucleos(t)ide analog antiviral treatment increased year by year, from 51.0% in 2012-2013 to 99.8% in 2022. Conclusion: The CR-HepB registration data reflect the changes in clinical characteristics and antiviral treatment patterns in patients with chronic HBV infection in China over the past ten years and can thus provide a reference to promote hepatitis B diagnosis and treatment practice, as well as scientific research.

[Survey of Helicobacter pylori levofloxacin and clarithromycin resistance rates and drug resistance genes in Ningxia, 2020-2022].

Objective: To explore the rate of Helicobacter pylori (Hp) resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia, and to assess the concordance between phenotypic resistance and genotypic resistance. Methods: Cross-sectional study. Patients diagnosed with Hp infection in 14 hospitals in Ningxia region from February 2020 to May 2022 were retrospectively selected. Hp strains were isolated from gastric biopsy specimens of Hp-infected patients and subjected to phenotypic drug sensitivity testing and detection of resistance genes to analyze the rate of Hp resistance to levofloxacin and clarithromycin and the common mutation patterns of resistance genes in Ningxia region; and the concordance rate and Kappa concordance test were used to assess the concordance between phenotypic resistance and genotypic resistance. Results: A total of 1 942 Hp strains were isolated and cultured, and among the infections, 1 069 cases (55.0%) were male and 873 cases (45.0%) were female, aged (50.0±12.5) years (15-86 years). The rates of Hp resistance to levofloxacin and clarithromycin in Ningxia were 42.1% (818/1 942) and 40.1% (779/1 942), respectively, and the rate of dual resistance to both was 22.8% (443/1 942). The rate of resistance to levofloxacin and clarithromycin of Hp strains from female patients was higher than in male patients (levofloxacin: 50.4%(440/873) vs 35.4%(378/1 069); clarithromycin: 44.4%(388/873) vs 36.6%(391/1 069), both P<0.001). Among the GyrA gene mutations associated with levofloxacin resistance, the differences in mutation rate of amino acid at positions 87 and 91 were statistically significant in both drug-resistant and sensitive strains(both P<0.001), except for Asn87Thr. Hp strains were statistically significant for levofloxacin (Kappa=0.834, P<0.001) and clarithromycin (Kappa=0.829, P<0.001) had good concordance in resistance at the phenotypic and genotypic levels. Conclusion: The resistance of Hp to levofloxacin and clarithromycin in Ningxia region is severe, and there is good consistency between genotypic and phenotypic resistance.

[Cardiac amyloidosis: pathological classification and clinical analysis of 48 cases].

Objective: To investigate the histological features and clinical manifestations in different types of cardiac amyloidosis to improve diagnostic accuracy. Methods: The histopathological features and clinical manifestations of 48 patients diagnosed with cardiac amyloidosis by Congo red stain and electron microscopy through endomyocardial biopsy were collected in West China Hospital of Sichuan University from January 2018 to December 2021. Immunohistochemical stains for immunoglobulin light chains (κ and λ) and transthyretin protein were carried out, and a review of literature was made. Results: The patients age ranged from 42 to 79 years (mean 56 years) and the male to female ratio was 1.1 to 1.0. The positive rate of endomyocardial biopsy was 97.9% (47/48), which was significantly higher than that of the abdominal wall fat (7/17). Congo red staining and electron microscopy were positive in 97.9% (47/48) and 93.5% (43/46), respectively. Immunohistochemical stains showed 32 cases (68.1%) were light chain type (AL-CA), including 31 cases of AL-λ type and 1 case of AL-κ type; 9 cases (19.1%) were transthyretin protein type (ATTR-CA); and 6 cases (12.8%) were not classified. There was no significant difference in the deposition pattern of amyloid between different types (P>0.05). Clinical data showed that ATTR-CA patients had less involvement of 2 or more organs and lower N-terminal pro-B-type natriuretic peptide (NT-proBNP) than the other type patients (P<0.05). The left ventricular stroke volume and right ventricular ejection fraction of ATTR-CA patients were better than the other patients (P<0.05). Follow-up data of 45 patients was obtained, and the overall mean survival time was 15.6±2.0 months. Univariate survival analysis showed that ATTR-CA patients had a better prognosis, while cardiac amyloidosis patients with higher cardiac function grade, NT-proBNP >6 000 ng/L, and troponin T >70 ng/L had a worse prognosis (P<0.05). Multivariate survival analysis showed that NT-proBNP and cardiac function grade were independent prognostic factors for cardiac amyloidosis patients. Conclusions: AL-λ is the most common type of cardiac amyloidosis in this group. Congo red staining combined with electron microscopy can significantly improve the diagnosis of cardiac amyloidosis. The clinical manifestations and prognosis of each type are different and can be classified based on immunostaining profile. However, there are still a few cases that cannot be typed; hence mass spectrometry is recommended if feasible.

[Effects of specimen preservation and transportation on blood paraquat concentration in rats].

Objective: To investigate the effects of duration, temperature and shake on paraquat (PQ) concentration in the blood of PQ-exposed rats during the specinen preservation and transportation. Methods: In March 2021, 60 SD male rats of Specific Pathogen Free class were randomly divided into low-dose group (10 mg/kg PQ) and high-dose group (80 mg/kg PQ). Each group was divided into 5 subgroups (normal temperature group, cold storage group, 37 ℃ storage group, shaking on normal temperature group and shaking on 37 ℃ group), six rats in each subgroup. The rats were given intraperitoneal injection of PQ, 1 h after exposure, the blood samples were obtained by cardiac extraction. After different interventions, the concentrations of PQ were detected and compared before and after the intervention in each subgroup. Results: In the shaking on 37 ℃ group, the results of PQ concentrations in PQ-exposed rats were significantly lower than those before the intervention (P<0.05). In the other subgroups, the results were not significantly different compared with before intervention (P>0.05) . Conclusion: The concentration of PQ in the blood of rats exposed to PQ was decreased by shaking for 4 hours at 37 ℃.

Expression of FOXO3 in the skin follicles of goose embryos during embryonic development.

1. The Forkhead box O3 (FOXO3) transcription factor is a crucial regulator in controlling cell metabolism, proliferation, apoptosis, migration and response to oxidative stress. However, FOXO3 has not previously been studied much in the embryonic skin follicles of geese.2. This study used Zhedong white geese (Anser cygnoides), Jilin white geese (Anser cygnoides) and Hungarian white geese (Anser anser). The feather follicle structure in the dorsal skin during embryonic stages was examined with haematoxylin and eosin (HE) and Pollak staining. The FOXO3 protein content in the embryonic dorsal skin from feather follicles was detected using western blotting and quantitative real-time PCR.3. The mRNA expression level of FOXO3 in the dorsal skin of Jilin white geese was highly expressed on embryonic day 23 (E23; P < 0.01), while mRNA expression of FOXO3 was highly expressed in the feather follicle of Hungarian white geese at E28 (P < 0.01). The expression of FOXO3 protein mainly concentrated in the early embryonic phase among these goose breeds (P < 0.05). This suggested that FOXO3 plays a crucial role in the development and growth of embryonic dorsal skin of feather follicles. The location of the FOXO3 protein was determined using the IHC technique, which further verified the effect of FOXO3 in the dorsal skin for feather follicles during embryogenesis.4. The study demonstrated the differential expression and localisation of the FOXO3 gene among different goose species. It was speculated that the gene could potentially improve goose feather follicle development and feather-related traits and provide a basis for further understanding of FOXO3 function in the dorsal tissue of goose embryos.

[Treat-all: challenges of partial response and low-level viremia].

The recently updated "Guidelines for the Prevention and Treatment of Chronic Hepatitis B" in China have brought about significant changes. The new treatment indications almost mandate the implementation of a Treat-all strategy for the chronically HBV-infected population in China. While simultaneous negativity for hepatitis B surface antigen (HBsAg) and hepatitis B virus (HBV) DNA has long been an accepted criterion for treatment discontinuation, there has been controversies over the initiation of treatment criteria starting with HBsAg and HBV DNA positivity. Despite the inconsistent treatment criteria, the academic community has started supporting treat-all strategies in recent years due to the decreasing cost of treatment, prolonged management duration, and growing evidence of poor outcomes in untreated populations. Therefore, this update to the Chinese HBV guidelines represents a new direction that suggests "The greatest truths are the simplest." However, in the process of rolling out the Treat-all strategy, we must remain cautious of possible issues arising from the new strategy. Among them, the problem of partial response or low-level viremia following treatment may become more prominent due to the inclusion of a significant number of patients with normal or low levels of alanine transaminase. As existing evidence suggests that low-level viremia increases the risk of HCC in patients, it is essential to monitor and explore optimal therapeutic options for these patients.

[Interpretation of the essential updates in guidelines for the prevention and treatment of chronic hepatitis B (Version 2022)].

Chinese Society of Hepatology and Chinese Society of Infectious Diseases, Chinese Medical Association update the guidelines for the prevention and treatment of chronic hepatitis B (version 2022) in 2022. The latest guidelines recommend more extensive screening and more active antiviral treating for hepatitis B virus infection. This article interprets the essential updates in the guidelines to help deepen understanding and better guide the clinical practice.

Factors affecting cement leakage in percutaneous vertebroplasty: a retrospective cohort study of 309 patients.

OBJECTIVE: Percutaneous vertebroplasty has been widely applied as a treatment for osteoporotic vertebral compression fracture. However, the incidence of cement leakage is high. The purpose of study is to identify the independent risk factors for cement leakage. PATIENTS AND METHODS: A total of 309 patients who suffered from osteoporotic vertebral compression fracture (OVCF) and underwent percutaneous vertebroplasty (PVP) were enrolled in this respective cohort study from January 2014 to January 2020. Clinical and radiological characteristics were assessed to identify independent predictors for each type of cement leakage, including age, gender, course of disease, fracture level, morphology of vertebral fracture, fracture severity, cortical disruption in vertebral wall or endplate, fracture line connected with basivertebral foramen, type of cement dispersion, and intravertebral cement volume. RESULTS: In leakage of B-type, fracture line connected with basivertebral foramen was identified as an independent risk factor [Adjusted OR: 2.837, 95% CI: (1.295, 6.211), p = 0.009]. For leakage of C-type, acute course of the disease, more severity of the fractured body, wall disruption and intravertebral cement volume (IVCV) were identified as independent risk factors [Adjusted OR: 0.409, 95% CI: (0.257, 0.650), p = 0.000]; [Adjusted OR: 3.128, 95% CI: (2.202, 4.442), p = 0.000]; [Adjusted OR: 6.387, 95% CI: (3.077, 13.258), p = 0.000]; [Adjusted OR: 1.619, 95% CI: (1.308, 2.005), p = 0.000]. Regarding leakage of D-type, biconcave fracture and endplate disruption were identified as independent risk factors [Adjusted OR: 6.499, 95% CI: (2.752, 15.348), p = 0.000]; [Adjusted OR: 3.037, 95% CI: (1.421, 6.492), p = 0.004]. For S-type, fracture in thoracic level and less severity of the fractured body were identified as independent risk factors [Adjusted OR: 0.105, 95% CI: (0.059, 0.188), p = 0.000]; [Adjusted OR: 0.580, 95% CI: (0.436, 0.773), p = 0.000]. CONCLUSIONS: Cement leakage was very common with PVP. Each cement leakage had its own influence factors. Preoperative identification of above influence factors for cement leakage could avoid the occurrence of severe sequelae.

[Porphyromonas gingivalis infection causes umbilical vein endothelial barrier dysfunction in vitro by down-regulating ZO-1, occludin and VE-cadherin expression].

OBJECTIVE: To explore the molecular mechanisms of Porphyromonas gingivalis infection-induced umbilical vein endothelial barrier dysfunction in vitro. METHODS: Human umbilical vein endothelial cells (HUVECs) were cultured in vitro, and after the formation of the endothelial barrier, the cells were infected with P. gingivals at a multiplicity of infection (MOI). The transepithelial electrical resistance (TEER) of the cell barrier was measured, and FITC-dextran trans-endothelial permeability assay and bacterial translocation assay were performed to assess the endothelial barrier function. The expression levels of cell junction proteins including ZO-1, occludin and VE-cadherin in the cells were examined by qRT-PCR and Western blotting. RESULTS: In freshly seeded HUVECs, TEER increased until reaching the maximum on Day 5 (94 Ωcm2), suggesting the formation of the endothelial barrier. P. gingivals infection caused an increase of the permeability of the endothelial barrier as early as 0.5 h after bacterial inoculation, and the barrier function further exacerbated with time, as shown by significantly lowered TEER, increased permeability of FITC-dextran (40 000/70 000), and increased translocation of SYTO9-E. coli cross the barrier. MTT assay suggested that P. gingivals infection did not significantly affect the proliferation of HUVECs (P>0.05), but in P. gingivalsinfected cells, the expressions of ZO-1, occludin and VE-cadherin increased significantly at 24 and 48 h after bacterial inoculation (P < 0.05). CONCLUSION: P. gingivals may disrupt the endothelial barrier function by down-regulating the expressions of the cell junction proteins (ZO-1, occludin, VE-cadherin) and increasing the permeability of the endothelial barrier.