Genome-Wide Mendelian Randomization Identifies Putatively Causal Gut Microbiota For Multiple Peptic Ulcer Diseases

OBJECTIVE: The pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation. DESIGN: The largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted mode, and simple mode, were employed to assess the causal relationships between gut microbiota and these five PUDs. RESULT: In the intestinal microbiome of 119 known genera, we found a total of 14 causal associations with various locations of PUDs and reported the potential pathogenic bacteria of CONCLUSION: In this study, the pathogenic bacterial genera in the gut microbiota that promote the occurrence of PUDs were found to be causally related. There are multiple correlations between intestinal flora and PUDs, overlapping PUDs have overlapping associated genera. The variance in ulcer-related bacterial genera across different locations underscores the potential influence of anatomical locations and physiological functions

Gonadotropin-releasing hormone analogue and recombinant human growth hormone treatment for idiopathic central precocious puberty in girls

PurposeTo investigate the effectiveness and safety of gonadotropin-releasing hormone analogue (GnRHa) in combination with recombinant human growth hormone (rhGH) in girls with central precocious puberty (CPP).MethodsClinical data of 80 girls diagnosed with idiopathic central precocious puberty (ICPP) between January 2017 and June 2021 were retrospectively analyzed. Treatment strategy involved GnRHa alone (group A: n=34) and GnRHa+rhGH (group B: n=46). Children’s heights (Ht), weights (Wt) and sex hormone levels were measured every 3 months after treatment and bone age (BA) every six months. Heights, growth velocity (GV), predicted adult height (PAH), weights, body mass index (BMI), sex hormone levels and bone age were compared between the two groups.ResultsChildren in group B showed greater height gain at the 12th, 24th and 30th months after treatment (p<0.05) than those in group A, had faster growth rates in the first and second year following treatment (p<0.05) and better PAH (p<0.05). No statistical differences in weight or BMI were found between the two groups before treatment or at any time after treatment (p>0.05). Levels of LH and FSH were lower in both groups after treatment with no statistical differences between groups (p>0.05). The gap between bone age and chronological age gradually decreased in both groups and no abnormal progression of bone age or other adverse side effects occurred.ConclusionsThe combination of GnRHa with rhGH produced better height gains than GnRHa alone for patients with CPP. The gonadal axis was suppressed and progression of bone age delayed with good safety and efficacy

Use of \u3e100,000 NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium whole genome sequences improves imputation quality and detection of rare variant associations in admixed African and Hispanic/Latino populations

Most genome-wide association and fine-mapping studies to date have been conducted in individuals of European descent, and genetic studies of populations of Hispanic/Latino and African ancestry are limited. In addition, these populations have more complex linkage disequilibrium structure. In order to better define the genetic architecture of these understudied populations, we leveraged \u3e100,000 phased sequences available from deep-coverage whole genome sequencing through the multi-ethnic NHLBI Trans-Omics for Precision Medicine (TOPMed) program to impute genotypes into admixed African and Hispanic/Latino samples with genome-wide genotyping array data. We demonstrated that using TOPMed sequencing data as the imputation reference panel improves genotype imputation quality in these populations, which subsequently enhanced gene-mapping power for complex traits. For rare variants with minor allele frequency (MAF) \u3c 0.5%, we observed a 2.3- to 6.1-fold increase in the number of well-imputed variants, with 11–34% improvement in average imputation quality, compared to the state-of-the-art 1000 Genomes Project Phase 3 and Haplotype Reference Consortium reference panels. Impressively, even for extremely rare variants with minor allele count 86%. Subsequent association analyses of TOPMed reference panel-imputed genotype data with hematological traits (hemoglobin (HGB), hematocrit (HCT), and white blood cell count (WBC)) in ~21,600 African-ancestry and ~21,700 Hispanic/Latino individuals identified associations with two rare variants in the HBB gene (rs33930165 with higher WBC [p = 8.8x10-15] in African populations, rs11549407 with lower HGB [p = 1.5x10-12] and HCT [p = 8.8x10-10] in Hispanics/Latinos). By comparison, neither variant would have been genome-wide significant if either 1000 Genomes Project Phase 3 or Haplotype Reference Consortium reference panels had been used for imputation. Our findings highlight the utility of the TOPMed imputation reference panel for identification of novel rare variant associations not previously detected in similarly sized genome-wide studies of under-represented African and Hispanic/Latino populations

Genome-wide Mendelian randomization identifies putatively causal gut microbiota for multiple peptic ulcer diseases

ObjectiveThe pathogenesis of peptic ulcer diseases (PUDs) involves multiple factors, and the contribution of gut microbiota to this process remains unclear. While previous studies have associated gut microbiota with peptic ulcers, the precise nature of the relationship, whether causal or influenced by biases, requires further elucidation.DesignThe largest meta-analysis of genome-wide association studies was conducted by the MiBioGen consortium, which provided the summary statistics of gut microbiota for implementation in the Mendelian randomization (MR) analysis. Summary statistics for five types of PUDs were compiled using the FinnGen Consortium R8 release data. Various statistical techniques, including inverse variance weighting (IVW), MR-Egger, weighted median (WM), weighted mode, and simple mode, were employed to assess the causal relationships between gut microbiota and these five PUDs.ResultIn the intestinal microbiome of 119 known genera, we found a total of 14 causal associations with various locations of PUDs and reported the potential pathogenic bacteria of Bilophila et al. Among them, four had causal relationships with esophageal ulcer, one with gastric ulcer, three with gastroduodenal ulcer, four with duodenal ulcer, and two with gastrojejunal ulcer.ConclusionIn this study, the pathogenic bacterial genera in the gut microbiota that promote the occurrence of PUDs were found to be causally related. There are multiple correlations between intestinal flora and PUDs, overlapping PUDs have overlapping associated genera. The variance in ulcer-related bacterial genera across different locations underscores the potential influence of anatomical locations and physiological functions

Observation of high-temperature superconductivity in the high-pressure tetragonal phase of La2PrNi2O7-{\delta}

The recent discovery of high-temperature superconductivity in the Ruddlesden-Popper phase La3Ni2O7 under high pressure marks a significant breakthrough in the field of 3d transition-metal oxide superconductors. For an emerging novel class of high-Tc superconductors, it is crucial to find more analogous superconducting materials with a dedicated effort toward broadening the scope of nickelate superconductors. Here, we report on the observation of high-Tc superconductivity in the high-pressure tetragonal I4/mmm phase of La2PrNi2O7 above ~10 GPa, which is distinct from the reported orthorhombic Fmmm phase of La3Ni2O7 above 14 GPa. For La2PrNi2O7, the onset and the zero-resistance temperatures of superconductivity reach Tconset = 78.2 K and Tczero = 40 K at 15 GPa. This superconducting phase shares the samilar structural symmetry as many cuprate superconductors, providing a fresh platform to investigate underlying mechanisms of nickelate superconductors.Comment: 19 pages and 6 figure

Patchouli Alcohol Modulates the Pregnancy X Receptor/Toll-like Receptor 4/Nuclear Factor Kappa B Axis to Suppress Osteoclastogenesis

The incidence of osteoporosis, which is primarily characterized by plethoric osteoclast (OC) formation and severe bone loss, has increased in recent years. Millions of people worldwide, especially postmenopausal women, suffer from osteoporosis. The drugs commonly used to treat osteoporosis still exist many disadvantages, but natural extracts provide options for the treatment of osteoporosis. Therefore, the identification of cost-effective natural compounds is important. Patchouli alcohol (PA), a natural compound extracted from Pogostemon cablin that exerts anti-inflammatory effects, is used as a treatment for gastroenteritis. However, no research on the use of Patchouli alcohol in osteoporosis has been reported. We found that PA dose-dependently inhibited the receptor activator of nuclear factor kappa-B ligand (RANKL)-induced formation and function of OCs without cytotoxicity. Furthermore, these inhibitory effects were reflected in the significant effect of PA on the NF-κB signaling pathway, as PA suppressed the transcription factors NFATc1 and c-Fos. We also determined that PA activated expression of the nuclear receptor pregnane X receptor (PXR) and promoted the PXR/Toll-like receptor 4 (TLR4) axis to inhibit the nuclear import of NF-κB (p50 and p65). Additionally, PA exerted therapeutic effects against osteoporosis in ovariectomized (OVX) mice, supporting the use of PA as a treatment for osteoporosis in the future

Search for the decay J/ψ→γ+invisibleJ/\psi\to\gamma + \rm {invisible}

We search for $J/\psi$ radiative decays into a weakly interacting neutral particle, namely an invisible particle, using the $J/\psi$ produced through the process $\psi(3686)\to\pi^+\pi^-J/\psi$ in a data sample of $(448.1\pm2.9)\times 10^6$ $\psi(3686)$ decays collected by the BESIII detector at BEPCII. No significant signal is observed. Using a modified frequentist method, upper limits on the branching fractions are set under different assumptions of invisible particle masses up to 1.2 $\mathrm{\ Ge\kern -0.1em V}/c^2$. The upper limit corresponding to an invisible particle with zero mass is 7.0$\times 10^{-7}$ at the 90\% confidence level

Amplitude analysis of Ds+→π+π−π+D_s^{+} \rightarrow \pi^{+} \pi^{-} \pi^{+}

Utilizing the data set corresponding to an integrated luminosity of $3.19$ fb$^{-1}$ collected by the BESIII detector at a center-of-mass energy of 4.178 GeV, we perform an amplitude analysis of the $D_s^+\to\pi^+\pi^-\pi^+$ decay. The sample contains 13,797 candidates with a signal purity of $\sim$80%. The amplitude and phase of the contributing $\pi\pi$ ${\cal S}$ wave are measured based on a quasi-model-independent approach, along with the amplitudes and phases of the ${\cal P}$ and ${\cal D}$ waves parametrized by Breit-Wigner models. The fit fractions of different intermediate decay channels are also reported.Comment: 14 pages, 6 figure

Measurement of the cross section of e+e−→Ξ−Ξˉ+e^+e^-\rightarrow\Xi^{-}\bar\Xi^{+} at center-of-mass energies between 3.510 and 4.843 GeV

Using $e^+e^-$ collision data corresponding to a total integrated luminosity of 12.9 $fb^{-1}$ collected with the BESIII detector at the BEPCII collider, the exclusive Born cross sections and the effective form factors of the reaction $e^+e^-\rightarrow\Xi^{-}\bar\Xi^{+}$ are measured via the single baryon-tag method at 23 center-of-mass energies between 3.510 and 4.843 GeV. Evidence for the decay $\psi(3770)\rightarrow\Xi^{-}\bar\Xi^{+}$ is observed with a significance of 4.5$\sigma$ by analyzing the measured cross sections together with earlier BESIII results. For the other charmonium(-like) states $\psi(4040)$, $\psi(4160)$, $Y(4230)$, $Y(4360)$, $\psi(4415)$, and $Y(4660)$, no significant signal of their decay to $\Xi^-\bar \Xi^+$ is found. For these states, upper limits of the products of the branching fraction and the electronic partial width at the 90% confidence level are provided.Comment: 18 pages, 10 pages, 4 table

First Observation of a Three-Resonance Structure in e+e−→e^+e^-\rightarrow{non-open} Charm Hadrons

We report the measurement of the cross sections for $e^+e^-$$\rightarrow${nOCH} (nOCH stands for non-open charm hadrons) with improved precision at center-of-mass energies from 3.645 to 3.871 GeV. We observe for the first time a three-resonance structure in the energy-dependent lineshape of the cross sections, which are $\mathcal R(3760)$, $\mathcal R(3780)$ and $\mathcal R(3810)$ with significances of $9.4\sigma$, $15.7\sigma$, and $9.8\sigma$, respectively. The $\mathcal R(3810)$ is observed for the first time. We found two solutions in analysis of the cross sections. For solution I [solution II], we measure the mass, the total width and the product of electronic width and nOCH decay branching fraction to be $(3805.8 \pm 1.1 \pm 2.7)$ [$(3805.8 \pm 1.1 \pm 2.7)$] MeV/$c^2$, $(11.6 \pm 2.6 \pm 1.9)$ [$(11.5 \pm 2.5 \pm 1.8)$] MeV, and $(10.8\pm 3.2\pm 2.3)$ [$(11.0\pm 2.9\pm 2.4)$] eV for the $\mathcal R(3810)$, respectively. In addition, we measure the branching fractions ${\mathcal B}({\mathcal R}(3760)$$\rightarrow${nOCH}$)=(24.5 \pm 13.4 \pm 27.4)\% [(6.8 \pm 5.4 \pm 7.6)\%]$ for the first time, and ${\mathcal B}(\mathcal R(3780)$$\rightarrow${nOCH}$)=(11.6 \pm 5.8 \pm 7.8)\% [(10.3 \pm 4.5 \pm 6.9)\%]$. Moreover, we determine the open-charm (OC) branching fraction ${\mathcal B}({\mathcal R}$$(3760)\rightarrow${OC}$)=(75.5 \pm 13.4 \pm 27.4)\% [(93.2 \pm 5.4 \pm 7.6)\%]$, which supports the interpretation of $\mathcal R(3760)$ as an OC pair molecular state, but contained a simple four-quark state component. The first uncertainties are from fits to the cross sections, and the second are systematic