Bowel Habits, Obesity, Intestinal Microbiota and Their Influence on Hemorrhoidal Disease: a Mendelian Randomization Study.

Purpose: Hemorrhoids (HEM) are the most common perianal disease, but current observational studies have yielded inconsistent results in investigating the risk factors. Our further exploration of the risk factors will help prevent the disease. Patients and Methods: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis using publicly available genome-wide association studies (GWAS) statistics from multiple consortia. The inverse-variance weighted (IVW) method was used for the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression, and Cochrane's Q value, to detect and correct the effects of horizontal pleiotropy. Results: Genetically determined constipation (OR = 0.97, 95% CI: 0.91-1.03, P = 0.28) and diarrhea (OR = 1.00, 95% CI: 0.99-1.01, P = 0.90) did not have a causal effect on HEM but stool frequency (OR = 1.28, 95% CI: 1.05-1.55, P = 0.01), waist-to-hip ratio adjusted for BMI (OR = 1.11, 95% CI: 1.06-1.64, P = 1.59×10-5), and order Burkholderiales (OR = 1.09, 95% CI = 1.04-1.14, p = 1.63×10-4) had a causal effect on. Furthermore, we found a significant causal effect of constipation on HEM in the reverse MR analysis (OR = 1.21, 95% CI: 1.13-1.28, P = 3.72×10-9). The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates, as indicated by the sensitivity analysis. Conclusion: Our MR analysis reveals a causal association between stool frequency and waist-to-hip ratio with HEM, despite variations in results reported by observational studies. Unexpectedly, we found a relationship between the order Burkholderiales in the gut flora and HEM, although the mechanism is unclear.

Malignant Extrarenal Rhabdoid tumor derived from the greater omentum: A case report and literature review.

BACKGROUND: Malignant extrarenal rhabdoid tumor (MERT) is a rare and highly metastatic tumor, which is more than 75% of patients dying within 6 months of initial diagnosis, and it often leads to misdiagnosis and delayed treatment. CASE: This paper reports a 16-year-old girl who presented with the chief complaint of acute abdominal pain. She underwent laparoscopic exploration and excisional biopsy, then pathological examination and immunohistochemistry revealed "extrarenal malignant rhabdomyoma." One month after operation, she died of intra-abdominal hemorrhage and multiple organ dysfunction. CONCLUSION: MERT were often misdiagnosed and had a poor prognosis. The surgery and chemotherapy are usually beneficial to prolong the survival time of patients with MERT.

A C4-modified bipyridinium multi-mode stationary phase for reversed phase, hydrophilic interaction and ion exchange chromatography.

A novel C4-modified bipyridinium stationary phase (Sil-DPC4) was prepared and characterized by elemental analysis (EA) and Fourier transform infrared spectrometry (FT-IR) and further investigated for multi-mode liquid chromatography. The chromatographic performances of Sil-DPC4 were evaluated by reversed-phase chromatography using polycyclic aromatic hydrocarbons (PAHs), phenylamines and phenols, hydrophilic interaction chromatography using nucleosides and nucleobases, and ion exchange chromatography using inorganic ions and organic ions. The effects of the acetonitrile content, salt concentration and pH value of the mobile phase on the retention of Sil-DPC4 were also investigated. Sil-DPC4 showed multiple retention mechanisms including π-π, hydrophobic and electrostatic interactions for PAHs, phenylamines and phenols compared with a dipyridine modified silica stationary phase (Sil-DP) and C18 in RPLC, faster separation for nucleosides and nucleobases compared with Sil-DP, and higher hydrophilicity than HILIC in HILIC, and stronger retention and better separation ability for inorganic ions and organic ions in comparison to Sil-DP in IEC. Besides, Sil-DPC4 was used successfully to detect iodide in artificial seawater and had the potential to analyze radionuclide iodine-131 in seawater. In conclusion, multiple retention mechanisms of Sil-DPC4 could make it have potential applications in complex samples.

Honokiol attenuates mitochondrial fission and cell apoptosis by activating Sirt3 in intracerebral hemorrhage.

BACKGROUND: Sirtuin-3 (Sirt3) has been documented to protect against mitochondrial dysfunction and apoptosis. Honokiol (HKL) is a Sirt3 pharmacological activator with reported neuroprotective effects in multiple neurological disorders. The present study aimed to explore the neuroprotective effects of HKL and the role of Sirt3 following intracerebral hemorrhage (ICH). METHODS: An in vivo ICH model in rats was established by injecting autologous blood into the right basal ganglia. PC12 cells were stimulated with hemin. For the in vivo investigation, the modified Neurological Severity Scores and the Morris water maze test were performed to assess neurological deficits. Hematoxylin-Eosin and Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining were employed to evaluate the histopathology and apoptosis. Immunohistochemical staining was used to investigate the expression of Sirt3. Adenosine triphosphate (ATP) levels were quantified to assess mitochondrial dysfunction. Cell counting kit-8, lactate dehydrogenase assay, and flow cytometry were used to analyze cell vitality and apoptosis in vitro. Immunofluorescence staining was performed to observe mitochondrial morphology and dynamin-related protein 1 (Drp1) localization to mitochondria. Western blot was applied to quantify the expression of Sirt3, Bax, Bcl-2, cleaved-caspase-3, Drp1, phosphorylation of Drp1 at serine-616, and phosphorylation of Drp1 at serine-637 in vivo and in vitro. RESULTS: HKL treatment alleviated neurological deficits, attenuated the histopathological damage and cell apoptosis, and restored the decreased ATP levels in ICH rats. HKL improved cell survival rate, reduced cell apoptosis, and inhibited mitochondrial fission in PC12 cells. Moreover, both in vivo and in vitro models showed increased phosphorylation of Drp1 at Ser616, and reduced phosphorylation of Drp1 at Ser637. Meanwhile, immunofluorescence co-localization analysis revealed that hemin increased the overlap of Drp1 and mitochondria in PC12 cells. The phosphorylation and mitochondrial translocation of Drp1 were effectively reversed by HKL treatment. Importantly, the selective Sirt3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine suppressed these effects. CONCLUSION: Our findings demonstrated that HKL ameliorated ICH-induced apoptosis and mitochondrial fission by Sirt3, suggesting that HKL has immense prospects for the treatment of ICH.

New Monoterpenoid Indole Alkaloids from Tabernaemontana crassa Inhibit ß-Amyloid42 Production and Phospho-Tau (Thr217).

Eleven monoterpenoid indole alkaloids, including three new ones, tabercrassines A-C (1-3), were isolated from the seeds of Tabernaemontana crassa. Tabercrassine A (1) is an ibogan-ibogan-type bisindole alkaloid which is formed by the polymerization of two classic ibogan-type monomers through a C3 unit aliphatic chain. Their structures were established by extensive analysis of HRESIMS, NMR, and ECD spectra. Cellular assays showed that alkaloids 1-3 all reduce Aß42 production and inhibit phospho-tau (Thr217), a new biomarker of Alzheimer's disease [AD] associated with BACE1-, NCSTN-, GSK3ß-, and CDK5-mediated pathways, suggesting these alkaloids' potential against AD.

Two new monoterpenoid indole alkaloids from the kernels of Kopsia arborea.

Two new monoterpenoid indole alkaloids, (2 R, 7 R, 16 R, 20 R, 21S)-12-hydroxypleiocarpine (1) and (2S, 7 R, 16S, 20 R, 21S)-N-methoxycarbonyl-11,12-methylenedioxy-Δ14,15-kopsinaline (2), along with six known alkaloids were isolated from the methanol extract of the kernels of Kopsia arborea. Their structures including the absolute configurations were elucidated by HRESIMS, NMR spectroscopy, and quantum computational methods. Their cytotoxicity against two human cancer cell lines were also evaluated.

The effects of allelochemicals from root exudates of Flaveria bidentis on two Bacillus species.

To determine the allelopathic effects of root exudates from Flaveria bidentis on function of Bacillus, pot experiment was used to collect root exudates from living plants and test its allelopathic effects on function of Bacillus frigoritolerans and Bacillus megaterium, which were two dominant bacteria in the rhizosphere soil of F. bidentis. To obtain the allelopathic substances, the root exudates were successively extracted by N-hexane, dichloromethane, ethyl acetate, and N-butanol, and their allelopathic effects were tested. The results showed that B. frigoritolerans and B. megaterium considerably increased the concentration of available phosphorus and nitrogen, respectively, when the soil was treated with different concentrations of root exudates. Among the four organic solvent extracts, dichloromethane extracts significantly increased the abundances of B. frigoritolerans and B. megaterium and promoted their nitrogen-fixing and phosphate-solubilizing abilities. Phenol was detected in dichloromethane extracts by gas chromatograph-mass spectrometer (GC-MS). Meanwhile, phenol promoted the ability to fix nitrogen of B. megaterium and its growth by increasing the soil available nitrogen concentration, but phenol promoted the ability to solubilize phosphate of B. frigoritolerans only in 0.1mg/mL concentration. Therefore, phenol was an allelochemicals in the root exudates of F. bidentis that affects the growth and activities of B. megaterium.

Geological Characteristics of Lower Paleozoic Shale Gas Accumulation in the Yuxi Region, Southern Sichuan Basin: In View of High-Density Methane Inclusions.

Twelve shale fracture veins and forty-nine fluid inclusion assemblages within the veins of 3800-4200 m in three wells located in different tectonic zones in the Yuxi Region, southern Sichuan Basin were selected in this study. The burial and thermal histories of single wells were reconstructed, and time-temperature-pressure of oil and gas filling were clarified using microscopy observation, Raman microprobe analyses, geochemical tests, and fluid inclusion microtemperature measurement. The shale fracture veins of the Wufeng-Longmaxi Formation in the Yuxi Region are mainly formed vertically and horizontally, where the vein-forming fluids are derived from endogenous fluids. A large number of methane inclusions, bituminous inclusions, and methane-bearing bituminous inclusions within the veins confirm the process of oil cracking gas and kerogen cracking gas. The homogeneous temperature (Th) of the aqueous inclusions contemporaneous with the bituminous inclusions ranges from 109.3 to 174.1 °C, which were trapped during 220 to 250 Ma. The homogeneous temperature of the aqueous inclusions contemporaneous with the methane inclusions ranges from 137.3 to 226.8 °C, which were trapped during 160 to 195 Ma and 51 to 56 Ma. The trapped pressure calculated by high-density methane inclusions (0.246-0.293 g/cm3) is between 82.9 and 140.1 MPa, with a pressure coefficient between 1.64 and 2.07. The formation pressure coefficient is nearly two, indicating that the current overpressure is inherited from the overpressure at the maximum burial depth. The earlier the fracture vein opening, the less the damage to the shale gas accumulation, and the more opening-closing phases, the lower the homogeneous temperature of the gas-liquid two-phase aqueous inclusions coeval with the high-density methane inclusions and the greater the degree of damage to the shale gas accumulation. The results provide a basis for further study on the genesis of overpressure and the migration of shale gas.

Single-Cell Sequencing Yields Insights in the Evolution of Foot-and-Mouth Disease Virus Persistent Infection.

Foot-and-mouth disease virus (FMDV) could cause acute infection in host cells, or they could coexist with host cells to generate persistent infection. In persistent infection, the virus could survive for a long time in the host and could be transmitted between different host cells. In the case of FMDV-persistent infection cell line, there is a remarkable significant cellular heterogeneity in the FMDV-persistent infection cell line due to differences of viral load in the individual cells within the cell line. However, the mechanisms of FMDV-persistent infection are not well understood. It is now generally accepted that multiple factors contribute to the coevolution of viruses and cells during the course of persistent infection. The outcome would influence the development of persistent FMDV infection conjointly, reaching a state of equilibrium ultimately. Therefore, in order to elucidate the mechanism of cellular heterogeneity in FMDV-persistent infection cell line, single-cell sequencing was performed on BHK-Op, and pseudotime trajectory plot was draw through cell cluster. Based on the cell clusters, we predicted the development and progression of the FMDV-persistent infection. It could be well explained by the fact that, in BHK-Op cells, there are a fraction of infected cells and a fraction of virus-exposed but uninfected bystander cells. By further comparing the transcripts in cell clusters, we found that these genes were involved in changes in ribosome biogenesis, cell cycle, and intracellular signaling including the interferon signaling pathway and mitogen-activated protein kinase (MAPK) signaling pathway. Through comprehensive cross-tabulation analysis of differential expressed genes in various cluster of cells, we identified a high association of Fos, a downstream transcription factor of the MAPK/extracellular signal-regulated kinase (ERK) signaling pathway, with viral replication during the formation of FMDV-persistent infection. Through the further study of Fos, we found that downregulation of Fos facilitates viral clearance during FMDV-persistent infection. Upregulation of c-Raf, which is the upstream of the MAPK/ERK signaling pathway, could promote FMDV replication through downregulation of Fos. Our research is the first to provide insight into the mechanism of the formation FMDV-persistent infection through single-cell sequencing using persistent infection cell line. Pseudotime trajectory analysis was the first time to apply for FMDV-persistent infection cell line. Our work highlights the detailed overview of the evolution of FMDV-persistent infection. We also analyzed the differential expressed genes in the replication or elimination of FMDV within the host. We found that the MAPK/ERK signaling pathway and its downstream transcription factor Fos play an important role in FMDV-persistent infection.

Selenium nanoparticles coupling with Astragalus Polysaccharides exert their cytotoxicities in MCF-7 cells by inhibiting autophagy and promoting apoptosis.

BACKGROUND: Astragalus Polysaccharides (APS) had been reported to exhibit antitumor activities. Given that nanoparticles possessed unique advantages in cancer treatment, APS was used as the modifier to prepare gold, silver and selenium nanoparticles (APS-Au, APS-Ag and APS-Se NPs) in the present study. METHODS: The three nanoparticles were synthesized via a green approach and characterized by DLS, TEM, XRD, FT-IR and UV-Vis. The inhibitory effects of these nanoparticles on various tumor cells proliferation were examined by MTT assay in vitro. Reactive oxygen species (ROS), mitochondrial membrane potential (MMP) and the expression of apoptosis and autophagy-related proteins were also detected. RESULTS: Among these, APS-Se NPs displayed the most potent antitumor activities against MCF-7 cells in vitro. Flow cytometric analysis suggested that after cells were exposed to elevated concentrations of APS-Se NPs (10, 20 and 40 µmol/L), the rate of apoptosis was increasing (16.63 ± 0.89, 38.60 ± 3.46 and 44.38 ± 2.62%, respectively). Further analysis by immunofluorescence revealed an increase in intracellular ROS and a loss of MMP. This was accompanied by increased LC3-I to LC3-II conversion. Also, western blot analysis demonstrated that the ratios of Bax/Bcl-2 and cleaved caspase9/caspase 9 rose, and LC3-II and p62 protein levels increased. The addition of chloroquine, an inhibitor of autophagy, further enhanced protein expression of p62 and LC3-II. CONCLUSION: APS-Se NPs exerted their cytotoxic activity in MCF-7 cells by blocking autophagy and facilitating mitochondrial pathway-mediated apoptosis.

Combination of Chinese medicinal formulas and chemotherapy for triple-negative breast cancer strengthens body resistance to eliminate pathogenic factors.

BACKGROUND: To evaluate the efficacy and safety of strengthening the body's resistance to eliminate pathogenic factors in Chinese medicinal formulas combined with chemotherapy (hereafter referred to as combined therapy [CT]) in triple-negative breast cancer. METHODS: By searching the 7 electronic databases, PubMed, EMBASE, Web of Science, Cochrane Library, Chinese Academic Journal, Wanfang Database, and Chinese Science and Technology Journal, from the beginning of the establishment to April 2022 to identify eligible randomized controlled trial studies. RESULTS: The meta-analysis showed that compared with chemotherapy, CT can effectively improve the objective remission rate (risk ratio [RR]: 1.39; 95% confidence interval [CI]: 1.28, 1.52; P < .00001, I2 = 3%), reduce the recurrence rate (RR: 0.33; 95% CI: 0.14, 0.78; P = .01, I2 = 0%) metastasis rate (RR: 0.48; 95% CI: 0.31, 0.73; P = .0006, I2 = 0%) and the incidence of toxic and side reactions, lower tumor marker levels, regulated T lymphocyte subset changes, and increased average progression-free survival (standardized mean difference: 2.78; 95% CI: 1.41, 4.14; P < .0001, I2 = 97%), and improve the quality of life (RR: 1.55; 95% CI: 1.21, 1.99; P = .0005, I2 = 52%). CONCLUSION: This study suggests that CT appears to be an effective and safe treatment approach. Although this conclusion requires further confirmation owing to insufficient quality of the included trials.

Long-read assembly of the Chinese indigenous Ningxiang pig genome and identification of genetic variations in fat metabolism among different breeds.

Advances in long-read sequencing technology and genome assembly provide an opportunity to improve the pig genome and reveal the full range of structural variations (SVs) between local Chinese and European pigs. To date, little is known about the genomes of some unique Chinese indigenous breeds, such as the Ningxiang pig. Here, we report the sequencing and assembly of a highly contiguous Ningxiang pig genome (NX) via an integration of PacBio single-molecule real-time sequencing, Illumina next-generation sequencing, BioNano optical mapping and Hi-C (chromosome conformation capture) approaches. The assembled genome comprises 2.44 Gb with a contig N50 of 26.1 Mb and 418 contigs in total. These contigs are organized into 121 scaffolds with a scaffold N50 of 139.0 Mb. More than 99.1% of the assembled sequence could be localized to 19 pseudochromosomes and is annotated with 20,914 protein-coding genes and 34.04% repetitive sequences. Comparisons between the NX and European Duroc assemblies revealed many SVs in genes involved in the immune system, nervous system, lipid metabolism and environmental adaptation. The genetic variants include 47 Chinese domestic pig-specific SVs and the associated 74 genes may contribute to the differences in domestic traits compared to European pigs. Moreover, single nucleotide polymorphisms (SNPs) identified from whole genome resequencing data of 73 Chinese pigs, representing 17 geographically isolated breeds, showed their specific genetic variations, population structure and evolutionary patterns. Finally, we explore transcriptional regulation in the first intron of the MYL4 gene, as the genomic SV (281-bp deletion) in Ningxiang pig promotes its subcutaneous fat compared to European pig breeds. This work identifies a set of Asian-specific SVs and SNPs, which will be important resources for modern pig breeding and genetic conservation.

Taberdines L and M, two new alkaloids from Tabernaemontana divaricata.

Two new alkaloids, taberdines L (1) and M (2), together with six known alkaloids, were isolated from the twigs and leaves of Tabernaemontana divaricata. Taberdine L (1) represents the first optically active natural member of the allo iboga class of alkaloids with the ethyl side chain in a bridgehead position. Their structures including absolute configuration were elucidated by a combination of MS, NMR, and ECD calculation. The in vitro cytotoxic activities of 1 and 2 against five human cancer cell lines were also evaluated.

Next-generation sequencing sheds light on the interaction between virus and cell during foot-and-mouth disease virus persistent infection.

Foot-and-mouth disease virus (FMDV) infection can be either persistent or acute in susceptible animals. The mechanisms involved in FMDV replication and clearance during persistent infection remain unclear. To identify host factors that are critical for FMDV replication during persistent infection, we used RNA-seq to compare the transcriptomes of infected (BHK-Op) cells and bystander (BHK-VEC) cells, which are exposed to FMDV but not infected. In total, 1917 genes were differentially expressed between BHK-Op cells and BHK-VEC cells, which were involved in ribosome biogenesis, cell cycle, and dilated cardiomyopathy. We further identified host genes potentially involved in viral clearance during persistent FMDV infection by comprehensive crossover analysis of differentially expressed genes in ancestral host cells, evolved infected host cells, and evolved bystander cells, which are resistant to infection by wild-type FMDV and FMDV-Op that co-evolved with host cells during persistent infection. Among the identified genes were Cav1 and Ccnd1. Subsequent experiments showed that knockdown of Cav1 and Ccnd1 in host cells significantly promoted and inhibited FMDV replication, respectively, confirming that the overexpression of Cav1 and the downregulation of Ccnd1 contribute to virus clearance during persistent FMDV infection. In addition, we found that BHK-Op cells contained mixtures of multiple genotypes of FMDV viruses, shedding light on the diversity of FMDV genotypes during persistent infection. Our findings provide a detailed overview of the responses of infected cells and bystander cells to persistent FMDV infection.

Deep Learning-Based CT Image Characteristics and Postoperative Anal Function Restoration for Patients with Complex Anal Fistula.

Objective: This study aimed to optimize the CT images of anal fistula patients using a convolutional neural network (CNN) algorithm to investigate the anal function recovery. Methods: 57 patients with complex anal fistulas admitted to our hospital from January 2020 to February 2021 were selected as research subjects. Of them, CT images of 34 cases were processed using the deep learning neural network, defined as the experimental group, and the remaining unprocessed 23 cases were in the control group. Whether to process CT images depended on the patient's own wish. The imaging results were compared with the results observed during the surgery. Results: It was found that, in the experimental group, the images were clearer, with DSC = 0.89, precision = 0.98, and recall = 0.87, indicating that the processing effects were good; that the CT imaging results in the experimental group were more consistent with those observed during the surgery, and the difference was notable (P < 0.05). Furthermore, the experimental group had lower RP (mmHg), AMCP (mmHg) scores, and postoperative recurrence rate, with notable differences noted (P < 0.05). Conclusion: CT images processed by deep learning are clearer, leading to higher accuracy of preoperative diagnosis, which is suggested in clinics.

Metabolic activation of zolmitriptan mediated by CYP2D6.

Zolmitriptan (ZOL), a member of triptans, has been used for the treatment of migraine with definite therapeutic effects. However, several cases of liver injury associated with ZOL have been reported and the underlying mechanisms remain unclear.The present study aimed to investigate the metabolic activation of ZOL in vitro and in vivo. ZOL-derived glutathione (GSH) and N-acetyl cysteine (NAC) conjugates were detected in rat liver microsomal incubations. In addition, the GSH and NAC conjugates were also found in bile and urine of rats given ZOL, respectively.ZOL-derived GSH conjugate M1 was also observed in ZOL-treated rat primary hepatocytes, and the formation of M1 was inhibited by pre-cultured with quinidine (a selective inhibitor of CYP2D6). Combining with recombinant P450 enzymes incubations, we found that CYP2D6 was the predominant enzyme responsible for the metabolic activation of ZOL.ZOL can be metabolized to an α,ß-unsaturated imine intermediate by CYP2D6. Pre-treatment of primary hepatocytes with quinidine was able to reverse ZOL-induced cytotoxicity. The finding facilitates the understanding of the mechanisms involved in ZOL-associated liver adverse reactions.

Efficacy and Safety of Traditional Chinese Medicine in the Treatment of Immune Infertility Based on the Theory of "Kidney Deficiency and Blood Stasis": A Systematic Review and Meta-Analysis.

OBJECTIVE: This study aims to evaluate the efficacy and safety of traditional Chinese medicine (TCM) therapy of tonifying kidney and activating blood circulation (TKABC) based on the theory of "kidney deficiency and blood stasis" for the treatment of immune infertility. METHODS: Six electronic databases, including the Cochrane Library, PubMed, EMBASE, the China National Knowledge Infrastructure, Wanfang Data, and VIP information database, were searched from inception to January 2021 to identify eligible studies of randomized controlled trials (RCTs). The primary outcome measurements were the total effective rate and pregnancy rate, and the secondary outcome measurements included the negative conversion rate of serum antibodies and the incidence of adverse effects. The quantitative synthesis was performed using the Review Manager 5.3 software. The chi-square statistic and I 2 statistic were employed to investigate statistical heterogeneity. The fixed-effects model was used for a low heterogeneity (I 2 < 50%), and the random-effects model was applied if heterogeneity was moderate (50% < I 2 < 75%). Funnel plots were used to evaluate potential reporting bias when more than ten eligible studies were included. RESULTS: Thirteen RCTs involving 1298 patients with immune infertility of kidney deficiency and blood stasis were included. Compared with conventional group, TCM TKABC therapy showed a significant improvement on the total effective rate (RR: 1.38; 95% CI: 1.30,1.47; and I 2 = 0%), pregnancy rate (RR: 2.04; 95% CI: 1.73, 2.40; and I 2 = 30%), negative conversion rates of AsAb (RR: 1.42; 95% CI: 1.12,1.79; and I 2 = 62%), AEmAb rates (RR: 1.21; 95% CI: 1.04,1.41; and I2 = 0%), and AhCGAb with less adverse effects (RR: 0.24; 95% CI: 1.73, 2.40; and I 2 = 55%). However, the negative conversion rate of AoAb and ACAb showed no significant statistical difference. CONCLUSIONS: Our review suggests that TCM TKABC therapy based on the theory of kidney deficiency and blood stasis appears to be an effective and safe approach for patients with immune infertility. However, the methodological quality of included RCTs was unsatisfactory, and it is necessary to verify its effectiveness with more well-designed and high-quality multicenter RCTs.

Association between serum fibroblast growth factor 21 level and sight-threatening diabetic retinopathy in Chinese patients with type 2 diabetes.

INTRODUCTION: We conducted this cross-sectional study to explore the relationship between serum fibroblast growth factor 21 (FGF21) level and sight-threatening diabetic retinopathy (STDR). RESEARCH DESIGN AND METHODS: A total of 654 patients with type 2 diabetes were recruited. Diabetic retinopathy (DR) was evaluated by the bilateral retinal photography, and patients were assigned into groups of no DR (NDR) (n=345, 52.75%), non-sight-threatening diabetic retinopathy (NSTDR) (n=207, 31.65%), involving patients with mild or moderate non-proliferative retinopathy (NPDR) and STDR (n=102, 15.60%), including those with severe NPDR or proliferative diabetic retinopathy (PDR). Serum FGF21 levels were quantified by a sandwich ELISA. Patients were divided into quartiles according to their serum FGF21 level. RESULTS: There was a significant difference in serum FGF21 level among the three groups of patients (p<0.01). Compared with other quartiles (Q1-Q3), the patients in Q4 had a higher prevalence of DR and STDR (p<0.05). Compared with Q1, a positive association was observed between serum FGF21 level and DR in Q3 and Q4 (p<0.01). After adjusting for age, gender and other risk factors, serum FGF21 level in Q4 was found to be associated with increased risk of DR and STDR (p<0.01). Serum FGF21 level was noted as an independent risk factor for DR and STDR (p<0.01). Serum FGF21 level >478.76 pg/mL suggested the occurrence of DR and that level >554.69 pg/mL indicated STDR (p<0.01). CONCLUSIONS: Serum FGF21 level was a biomarker for the risk of developing DR or STDR. The risk of STDR increased when the serum FGF21 level of patients with type 2 diabetes was >554.69 pg/mL.

Integrated characterization of SARS-CoV-2 genome, microbiome, antibiotic resistance and host response from single throat swabs.

The ongoing coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, poses a severe threat to humanity. Rapid and comprehensive analysis of both pathogen and host sequencing data is critical to track infection and inform therapies. In this study, we performed unbiased metatranscriptomic analysis of clinical samples from COVID-19 patients using a recently developed RNA-seq library construction method (TRACE-seq), which utilizes tagmentation activity of Tn5 on RNA/DNA hybrids. This approach avoids the laborious and time-consuming steps in traditional RNA-seq procedure, and hence is fast, sensitive, and convenient. We demonstrated that TRACE-seq allowed integrated characterization of full genome information of SARS-CoV-2, putative pathogens causing coinfection, antibiotic resistance, and host response from single throat swabs. We believe that the integrated information will deepen our understanding of pathogenesis and improve diagnostic accuracy for infectious diseases.