Safety and clinical efficacy of double posterolateral coaxial portals for endoscopic management of posterior ankle impingement syndrome.

Background: This study aims to analyze the safety and clinical efficacy of using double posterolateral coaxial portals for endoscopic treatment of posterior ankle impingement syndrome (PAIS), a procedure that has gained popularity in recent times. Methods: Six fresh foot samples were randomly selected to measure the distances of two posterolateral portals to the sural nerve in different positions (plantar flexion 10°, dorsiflexion 30°, and plantar flexion 30°) for safety evaluation. A prospective analysis was conducted on the clinical efficacy of the operative approach for endoscopic management of posterior ankle impingement syndrome, including evaluation of effectiveness and complications. Results: In this study, the mean distances of the first and second portals to the sural nerve were measured in different ankle positions. The distances were found to be 2.26 ± 0.22 cm and 1.59 ± 0.12 cm in the plantar flexion 10° position, 2.21 ± 0.21 cm and 1.55 ± 0.12 cm in the dorsiflexion 30° position, and 2.46 ± 0.29 cm and 1.73 ± 0.19 cm in the plantar flexion 30° position, demonstrating a significant safety margin from the nerve. A total of 38 patients underwent endoscopic treatment for posterior ankle impingement syndrome using double posterolateral coaxial portals between January 2012 and December 2017. This surgical approach provided access to the subtalar joint and posterior ankle region. The patients were followed up for an average of 38.2 months (24-72 months), with a satisfaction rate of 94.7%. There were no reported complications, and significant improvements were observed in both visual analogue scale (VAS) and The American Orthopedic Foot and Ankle Society Score (AOFAS) scores postoperatively. The VAS score decreased from 5.68 to 0.51 (P < 0.001), while the AOFAS score increased from 71.68 to 92.34 (P < 0.001), resulting in an excellent/good rate of 97.3%. Conclusion: The use of double posterolateral coaxial portals in the treatment of posterior ankle impingement syndrome offers several advantages, including improved safety, reduced risk of nerve injury, enhanced visualization of the posterior ankle and subtalar joint, favorable clinical outcomes, and minimal complications.

Associations of maternal serum concentration of iron-related indicators with birth outcomes in Chinese: a pilot prospective cohort study.

BACKGROUND: Previous studies of maternal iron and birth outcomes have been limited to single indicators that do not reflect the comprehensive relationship with birth outcomes. We aimed to investigate the relationship between maternal iron metabolism and neonatal anthropometric indicators using comprehensive iron-related indicators. METHODS: A total of 914 Chinese mother-child dyads were enrolled in this prospective study. Subjects' blood samples were collected at ≤ 14 weeks of gestation. Serum concentrations of iron-related indicators were measured by enzyme-linked immunosorbent assay (ELISA). Femur length was measured by B-ultrasound nearest delivery. Neonatal anthropometric indicators were collected from medical records. RESULTS: After adjustment for potential covariates, higher iron (per one standard deviation, SD increase) was detrimentally associated with - 0.22 mm lower femur length, whereas higher transferrin (per one SD increase) was associated with 0.20 mm higher femur length. Compared with normal subjects (10th-90th percentiles), subjects with extremely high (> 90th percentile) iron concentration were detrimentally associated with lower femur length, birth weight, and chest circumference, and a higher risk of low birth weight, LBW (HR: 3.92, 95%CI: 1.28, 12.0). Subjects with high concentration of soluble transferrin receptor, sTFR and transferrin (> 90th percentile) were associated with higher femur length. Subjects with low concentration of iron and ferritin concentrations (< 10th percentile) were associated with a higher risk of LBW (HR: 4.10, 95%CI: 1.17, 14.3) and macrosomia (HR: 2.79, 95%CI: 1.06, 7.35), respectively. CONCLUSIONS: Maternal iron overload in early pregnancy may be detrimentally associated with neonatal anthropometric indicators and adverse birth outcomes.

Zhisou powder suppresses airway inflammation in LPS and CS-induced post-infectious cough model mice via TRPA1/TRPV1 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhisou Powder (ZSP), a traditional Chinese medicine (TCM) prescription, has been widely used in the clinic for the treatment of post-infectious cough (PIC). However, the exact mechanism is not clear. AIM OF THE STUDY: The aim of this study was to investigate the ameliorative effect of ZSP on PIC in mice. The possible mechanisms of action were screened based on network pharmacology, and the potential mechanisms were explored through molecular docking and in vivo experimental validation. MATERIALS AND METHODS: Lipopolysaccharide (LPS) (80µg/50 µL) was used to induce PIC in mice, followed by daily exposure to cigarette smoke (CS) for 30 min for 30 d to establish PIC model. The effects of ZSP on PIC mice were observed by detecting the number of coughs and cough latency, peripheral blood and bronchoalveolar lavage fluid (BALF) inflammatory cell counts, enzyme-linked immunosorbent assay (ELISA), and histological analysis. The core targets and key pathways of ZSP on PIC were analyzed using network pharmacology, and TRPA1 and TRPV1 were validated using RT-qPCR and western blotting assays. RESULTS: ZSP effectively reduced the number of coughs and prolonged the cough latency in PIC mice. Airway inflammation was alleviated by reducing the expression levels of the inflammatory mediators TNF-α and IL-1ß. ZSP modulated the expression of Substance P, Calcitonin gene-related peptide (CGRP), and nerve growth factor (NGF) in BALF. Based on the results of network pharmacology, the mechanism of action of ZSP may exert anti-neurogenic airway-derived inflammation by regulating the expression of TRPA1 and TRPV1 through the natural active ingredients α-spinastero, shionone and didehydrotuberostemonine. CONCLUSION: ZSP exerts anti-airway inflammatory effects through inhibition of TRPA1/TRPV1 channels regulating neuropeptides to alleviate cough hypersensitivity and has a favorable therapeutic effect on PIC model mice. It provides theoretical evidence for the clinical application of ZSP.

Peptidoglycan biosynthesis-associated enzymatic kinetic characteristics and ß-lactam antibiotic inhibitory effects of different Streptococcus pneumoniae penicillin-binding proteins.

Penicillin-binding proteins (PBPs) include transpeptidases, carboxypeptidases, and endopeptidases for biosynthesis of peptidoglycans in the cell wall to maintain bacterial morphology and survival in the environment. Streptococcus pneumoniae expresses six PBPs, but their enzymatic kinetic characteristics and inhibitory effects on different ß-lactam antibiotics remain poorly understood. In this study, all the six recombinant PBPs of S. pneumoniae displayed transpeptidase activity with different substrate affinities (Km = 1.56-9.11 mM) in a concentration-dependent manner, and rPBP3 showed a greater catalytic efficiency (Kcat = 2.38 s-1) than the other rPBPs (Kcat = 3.20-7.49 × 10-2 s-1). However, only rPBP3 was identified as a carboxypeptidase (Km = 8.57 mM and Kcat = 2.57 s-1). None of the rPBPs exhibited endopeptidase activity. Penicillin and cefotaxime inhibited the transpeptidase and carboxypeptidase activity of all the rPBPs but imipenem did not inhibited the enzymatic activities of rPBP3. Except for the lack of binding of imipenem to rPBP3, penicillin, cefotaxime, and imipenem bound to all the other rPBPs (KD = 3.71-9.35 × 10-4 M). Sublethal concentrations of penicillin, cefotaxime, and imipenem induced a decrease of pneumococcal pbps-mRNA levels (p < 0.05). These results indicated that all six PBPs of S. pneumoniae are transpeptidases, while only PBP3 is a carboxypeptidase. Imipenem has no inhibitory effect on pneumococcal PBP3. The pneumococcal genes for encoding endopeptidases remain to be determined.

Integrating Network Pharmacology and In vivo Experimental Validation to Reveal the Mechanism of FuZheng YiLiu Formula on Estrogen Receptor Positive Breast Cancer.

BACKGROUND AND PURPOSE: FuZheng YiLiu Formula (FZYL) is a commonly used formula for postoperative estrogen receptor-positive (ER+) breast cancer and post-radiotherapy deficiency of both Qi and Yin. FZYL has been used in clinical practice for decades because of its ability to effectively improve the symptoms of deficiency in cancer patients. However, its mechanism needs to be further clarified. In this paper, we will observe the effect of FZYL on mice with ER+ breast cancer and explore the mechanism by which it improves the symptoms of ER+ breast cancer. MATERIALS AND METHODS: A tumor xenograft mouse model was established to detect tumor growth in vivo in order to evaluate the pharmacological effects of FZYL on ER+ breast cancer. The main targets of FZYL were identified by extracting the FZYL components and the corresponding potential target genes of breast cancer from the established database and constructing a protein-protein interaction network of shared genes using the string database. GO functional annotation and KEGG pathway enrichment analysis were performed, and molecular docking, molecular dynamics simulations, western blotting analysis, and RT-qPCR were performed to confirm the validity of targets in the relevant pathways. RESULTS: FZYL was able to significantly reduce the size of tumors in vivo and had a significant therapeutic effect on tumor xenograft mice. GO and KEGG pathway enrichment analyses indicated that the effects of FZYL may be mediated by oxidative stress levels, apoptotic signaling pathways, and cell cycle proliferation. By RT-qPCR and protein blotting assays, FZYL targeted the key targets of TP53, JUN, ESR1, RELA, MYC, and MAPK1 to exert its effects. The key active components of FZYL are quercetin, luteolin, stigmasterol, and glycitein. Molecular docking and molecular dynamics simulation results further demonstrated that the key active components of FZYL are stably bound to the core targets. CONCLUSION: In this study, the potential active ingredients, potential core targets, key biological pathways, and signaling pathways involved in the treatment of breast cancer with FZYL were identified, providing a theoretical basis for further anti ER+ breast cancer research.

Comparative efficacy and safety of Chinese patent medicines of acute ischemic stroke: A network meta-analysis.

BACKGROUND: Acute ischemic stroke (AIS) is characterized by high morbidity, disability, mortality, recurrence, and economic burden. Clinical trials have demonstrated that the clinical efficacy of combining oral Chinese patent medicines (CPMs) with chemical drugs (CDs) is better than that of CDs alone. In this study, we performed a network meta-analysis (NMA) of RCTs to assess the efficacy of different CPMs in combination with CDs in the treatment of AIS. METHODS: Search 6 databases from the beginning to January 10, 2023. The Cochrane Risk of Bias tool assessed the methodological quality of the included studies. The NMA was then performed using the STATA 13.0 program. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the studied treatments, and cluster analysis was used to compare the effects of CPMs between 2 different outcomes. RESULTS: A total of 94 eligible RCTs, involving 9581 participants, were included in this analysis. Nine CPMs, including Nao-mai-li granule (NML), Nao-mai-tai granule (NMT), Qi-long granule (QL), Long-sheng-zhi capsule (LSZ), Nao-xin-tong capsule (NXT), Nao-xue-shu oral liquid (NXS), Tong-xin-luo capsule (TXL), Xiao-shuan-chang-rong capsule (XSCR), and Xue-shuan-xin-mai-ning capsule (XSXMN) were included. Regarding the clinical effective rate, all types of CPMs + CDs treatments were significantly better than CDs treatments alone, with significant differences among the 9 selected CPMs. Compared with CDs, results showed that NXS + CDs performed best in improving clinical effective rate [OR = 4.73; 95% CI: 1.26-17.78; (SUCRA: 76.1%)]. TXL + CDs showed the most effective effect in alleviating National Institutes of Health Stroke Scale (NIHSS) [MD = -3.84; 95% CI: -5.23, -2.45; (SUCRA: 81.6%)]; NXT + CDs were most effective in improving Barthel index [MD = 13.05; 95% CI: 3.98-22.12; (SUCRA: 63.5%)]. Combined with other outcome indicators and the results of cluster analysis, NXS + CDs may assist in the potential optimal treatment regimen for AIS. CONCLUSION: In conclusion, CPMs were found to be beneficial as adjuvant therapy in patients with AIS. Taking into account the clinical effective rate and other outcomes, NXS + CDs may be the most effective option to improve the condition of AIS patients.

A study of the proteomic expression in patients with complicated parapneumonic pleural effusion.

Introduction: The present study aimed to investigate the differences in the proteomic expression between uncomplicated parapneumonic pleural effusion (UPPE) and complicated parapneumonic pleural effusion (CPPE). Material and methods: There were 10 patients with UPPE and 10 patients with CPPE. These patients were combined due to the complication of pleural effusion and further divided into group A and group B. An LC-MS analysis was conducted with the extraction of high-abundance proteins, and proteins with 1.5-fold or higher difference multiples were identified as differential proteins. Then, gene ontology (GO) and KEGG analyses were conducted on the differential proteins between the groups. Results: Compared with the UPPE group, there were 38 upregulated proteins and 29 downregulated proteins in the CPPE group. The GO analysis revealed that the CPPE group had enhanced expressions in monosaccharide biosynthesis, glucose catabolism, fructose-6-phosphate glycolysis, glucose-6-phosphate glycolysis, and NADH regeneration as well as reduced expressions in fibrinogen complexes, protein polymerization, and coagulation. Moreover, the KEGG analysis showed that the CPPE group had enhanced expressions in amino acid synthesis, the HIF-1 signalling pathway, and glycolysis/glycoisogenesis and decreased expressions in platelet activation and complement activation. Conclusions: In pleural effusion in patients with CPPE, there are enhanced expressions of proteins concerning glucose and amino acid metabolism, NADH regeneration, and HIF-1 signalling pathways together with decreased expressions of proteins concerning protein polymerization, blood coagulation, platelet activation, and complement activation.

Are New Phthalate Ester Substitutes Safer than Traditional DBP and DiBP? Comparative Endocrine-Disrupting Analyses on Zebrafish Using In Vivo, Transcriptome, and In Silico Approaches.

Although previous studies have confirmed the association between phthalate esters (PAEs) exposure and endocrine disorders in humans, few studies to date have systematically assessed the threats of new PAE alternatives to endocrine disruptions. Herein, zebrafish embryos were continuously exposed to two PAEs [di-n-butyl phthalate (DBP) and diisobutyl phthalate (DiBP)], two structurally related alternatives [diiononyl phthalate (DINP) and diisononyl hexahydrophthalate (DINCH)], and two non-PAE substitutes [dipropylene glycol dibenzoate (DGD) and glyceryl triacetate (GTA)], and the endocrine-disrupting effects were investigated during the early stages (8-48 hpf). For five endogenous hormones, including progesterone, testosterone, 17ß-estradiol, triiodothyronine (T3), and cortisol, the tested chemicals disturbed the contents of at least one hormone at environmentally relevant concentrations (≤3.9 µM), except DINCH and GTA. Then, the concentration-dependent reduced zebrafish transcriptome analysis was performed. Thyroid hormone (TH)- and androgen/estrogen-regulated adverse outcome pathways (AOPs) were the two types of biological pathways most sensitive to PAE exposure. Notably, six compounds disrupted four TH-mediated AOPs, from the inhibition of deiodinases (molecular initiating event, MIE), a decrease in T3 levels (key event, KE), to mortality (adverse outcome, AO) with the quantitatively linear relationships between MIE-KE (|r| = 0.96, p = 0.002), KE-AO (|r| = 0.88, p = 0.02), and MIE-AO (|r| = 0.89, p = 0.02). Multiple structural analyses showed that benzoic acid is the critical toxicogenic fragment. Our data will facilitate the screening and development of green alternatives.

Buccal acupuncture combined with ultrasound-guided dry needle-evoked inactivation of trigger points to treat cervical and shoulder girdle myofascial pain syndrome.

BACKGROUND: Myofascial pain syndrome (MPS) is a common disease with easy persistence and recurrence. In clinical practice, although many methods have been adopted to prevent and treat MPS, the control of MPS is still not satisfactory. OBJECTIVE: To compare the safety and effectiveness of buccal acupuncture, inactivation of trigger points (MTrPs), and their combination in the treatment of MPS. METHODS: Two hundred MPS patients in the pain clinic were randomly divided into four groups (n= 50) to receive oral drugs (Group A), oral drugs + buccal needle (Group B), oral drugs + MTrP inactivation (Group C), or oral drugs + buccal needle + MTrP inactivation (Group D). RESULTS: The visual analogue scale (VAS) and cervical range of motion (ROM) of Group D were significantly lower than those of the other three groups, and the pressure pain threshold (PPT) value of labelled MTrPs was significantly higher than those of the other three groups (P< 0.05). The excellent rate and total effective rate of Group D were significantly higher than those of the other three groups. Group C had the highest pain score and the lowest acceptance score. The results showed that buccal acupuncture combined with ultrasound-guided dry needle-evoked inactivation of MTrPs can significantly reduce the VAS score of MPS patients, improve the range of motion of the cervical spine, and improve patient satisfaction. CONCLUSIONS: This study provides a highly accepted and satisfactory treatment for MPS, which is worthy of clinical promotion.

Associations of serum concentrations of metal nutrients with postpartum anemia among pregnant Chinese women: A large retrospective cohort study.

Background and Aims: The association between serum concentrations of metal nutrients in pregnancy and postpartum anemia has not been widely studied. This study aimed to determine this association in a large retrospective cohort study. Methods: We included 14,829 Chinese women with singleton pregnancies. Serum concentrations of metals before 28 weeks of gestation, the occurrence of postpartum anemia and other potential covariates were obtained from their laboratory or medical records. Cox regression and restricted cubic spline regression models were used to explore the relationship between serum concentrations of metal nutrients in pregnancy and postpartum anemia. Results: After adjustment for covariates, higher concentrations of iron (Fe), magnesium (Mg) and zinc (Zn) and lower concentrations of copper (Cu) were associated with a lower risk of postpartum anemia. Compared with those whose serum concentrations of metal nutrients were in the bottom quintile (Q1), the hazard ratios (HRs) of those whose serum concentrations of metal nutrients were in the top quintile (Q5) were 0.57 (95% confidence interval (CI): 0.50, 0.64) for Fe, 0.67 (95% CI: 0.60, 0.76) for Mg, 0.82 (95% CI: 0.73, 0.93) for Zn, and 1.44 (95% CI: 1.28, 1.63) for Cu. L-shaped curve relationships were found between increasing concentrations of Fe, Mg, and Zn and incidence of postpartum anemia. Higher serum concentrations of Cu were associated with an increased risk of postpartum anemia. Serum concentrations of Fe in Q5 were associated with a lower risk of postpartum anemia when they coincided with serum concentrations of Mg in Q5, Zn in Q5, or Cu in Q1. Conclusion: Higher serum concentrations of Fe, Mg, and Zn, and lower serum concentrations of Cu were associated with a lower risk of postpartum anemia among pregnant women.

Prediction of zebrafish embryonic developmental toxicity by integrating omics with adverse outcome pathway.

New approach methodologies (NAMs), especially omics-based high-throughput bioassays have been developed rapidly, providing rich mechanistic information such as molecular initiation events (MIEs) and (sub)cellular key events (KEs) in adverse outcome pathways (AOPs). However, how to apply the knowledge of MIEs/KEs to predict adverse outcomes (AOs) induced by chemicals represents a new challenge for computational toxicology. Here, an integrated method named ScoreAOP was developed and evaluated to predict chemicals' developmental toxicity for zebrafish embryos by integrating four related AOPs and dose-dependent reduced zebrafish transcriptome (RZT). The rules of ScoreAOP included 1) sensitivity of responsive KEs demonstrated by point of departure of KEs (PODKE), 2) evidence reliability and 3) distance between KEs and AOs. Moreover, eleven chemicals with different modes of action (MoAs) were tested to evaluate ScoreAOP. Results showed that eight of the eleven chemicals caused developmental toxicity at tested concentration in apical tests. All the tested chemicals' developmental defects were predicted using ScoreAOP, whereas eight out of the eleven chemicals predicted by ScoreMIE which was developed to score MIEs disturbed by chemicals based on in vitro bioassays data. Finally, in terms of mechanism explanation, ScoreAOP clustered chemicals with different MoAs while ScoreMIE failed, and ScoreAOP revealed the activation of aryl hydrocarbon receptor (AhR) plays a significant role in dysfunction of cardiovascular system, resulting in zebrafish developmental defects and mortality. In conclusion, ScoreAOP represents a promising approach to apply mechanism information obtained from omics to predict AOs induced by chemicals.

Nocardia cyriacigeorgica infection in a patient with repeated fever and CD4+ T cell deficiency: A case report.

BACKGROUND: Nocardia pneumonia shares similar imaging and clinical features with pulmonary tuberculosis and lung neoplasms, but the treatment and anti-infective medication are completely different. Here, we report a case of pulmonary nocardiosis caused by Nocardia cyriacigeorgica (N. cyriacigeorgica), which was misdiagnosed as community-acquired pneumonia (CAP) with repeated fever. CASE SUMMARY: A 55-year-old female was diagnosed with community-acquired pneumonia in the local hospital because of repeated fever and chest pain for two months. After the anti-infection treatment failed in the local hospital, the patient came to our hospital for further treatment. Enhanced computed tomography showed multiple patchy, nodular and strip-shaped high-density shadows in both lungs. A routine haematological examination was performed and showed abnormalities in CD19+ B cells and CD4+ T cells. Positive acid-fast bifurcating filaments and branching gram-positive rods were observed in the bronchoalveolar lavage fluid of the patient under an oil microscope, which was identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry as N. cyriacigeorgica. The patient's condition quickly improved after taking 0.96 g compound sulfamethoxazole tablets three times a day. CONCLUSION: The antibiotic treatment of Nocardia pneumonia is different from that of common CAP. Attention should be given to the pathogenic examination results of patients with recurrent fever. Nocardia pneumonia is an opportunistic infection. Patients with CD4+ T-cell deficiency should be aware of Nocardia infection.

Human functional genomics reveals toxicological mechanism underlying genotoxicants-induced inflammatory responses under low doses exposure.

Understanding the toxicological mechanisms of chemicals is essential for accurate assessments of environmental health risks. Inflammation could play a critical role in the adverse health outcomes caused by genotoxicants; however, the toxicological mechanisms underlying genotoxicants-induced inflammatory response are still limited. Here, functional genomics CRISPR screens were performed to enhance the mechanistic understanding of the genotoxicants-induced inflammatory response at low doses exposure. Key genes and pathways associated with the activities of immune cells and the production of cytokines were identified by CRISPR screens of 6 model genotoxicants. Gene network analysis revealed that three genes (TLR10, HCAR2 and TRIM6) were involved in the regulation of neutrophil apoptosis and cytokine release, and TLR10 shared a similar functional pattern with HCAR2 and TRIM6. Furthermore, adverse outcome pathway (AOP) network analysis revealed that TLR10 was involved in the molecular initiating events (MIEs) or key events (KEs) in the inflammatory response AOPs of all the 6 genotoxicants, which provided mechanistic links between TLR10 and genotoxicants-induced inflammation and respiratory diseases. Finally, functional validation tests demonstrated that TLR10 exhibited inhibitory effects on genotoxicants-induced inflammatory responses in both epithelial and immune cells. This study highlights the powerful utility of the integration of CRISPR screen and AOP network analysis in illuminating the toxicological causal mechanisms of environmental chemicals.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study.

OBJECTIVE: To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12. RESULTS: In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred. CONCLUSIONS: GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Mechanism of action of Daqinjiao decoction in treating cerebral small vessel disease explored using network pharmacology and molecular docking technology.

BACKGROUND AND PURPOSE: Cerebral small vessel disease (CSVD) is a clinically commonly-seen slow-progressing cerebral vascular disease. As a classic Chinese formula for the treatment of stroke, Daqinjiao Decoction (DQJD) is now used to treat CSVD with desirable effect. Since the mechanism of action is still unclear, this article will explore the therapeutic effect and mechanism of action of the formula using network pharmacology technology. METHODS: The major chemical components and potential target genes of DQJD were screened by bioinformatics. The key targets in CSVD were identified based on network modules. Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed. Pharmacodynamics of the decoction was evaluated by establishing a rat model with bilateral common carotid artery occlusion in the brain. Molecular docking, Western blot analysis and quantitative real-time polymerase chain reaction (QRT-PCR) were performed to confirm the effectiveness of targets in related pathways. RESULTS: Network pharmacology showed that 16 targets and 30 pathways were involved in the DQJD-targeted pathway network. Results revealed that DQJD might play a role by targeting the key targets including Caspse3 and P53 and regulating the P53 signaling pathway. Cognitive function and neuronal cell changes of rats were evaluated using Morris water maze, open field test and HE staining. It was indicated that DQJD could keep the nerve cells intact and neatly arranged. The decoction could improve the memory and learning ability of rats compared with the model group. It decreased the protein and mRNA expression levels of Caspse3 and P53 significantly (p<0.01). CONCLUSION: The study shows that baicalein, quercetin and wogonin, the effective components of DQJD, may regulate multiple signaling pathways by targeting the targets like Caspse3 and P53 and treat CSVD by reducing the damage to brain nerve cells.

Molecular genetic characterization and meat-use functional gene identification in Jianshui yellow-brown ducks through combined resequencing and transcriptome analysis.

The Jianshui yellow-brown duck is a unique country-specific waterfowl species in Yunnan Province, well known for its tender meat. However, there is a lack of comprehensive systematic research on the molecular genetic characteristics, especially germplasm resources and economic traits, of the Jianshui yellow-brown ducks. This study investigated the molecular genetic characteristics of Jianshui yellow-brown ducks, compared their selection signals with those of ancestral mallard and meat-type Pekin ducks, and identified genes specific to their meat-use performance. Furthermore, this study also evaluated the breeding potential for its meat performance. In this study, phylogenetic trees, PCA and Admixture analysis were used to investigate the population genetic structure among local duck breeds in China; population genetic differentiation index (Fst), nucleotide diversity and Tajima's D were used to detect selected loci and genes in the population of Jianshui yellow-brown ducks; and transcriptome technology was used to screen for differentially expressed genes in the liver, sebum and breast muscle tissues, and finally, the results of the genome selection signals and transcriptome data were integrated to excavate functional genes affecting the meat performance of the Jianshui yellow-brown ducks. The results of the genetic structure of the population showed that Jianshui yellow-brown ducks were clustered into a separate group. Selection signal analysis indicated significant selection pressure on certain genes related to meat characteristics (ELOVL2, ELOVL3, GDF10, VSTM2A, PHOSPHO1, and IGF2BP1) in both Jianshui yellow-brown ducks and mallards. Transcriptomic data analysis suggested that ELOVL3, PHOSPHO1, and GDF10 are vital candidate genes influencing meat production and quality in Jianshui yellow-brown ducks. A comparison of selection signals between Jianshui yellow-brown ducks and Pekin ducks revealed only 21 selected genes in the Jianshui yellow-brown duck population, and no significant genes were related to meat traits. Moreover, whole-genome resequencing data suggested that the Jianshui yellow-brown duck represents a unique category with distinct genetic mechanisms. Through selection signaling and transcriptomic approaches, we successfully screened and identified important candidate genes affecting meat traits in Jianshui yellow-brown ducks. Furthermore, the Jianshui yellow-brown duck has good potential for improved meat performance, highlighting the need for further improvement.

Microevolutionary mechanism of high-altitude adaptation in Tibetan chicken populations from an elevation gradient.

As an indigenous breed, the Tibetan chicken is found in highland regions and shows physiological adaptations to high altitude; however, the genetic changes that determine these adaptations remain elusive. We assumed that the microevolution of the Tibetan chicken occurred from lowland to highland regions with a continuous elevation range. In this study, we analyzed the genome of 188 chickens from lowland areas to the high-altitude regions of the Tibetan plateau with four altitudinal levels. Phylogenetic analysis revealed that Tibetan chickens are significantly different from other altitude chicken populations. Reconstruction of the demographic history showed that the migration and admixture events of the Tibetan chicken occurred at different times. The genome of the Tibetan chicken was also used to analyze positive selection pressure that is associated with high-altitude adaptation, revealing the well-known candidate gene that participates in oxygen binding (HBAD), as well as other novel potential genes (e.g., HRG and ANK2) that are related to blood coagulation and cardiovascular efficiency. Our study provides novel insights regarding the evolutionary history and microevolution mechanisms of the high-altitude adaptation in the Tibetan chicken.

Comparative Efficacy of Chinese Patent Medicines for Clearing Heat and Dampness in the Treatment of NAFLD: A Network Meta-Analysis of Real-World Evidence.

Background: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common chronic liver disease, as well as a worldwide medical problem with a substantial socioeconomic burden. In China, Chinese patent medicines (CPMs) have been widely utilized as promising and effective therapy options for NAFLD. Traditional Chinese medicine (TCM) is a particular kind of medical science reliant on real-world clinical practices and evidence. Therefore, using the real-world data extracted from pragmatic randomized controlled trials (PRCTs) have more reference value for the application of CPMs in NAFLD. Method: Six databases were searched from their inception up to March 18, 2022. The methodological quality of the included study was evaluated by the Cochrane risk-of-bias tool. Then, The STATA 13.0 program was then used to do a network meta-analysis (NMA) of real-world studies. The surface under the cumulative ranking curve (SUCRA) probability values were applied to rank the examined treatments. Results: Forty-three PRCTs (4997 cases in total) were identified. Da-Huang-Li-Dan capsule (DHLD), Dan-Ning tablet (DN), Dang-Fei-Li-Gan-Ning capsule (DFLGN), Qiang-Gan capsule (QG), and Hua-Zhi-Rou-Gan granule (HZRG) were among the five CPMs tested. As far as the clinical effective rate of the primary outcome index was concerned, the top three CPMs were DN + CDs: OR = 0.19, 95% CIs: 0.12, 0.31 (SUCRA: 81.8%); DFLGN + CDs: OR = 0.21, 95% CIs: 0.09, 0.46 (SUCRA: 74.9%), and DHLD + CDs: OR = 0.26, 95% CIs: 0.10, 0.67 (SUCRA: 61.1%). In terms of liver function index, DN + CDs ranked first in ALT index: MD = 15.81, 95% CIs: 10.05, 21.57 (SUCRA: 85.5%), DFLGN + CDs ranked first in AST index: MD = 14.94, 95% CIs: 4.77, 25.11 (SUCRA: 83.6%), HZRG + CDs ranked first in TC index: MD = 0.53, 95% CIs: 0.28, 1.03 (SUCRA: 87.1%) and TG index: MD = 1.8, 95% CIs: 1.41, 2.30 (SUCRA: 79.9%). Conclusion: Using CPMs as a coadjuvant treatment might be positive efficacious intervention from which patients with NAFLD will derive benefits. When it came to the clinical effective rate and other outcomes, DN + CDs demonstrated a significant improvement in individuals with NAFLD.

The Role of Gut Microbiota-Bile Acids Axis in the Progression of Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), an emerging global health problem affecting 25-30% of the total population, refers to excessive lipid accumulation in the liver accompanied by insulin resistance (IR) without significant alcohol intake. The increasing prevalence of NAFLD will lead to an increasing number of cirrhosis patients, as well as hepatocellular carcinoma (HCC) requiring liver transplantation, while the current treatments for NAFLD and its advanced diseases are suboptimal. Accordingly, it is necessary to find signaling pathways and targets related to the pathogenesis of NAFLD for the development of novel drugs. A large number of studies and reviews have described the critical roles of bile acids (BAs) and their receptors in the pathogenesis of NAFLD. The gut microbiota (GM), whose composition varies between healthy and NAFLD patients, promotes the transformation of more than 50 secondary bile acids and is involved in the pathophysiology of NAFLD through the GM-BAs axis. Correspondingly, BAs inhibit the overgrowth of GM and maintain a healthy gut through their antibacterial effects. Here we review the biosynthesis, enterohepatic circulation, and major receptors of BAs, as well as the relationship of GM, BAs, and the pathogenesis of NAFLD in different disease progression. This article also reviews several therapeutic approaches for the management and prevention of NAFLD targeting the GM-BAs axis.

Network Meta-Analysis of Acupoint Catgut Embedding in Treatment of Simple Obesity.

Objective: To evaluate the clinical efficacy of acupoint catgut embedding in the treatment of simple obesity through network meta-analysis. Methods: PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Wanfang, and VIP database (VIP) were searched by using computer from 2011 to August 2021, and 35 RCT studies were retrieved. The quality of the literature was evaluated using the modified Jadad scoring table, and Stata 15.0 software was used for traditional meta-analysis and network meta-analysis. Results: Thirty-five RCTs (3040 cases in total) were included. Acupoint embedding, acupuncture, electroacupuncture, TCM, acupoint embedding + acupuncture, acupoint embedding + exercise diet therapy, acupoint embedding + TCM, exercise diet therapy, acupoint embedding + moxibustion, and acupoint embedding + cupping were investigated in the studies. The results of network meta-analysis were as follows: in terms of total effective rate, acupoint catgut embedding was superior to acupuncture, electroacupuncture, and exercise diet therapy (P < 0.05); electroacupuncture, acupoint catgut embedding + acupuncture, acupoint catgut embedding + exercise diet therapy, acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to acupuncture (P < 0.05); acupoint catgut + moxibustion was superior to electroacupuncture (P < 0.05); acupoint catgut + TCM, acupoint catgut + moxibustion, and acupoint catgut + cupping were superior to TCM treatment (P < 0.05); and electroacupuncture, acupoint catgut, acupoint catgut + acupuncture, acupoint catgut + exercise diet therapy, acupoint catgut + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to sports diet therapy (P < 0.05). Regarding weight loss, acupuncture treatment was superior to acupoint catgut embedding therapy (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to acupuncture and electroacupuncture treatment (P < 0.05); acupoint catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, and acupoint catgut embedding + moxibustion were superior to TCM treatment (P < 0.05); and acupoint catgut embedding, acupoint catgut embedding + acupuncture, catgut embedding + exercise diet therapy, acupoint catgut embedding + TCM, acupoint catgut embedding + moxibustion, and acupoint catgut embedding + cupping were superior to exercise diet therapy (P < 0.05). In terms of BMI reduction, acupoint catgut embedding + moxibustion and acupoint catgut embedding + cupping were more evident than acupuncture treatment (P < 0.05); and acupoint catgut embedding + moxibustion was more evident than electroacupuncture treatment (P < 0.05). Conclusion: Acupoint catgut embedding and its combination with other therapies are the first choice for the treatment of simple obesity.