[Charcoal-frying process and quality markers of Sanguisorbae Radix based on hemostatic effect].

Studies have reported that the hemostatic effect of Sanguisorbae Radix(SR) is significantly enhanced after processing with charcoal. However, the standard components(tannins and gallic acid) specified in the Chinese Pharmacopeia decrease in charcoal-fried Sanguisorbae Radix(CSR), which is contrast to the enhancement of the hemostatic effect. Therefore, this study aimed to optimize the charcoal-frying process of SR based on its hemostatic efficacy and comprehensively analyze the components of SR and its processed products, thus exploring the material basis for the hemostatic effect. The results indicated that SR processed at 250 ℃ for 14 min(14-min CSR) not only complied with the description in the Chinese Pharmacopeia but also demonstrated improved blood-coagulating and blood-adsorbing effects compared with raw SR(P<0.05). Moroever, 14-min CSR reduced the bleeding time in the rat models of tail snipping, liver bleeding, and muscle injury, surpassing both raw and excessively fried SR(16 min processed) as well as tranexamic acid(P<0.05). Ellagitannin, ellagic acid, methyl gallate, pyrogallic acid, protocatechuic acid, Mg, Ca, Mn, Cu, and Zn contributed to the hemostatic effect of CSR over SR. Among these substances, ellagitannin, ellagic acid, Mg, and Ca had high content in the 14 min CSR, reaching(106.73±14.87),(34.86±4.43),(2.81±0.23), and(1.21±0.23) mg·g~(-1), respectively. Additionally, the color difference value(ΔE~*ab) of SR processed to different extents was correlated with the content of the aforementioned hemostatic substances. In summary, this study optimized the charcoal-frying process as 250 ℃ for 14 min for SR based on its hemostatic effect. Furthermore, ellagic acid and/or the powder chromaticity are proposed as indicators for the processing and quality control of CSR.

Structural Basis of the Differential Function of the Two C. elegans Atg8 Homologs, LGG-1 and LGG-2, in Autophagy.

Multicellular organisms have multiple homologs of the yeast ATG8 gene, but the differential roles of these homologs in autophagy during development remain largely unknown. Here we investigated structure/function relationships in the two C. elegans Atg8 homologs, LGG-1 and LGG-2. lgg-1 is essential for degradation of protein aggregates, while lgg-2 has cargo-specific and developmental-stage-specific roles in aggregate degradation. Crystallography revealed that the N-terminal tails of LGG-1 and LGG-2 adopt the closed and open form, respectively. LGG-1 and LGG-2 interact differentially with autophagy substrates and Atg proteins, many of which carry a LIR motif. LGG-1 and LGG-2 have structurally distinct substrate binding pockets that prefer different residues in the interacting LIR motif, thus influencing binding specificity. Lipidated LGG-1 and LGG-2 possess distinct membrane tethering and fusion activities, which may result from the N-terminal differences. Our study reveals the differential function of two ATG8 homologs in autophagy during C. elegans development.

Clinicopathologic Features of Retroperitoneal Malignant Solitary Fibrous Tumors.

We aimed to explore the clinicopathologic and histologic characteristics, as well as the (differential) diagnosis of retroperitoneal malignant solitary fibrous tumors (RMSFTs) in this study. Nine cases of RMSFTs were recruited and identified by an experienced pathologist from the Pathology Department of Beijing Shijitan Hospital. Clinical information was extracted from medical records and obtained by phone calls. A systematic review of published literature on RMSFTs was conducted using PubMed. A pre-specified search strategy was adopted using the key words "solitary fibrous tumor" and "retroperitoneum." Case reports and literature published in the China Academic Journals (CNKI) and WAN FANG databases were also included. In total, 58 patients (33 males and 25 females) were included; their age ranged from 17 to 83 years, with a median age of 52 years. The tumor size ranged from 4 to 36 cm, and most patients had abdominal masses and pain. Of these patients, 56 underwent surgical resection, and two patients died and underwent an autopsy. All patients were followed up for up to 288 months (with a median follow-up of 36 months). RMSFTs are extremely rare. Their diagnosis mainly relies on the histological morphology and the expression profiles of a panel of pathologic molecules measured by immunohistochemistry. Diagnosis of RMSFTs is usually based on the expression of biomarkers such as vimentin, CD34, Bcl-2, CD99, and STAT6. Differential diagnosis includes spindle-shaped cell tumors, such as schwannoma, gastrointestinal stromal tumors, dermatofibrosarcoma protuberans, synovial sarcoma, malignant peripheral nerve sheath tumors, and fibrosarcoma. RMSFTs are prone to recur and even metastasize. Complete resection remains a major treatment, and close follow-up is highly recommended.

Low-dose chidamide restores immune tolerance in ITP in mice and humans.

Increased macrophage phagocytosis of antibody-coated platelets, as well as decreased numbers and/or impaired function of CD4+CD25+Foxp3+ regulatory T (Treg) cells, has been shown to participate in the pathogenesis of immune thrombocytopenia (ITP). Low-dose histone deacetylase inhibitors (HDACi's) are anti-inflammatory and immunomodulatory agents that can enhance immunosuppression in graft-versus-host disease by increasing the number and function of Foxp3+ Treg cells, but it is unclear whether they have the potential to promote immune tolerance and platelet release in ITP. In this study, we performed in vitro and in vivo experiments and found that a low-dose HDACi (chidamide) alleviated thrombocytopenia in passive and active murine models of ITP. Further, low-dose HDACi's attenuated macrophage phagocytosis of antibody-coated platelets, stimulated the production of natural Foxp3+ Treg cells, promoted the peripheral conversion of T cells into Treg cells, and restored Treg cell suppression in vivo and in vitro. Finally, we confirmed that low-dose HDACi's could regulate CTLA4 expression in peripheral blood mononuclear cells through modulation of histone H3K27 acetylation. Low-dose HDACi treatment in ITP could be offset by blocking the effect of CTLA4. Therefore, we propose that low-dose chidamide administration has potential as a novel treatment for ITP in the clinic.

Co-circulation of coxsackieviruses A-6, A-10, and A-16 causes hand, foot, and mouth disease in Guangzhou city, China.

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease occurring in children under 5 years of age worldwide, and Enterovirus A71 (EV-A71) and Coxsackievirus A16 (CVA-16) are identified as the predominant pathogens. In recent years, Coxsackievirus A6 (CVA-6) and Coxsackievirus A10 (CVA-10) have played more and more important role in a series of HFMD outbreaks. This study aimed to understand the epidemic characteristics associated with HFMD outbreak in Guangzhou, 2018. METHODS: The clinical and laboratory data of 1220 enterovirus-associated HFMD patients in 2018 were analysed in this study. Molecular diagnostic methods were performed to identify its serotypes. Phylogenetic analyses were depicted based on the complete VP1 gene. RESULTS: There were 21 enterovirus serotypes detected in Guangzhou in 2018. Three serotypes of enterovirus, CVA-6 (364/1220, 29.8%), CVA-10 (305/1220, 25.0%), and CVA-16 (397/1220, 32.5%), were identified as the causative pathogens and accounted for 87.3% among all 1220 HFMD patients. In different seasons, CVA-6 was the predominant pathogen of HFMD during autumn, and CVA-10 as well as CVA-16 were more prevalent in summer. Patients infected by CVA-6, CVA-10 or CVA-16 showed similar clinical features and laboratory characteristics, and the ratios of severe HFMD were 5.8, 5.9, and 1.5% in the three serotypes. Phylogenetic analyses of VP1 sequences showed that the CVA-6, CVA-10, and CVA-16 sequences belonged to the sub-genogroup E2, genogroup E, and genogroup B1, respectively. CONCLUSIONS: CVA-6, CVA-10, and CVA-16 were the predominant and co-circulated serotypes in Guangzhou China, 2018, which should be the new target for prevention and control of HFMD. Our findings provide useful information for diagnosis, treatment, and prevention of HFMD.

NQO1 C609T polymorphism is associated with esophageal cancer risk among Chinese: a meta-analysis.

NAD(P)H: quinone oxidoreductase 1 (NQO1) C609T gene polymorphism has been reported to influence the risk for esophageal cancer (EC) in many studies; however, the results remain controversial and ambiguous. We therefore carried out a meta-analysis of published case-control studies to investigate the association between NQO1 C609T polymorphism and EC susceptibility. Electronic searches were conducted on links between this variant and EC in several databases. Odds ratios (ORs) and 95% confidence intervals (CIs) for homozygous, dominant model, recessive model and allele were calculated to estimate the strength of associations in fixed and random effect models. Heterogeneity and publication bias were also assessed. A total of 11 case-control studies were identified, including1,619 cases and 2,101 controls. C allele was associated with a decreased susceptibility risk of EC compared with the T allele among Chinese (OR = 0.70; 95% CI = 0.59-0.84). The contrast of homozygotes and the recessive and dominant models produced the same pattern of results as the allele contrast. Our pooled data suggest a significant association exists between NQO1 C609T polymorphism and EC among Chinese.

IL-17A G197A and IL-17F T7488C polymorphisms and cancer risk in Asian populations: a meta-analysis.

PURPOSE: The association between Interleukin-17A (IL- 17A) G197A and IL-17F T7488C polymorphisms and risk for specific forms of cancer is inconclusive. We conducted a meta-analysis of all published studies to estimate the association of IL-17A G197A and IL-17F T7488C polymorphisms and cancer risk. METHODS: A systematic computerized searching of the PubMed and Web of Science databases was performed for relevant publications. Data were extracted and statistical analysis was performed using RevMan 5.2 software. RESULTS: Eight eligible case-control studies with 3,323 cases and 3,974 controls were included into this meta-analysis. The pooled odds ratios (ORs) showed that the IL-17A G197A polymorphism increased the risk for specific forms of cancer under the following genetic models: A vs G (OR = 1.31, 95 % CI 1.13-1.52, Ph - 0.02); AA vs GG (OR = 1.81, 95 % CI 1.30- 2.52, Ph = 0.007); AA /AG vs GG (OR = 1.26, 95 % CI 1.11- 1.43, Ph = 0.79); AA vs AG / GG (OR = 1.72, 95 % CI 1.16-2.53, Ph <0.0001). However, the IL-17F T7488C polymorphism did not increase or decrease cancer risk under all genetic models. Stratified analysis by cancer type revealed that the IL-17A G197A polymorphism may increase the risk of gastric cancer. Further subgroup analysis by country indicated that there was a statistically increased cancer risk in China. CONCLUSIONS: The present meta-analysis showed the IL- 17A G197A polymorphism is associated with a significantly increased risk for specific forms of cancer, especially in gastric cancer. Subsequent studies with large sample size are warranted to validate this association.

[Relationship between DTA Mutations and Thromboembolism in Patients with Myeloproliferative Neoplasms].

OBJECTIVE: To analyze the DTA (DNMT3A, TET2, ASXL1) mutations in patients with myeloproliferative neoplasms (MPN), and preliminarily explore their correlation with thromboembolism. METHODS: Clinical characteristics of 62 patients diagnosed de novo MPN at Central Hospital Affiliated to Shandong First Medical University from September 2016 to September 2022 were retrospectively analyzed. Next-generation sequencing was used to detect 35 MPN-related genes, and the DTA mutations in MPN patients and their relationship with thromboembolic events were analyzed. RESULTS: 75.8% (47/62) of the patients presented pathogenic non-driver mutations, and the mean number of pathogenic non-driver mutations per patient was 1.08. Among them, the most frequently mutated non-driver genes were TET2 (38.7%, 24/62), DNMT3A (9.7%, 6/62) and ASXL1 (6.5%, 4/62). The presence of DTA gene mutations was 50% (31/62) in the total MPN patients, and mainly accompanied by driver mutations. The mutation rate of DTA in patients aged ≥60 years was significantly higher than that in patients <60 years old (P =0.039). The incidence of thromboembolism in patients with DTA mutation was 58.1% (18/31), which was significantly higher than that in patients without DTA mutation (19.4%, 6/31) (P =0.002). The TET2 gene mutation rate in MPN patients with thromboembolism was 66.7% (16/24), which was significantly higher than that in patients without thromboembolism (21.1%, 8/38) (P =0.00). CONCLUSION: Patients with MPN have a higher incidence of DTA mutations, which are mainly accompanied by driver gene mutations. The incidence of thromboembolism in MPN patients with DTA mutations is higher than that in patients without DTA mutations. Especially, the elderly (≥60 years) essential thrombocythemia(ET) and polycythemia vera(PV) patients with TET2 mutation should be vigilant for thromboembolic events.

Inundative practice for screening siRNA management candidates against a notorious predatory beetle using olfactory silencing.

Calosoma maximoviczi, a predatory pest beetle, poses a significant threat to wild silk farm production due to its predation on wild silkworms. Given the coexistence of this species with beneficial silkworms in the farm orchards, chemical pesticides are not an ideal solution for controlling its population. In this study, we employed a comprehensive multi-target RNA interference (RNAi) approach to disrupt the olfactory perception of C. maximoviczi through independently silencing 16 odorant receptors (ORs) in the respective genders. Specifically, gene-specific siRNAs were designed to target a panel of ORs, allowing us to investigate the specific interactions between odorant receptors and ligands within this species. Our investigation led to identifying four candidate siOR groups that effectively disrupted the beetle's olfactory tracking of various odorant ligands associated with different trophic levels. Furthermore, we observed sex-specific differences in innate RNAi responses reflected by subsequent gene expression, physiological and behavioral consequences, underscoring the complexity of olfactory signaling and emphasizing the significance of considering species/sex-specific traits when implementing pest control measures. These findings advance our understanding of olfactory coding patterns in C. maximoviczi beetles and establish a foundation for future research in the field of pest management strategies.

Inhibitory effects of rosiglitazone on paraquat-induced acute lung injury in rats.

AIM: To investigate the effects of the PPAR-γ agonist rosiglitazone on acute lung injury induced by the herbicide paraquat (PQ) and the underlying mechanisms of action. METHODS: Male Sprague-Dawley rats were injected with PQ (20 mg/kg, ip). Rosiglitazone (3 or 10 mg/kg, ip) was administered 1 h before PQ exposure. Peripheral blood was collected at 4, 8, 24 and 72 h after PQ exposure for measuring the levels of MDA, TNF-α and IL-1ß, and the SOD activity. Lung tissues were collected at 72 h after PQ exposure to determine the wet-to-dry (W/D) ratios and lung injury scores, as well as the protein levels of NF-κBp65, PPAR-γ, Nrf2, IκBα and pIκBα. RESULTS: At 72 h after PQ exposure, the untreated rats showed a 100% cumulative mortality, whereas no death was observed in rosiglitazone-pretreated rats. Moreover, rosiglitazone pretreatment dose-dependently attenuated PQ-induced lung edema and lung histopathological changes. The pretreatment significantly reduced the levels of TNF-α, IL-1ß and MDA, increased SOD activity in the peripheral blood of PQ-treated rats. The pretreatment also efficiently activated PPAR-γ, induced Nrf2 expression and inhibited NF-κB activation in the lung tissues of PQ-treated rats. Furthermore, the pretreatment dose-dependently inhibited IκB-α degradation and phosphorylation, thus inhibiting NF-κB activation. CONCLUSION: Pretreatment with rosiglitazone protects rats against PQ-induced acute lung injury by activating PPAR-γ, inducing Nrf2 expression and inhibiting NF-κB activation.

[Challenges and strategies of drug innovation].

Drug research involves scientific discovery, technological inventions and product development. This multiple dimensional effort embodies both high risk and high reward and is considered one of the most complicated human activities. Prior to the initiation of a program, an in-depth analysis of "what to do" and "how to do it" must be conducted. On the macro level, market prospects, capital required, risk assessment, necessary human resources, etc. need to be evaluated critically. For execution, drug candidates need to be optimized in multiple properties such as potency, selectivity, pharmacokinetics, safety, formulation, etc., all with the constraint of finite amount of time and resources, to maximize the probability of success in clinical development. Drug discovery is enormously complicated, both in terms of technological innovation and organizing capital and other resources. A deep understanding of the complexity of drug research and our competitive edge is critical for success. Our unique government-enterprise-academia system represents a distinct advantage. As a new player, we have not heavily invested in any particular discovery paradigm, which allows us to select the optimal approach with little organizational burden. Virtue R&D model using CROs has gained momentum lately and China is a global leader in CRO market. Essentially all technological support for drug discovery can be found in China, which greatly enables domestic R&D efforts. The information technology revolution ensures the globalization of drug discovery knowledge, which has bridged much of the gap between China and the developed countries. The blockbuster model and the target-centric drug discovery paradigm have overlooked the research in several important fields such as injectable drugs, orphan drugs, and following high quality therapeutic leads, etc. Prejudice against covalent ligands, prodrugs, nondrug-like ligands can also be taken advantage of to find novel medicines. This article will discuss the current challenges and future opportunities for drug innovation in China.

Gastric and intestinal ectopic pancreas: Two case reports.

BACKGROUND: Ectopic pancreas may be unfamiliar to many people because it is rare and difficult to diagnose. However, this disease is highly susceptible to misdiagnosis and missed diagnosis. In this article, we report two cases of pancreatic heterotopia in the gastric sinus and small intestine, respectively, both of which were confirmed by histopathological examination. CASE SUMMARY: The first patient was a 43-year-old female which reported abdominal distension for 2 mo. The second was a 67-year-old female who experienced intermittent epigastric discomfort for 15 d. In both cases, there was no confirmed preoperative examination, and the postoperative pathology indicated the presence of ectopic pancreas. CONCLUSION: The diagnosis of ectopic pancreas is difficult, and is often prone to misdiagnosis and the possibility of being overlooked. Various laboratory tests and imaging tests should be carefully evaluated before surgery to achieve early detection, early diagnosis and early treatment.

Targeting ATAD3A-PINK1-mitophagy axis overcomes chemoimmunotherapy resistance by redirecting PD-L1 to mitochondria.

Only a small proportion of patients with triple-negative breast cancer benefit from immune checkpoint inhibitor (ICI) targeting PD-1/PD-L1 signaling in combination with chemotherapy. Here, we discovered that therapeutic response to ICI plus paclitaxel was associated with subcellular redistribution of PD-L1. In our immunotherapy cohort of ICI in combination with nab-paclitaxel, tumor samples from responders showed significant distribution of PD-L1 at mitochondria, while non-responders showed increased accumulation of PD-L1 on tumor cell membrane instead of mitochondria. Our results also revealed that the distribution pattern of PD-L1 was regulated by an ATAD3A-PINK1 axis. Mechanistically, PINK1 recruited PD-L1 to mitochondria for degradation via a mitophagy pathway. Importantly, paclitaxel increased ATAD3A expression to disrupt proteostasis of PD-L1 by restraining PINK1-dependent mitophagy. Clinically, patients with tumors exhibiting high expression of ATAD3A detected before the treatment with ICI in combination with paclitaxel had markedly shorter progression-free survival compared with those with ATAD3A-low tumors. Preclinical results further demonstrated that targeting ATAD3A reset a favorable antitumor immune microenvironment and increased the efficacy of combination therapy of ICI plus paclitaxel. In summary, our results indicate that ATAD3A serves not only as a resistant factor for the combination therapy of ICI plus paclitaxel through preventing PD-L1 mitochondrial distribution, but also as a promising target for increasing the therapeutic responses to chemoimmunotherapy.

Morphology and deformity of the shoulder and pelvis in the entire spine radiographs of adolescent idiopathic scoliosis.

Background: To investigate the deformity and asymmetry of the shoulder and pelvis in adolescent idiopathic scoliosis (AIS) patients. Methods: This retrospective cross-sectional study enrolled 223 AIS patients with a right thoracic curve or left thoracolumbar/lumbar curve who underwent spine radiographs at the Third Hospital of Hebei Medical University between November 2020 and December 2021. The following parameters were measured: Cobb angle, clavicular angle, glenoid obliquity angle, acromioclavicular joint deviation, femoral neck-shaft projection angle, iliac obliquity angle, acetabular obliquity angle, coronal trunk deviation distance, and spinal deformity deviation distance. The Mann-Whitney U test, Kruskal-Wallis H test were used for inter-group comparisons, and Wilcoxon signed-rank test were used for intra-group left and right sides comparisons. Results: Shoulder and pelvic imbalances were found in 134 and 120 patients, respectively, and there were 87, 109, and 27 cases of mild, moderate, and severe scoliosis, respectively. Compared with mild scoliosis patients, the difference in the acromioclavicular joint offset on bilateral sides was significantly increased in moderate and severe scoliosis [11.04, 95% confidence interval (CI): 0.09-0.14 for mild, 0.13-0.17 for moderate, and 0.15-0.27 for severe scoliosis, P=0.004], and the difference in the femoral neck-shaft projection angle on bilateral sides was significantly enhanced with scoliosis aggravation (14.14, 95% CI: 2.34-3.41 for mild, 3.00-3.94 for moderate, and 3.57-6.43 for severe scoliosis, P=0.001). The acromioclavicular joint offset was significantly larger on the left than that on the right in patients with a thoracic curve or double curves (thoracic curve -2.75, 95% CI: 0.57-0.69 for the left and 0.50-0.63 for the right, P=0.006; double curve -3.27, 95% CI: 0.60-0.77 for the left and 0.48-0.65 for the right, P=0.001). The femoral neck-shaft projection angle was significantly larger on the left than right in patients with a thoracic curve (-4.46, 95% CI: 133.78-136.20 for the left and 131.62-134.01 for the right, P<0.001), but larger on the right than left in patients with thoracolumbar/lumbar curve (thoracolumbar -2.98, 95% CI: 133.75-136.70 for the left and 135.13-137.82 for the right, P=0.003; lumbar -3.24, 131.97-134.56 for the left and 133.76-136.26 for the right, P=0.001). Conclusions: In AIS patients, shoulder imbalance has a greater impact on coronal balance and spinal scoliosis above the lumbar segment, whereas pelvic imbalance has a greater impact on sagittal balance and spinal scoliosis below the thoracic segment.

At-line monitoring of key parameters of nisin fermentation by near infrared spectroscopy, chemometric modeling and model improvement.

An analytical procedure has been developed for at-line (fast off-line) monitoring of 4 key parameters including nisin titer (NT), the concentration of reducing sugars, cell concentration and pH during a nisin fermentation process. This procedure is based on near infrared (NIR) spectroscopy and Partial Least Squares (PLS). Samples without any preprocessing were collected at intervals of 1 h during fifteen batch of fermentations. These fermentation processes were implemented in 3 different 5 l fermentors at various conditions. NIR spectra of the samples were collected in 10 min. And then, PLS was used for modeling the relationship between NIR spectra and the key parameters which were determined by reference methods. Monte Carlo Partial Least Squares (MCPLS) was applied to identify the outliers and select the most efficacious methods for preprocessing spectra, wavelengths and the suitable number of latent variables (n (LV)). Then, the optimum models for determining NT, concentration of reducing sugars, cell concentration and pH were established. The correlation coefficients of calibration set (R (c)) were 0.8255, 0.9000, 0.9883 and 0.9581, respectively. These results demonstrated that this method can be successfully applied to at-line monitor of NT, concentration of reducing sugars, cell concentration and pH during nisin fermentation processes.

Encephalic Schistosoma japonicum resembles brainstem neoplasm: Case report and literature review.

Encephalic schistosomiasis is a rare and severe parasitic disease which manifests as granuloma formation around ectopic eggs that migrate to the brain. We present a rare case of a pseudotumoral form of Schistosoma japonicum in the brainstem that was initially misidentified as a malignant tumor. The patient presented with intermittent headaches, diplopia, and left limb weakness. Neurological examination revealed hypoesthesia of the left lower limb, limitation of right eye abduction, and decreased muscle strength of the left upper limb. The cerebrospinal fluid tested positive for antibodies against S. japonicum. After standard treatment for schistosomiasis, the patient achieved complete remission. This case highlights that encephalic schistosomiasis can occur in the brainstem and resemble a neoplasm on magnetic resonance imaging. Once diagnosed, however, complete remission is achievable by non-invasive medical treatment.

Prevalence of antimicrobial resistance among Salmonella isolates from chicken in China.

We evaluated the antimicrobial resistance of Salmonella isolated in 2008 from a chicken hatchery, chicken farms, and chicken slaughterhouses in China. A total of 311 Salmonella isolates were collected from the three sources, and two serogroups of Salmonella were detected, of which 133 (42.8%) consisted of Salmonella indiana and 178 (57.2%) of Salmonella enteritidis. The lowest percentage of S. indiana isolates was found in the chicken hatchery (4.2%), followed by the chicken farms (54.9%) and the slaughterhouses (71.4%). More than 80% of the S. indiana isolates were highly resistant to ampicillin (97.7%), amoxicillin/clavulanic acid (87.9%), cephalothin (87.9%), ceftiofur (85.7%), chloramphenicol (84.9%), florfenicol (90.9%), tetracycline (97.7%), doxycycline (98.5%), kanamycin (90.2%), and gentamicin (92.5%). About 60% of the S. indiana isolates were resistant to enrofloxacin (65.4%), norfloxacin (78.9%), and ciprofloxacin (59.4%). Of the S. indiana isolates, 4.5% were susceptible to amikacin and 5.3% to colistin. Of the S. enteritidis isolates, 73% were resistant to ampicillin, 33.1% to amoxicillin/clavulanic acid, 66.3% to tetracycline, and 65.3% to doxycycline, whereas all of these isolates were susceptible to the other drugs used in the study. The S. indiana isolates showed resistance to 16 antimicrobial agents. Strains of Salmonella (n = 108) carrying the resistance genes floR, aac(6')-Ib-cr, and bla(TEM) were most prevalent among the 133 isolates of S. indiana, at a frequency of 81.2%. The use of pulsed-field gel electrophoresis to analyze the S. indiana isolates that showed similar antimicrobial resistance patterns and carried resistance genes revealed six genotypes of these organisms. Most of these isolates had the common pulsed-field gel electrophoresis patterns found in the chicken hatchery, chicken farms, and slaughterhouses, suggesting that many multidrug-resistant isolates of S. indiana prevailed in the three sources. Some of these isolates were not derived from a specific clone, but represented a variety of genotypes of S. indiana.

[Effects of hyperbaric oxygen therapy in the management of chronic wounds and its correlation with CD34(+) endothelial progenitor cells].

OBJECTIVE: To evaluate the effects of hyperbaric oxygen (HBO) therapy in the management of chronic wound and observe the correlation between wound healing and CD34+ endothelial progenitor cells (EPCs). METHODS: A total of 119 patients with chronic wound in lower extremities lasting > 3 months were recruited for this randomized, single-center, placebo-controlled clinical trial. The changes of CD34+ average count before and after HBO therapy were detected by flow cytometry (FACS). There were 97 patients on long-term HBO therapy and in 22 patients on hyperbaric air therapy as control group. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell were determined respectively by FACs. The outcomes of two groups were compared. Treatment was administered within a single-place hyperbaric chamber for 90-min daily (session duration 120 min) for 5 days a week for 4 weeks (20 treatment sessions). RESULTS: The wound size decreased at the 4-week end point (62.7% ± 22.3% in the HBO group vs 34.4% ± 20.6% in the control group, P < 0.05). After 10 episodes of HBO therapies for chronic non-healing wound, the peripheral CD34+ EPCs average count rose from 0.24% ± 0.03% at pre-treatment to 1.32% ± 0.05% while the number was 1.75% ± 0.17% after 20 episodes of HBO (P < 0.05). Both were significantly different from that of the patients at pre-treatment. However the overall circulating white cell count was not significantly elevated. The CD34/Scal-1+ and CD34/CXCR4 dual-positive populations of gated cell in HBO group were 5.8 and 5.2 folds than those at pre-treatment respectively. The number of EPCs was positively correlated with wound healing in lower extremities (correlation coefficient 0.84; P < 0.01). CONCLUSION: Adjunctive treatment of HBO facilitates the healing of chronic non-healing wound in selected patients through the mobilization of EPCs.

Long noncoding RNA SNHG3 promotes glioma tumorigenesis by sponging miR-485-5p to upregulate LMX1B expression.

LIM homeobox transcription factor 1-beta (LMX1B) has recently been found to be highly expressed in advanced gliomas and is associated with poor survival. However, the regulatory molecular mechanism of LMX1B expression in gliomas remains unclear. In this study, bioinformatics analysis showed that miR-485-5p may be the potential upstream regulator of LMX1B, and long noncoding RNA (lncRNA) small nucleolar RNA host gene 3 (SNHG3) may function as a competitive endogenous RNA to sponge miR-485-5p. In addition, the expression of SNHG3 and LMX1B in advanced glioma tissues was significantly upregulated, while the expression of miR-485-5p was significantly downregulated. SNHG3 overexpression reduced the expression of miR-485-5p; increased the expression of LMX1B; and promoted the proliferation, migration, and invasion of glioma cells. In contrast, miR-485-5p overexpression reduced the expression of LMX1B and inhibited cell proliferation, migration, and invasion. The luciferase reporter assay and RNA immunoprecipitation assay further confirmed the interaction between SNHG3 and miR-485-5p and between miR-485-5p and LMX1B. In addition, subcutaneous and orthotropic xenograft models confirmed that lncRNA SNHG3 silencing or miR-485-5p overexpression significantly reduced the growth of glioma xenografts and prolonged survival time. These results indicate that lncRNA SNHG3 can regulate the expression of LMX1B by sponging miR-485-5p, thereby promoting the proliferation, migration, and invasion of glioma cells. This study provides the first evidence that the SNHG3/miR-485-5p/LMX1B axis is involved in glioma tumorigenesis and highlights the potential of SNHG3 and miR-485-5p as therapeutic targets for glioma.

Fine tuning of medium chain fatty acids levels increases fruity ester production during alcoholic fermentation.

Pichia fermentans Z9Y-3 and its intracellular enzymes were inoculated along with S. cerevisiae in synthetic grape must to modulate fruity ester production. The levels of ester-related enzymes, ester precursors, and fruity esters were monitored every 24 h during fermentation. Results showed that the levels of ethyl acetate, acetate higher alcohol esters (AHEs), short chain fatty acid ethyl esters (SFEs), and medium chain fatty acid ethyl esters (MFEs) were significantly enhanced in mixed fermentation. Pearson correlation analysis further revealed that higher alcohols and fatty acids played a more important role in fruity ester production than enzymes; Particularly, the correlation coefficient between fatty acids and MFEs was 0.940. In addition, supplementation of medium chain fatty acids (7.2 mg/L) at the metaphase of single S. cerevisiae fermentation improved ethyl acetate, AHE, SFE, and MFE production by 42.56%, 21.00%, 61.33%, and 90.04%, respectively, although the high level of ethyl acetate might result in off-flavors.