Bioactivity and genome analysis of Bacillus amyloliquefaciens GL18 isolated from the rhizosphere of Kobresia myosuroides in an alpine meadow.

The unique eco-environment of the Qinghai-Tibet Plateau breeds abundant microbial resources. In this research, Bacillus amyloliquefaciens GL18, isolated from the rhizosphere of Kobresia myosuroides from an alpine meadow, and the antagonistic activity, bacteriostatic hydrolase activity, and low temperature, salt, and drought resistance of it were determined and analysed. The seedlings of Avena sativa were root-irrigated using bacteria suspensions (cell concentration 1 × 107 cfu/mL) of GL18, and the growth-promoting effect of GL18 on it was determined under cold, salt and drought stress, respectively. The whole genome of GL18 was sequenced, and its functional genes were analysed. GL18 presented significant antagonistic activity to Fusarium graminearum, Fusarium acuminatum, Fusarium oxysporum and Aspergillus niger (inhibition zone diameter > 17 mm). Transparent zones formed on four hydrolase detection media, indicating that GL18 secreted cellulase, protease, pectinase and ß-1,3-glucanase. GL18 tolerated conditions of 10 °C, 11% NaCl and 15% PEG-6000, presenting cold, salt and drought resistance. GL18 improved the cold, salt and drought tolerance of A. sativa and it showed significant growth effects under different stress. The total length of the GL18 genome was 3,915,550 bp, and the number of coding DNA sequence was 3726. Compared with the clusters of orthologous groups of proteins, gene ontology and kyoto encyclopedia of genes and genomes databases, 3088, 2869 and 2357 functional genes were annotated, respectively. GL18 contained gene clusters related to antibacterial substances, functional genes related to the synthesis of plant growth-promoting substances, and encoding genes related to stress resistance. This study identified an excellent Bacillus strain and provided a theoretical basis for improving stress resistance and promoting the growth of herbages under abiotic stress.

MicroRNA-137 inhibits pituitary prolactinoma proliferation by targeting AKT2.

PURPOSE: Prolactinoma is the most common type of pituitary adenoma. Most prolactinoma need medical treatment, but some of them are aggressive and require surgery. In previous decades, some miRNAs have been manifested as oncogenes or tumor suppressors. Consequently, miRNAs' abnormal expression involves tumorigenesis, invasion, and metastasis of different types of tumors, including pituitary tumors. The current study aim to explore the aggressiveness-associated miRNAs in prolactinoma and underlying molecular mechanisms based on the bioinformatic analysis and fundamental experiment studies. METHODS: GSE46294 miRNA expression profile from the Gene Expression Omnibus (GEO) database was downloaded. Differentially expressed miRNAs (DEMs) were filtered from this data. Subsequently, the target genes of downregulated miRNAs were analyzed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RT-qPCR, western blot, and CCK-8 assays were used to validate the effect of miR-137 on the proliferation of MMQ cells through AKT2. Finally, the binding site of rat miR-137 to AKT2 were predicted by Targetscan and Bibiserv database, and verified by double luciferase reporter assay. RESULTS: Twenty-four changed DEMs (fourteen upregulated and ten downregulated) were identified. Target genes of downregulated DEMs were classified into three groups by GO terms. KEGG pathway enrichment analysis revealed these target genes enriched in the PI3K-Akt pathway. We also confirmed that miR-137 can target AKT2 and inhibit the proliferation of MMQ cells induced by AKT2. CONCLUSION: MiR-137 suppressed prolactinomas' aggressive behavior by targeting AKT2.

Strategies for patients with recurrent nasopharyngeal carcinoma involved internal carotid artery who are intolerant to embolization.

BACKGROUND: The surgical treatment of recurrent nasopharyngeal carcinoma (rNPC) involving the internal carotid artery (ICA) is challenging, as the massive bleeding caused by intraoperative rupture of the ICA is life-threatening. We reported that ICA embolization is an effective pretreatment to avoid fatal bleeding, but some patients cannot tolerate the procedure. We used endovascular vascular protection (ICA stents), vascular sacrifice (bypass grafting) and extravascular vascular protection (transcervical external stent placement) of the ICA to provide alternative options for these patients. METHODOLOGYy: This study enrolled patients with rNPC adjacent to or invading the ICA who were unsuitable for ICA embolization from January 2015 to June 2020. ICA pretreatment combined with endoscopic nasopharyngectomy (ENPG) was performed for the 30 patients. We report the survival outcome and incidence of complications after ICA pretreatment. RESULTS: ICA pretreatment was performed for the 30 enrolled patients, among whom 8 underwent endoscopic-assisted transcervical protection of the parapharyngeal ICA combined with ENPG, 6 underwent bypass grafting, and 16 underwent ICA stent implantation followed by ENPG. After pretreatment, at a median follow-up of 43 months (range, 2-80 months), the 3-year locoregional overall survival (OS), progression-free survival (PFS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) were 62.9%, 61.3%, 70.2%, and 71.4%, respectively. CONCLUSIONS: ICA pretreatment combined with salvage ENPG enables the feasible and effective resection of rNPC lesions involving the ICA in patients who cannot tolerate ICA embolization. Therefore, this treatment may be an effective method for improving outcomes. Multidisciplinary therapy is needed to reduce operation-related complications.

Stent pretreatment for internal carotid artery exposed to necrotic lesions in nasopharyngeal carcinoma.

BACKGROUND: Post radiation nasopharyngeal necrosis (PRNN) invading the internal carotid artery (ICA) contributes to the death of 69.2-72.7% of PRNN patients. ICA occlusion is an effective treatment to avoid fatal bleeding, while some patients are intolerant. We present a novel method that allows for these patients without interrupting blood flow through the ICA. METHODOLOGY: This study enrolled patients with PRNN-invaded ICA who were not suitable for ICA occlusion from April 2020 to November 2022. ICA stent pretreatment was performed in the 36 patients and followed the endoscopic nasopharyngectomy (ENPG) or conservative treatment for PRNN. We report the survival outcome and incidence of complications after stent implantation and compare the survival outcomes of ENPG and conservative treatment for PRNN followed by stent implantation. RESULTS: ICA stent pretreatment was performed in the 36 enrolled patients, among which 14 underwent ENPG, and 22 received conservative treatment. 27.8% patients died after a median follow-up of 15 months. The Kaplan-Meier estimates of overall survival were higher in the ENPG group than in the conservative treatment group. Karnofsky performance status (KPS) was significantly higher in the ENPG group than in the non-ENPG group. CONCLUSIONS: The innovative application of ICA stents is a promising treatment to improve outcomes in patients with PRNN invading the ICA who are unsuitable for ICA embolization, especially when followed by endoscopic surgery. However, methods to avoid postoperative cerebral ischemia and nasopharyngeal hemorrhage still require further study.

[Effects of subanesthetic dose of esketamine on opioid consumption after thoracoscopic surgery].

Objective: To investigate the effect of continuous intravenous infusion of subanesthetic dose of esketamine intraoperatively on postoperative opioid consumption in patients undergoing thoracoscopic surgery. Methods: A total of 71 patients with elective thoracoscopic lung surgery in the First Affiliated Hospital of Zhengzhou University from December 2020 to December 2021 were selected. Patients who were classified as grade Ⅰ or Ⅱ by the American Society of Anesthesiologists (ASA) and aged 18-70 years were included, including 32 males and 39 females, with a body mass index (BMI) of 18.5-30.0 kg/m2. The patients were randomly divided into three groups: (1) Control group (group C, n=24): continuous intravenous infusion of normal saline at the same rate during surgery; (2) Subanesthetic dose of esketamine 0.125 mg·kg-1·h-1 group (group ES1, n=23): continuous intravenous infusion of esketamine at a rate of 0.125 mg·kg-1·h-1 during surgery; (3) Subanesthetic dose of esketamine 0.250 mg·kg-1·h-1 group (group ES2, n=24): continuous intravenous infusion of esketamine at a rate of 0.250 mg·kg-1·h-1 during surgery. The main outcome measures were the total consumptions of hydromorphone of 3 groups within 24 and 48 hours after surgery. The secondary outcome measures were the extubation time, length of postanesthesia care unit (PACU) stay, the time of first feeding, and the incidences of adverse effects within 24 h after surgery in 3 groups. Results: The 24 h postoperative consumption of hydromorphone in group C, ES1 and ES2 was (5.4±1.0) mg, (4.5±1.5) mg and (4.0±0.8) mg, respectively. Likewise, the 48 h postoperative consumption of hydromorphone was (9.7±2.2) mg, (9.0±3.0) mg and (7.7±1.8) mg, respectively. Compared with group C, the 24 h postoperative hydromorphone consumptions were significantly reduced in group ES1 and ES2 (both P<0.05). The extubation time, length of PACU stay and the time of first feeding after surgery in group C were (23±10) min,(70±12) min,(17±3) h,in group ES1 were (22±4) min,(69±11) min,(14±5) h,in group ES2 were (16±8) min,(58±12) min,(14±3) h, respectively. Compared with group C and group ES1, both of the extubation time and length of PACU stay were shortened in group ES2 (both P<0.05). Compared with group C, the first postoperative feeding time of group ES1 and ES2 was shortened (both P<0.05). There were no differences in the incidences of adverse effects at postoperative 24 h among 3 groups (all P>0.05). Conclusion: Continuously intravenous infusion of subanesthetic esketamine at a rate of 0.250 mg·kg-1·h-1 can significantly reduce the postoperative opioid consumption and improve the patient's outcomes.

[Clinicopathological features of pulmonary epithelioid hemangioendothelioma: a study of 18 cases].

Objective: To investigate the clinicopathological features of pulmonary epithelioid hemangioendothelioma (PEHE). Methods: Eighteen cases of PEHE were collected from August 2011 to December 2018 at the First Affiliated Hospital of Zhengzhou University. All cases were retrospectively studied by hematoxylin and eosin staining and immunohistochemistry (IHC). The clinicopathological features were reviewed; the status of CAMTA1 and TFE3 gene was analyzed and patients' outcome was followed up. Results: Of the 18 cases, there were 11 males and 7 females with a male to female ratio of 1.6 to 1.0. The patients' age ranged from 36 to 68 years (mean 52 years). Twelve cases (12/18) showed a single nodule and six cases (6/18) showed multiple bilateral nodules. Seven cases (7/18) involved other organs besides lung. Seventeen (17/18) patients presented with respiratory symptoms and one patient (1/18) presented with abdominal pain. Grossly, the tumors were greyish-white nodules with indistinct borders. Microscopically the tumor cells were epithelioid and arranged in strands and nests, and cytoplasmic vacuoles were commonly noted. The stroma was myxochondroid or hyaline. By IHC, the tumor cells were positive for CD31(18/18), CD34 (16/18), ERG (18/18) and Fli-1 (18/18); CKpan was focally positive in 5 cases (5/18). TFE3 was positive in 3 cases (3/18), and Ki-67 index ranged from 5% to 30%. FISH analysis showed seventeen cases (17/18) had CAMAT1 rearrangement, one case had TFE3 rearrangement displaying a split signal. Eight patients (8/18) had surgical excision, three patients (3/18) had surgery and chemotherapy, and seven patients (7/18) had chemotherapy only. Four patients (4/18) died of the disease. Conclusions: Patients with PEHE have non-specific symptoms, and correct diagnosis depends on pathologic biopsy and the exclusion of other tumors with epithelioid morphology. Some patients with PEHE have poor prognosis, particularly in those who have multiple nodules, peripheral invasion or metastasis.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

[Clinicopathological features and prognostic factors of primary pulmonary adenoid cystic carcinoma: a study of 59 cases].

Objective: To investigate the clinicopathological features and prognostic indicators of primary pulmonary adenoid cystic carcinoma. Methods: Fifty-nine cases of primary pulmonary adenoid cystic carcinoma were collected from August 2011 to December 2017 at the First Affiliated Hospital of Zhengzhou University. All cases were retrospectively studied by hematoxylin-eosin staining and immunohistochemistry. The clinicopathological features were reviewed and patient survival analysis was performed using Kaplan-Meier method and Cox regression model. Status of epidermal growth factor receptor (EGFR), KRAS, BRAF genes was analyzed in 15 of the 59 study cases. Results: Among 59 cases, there were 25 males and 34 females with male to female ratio of 1.0 to 1.4. The patient age ranged from 29 to 81 years with a mean age of 55 years. The tumor max diameters ranged from 1.0 to 9.6 cm with an average diameter of 2.8 cm. Fifteen (25.4%) patients were smokers while 44 patients (74.6%) were non-smokers. Tumors predominantly occurred in the trachea (28/59,47.5%), the left main bronchus (7/59,11.9%) and the right bronchus (5/59,8.5%). Grossly, the tumors were well circumscribed, greyish-white nodules. Microscopically the tumor cells were small and uniform, and arranged in tubular, cribriform, and solid patterns. Immunohistochemistry showed that the tumor cells were positive for CK7, S-100 protein, Sox-10, CD117 and p63. TTF1 was only positive in 2 cases and Ki-67 index ranged from 3% to 40%. Eighteen cases (30.5%) were gradeⅠ, 26 cases (40.1%) grade Ⅱ, and 15 cases (25.4%) grade Ⅲ. Overall, 39 cases (66.1%), 7 cases (11.9%), 10 cases (16.9%), and 3 cases (5.1%) were at stages Ⅰ, Ⅱ, Ⅲ, and Ⅳ, respectively. Twenty-three patients (39.0%) received surgical therapy, 3 patients (5.1%) surgery combined with radiotherapy, 9 patients (15.2%) surgery combined with chemotherapy, and 24 cases (40.7%) chemotherapy only. No mutation of EGFR, KRAS and BRAF was detected in all 15 tested cases. The overall survival rate at the first, third and fifth years was 94.9%, 86.4% and 84.7%, respectively. Prognostic analysis showed that patient's age and tumor size were statistically associated with the survival (P<0.05). Conclusions: Majority of the patients with primary pulmonary adenoid cystic carcinoma are at an early clinical stage with a favorable prognosis. The size of the tumor and the age of the patients are independent prognostic indicators.

[Tracheobronchopathia osteochondroplastica: a clinicopathological analysis of 18 cases].

Objective: To investigate the clinical symptoms, imaging features, pathologic manifestations and diagnosis of tracheobronchopathia osteochondroplastica (TO). Methods: The clinical data, imaging and pathologic features and outcome of 18 TO patients diagnosed at the First Affiliated Hospital of Zhengzhou University from August 2011 to August 2018 were collected and analyzed. Results: The 18 TO patients included 10 males and 8 females; patients' age range was 31 to 64 years (mean 52 years). Six patients (6/18) were smokers. The main presenting clinical symptoms included cough in 15 cases, expectoration in eight cases (8/18), hemoptysis in five cases (5/18), chest tightness in four cases, wheezing in three cases and chest pain in two cases. The time interval between the initial symptoms and diagnosis was 1.5 to 360.0 months, and the average time interval was 45.2 months. Blood calcium and phosphorus were normal in 18 patients (18/18). Chest X-ray showed no direct evidence of TO. Six patients (6/18) showed irregular changes in the trachea or bronchial wall by chest CT scan. Three patients (3/18) had mild ventilatory obstruction. TO was classified as: 10 cases (10/18) were scattered type, seven cases (7/18) were diffuse type and one case (1/18) was confluent type. Epithelial squamous metaplasia, submucosal cartilage, submucosal ossification and hematopoietic bone marrow within the ossified areas were the characteristic histopathologic findings of TO. Conclusions: TO is a rare benign disorder that shows atypical presentation. CT scan is insensitive, the histopathology shows submucosal cartilage or ossification. TO should be diagnosed by comprehensive consideration of clinical symptoms, imaging and pathology.

Identification and diversity of Y-chromosome haplotypes in Qinghai yak populations.

The aim of the present study was to perform a preliminary analysis of the characterization and diversity of Y-chromosome haplotypes/haplogroups in yak of Qinghai Province, China. A total of 322 male yaks from nine populations belonging to three officially recognized breeds (Gaoyuan, Huanhu and Datong) were sampled. Animals were genotyped using six previously reported Y-SNPs present in the SRY, USP9Y, UTY, AMELY and OFD1Y genes and four new Y-SNPs in the OFD1Y gene (g.569A>C, g.578A>C, g.608G>T and g.653G>C) identified in this study. Seven Y-chromosome haplotypes (H1-H7) were identified according to the combination of the 10 Y-SNPs. H1, H2 and H6 were the most common and shared haplotypes across all yak populations/breeds. Private haplotypes H3 and H7 were detected in the Datong breed; H4 in Guoleimude, Qumalai, Qilian, Tianjun and Ganglong populations; and H5 in Qumalai of Gaoyuan breed. Haplotype clustering and network analyses inferred two haplogroups, Y1 and Y2, indicating two divergent lineages of paternal origins of Qinghai yak. The analysis of molecular variance showed a significant difference among individuals (P < 0.0001) with more than 93% of the total genetic variation present within populations, suggesting a weak genetic structure among Qinghai yak populations. The overall Y-haplotype diversity was 0.538 ± 0.028, showing a relatively high diversity in Qinghai yak. The Gaoyuan and Datong breeds had similar haplotype diversities (0.547 ± 0.030 and 0.553 ± 0.083, respectively), which were higher than that of the Huanhu breed (0.441 ± 0.098). Our results support the conservation and sustainable use of unique yak genetic resources in Qinghai.

Cartilage-specific deletion of Alk5 gene results in a progressive osteoarthritis-like phenotype in mice.

OBJECTIVE: Previous studies have shown that Transforming growth factor-ß (TGF-ß)/TGFßRII-Smad3 signaling is involved in articular cartilage homeostasis. However, the role of TGF-ß/ALK5 signaling in articular cartilage homeostasis has not been fully defined. In this study, a combination of in vitro and in vivo approaches was used to elucidate the role of ALK5 signaling in articular cartilage homeostasis and the development of osteoarthritis (OA). DESIGN: Mice with inducible cartilage-specific deletion of Alk5 were generated to assess the role of ALK5 in OA development. Alterations in cartilage structure were evaluated histologically. The expressions of genes associated with articular cartilage homeostasis and TGF-ß signaling were analyzed by qRT-PCR, western blotting and immunohistochemistry. The chondrocyte apoptosis was detected by TUNEL staining and immunohistochemistry. In addition, the molecular mechanism underlying the effects of TGF-ß/ALK5 signaling on articular cartilage homeostasis was explored by analyzing the TGF-ß/ALK5 signaling-induced expression of proteoglycan 4 (PRG4) using specific inhibitors. RESULTS: Postnatal cartilage-specific deletion of Alk5 induced an OA-like phenotype with degradation of articular cartilage, synovial hyperplasia, osteophyte formation, subchondral sclerosis, as well as enhanced chondrocyte apoptosis, overproduction of catabolic factors, and decreased expressions of anabolic factors in chondrocytes. In addition, the expressions of PRG4 mRNA and protein were decreased in Alk5 conditional knockout mice. Furthermore, our results showed, for the first time, that TGF-ß/ALK5 signaling regulated PRG4 expression partially through the protein kinase A (PKA)-CREB signaling pathway. CONCLUSIONS: TGF-ß/ALK5 signaling maintains articular cartilage homeostasis, in part, by upregulating PRG4 expression through the PKA-CREB signaling pathway in articular chondrocytes.

A large iron isotope effect in SmFeAsO(1 - x)F(x) and Ba(1 - x)K(x)Fe(2)As(2).

The recent discovery of superconductivity in oxypnictides with a critical transition temperature (T(C)) higher than the McMillan limit of 39 K (the theoretical maximum predicted by Bardeen-Cooper-Schrieffer theory) has generated great excitement. Theoretical calculations indicate that the electron-phonon interaction is not strong enough to give rise to such high transition temperatures, but strong ferromagnetic/antiferromagnetic fluctuations have been proposed to be responsible. Superconductivity and magnetism in pnictide superconductors, however, show a strong sensitivity to the crystal lattice, suggesting the possibility of unconventional electron-phonon coupling. Here we report the effect of oxygen and iron isotope substitution on T(C) and the spin-density wave (SDW) transition temperature (T(SDW)) in the SmFeAsO(1 - x)F(x) and Ba(1 - x)K(x)Fe(2)As(2) systems. The oxygen isotope effect on T(C) and T(SDW) is very small, while the iron isotope exponent alpha(C) = -dlnT(C)/dlnM is about 0.35 (0.5 corresponds to the full isotope effect). Surprisingly, the iron isotope exchange shows the same effect on T(SDW) as T(C). This indicates that electron-phonon interaction plays some role in the superconducting mechanism, but a simple electron-phonon coupling mechanism seems unlikely because a strong magnon-phonon coupling is included.

Deltonin induced both apoptosis and autophagy in head and neck squamous carcinoma FaDu cell.

For decades, despite the advancement of medical science, the prognosis of head and neck squamous cell carcinoma (HNSCC), has not improved. Deltonin is one of the major active components of Dioscorea Zingiberensis Wright that has been used for anthrax, rheumatic heart disease, rheumatoid arthritis etc. By employing HNSCC FaDu cell and normal human epidermal keratinocyte, we investigate deltonin efficacy and associated mechanism in both cell culture and nude mice xenografts. Deltonin treatment selectively prevents proliferation of FaDu cells by cell-cycle arrest and induction of apoptosis, via activating checkpoint kinase Chk1and Chk2 as well as caspases 8, 9 and 3. Meanwhile, we found that treatment with deltonin induced autophagy, which played a protective role against deltonin-induced apoptosis. Further studies revealed that deltonin activated autophagy by Akt-mTOR signaling. Additionally, xenograft model showed that administration of deltonin significantly inhibited tumor growth and prolonged survival of tumor bearing mice. Our studies suggested that deltonin might be a potential chemotherapeutic agent against HNSCC, which might contribute to clinical application and pharmacological study of deltonin in future anti-cancer research.

An inexact multi-objective programming model for water resources management in industrial parks of Binhai New Area, China.

In recent years, Binhai New Area of Tianjin has been suffering severe water shortage due to climate change and industrial activities. Integrated and effective water resources management approaches are urgent for the sustainable development of industrial parks in Binhai New Area. However, uncertainties exist in many aspects of the water resources system and are inevitably problematic for water resources planning and policy-making. To address these uncertainties, an interval multiple-objective programming model was developed here to support the long-term planning of industrial water resources management in Binhai New Area, Tianjin, China. The model incorporated both multiple-objective programming and interval linear programming into a general programming framework. The developed model could handle the uncertainties and complexities of the water management system, and also allowed decision makers to adjust fuzzy objective control decision variables to satisfy multiple holistic and interactive objectives. The solutions are useful for planning adjustments of the existing water allocation patterns in Binhai New Area.

Module function and two-way clustering analysis of Epstein-Barr virus-related nasopharyngeal cancer.

This study sought to identify and characterize the function of genes as diagnostic markers for Epstein-Barr virus (EBV)-related nasopharyngeal cancer (NPC). The gene expression profile of GSE13597 was downloaded from the Gene Expression Omnibus database, which included 28 EBV-related NPC gene expression profile data sets, 25 disease samples, and 3 control samples. Data were pre-processed, and differentially expressed genes were screened using the R language. The co-expression coefficient was calculated to construct a co-expression network using Cytoscape. ClusterONE was used to perform module analysis to find enriched gene families. The BiCAT software was used to perform a two-way clustering analysis of differentially expressed gene expression profiles based on the co-expression networks and to verify the enriched gene families, followed by functional enrichment analysis of these gene families. The MCM gene family was found to be enriched in EBV-related NPC. This gene family is essential for eukaryotic DNA replication. Functional analysis of differentially expressed genes in the co-expression network revealed that the enriched biological processes and pathways were mainly involved in the cell cycle. EBV-related NPC is likely associated mainly with the process of cell reproduction, providing a strong basis for the prevention, diagnosis, and treatment of EBV-related NPC and a direction for targeted chemotherapy.

First Report of Leaf Spot Caused by Corynespora cassiicola on Kiwifruit (Actinidia chinensis) in China.

Kiwifruit (Actinidia) is a common fruit cultivated in many countries. Actinidia deliciosa and A. chinensis are two commercially important kiwifruit species. Over 70,000 ha are grown annually in China. In 2012, a leaf spot disease of A. chinensis was observed in several orchards in Leye County (106°34' E, 24°47' N), Guangxi Zhuang Autonomous Region, China. The disease mainly damaged the leaves during the fruit development stage through to the maturity stage. Initially reddish-brown small lesions appeared on the leaves; later, typical symptoms were tan to taupe lesions surrounded by purple brown margins, nearly circular to irregular, 2 to 10 × 2.2 to 15.5 mm in diameter. Some lesions exhibited a concentric pattern. The lesions eventually coalesced, causing extensive leaf necrosis and defoliation. The fungus that sporulated from lesions had the following morphological characteristics: light brown conidiophores with slightly swollen apexes, light brown conidia formed singly or in acropetal chains, straight or curved, cylindrical to oblavate, 52.9 to 240.5 µm long (avg. 138.9 µm) and 5.3 to 13.6 µm wide (avg. 8.4 µm), 5 to 12 distoseptate, with a flat, darkened, and thickened hilum. These morphological characteristics corresponded with that of Corynespora cassiicola (Berk. & Curt.) Wei (1). To isolate the pathogen of the disease, small pieces of symptomatic foliar tissues, including young lesions, typical older lesions, and atypical older lesions with concentric pattern were surface sterilized with 75% ethanol for 30 to 60 s, disinfected in 0.1% HgCl2 for 1 min followed by washing with sterile water, plated on PDA, and incubated at 28°C for 7 to 10 days. Gray to dark gray colonies and conidia of C. cassiicola were observed. To validate the identity of the fungus, the sequence of the ITS region of one of the purified strains, LYCc-1, was determined. DNA was extracted from the isolate that was grown on PDA at 28°C for 4 days, and the ITS region was amplified using the universal primer pair ITS4/ITS5 (2). The double strand consensus sequence was submitted to GenBank (KJ747095) and had 99% nt identity with published sequences of C. cassiicola in GenBank (JN853778, FJ852574, and FJ852587). Pathogenicity tests were carried out on detached leaves in petri dishes in an incubator at 28°C and on whole plants in a glasshouse at 25 ± 3°C. The isolations did not produce enough conidia in pure culture, so mycelial discs were used in pathogenicity tests. For both assays, 60-day-old healthy kiwifruit leaves were inoculated with a 5-mm mycelial disc obtained from the periphery of a 5-day-old C. cassiicola strain (LYCc-1) grown on PDA. The PDA discs were placed on the leaf surface with their mycelial surface down and secured with sterile wet cotton. Controls consisted of leaves that were inoculated with sterile PDA discs. For the detached leaf assay, the leaves were placed on filter paper reaching water saturation in petri dishes, and for the whole plant assays the inoculated leaves were kept moist with intermittent water sprays for 48 h. Four leaves of each plant were inoculated with the isolate in both assays, and experiment was repeated twice. Eight inoculated leaves of the detached leaf assay all showed the first water soaked lesions 36 h after inoculation, followed by extensive leaf rot 72 h after inoculation, and yielded abundant conidia of C. cassiicola. Six out of eight leaves inoculated on whole plants showed the first lesions 5 days after inoculation, whereas control leaves remained healthy. Only C. cassiicola was re-isolated from the lesions in both assays, fulfilling Koch's postulates. This is the first report of leaf spot caused by C. cassiicola on kiwifruit in China. References: (1) M. B. Ellis. Dematiaceous Hyphomycetes. CMI, Kew, Surrey, UK, 1971. (2) T. J. White et al. In: PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.

[Prevalence and epidemiological characteristics of major chronic diseases in people living with HIV in Taizhou, Zhejiang Province, 1998-2022].

Objective: To understand the prevalence of major chronic diseases of diabetes, cardiovascular disease and malignant tumor in people living with HIV in Taizhou. Methods: The data were collected from China Information System for Disease Control and Prevention and Taizhou Chronic Disease Information Management System. A total of 5 126 people living HIV under follow-up in Taizhou from 1998 to 2022 were included in the analysis. Software SAS 9.4 was used for χ2 test, trend analysis and logistic regression analysis. Results: In the 5 126 people living with HIV, the reported prevalence rates of diabetes,cardiovascular disease and malignant tumor were 10.28% (527/5 126),3.98% (204/5 126) and 6.01% (308/5 126), respectively. 37.00% (195/527) and 48.58% (256/527), 40.20% (82/204) and 48.53% (99/204), 37.66% (116/308) and 48.38% (149/308) were diagnosed as diabetes, cardiovascular disease and malignant tumor before and after confirmation of HIV infection. From 2013 to 2022, the proportion of HIV infected people diagnosed with diabetes, cardiovascular disease and malignant tumor after confirmation increased (trend χ2=79.98,P<0.001; trend χ2=17.44,P<0.001; trend χ2=32.06,P<0.001). Based on the analysis on the factors for complicated chronic diseases in people living with HIV, it was found that women under 60 years old (aOR=0.66, 95%CI: 0.50-0.86) and those with access to antiviral treatment for >5 years before 2016 (aOR=0.54,95%CI:0.37-0.78) were less likely to develop complicated chronic diseases, and those under 60 years old with initial CD4+T lymphocytes counts <200 cells/µl (aOR=1.32, 95%CI: 1.02-1.70), those aged 40-49 and 50-59 years (aOR=2.88, 95%CI:2.20-3.79; aOR=5.43, 95%CI: 4.10-7.21) as well as those without a record of treatment medication use after 2016 (aOR=1.95,95%CI:1.20-3.16) were more likely to develop complicated chronic diseases. The probability of developing complicated chronic diseases might increase with age in people living with HIV. Conclusions: From 1998 to 2022, there was a certain proportion of complicated chronic diseases among HIV infected individuals in Taizhou, and the proportion of diagnosed cases increased after HIV infection was confirmed. It is necessary to conduct early chronic disease screening, behavior intervention and standardized management in people living with HIV.

Isoniazid urine spectrophotometry for prediction of serum pharmacokinetics in adults with TB.

BACKGROUND: Isoniazid (INH) is an important drug in many TB regimens, and unfavorable treatment outcomes can be caused by suboptimal pharmacokinetics. Dose adjustment can be personalized by measuring peak serum concentrations; however, the process involves cold-chain preservation and laboratory techniques such as liquid chromatography (LC)/mass spectrometry (MS), which are unavailable in many high-burden settings. Urine spectrophotometry could provide a low-cost alternative with simple sampling and quantification methods. METHODS: We enrolled 56 adult patients on treatment for active TB. Serum was collected at 0, 1, 2, 4, 6, and 8 h for measurement of INH concentrations using validated LC-MS/MS methods. Urine was collected at 0-4, 4-8, and 8-24 h intervals, with INH concentrations measured using colorimetric methods. RESULTS: The median peak serum concentration and total serum exposure over 24 h were 4.8 mg/L and 16.4 mg*hour/L, respectively. Area under the receiver operator characteristic curves for urine values predicting a subtherapeutic serum concentration (peak <3.0 mg/L) were as follows: 0-4 h interval (AUC 0.85, 95% CI 0.7-0.96), 0-8 h interval (AUC 0.85, 95% CI 0.71-0.96), and 0-24 h urine collection interval (AUC 0.84, 95% CI 0.68-0.96). CONCLUSION: Urine spectrophotometry may improve feasibility of personalized dosing in high TB burden regions but requires further study of target attainment following dose adjustment based on a urine threshold.

CONTEXTE: L'isoniazide (INH) est un médicament important dans de nombreux schémas thérapeutiques contre la TB, et des résultats thérapeutiques défavorables peuvent être dus à une pharmacocinétique sous-optimale. L'ajustement de la dose peut être personnalisé en mesurant les concentrations sériques maximales ; cependant, le processus implique la conservation de la chaîne du froid et des techniques de laboratoire telles que la chromatographie liquide (LC)/spectrométrie de masse (MS), qui ne sont pas disponibles dans de nombreuses régions à forte charge de morbidité. La spec-trophotométrie urinaire pourrait constituer une alternative peu coûteuse avec des méthodes d'échantillonnage et de quantification simples. MÉTHODES: Nous avons recruté 56 patients adultes sous traitement pour une TB active. Le sérum a été prélevé à 0, 1, 2, 4, 6 et 8 h pour mesurer les concentrations d'INH à l'aide de méthodes LC-MS/MS validées. L'urine a été prélevée à des intervalles de 0­4, 4­8 et 8­24 h, et les concentrations d'INH ont été mesurées à l'aide de méthodes colorimétriques. RÉSULTATS: La concentration sérique maximale médiane et l'exposition sérique totale sur 24 h étaient respectivement de 4,8 mg/L et de 16,4 mg*heure/L. L'aire sous les courbes caractéristiques de l'opérateur récepteur a été mesurée à l'aide de méthodes color-imétriques. Les aires sous les courbes caractéristiques des récepteurs pour les valeurs urinaires prédisant une concentration sérique sous-thérapeutique (pic <3,0 mg/L) étaient les suivantes : intervalle 0­4 h (AUC 0,85 ; IC 95% 0,7­0,96), intervalle 0­8 h (AUC 0,85 ; IC 95% 0,71­0,96), et intervalle de collecte d'urine 0­24 h (AUC 0,84 ; IC 95% 0,68­0,96). CONCLUSION: La spectrophotométrie urinaire peut améliorer la faisabilité d'un dosage personnalisé dans les régions à forte charge de TB, mais nécessite une étude plus approfondie de l'atteinte de la cible après l'ajustement de la dose sur la base d'un seuil urinaire.

[Effect of preemptive analgesia with ibuprofen on postoperative pain after mandibular third molar extraction: a randomized controlled trial].

Objective: To evaluate the impact of preemptive analgesia with ibuprofen on postoperative pain following the extraction of impacted mandibular third molars in a Chinese population, aiming to provide a clinical reference for its application. Methods: This multicenter, randomized, double-blind, placebo-controlled parallel-group trial was conducted from April 2022 to October 2023 at the Capital Medical University School of Stomatology (40 cases), Beijing TianTan Hospital, Capital Medical University (22 cases), and Beijing Chao-Yang Hospital, Capital Medical University (20 cases). It included 82 patients with impacted mandibular third molars, with 41 in the ibuprofen group and 41 in the control group. Participants in the ibuprofen group received 300 mg of sustained-release ibuprofen capsules orally 15 min before surgery, while the control group received a placebo. Both groups were instructed to take sustained-release ibuprofen capsules as planned for 3 days post-surgery. Pain intensity was measured using the numerical rating scale at 30 min, 4 h, 6 h, 8 h, 24 h, 48 h, and 72 h after surgery, and the use of additional analgesic medication was recorded during days 4 to 6 postoperatively. Results: All 82 patients completed the study according to the protocol. No adverse events such as nausea, vomiting, or allergies were reported in either group during the trial. The ibuprofen group exhibited significantly lower pain scores at 4 h [2.0 (1.0, 4.0) vs. 4.0 (3.0, 5.0)] (Z=-3.73, P<0.001), 6 h [2.0 (1.0, 4.0) vs. 5.0(2.5, 6.0)] (Z=-3.38, P<0.001), and 8 h [2.0 (1.0, 4.0) vs. 5.0 (2.0, 6.0)] (Z=-2.11, P=0.035) postoperatively compared to the control group. There were no statistically significant differences in pain scores between the groups at 30 min, 24 h, 48 h, and 72 h postoperatively (P>0.05). Additionally, 11 out of 41 patients (26.8%) in the ibuprofen group and 23 out of 41 patients (56.1%) in the control group required extra analgesic medication between days 4 and 6 post-surgery, with the ibuprofen group taking significantly fewer additional pills [0.0 (0.0, 1.0) vs. 1.0 (0.0, 3.0)] (Z=-2.81, P=0.005). Conclusions: A pain management regimen involving 300 mg of oral sustained-release ibuprofen capsules administered 15 minutes before surgery and continued for 3 d postoperatively effectively reduces pain levels and the total amount of analgesic medication used after the extraction of impacted mandibular third molars. Considering its efficacy, safety, and cost-effectiveness, ibuprofen is recommended as a first-line drug for perioperative pain management, enhancing patient comfort during diagnosis and treatment in a feasible manner.

[Prevalence of frailty and related factors in middle-aged and elderly people in island and mountainous areas of Taizhou, Zhejiang Province].

Objective: To compare the prevalence of frailty and related factors in middle-aged and elderly people aged ≥45 years in island and mountainous areas of Taizhou, Zhejiang Province. Methods: Based on cross-sectional design, stratified cluster sampling and quota sampling methods were adopted. One administrative district was randomly selected from each of six coastal and three inland administrative districts in Taizhou during July to August, representing two different geographical terrains. In the island area (Jiaojiang District), all residents aged ≥45 years were included by cluster sampling. In the mountainous area (Xianju County), participants were selected through quota sampling, with same gender and age distributions. Data about their demographic characteristics, lifestyle and health-related factors were collected through questionnaire surveys and laboratory examinations. The prevalence of frailty was assessed using the Fried frailty phenotype scale. Hierarchical analysis and multivariate logistic regression analysis were used to compare the influencing factors of frailty. Results: A total of 1 011 local residents were studied, in whom island and mountainous residents accounted for 48.1% (486/1 011) and 51.9% (525/1 011) respectively; men and women accounted for 45.9% (464/1 011) and 54.1% (547/1 011) respectively. Middle-aged (45-49 years), younger elderly (60-74 years), and older elderly (≥75 years) residents accounted for 38.6% (390/1 011), 44.6% (451/1 011), and 16.8% (170/1 011) respectively. The overall prevalence rate of frailty was 3.6% (36/1 011), the prevalence rate was 3.7% (17/464) in men and 3.5% (19/547) in women. The prevalence rates in age groups 45-59,60-74 years and ≥75 years were 0.3% (1/390), 2.2% (10/451), and 14.7% (25/170), respectively. The prevalence rates of frailty and pre-frailty in island area were 6.0% (29/486) and 39.1% (190/486), respectively, which was higher than those in mountainous area (1.3%, 7/525) and (30.9%, 162/525). After adjusting for potential confounding factors, the risk for frailty in island residents was significantly higher than that in mountainous residents (aOR=1.55,95%CI: 1.07-2.25,P=0.019). In island area, older age (60-74 years:aOR=2.52,95%CI: 1.56-4.13; ≥75 years:aOR=11.65,95%CI:5.38-26.70), being women (aOR=1.94,95%CI: 1.20-3.17), suffering from depression (aOR=1.09,95%CI:1.02-1.17) were associated with frailty symptoms. In mountainous area, older age was also associated with an increased risk of frailty symptoms, but the OR value was lower than those in island area (60-74 years: aOR=1.74,95%CI:1.04-2.94;≥75 years: aOR=4.78,95%CI:2.45-9.50). Polydrug use (aOR=2.08,95%CI: 1.14-3.80) and suffering from depression (aOR=1.10,95%CI: 1.02-1.18) had significant positive association with frailty symptoms. Higher education level had significant negative association with frailty symptoms (junior high school: aOR=0.40,95%CI: 0.21-0.75; senior high school and technical secondary school: aOR=0.29,95%CI: 0.15-0.53; college or above:aOR=0.22,95%CI: 0.11-0.42). Conclusions: The prevalence of frailty in middle-aged and elderly community residents was significantly higher in island area than in mountainous area in Taizhou. The frailty-related factors varied with area. The elderly people (≥75 years) and women in island area had higher risk for frailty. Older age and suffering from depression were the independent risk factors for frailty. It is necessary to pay attention to the health risk factors and special environment in island area, and take comprehensive intervention measures to delay the process of debilitation and improve the quality of life of middle-aged and elderly people.