The Impact of Frailty Status on Pulmonary Function and Mortality in Older Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVES: We aimed to evaluate the effect of frailty on lung function and disease outcomes in older adults with chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective observational cohort. SETTING AND PARTICIPANTS: At baseline, comprehensive geriatric assessment and pulmonary function tests were extracted from the case management care system of the geriatric department of a tertiary medical center. MEASUREMENTS: Frailty was assessed by the modified Rockwood frailty index. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the primary outcome. Both the Friedman test and generalized estimating equations were used to evaluate the rate of decline in lung function. RESULTS: Among 151 enrolled older patients, comprising 69 non-COPD and 82 COPD subjects, the mean age was 80.9±8.3 years. After a median follow-up of 2.87 years, the serial forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), and forced expiratory flow at 25-75% of FVC (FEF25-75%) showed significantly different slope changes between older COPD patients with and without frailty. The mortality hazard ratio (HR) was 2.53 for COPD without frailty and 3.62 for COPD with frailty, versus those without COPD. Among COPD patients, the factors most strongly associated with mortality were timed up-and-go, activities of daily living (ADLs), instrumental ADLs, FEV1/FVC, and serum HCO3-. After adjustment for potential confounders, ADLs and FEV1/FVC remained independent mortality predictors. CONCLUSION: Among older patients with COPD, frailty was common and associated with pulmonary function decline, and mortality risk was higher in frail than in non-frail subjects.

[Clinical and pathological characteristics of gastric adenocarcinoma of fundic gland type].

To analyze the clinical, endoscopic and pathological feature of gastric adenocarcinoma of fundic gland type (GA-FG) (18 cases) collected from Sir Run Run Shaw Hospital, affiliated with Zhejiang University School of Medicine and Taizhou Hospital of Zhejiang Province from January 2019 to July 2022. There were 18 cases of patient of GA-FG, including male 12 cases, female 6 cases, aged from 38 to 78 years old, with average age of 60.5 years old. Gastroscopy showed that bulging or flat lesions of gastric fundus were 0.2-5.5 cm in size, and the mucosal surface was smooth, redness or rough. Histologic examination showed that tumor cells were dominated by chief cells and scattered with a few oxyntic cells, formed a complex gland that anastomoses each other, and infiltrated to the submucosa. The results of immunohistochemistry showed that tumor cells were positive for the expression of mucin-6 (MUC6) and Pepsinogen 1, and partial expression of synaptophysin (Syn). GA-FG is a rare type of gastric adenocarcinoma with good differentiation, and currently only a few cases have been reported, and often easily been misdiagnosed or missed. Therefore, to master the characteristics of clinic and pathology is helpful to improve the ability of clinical pathologists in differential diagnosis.

[Summary of experience with patterning cropped and shaped mesh repair for perineal hernia after abdominoperineal excision in rectal cancer].

Objective: To examine the patterning cropped and shaped mesh repair for perineal hernia after abdominoperineal excision (APE) in rectal cancer. Methods: The clinical data of 8 patients with perineal hernia after APE who accepted surgical treatment in the Department of Hepatopancreatobiliary and Hernia Surgery, the First Affiliated Hospital of Fujian Medical University from March 2017 to December 2022 were retrospectively reviewed. There were 3 males and 5 females, aged (67.6±7.2) years (range: 56 to 76 years). Eight patients developed a perineal mass at (11.3±2.9) months (range: 5 to 13 months) after APE. After surgical separation of adhesion and exposing the pelvic floor defect, a 15 cm×20 cm anti-adhesion mesh was fashioned as a three-dimensional pocket shape to fit the pelvic defect, then fixed to the promontory or sacrum and sutured to the pelvic sidewalls and the anterior peritoneum, while two side slender slings were tailored in front of the mesh and fixed on the pectineal ligament. Results: The repair of their perineal hernias went well, with an operating time of (240.6±48.8) minutes (range: 155 to 300 minutes). Five patients underwent laparotomy, 3 patients tried laparoscopic surgery first and then transferred to laparotomy combined with the perineal approach. Intraoperative bowel injury was observed in 3 patients. All patients did not have an intestinal fistula, bleeding occurred. No reoperation was performed and their preoperative symptoms improved significantly. The postoperative hospital stay was (13.5±2.9) days (range: 7 to 17 days) and two patients had postoperative ileus, which improved after conservative treatment. Two patients had a postoperative perineal hernia sac effusion, one of them underwent placement of a tube to puncture the hernia sac effusion due to infection, and continued irrigation and drainage. The postoperative follow-up was (34.8±14.0) months (range: 13 to 48 months), and 1 patient developed recurrence in the seventh postoperative month, no further surgery was performed. Conclusions: Surgical repair of the perineal hernia after APE can be preferred transabdominal approach, routine application of laparoscopy is not recommended, combined abdominoperineal approach can be considered if necessary. The perineal hernia after APE can be repaired safely and effectively using the described technique of patterning cropped and shaped mesh repair.

[Analysis of volatile organic components of organic solvents used in Bao'an District of Shenzhen].

Objective: To understand the volatile organic components in the organic solvents used by enterprises in Baoan District, Shenzhen. Methods: From January to December 2020, a total of 541 organic solvent samples used by 86 companies were collected for volatile organic component analysis, and the main volatile components and high-risk occupational hazards in organic solvents used in different industries were analyzed. Results: A total of 201 volatile organic components were detected in 541 organic solvents. The top 5 components detected include xylene (29.76%, 116/541), toluene (21.81%, 118/541), methanol (20.70%, 112/541), n-hexane (14.79%, 80/541) and ethylbenzene (14.23%, 77/541). The detection rates of benzene, trichloroethylene, n-hexane, and 1, 2-dichloroethane, which were high-risk occupational hazards, were 2.40% (13/541), 3.70% (20/541), 14.79% (80/541), and 1.66% (9/541), respectively. The volatile components in organic solvents used in different industries was different. Benzene is more frequently detected in organic solvents used in the printing industry, trichloroethylene was more frequently detected in organic solvents used in the electronics industry, and n-hexane was more commonly found in organic solvents used in the electronics industry, printing and other industries, and 1, 2-dichloroethane has been more frequently detected in organic solvents used in the machinery industry. Conclusion: There are many types of organic solvents used by enterprises in Bao'an District, with complex components and differences in different industries.

[A survey of cervical and lumbar spine diseases of express delivery employees].

Objective: To understand the current situation and influencing factors of cervical and lumbar spine diseases of the express delivery employees, and provide scientific basis for carrying out their occupational health protection in a targeted manner. Methods: From February 2020 to January 2021, the current situation research method was used to obtain 527 express delivery employees by cluster sampling. Online questionnaires were used to investigate sociodemographic characteristics and emotional characteristics, and clinical data were obtained by digital X-ray (DR) examination of the neck and waist. Pearson χ(2) test and multivariate logistic regression were used to analyze the influencing factors of cervical and lumbar spine diseases in express delivery employees. Results: The prevalence rates of cervical spine and lumbar spine diseases among express delivery employees were 49.15% (259/527) and 67.74% (357/527) , respectively. Univariate analysis showed that there were statistically significant differences in the distribution of cervical and lumbar spine disease among express delivery employees with different ages, length of service, working hours per week, and different degrees of distress due to emotional factors (P<0.05) . Multivariate analysis showed that express delivery employees aged ≥25 years old had a higher risk of cervical spine disease (P<0.05) , the express delivery employees who worked 49-55 hours per week had a lower risk of cervical spine disease (P<0.05) . Express delivery employees aged≥35 years old had a lower risk of lumbar spine disease (P<0.05) , and the risk of lumbar spine disease was higher among express delivery workers who suffered moderate or more distress due to emotional factors (such as anxiety, depression, or irritability) in the past 4 weeks (P<0.05) . Conclusion: The prevalence of cervical and lumbar spine diseases is relatively high among express delivery employees. It is recommended to adjust the weekly working hours of express delivery employees, organize psychological counseling training, and effectively protect the occupational health rights of express delivery employees.

[Investigation on occupational injury of sanitation workers in Shenzhen City].

Objective: To understand the occurrence of occupational injuries among sanitation workers in Shenzhen, and provide a scientific basis for the prevention of occupational injuries among sanitation workers. Methods: From May to November 2020, a cluster sampling method was used to select some street sanitation workers in Shenzhen to conduct a questionnaire survey. A total of 2200 questionnaires were recovered, of which 2167 were valid (98.5% effective recovery rate) . The socio-demographic data, length of service, type of work and occurrence of occupational injuries of sanitation workers were collected, and the distribution characteristics of occupational injuries and their relationship with factors such as type of work were analyzed. Results: Among the 2167 sanitation workers, 240 (11.1%) had experienced occupational injuries. The most common occupational injuries among sanitation workers were sharp injury, heat stroke and motor vehicle traffic accident, with the incidence rates of 6.1% (133/2167) , 2.4% (53/2167) and 1.7% (36/2167) respectively. There were statistically significant differences in the distribution of occupational injuries among sanitation workers with different lengths of work and types of work (P<0.05) . The incidence of occupational injury among sanitation workers with more than 5 years of service was significantly higher than that of workers with less than 5 years of service (P<0.05) . The incidence of sharp injury among garbage sorting and transportation personnel was higher (7.9%, 21/265) , the incidence of heat stroke among manual cleaners was higher (3.1%, 42/1366) , and the incidence of motor vehicle traffic accident among mechanized cleaners was higher (5.4%, 10/184) . Conclusion: There are many cases of occupational injuries among sanitation workers in Shenzhen. Targeted measures should be taken to prevent the occurrence of different types of work and different types of occupational injuries, and to improve the occupational health level of sanitation workers.

[A preliminary comparison on ophthalmic examination indices of workers with different occupations in Shenzhen].

Objective: To compare the ophthalmic examination indices of different occupational groups in Shenzhen and analyze the possible health problems, so as to provide research basis for further health intervention. Methods: In March 2021, 5426 professionals with ophthalmic examination index data were selected from the basic health database of "Shenzhen occupational population protection action". Among them, radiation workers (694), port operators (1756), sanitation workers (946), teachers (224), video workers (154), police (927) and firefighters (100) were selected as the investigated occupational population. They were exposed to noise 625 workers with traditional occupational hazards such as noise, chemical poisons and dust were used as the control population.Ophthalmic examination indices included right eye vision, left eye vision, outer eye, conjunctiva, cornea, lens, and fundus oculi. The differences of each index in different occupational groups were compared. Results: Compared with the control group, the port operator group showed lower abnormal rates of binocular vision and fundus oculi (P<0.05), but higher abnormal rates of conjunctiva (P=0.029), the environmental sanitation worker group showed higher abnormal rates of binocular vision and conjunctiva (all P<0.01), the teacher group had higher abnormal rates of binocular vision, but only the difference of left eye vision was statistically significant (P=0.021), and the video worker group had higher abnormal rates of right and left eyes vision (P=0.029、0.006) . Conclusion: There were some degrees of ophthalmic problems in different occupational population, therefore targeted intervention measures should be taken according to the characteristics of each group.

Interface effects of Schottky devices built from MoS2and high work function metals.

Schottky junctions, formed by high work function metals and semiconductors, are important devices in electronics and optoelectronics. The metal deposition in traditional Schottky interfaces usually damages the semiconductor surface and causes defect states, which reduces the Schottky barrier height and device performance. This can be avoided in the atomically smooth interface formed by two-dimensional (2D) metals and semiconductors. For better interface tailoring engineering, it is particularly important to understand various interface effects in such 2D Schottky devices under critical or boundary conditions. Here we report the fabrication and testing of three types of MoS2devices, i.e., using PtTe2, Cr and Au as contact materials. While the Cr/MoS2contact is an ohmic contact, the other two are Schottky contacts. The van-der-Waals interface of PtTe2-MoS2results in a well-defined OFF state and a significant rectification ratio of 104. This parameter, together with an ideality factor 2.1, outperforms the device based on evaporated Au. Moreover, a device in the intermediate condition is also presented. An abrupt increase in the reverse current is observed and understood based on the enhanced tunneling current. Our work manifests the essential role of doping concentration and provides another example for 2D Schottky interface design.

Ethnic disparities in mortality among overweight or obese adults with newly diagnosed type 2 diabetes: a population-based cohort study.

PURPOSE: Ethnic variation in risk of type 2 diabetes is well established, but its impact on mortality is less well understood. This study investigated the risk of all-cause and cardiovascular mortality associated with newly diagnosed type 2 diabetes in White, Asian and Black adults who were overweight or obese. METHODS: This population-based cohort study used primary care records from the UK Clinical Practice Research Datalink, linked with secondary care and death registry records. A total of 193,528 obese or overweight adults (BMI of 25 or greater), with ethnicity records and no pre-existing type 2 diabetes were identified between 01 January 1995 and 20 April 2018. Multivariable Cox proportional hazards regression estimated hazards ratios (HR) for incident type 2 diabetes in different ethnic groups. Adjusted hazards ratios for all-cause and cardiovascular mortality were determined in individuals with newly diagnosed type 2 diabetes. RESULTS: During follow-up (median 9.8 years), the overall incidence rate of type 2 diabetes (per 1,000 person-years) was 20.10 (95% CI 19.90-20.30). Compared to Whites, type 2 diabetes risk was 2.2-fold higher in Asians (HR 2.19 (2.07-2.32)) and 30% higher in Blacks (HR 1.34 (1.23-1.46)). In individuals with newly diagnosed type 2 diabetes, the rates (per 1,000 person-years) of all-cause mortality and cardiovascular mortality were 24.34 (23.73-24.92) and 4.78 (4.51-5.06), respectively. Adjusted hazards ratios for mortality were significantly lower in Asians (HR 0.70 (0.55-0.90)) and Blacks (HR 0.71 (0.51-0.98)) compared to Whites, and these differences in mortality risk were not explained by differences in severity of hyperglycaemia. CONCLUSIONS/INTERPRETATION: Type 2 diabetes risk in overweight and obese adults is greater in Asian and Black compared to White ethnic populations, but mortality is significantly higher in the latter. Greater attention to optimising screening, disease and risk management appropriate to all communities with type 2 diabetes is needed.

Polarized proton acceleration in ultraintense laser interaction with near-critical-density plasmas.

The production of polarized proton beams with multi-GeV energies in ultraintense laser interaction with targets is studied with three-dimensional particle-in-cell simulations. A near-critical density plasma target with prepolarized proton and tritium ions is considered for the proton acceleration. The prepolarized protons are initially accelerated by laser radiation pressure before injection and further acceleration in a bubblelike wakefield. The temporal dynamics of proton polarization is tracked via the Thomas-Bargmann-Michel-Telegdi equation and it is found that the proton polarization state can be altered by both the laser field and the magnetic component of the wakefield. The dependence of the proton acceleration and polarization on the ratio of the ion species is determined and it is found that the protons can be efficiently accelerated as long as their relative fraction is less than 20%, in which case the bubble size is large enough for the protons to obtain sufficient energy to overcome the bubble injection threshold.

Wide-spectrum photodetector constructed on a centimeter-scale flexible SnSe2film using a new one-step strategy.

Two-dimensional (2D) materials attached with flexible substrates enable possibilities to apply their superior properties to the rapidly increasing demand for foldable displays and wearable biosensors in the internet-of-things technology. However, previous two-step strategy to construct the flexible devices, namely first obtaining 2D materials elsewhere and then transferring them onto flexible substrates, can cause huge problems, including irreversibly undermining the device performance and limiting the material size. Here we propose a new one-step strategy (other than the liquid phase processing and low temperature synthesis methods), namely directly depositing appropriate 2D materials onto flexible substrates, which involves no transferring and can maintain the crystal quality and properties to the greatest extent. More importantly, this strategy in principle has no limit in the film size, hence removing a main obstacle for the practical use of flexible films, such as complex logic operations and large-area optoelectronic applications. Using this strategy, a centimeter-scale SnSe2film is directly grown on polydimethylsiloxane, which is characterized as a uniform, out-of-plane oriented and semiconducting film that is robust to deformations. Based on the film, a flexible photodetector is fabricated and distinct photoresponse to a broad spectrum of light (405-830 nm) is observed, with remarkable technical parameters.

[GCS score combined with CT score and serum S100B protein level Can evaluate severity and early prognosis of acute traumatic brain injury].

OBJECTIVE: To explore the value of Glasgow Coma Scale (GCS) score and CT score combined with serum S100B protein level for evaluation of injury severity and predicting early prognosis of acute traumatic brain injury (TBI). OBJECTIVE: A total of 108 patients with TBI admitted within 24 h after injury in the Emergency Department of West China Hospital from May, 2019 to May, 2020 were enrolled in this study. The clinical data, laboratory test results, CT examination, GCS score, Full Outline of Unresponsiveness score, Fisher CT classification, Rotterdam CT score, and serum S100B protein level of the patients were collected upon admission. The patients were followed up for 28 days and divided based on their Glasgow Outcome Scale (GOS) scores into poor prognosis group (GOS 1-3) and good prognosis group (GOS 4-5). The indexes related to poor prognosis were analyzed for their efficacy for predicting the patinets' prognosis. According to the results of head CT, the patients were divided into CT- positive (CT+) group and CT- negative (CT-) group, and the efficacy of serum S100B protein level for predicting CT positivity was evaluated. OBJECTIVE: Compared with those with favorable prognosis, the patients with poor prognosis had significantly lower GCS scores (P < 0.01) and higher Rotterdam CT score and serum S100B protein levels (P < 0.01). Among the 3 index, serum S100B protein level had the highest AUC value (0.79); among the combined indexes, GCS score combined with serum S100B protein had the highest AUC value (0.80). Serum S100B protein level was significantly higher in CT+ group than in CT - group (P < 0.05) with a significant correlation with Rotterdam CT score (r=0.26, P < 0.01). OBJECTIVE: Serum S100B protein level, GCS score, and Rotterdam CT score can be used as indicators for evaluating the severity of acute TBI, and they are all closely related with early prognosis of the patients. The combination of serum S100B protein, GCS score and Rotterdam CT score has better performance than any of the 3 indexes alone for predicting early prognosis of the patients. Serum S100B protein level is correlated with head imaging findings of patients with acute TBI, but its value in selection of appropriate imaging modalities awaits further investigation.

Data-driven machine-learning analysis of potential embolic sources in embolic stroke of undetermined source.

BACKGROUND AND PURPOSE: Hierarchical clustering, a common 'unsupervised' machine-learning algorithm, is advantageous for exploring potential underlying aetiology in particularly heterogeneous diseases. We investigated potential embolic sources in embolic stroke of undetermined source (ESUS) using a data-driven machine-learning method, and explored variation in stroke recurrence between clusters. METHODS: We used a hierarchical k-means clustering algorithm on patients' baseline data, which assigned each individual into a unique clustering group, using a minimum-variance method to calculate the similarity between ESUS patients based on all baseline features. Potential embolic sources were categorised into atrial cardiopathy, atrial fibrillation, arterial disease, left ventricular disease, cardiac valvulopathy, patent foramen ovale (PFO) and cancer. RESULTS: Among 800 consecutive ESUS patients (43.3% women, median age 67 years), the optimal number of clusters was four. Left ventricular disease was most prevalent in cluster 1 (present in all patients) and perfectly associated with cluster 1. PFO was most prevalent in cluster 2 (38.9% of patients) and associated significantly with increased likelihood of cluster 2 [adjusted odds ratio: 2.69, 95% confidence interval (CI): 1.64-4.41]. Arterial disease was most prevalent in cluster 3 (57.7%) and associated with increased likelihood of cluster 3 (adjusted odds ratio: 2.21, 95% CI: 1.43-3.13). Atrial cardiopathy was most prevalent in cluster 4 (100%) and perfectly associated with cluster 4. Cluster 3 was the largest cluster involving 53.7% of patients. Atrial fibrillation was not significantly associated with any cluster. CONCLUSIONS: This data-driven machine-learning analysis identified four clusters of ESUS that were strongly associated with arterial disease, atrial cardiopathy, PFO and left ventricular disease, respectively. More than half of the patients were assigned to the cluster associated with arterial disease.

Community diversity and abundance of ammonia-oxidizing archaea and bacteria in shrimp pond sediment at different culture stages.

AIMS: Ammonia oxidation is a significant process of nitrogen cycles in a lot of ecosystems sediments while there are few studies in shrimp culture pond (SCP) sediments. This paper attempted to explore the community diversity and abundance of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in SCP sediments at different culture stages. METHODS AND RESULTS: We collected SCP sediments and analysed the community diversity and abundance of AOA and bacteria in shrimp pond sediment at different culture stages using the ammonia monooxygenase (amoA) gene with quantitative PCR (qPCR) and 16S rRNA gene sequencing. The AOB-amoA gene abundance was showed higher than AOA-amoA gene abundance in SCP sediments on Day 50 and Day 60 after shrimp larvae introducing into the pond, and the diversity of AOA in SCP sediments was higher than that of AOB. The phylogenetic tree revealed that the most of AOA were the member of Nitrosopumilus and Nitrososphaera, and the majority of AOB sequences were clustered into Nitrosospira, Nitrosomonas clusters 6a and 7. The AOA community has close relationship with total organic carbon (TOC), pH, total phosphorus (TP), nitrate reductase, urease, acid phosphatase and ß-glucosidase. The AOB community was related to TOC, C/N and nitrate reductase. CONCLUSIONS: AOA and AOB play the different ecological roles in SCP sediments at different culture stages. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results suggested that the different community diversity and abundance of AOA and AOB in SCP sediments, which may improve our ecological cognition of shrimp culture stages in SCP ecosystems.

MiR-582-5p inhibits the growth and invasion of osteosarcoma cell by targeting NOVA1.

OBJECTIVE: To investigate the role of microRNA-582-5p (miR-582-5p) on osteosarcoma (OS) cell behaviors and provide potential therapeutic targets for OS. MATERIALS AND METHODS: Expression levels of miR-582-5p in OS cell lines and normal cell lines were measured by quantitative real-time PCR. Cell proliferation, migration and invasion capacities were assessed by cell counting kit-8 assay, wound-healing assay, and transwell invasion assay, respectively. Downstream target of miR-582-5p was confirmed by Luciferase activity reporter assay and Western blotting assay. RESULTS: MiR-582-5p expression was downregulated in OS cell lines compared with normal cell lines. Overexpression of miR-582-5p inhibits OS cell proliferation, migration, and invasion capacities. Neuro-oncological ventral antigen 1 (NOVA1) was chosen as target gene of miR-582-5p by bioinformatics analysis and Luciferase reporter assay. Moreover, overexpression of NOVA1 could impair tumor suppression role of miR-582-5p on OS cell behaviors. CONCLUSIONS: MiR-582-5p exerts tumor-suppressive role on OS cell behaviors via targeting NOVA1 in vitro, which will help us to understand the mechanisms underlying OS progression.

[Reevaluation of equivocal HER2 status detected by immunohistochemistry according to the 2019 guidelines for HER2 detection].

Objective To understand the effects and clinical significance of the 2019 guidelines for the human epidermal growth factor receptor 2 (HER2) detection. Methods: According to the 2014 guidelines, 548 cases of invasive breast cancer with equivocal HER2 (2+) detected by immunohistochemistry (IHC) in Taizhou Enze Medical Center, Zhejiang Province, China from 2013 to 2019 were selected. The results of IHC and HER2/CEPl7 double-probe were reevaluated and divided into groups according to the 2019 guidelines for the comparative analysis. Results: Among the 548 IHC HER2 (2+) invasive breast cancers, the number of positive, equivocal and negative cases for HER2 were 96 (17.52%), 81 (14.78%) and 371 (67.70%), respectively, according to the 2014 guidelines. However, according to the 2019 guidelines, 10 cases (1.82%) were reclassified as IHC 1+, 2 cases in the group 2 were reclassified as negative, and all the originally equivocal cases in group 4 were reclassified as negative. Finally, the total number of positive and negative cases for HER2 were 94 (17.15%) and 454 (82.85%), respectively. Conclusions: After applying the 2019 guidelines, the number of IHC 2+ cases decreases, and the positive rate for HER2 also decreases slightly due to the reevaluation change in groups 2 and 4, leading to reclassification of the cases that were deemed equivocal according to the 2014 guidelines. In general, the new 2019 guidelines are more reasonable and easier to use.

[Clinical characteristics of patients with Klebsiella pneumoniae pyogenic liver abscess].

Objective: To summarize the clinical features of patients with Klebsiella pneumoniae pyogenic liver abscess(KP-PLA). Methods: Clinical data of 133 patients with pyogenic liver abscess(PLA) and positive results of blood or pus culture were retrospectively analyzed in Huashan Hospital Affiliated to Fudan University from 2009 to 2018. According to the culture results, patients were divided into KP-PLA group (n=92) and non-KP-PLA group (n=41). Results: KP-PLA and non-KP-PLA were similar in gender composition with males accounting for 67.39% and 70.73%, and had age of (56.8±13.8) years and (55.0±13.0) years (χ(2)=0.146, 0.708, P>0.05) respectively. The underlying diseases were more common in KP-PLA group, including diabetes accounting for 45.65% and 24.39%, and hypertension accounting for 32.61% and 14.63% (χ(2)=5.384, 4.642, P<0.05) respectively. Patients with KP-PLA had more invasive infections beyond liver than those with non-KP-PLA, which were 27.17% and 9.76% (χ(2)=5.046, P=0.025). The laboratory results showed that hemoglobin levels in KP-PLA and non-KP-PLA were (109.88±20.97) g/L and (97.75±20.25) g/L (t=3.086, P=0.002). Serum alkaline phosphatase levels were 146.50 (114.50, 237.50) U/L and 220.50 (120.00, 316.75) U/L in KP-PLA and non-KP-PLA (U=2 239.500, P=0.048) patients. Conclusions: KP-PLA mainly develops in middle-aged and elderly men, especially those with diabetes and hypertension. Patients with KP-PLA need to be paid more attention for invasive manifestations beyond liver.

Cell-to-cell spread of vaccinia virus is promoted by TGF-ß-independent Smad4 signalling.

The induction of Smad signalling by the extracellular ligand TGF-ß promotes tissue plasticity and cell migration in developmental and pathological contexts. Here, we show that vaccinia virus (VACV) stimulates the activity of Smad transcription factors and expression of TGF-ß/Smad-responsive genes at the transcript and protein levels. Accordingly, infected cells share characteristics to those undergoing TGF-ß/Smad-mediated epithelial-to-mesenchymal transition (EMT). Depletion of the Smad4 protein, a common mediator of TGF-ß signalling, results in an attenuation of viral cell-to-cell spread and reduced motility of infected cells. VACV induction of TGF-ß/Smad-responsive gene expression does not require the TGF-ß ligand or type I and type II TGF-ß receptors, suggesting a novel, non-canonical Smad signalling pathway. Additionally, the spread of ectromelia virus, a related orthopoxvirus that does not activate a TGF-ß/Smad response, is enhanced by the addition of exogenous TGF-ß. Together, our results indicate that VACV orchestrates a TGF-ß-like response via a unique activation mechanism to enhance cell migration and promote virus spread.

The unfolded protein response modulates the autophagy-mediated egg production in the mosquito Aedes aegypti.

Mosquitoes must feed on vertebrate blood for egg development. As a consequence, some mosquito species are vectors for pathogens that cause devastating diseases in humans. Hence, understanding the mechanisms that control egg developmental cycles is important for developing novel approaches for the control of mosquito-borne diseases. The unfolded protein response (UPR) is a cellular stress response related to endoplasmic reticulum (ER) stress. The UPR is activated in response to an accumulation of unfolded or misfolded proteins in the ER. Massive proteins have been shown to be produced during egg development, and it is obvious that unfolded or misfolded proteins may arise during vitellogenesis. It has been shown that autophagy in the mosquito fat body plays a central role in the progression of gonadotrophic cycles in the mosquito Aedes aegypti. However, the molecular mechanisms underlying the induction of UPR and the correlation between UPR and autophagy remain unclear. Here, we demonstrate that autophagy is activated during vitellogenesis and that the activation of autophagy is correlated with the UPR. We also show that the expressions of UPR and autophagy can be induced in an in vitro fat body culture system through an amino acid treatment. In addition, the expressions of UPR, autophagy-specific markers and vitellogenin were also induced during dithiothreitol treatment. Interestingly, the silencing of UPR-related genes significantly reduced the expression of autophagy-specific markers and inhibited mosquito fecundity. Taken together, we conclude that autophagy-mediated egg production in the mosquito A. aegypti is regulated by UPR.