[Analysis of the factors influencing the severity of coronavirus disease 2019 in patients with myeloproliferative neoplasms based on an online questionnaire].

Objective: To explore the variables associated with the severity of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 omicron variant during the epidemic in patients with myeloproliferative neoplasms (MPN). Methods: A cross-sectional study. During the SARS-CoV-2 omicron variant pandemic from December 15, 2022, to March 15, 2023, COVID-19 related data for patients with MPN who were treated at Peking University People's Hospital were collected through an online questionnaire-based survey. All questionnaires and clinical data were checked by medical assistants. Logistic multivariate analysis was used to explore the prevalence and variables associated with the severity of COVID-19 in patients with MPN. Results: A total of 239 patients with MPN, including 90 (37.7%) presenting with essential thrombocythemia (ET), 50 (20.9%) with polycythemia vera (PV), and 99 (41.4%) with myelofibrosis (MF), were enrolled in the study. The 99 patients with MF included 87 (87.9%) with primary MF, 5 (5.1%) with post-PV MF, and 7 (7.1%) with post-ET MF. Overall, 239 (100%) patients reported that they experienced COVID-19 during the pandemic. Of these, 226 (94.6%) had mild disease, 4 (1.7%) had moderate disease, 7 (2.9%) had severe disease, and 2 (0.8%) had critical disease. Two (0.8%) patients with severe COVID-19 died, one of which suffered from MT and the other from PV. Multivariate analysis showed that older age (OR=2.36, 95%CI 1.24-4.49), MF (OR=10.22, 95%CI 1.13-92.80), or comorbidity (OR=5.25, 95%CI 1.25-22.03) were associated with a significantly higher risk of developing moderate, severe, or critical COVID-19. Among patients with MF, higher risk stratification reflected an increased risk of developing moderate, severe, or critical COVID-19 (P=0.034). Conclusion: During the omicron pandemic, older age, MF (especially higher-risk categories), and comorbidity were associated with a higher risk of developing moderate, severe, or critical COVID-19.

[The current status and future prospects of mesenchymal stem cell transplantation for the treatment of knee articular cartilage injuries and osteoarthritis].

The prevalence of articular cartilage injuries and osteoarthritis (OA) is high, affecting a wide range of individuals. The self-repair ability of cartilage tissue is poor, and once damaged, it will irreversibly progress to OA. Mesenchymal stem cells (MSCs) play an important role in the field of regenerative medicine and are considered one of the most promising seed cells for cartilage repair and regeneration. In this article, based on the latest clinical research findings from both domestic and international sources, the theoretical basis, treatment goals, significance, sources, characteristics, clinical implementation plans, and efficacy of using MSCs for the treatment of cartilage injuries or osteoarthritis are reviewed. The article also discusses the challenges faced and future directions that need to be addressed in the clinical application of MSCs.

[Dose-response association between fluid overload and hospital mortality in patients with sepsis].

Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.

Prophylactic therapy for prevention of surgical site infection after extraction of third molar: An overview of reviews.

BACKGROUND: To compare the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars with different degree of impaction. MATERIAL AND METHODS: Systematic reviews and meta-analyses evaluating the effect of different prophylactic therapies on prevention of surgical site infection after extraction of third molars were included. An electronic search was performed in PubMed, EMBASE, and the Cochrane Database of Systematic reviews. AMSTAR 2 tool was used to evaluate the confidence in results from the included reviews. Descriptive analyses were performed. RESULTS: Six reviews were included. A significant benefit of different antibiotics to the prevention of site infection after extraction of third molars was reported. Amoxicillin/amoxicillin clavulanic acid could significantly reduce the rate of surgical site infection versus placebo. Chlorhexidine gel could significantly reduce the frequency of alveolar osteitis versus placebo. CONCLUSIONS: Based on the limited evidence, there is a significant benefit of prophylactic therapy while the comparative effect of different types of prophylactic regimes are controversial.

[Revision rate of periprosthetic joint infection post total hip or knee arthroplasty of 34 hospitals in China between 2015 and 2017: a multi-center survey].

Objective: To investigate the rate of periprosthetic joint infection (PJI) revision surgeries and clinical information of hip-/knee- PJI cases nationwide from 2015 to 2017 in China. Methods: An epidemiological investigation. A self-designed questionnaire and convenience sampling were used to survey 41 regional joint replacement centers nationwide from November 2018 to December 2019 in China. The PJI was diagnosed according to the Musculoskeletal Infection Association criteria. Data of PJI patients were obtained by searching the inpatient database of each hospital. Questionnaire entries were extracted from the clinical records by specialist. Then the differences in rate of PJI revision surgery between hip- and knee- PJI revision cases were calculated and compared. Results: Total of 36 hospitals (87.8%) nationwide reported data on 99 791 hip and knee arthroplasties performed from 2015 to 2017, with 946 revisions due to PJI (0.96%). The overall hip-PJI revision rate was 0.99% (481/48 574), and it was 0.97% (135/13 963), 0.97% (153/15 730) and 1.07% (193/17 881) in of 2015, 2016, 2017, respectively. The overall knee-PJI revision rate was 0.91% (465/51 271), and it was 0.90% (131/14 650), 0.88% (155/17 693) and 0.94% (179/18 982) in 2015, 2016, 2017, respectively. Heilongjiang (2.2%, 40/1 805), Fujian (2.2%, 45/2 017), Jiangsu (2.1%, 85/3 899), Gansu (2.1%, 29/1 377), Chongqing (1.8%, 64/3 523) reported relatively high revision rates. Conclusions: The overall PJI revision rate in 34 hospitals nationwide from 2015 to 2017 is 0.96%. The hip-PJI revision rate is slightly higher than that in the knee-PJI. There are differences in revision rates among hospitals in different regions.

[Exposure level of neonicotinoid pesticides and their metabolites in pregnant women in the suburb of Shanghai].

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 µg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 µg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.

Spontaneous Ferromagnetism Induced Topological Transition in EuB_{6}.

The interplay between various symmetries and electronic bands topology is one of the core issues for topological quantum materials. Spontaneous magnetism, which leads to the breaking of time-reversal symmetry, has been proven to be a powerful approach to trigger various exotic topological phases. In this Letter, utilizing the combination of angle-resolved photoemission spectroscopy, magneto-optical Kerr effect microscopy, and first-principles calculations, we present the direct evidence on the realization of the long-sought spontaneous ferromagnetism induced topological transition in soft ferromagnetic EuB_{6}. Explicitly, we reveal the topological transition is from Z_{2}=1 topological insulator in paramagnetic state to χ=1 magnetic topological semimetal in low temperature ferromagnetic state. Our results demonstrate that the simple band structure near the Fermi level and rich topological phases make EuB_{6} an ideal platform to study the topological phase physics.

Three novel structural variations at the major histocompatibility complex and IL12B predispose to psoriasis.

BACKGROUND: Structural variations (SVs; defined as DNA variants ≥ 50 base pairs) have been associated with various complex human diseases. However, research to screen the whole genome for SVs predisposing to psoriasis is lacking. OBJECTIVES: To investigate the association of SVs and psoriasis. METHODS: Using imputation, we performed a genome-wide screen of SVs on five independent cohorts with 45 386 participants from the Han Chinese population. Fine-mapping analysis, genetic interaction analysis and RNA expression analysis were conducted to explore the mechanism of SVs. RESULTS: In total, we obtained 4535 SVs and identified two novel deletions [esv3608550, odds ratio (OR) 2·73 (P < 2·00 × 10-308 ); esv3608542, OR 0·47 (P = 7·40 × 10-28 )] at 6q21·33 (major histocompatibility complex), one novel Alu element insertion [esv3607339; OR 1·22 (P = 1·18 × 10-35 )] at 5q33·3 (IL12B) and confirmed one previously reported deletion [esv3587563; OR 1·30 (P = 9·52 × 10-60 )] at 1q21·2 (late cornified envelope) for psoriasis. Fine-mapping analysis including single-nucleotide polymorphisms (SNPs) and small insertions/deletions revealed that esv3608550 and esv3608542 were independently associated with psoriasis, and a novel independent SNP [rs9378188; OR, 1·65 (P = 3·46 × 10-38 )] was identified at 6q21·33. By genetic interaction analysis and RNA expression analysis, we speculate that the association of two deletions at 6q21·33 with psoriasis might relate to their influence on the expression of HLA-C. CONCLUSIONS: We have constructed the most comprehensive SV map for psoriasis thus far and enriched the genetic architecture and pathogenesis of psoriasis, and highlight the non-negligible impact of SVs on complex diseases.

Detection of optrA and poxtA genes in linezolid-resistant Enterococcus isolates from fur animals in China.

The emergence of linezolid-resistant (LR) enterococci found in food of animal origin arouses attention, but little is known about LR enterococci in fur animals. A total of 342 Enterococcus faecalis and 265 E. faecium strains isolated from fur animals in China from 2015 to 2017 were investigated to determine if LR enterococci (≥16 µg ml-1 ) are present. Overall, two E. faecalis and 12 E. faecium among these isolates were resistant to linezolid. In addition, all LR isolates were classified as multidrug-resistant isolates. We further explore the resistance genes of the LR enterococci, four E. faecalis and two E. faecium isolates contained optrA gene. Two of them co-harboured optrA and poxtA genes. We detected virulence genes in LR enterococci were the following: asa1, cylA, esp, gelE and hyl, among which the highest carrying rate gene was asa1. Besides, all of the LR enterococci we tested had the biofilm-forming ability. It is worth noting that we detected a novel ST type ST2010 from E. faecium 82-2. These data show LR enterococci exist in fur animals and have unique characteristics.

Rumen-protected methionine during heat stress alters mTOR, insulin signaling, and 1-carbon metabolism protein abundance in liver, and whole-blood transsulfuration pathway genes in Holstein cows.

We investigated effects of rumen-protected Met (RPM) during a heat stress (HS) challenge on (1) hepatic abundance of mTOR, insulin, and antioxidant signaling proteins, (2) enzymes in 1-carbon metabolism, and (3) innate immunity. Holstein cows (n = 32; mean ± standard deviation, 184 ± 59 d in milk) were randomly assigned to 1 of 2 environmental groups, and 1 of 2 diets [total mixed ration (TMR) with RPM (Smartamine M; 0.105% dry matter as top-dress) or TMR without (CON); n = 16/diet] in a split-plot crossover design. There were 2 periods with 2 phases. During phase 1 (9 d), all cows were in thermoneutral conditions (TN; temperature-humidity index = 60 ± 3) and fed ad libitum. During phase 2 (9 d), half the cows (n = 8/diet) were exposed to HS using electric heat blankets. The other half (n = 8/diet) remained in TN, but was pair-fed to HS counterparts. After a 14-d washout and 7-d adaptation period, the study was repeated (period 2) and environmental treatments were inverted relative to phase 2, but dietary treatments were the same. Blood was collected on d 6 of each phase 2 to measure immune function and isolate whole-blood RNA. Liver biopsies were performed at the end of each period for cystathione ß-synthase (CBS) and methionine adenosyltransferase activity, glutathione concentration, and protein abundance. Data were analyzed using PROC MIXED in SAS. Abundance of CUL3, inhibitor of antioxidant responses, tended to be downregulated by HS suggesting increased oxidative stress. Heat-shock protein 70 abundance was upregulated by HS. Phosphorylated mTOR abundance was greater overall with RPM, suggesting an increase in pathway activity. An environment × diet (E × D) effect was observed for protein kinase B (AKT), whereas there was a tendency for an interaction for phosphorylated AKT. Abundance of AKT was upregulated in CON cows during HS versus TN, this was not observed in RPM cows. For phosphorylated AKT, tissue from HS cows fed CON had greater abundance compared with all other treatments. The same effect was observed for EIF2A (translation initiation) and SLC2A4 (insulin-induced glucose uptake). An E × D effect was observed for INSR due to upregulation in CON cows during HS versus TN cows fed CON or RPM. There was an E × D effect for CBS, with lower activity in RPM versus CON cows during HS. The CON cows tended to have greater CBS during HS versus TN. An E × D effect was observed for methionine adenosyltransferase, with lower activity in RPM versus CON during HS. Although activity increased in CON during HS versus TN, RPM cows tended to have greater activity during TN. Neutrophil and monocyte oxidative burst and monocyte phagocytosis decreased with HS. An (E × D) effect was observed for whole-blood mRNA abundance of CBS, SOD1 and CSAD; RPM led to upregulation during TN versus HS. Regardless of diet, CDO1, CTH, and SOD1 decreased with HS. Although HS increased hepatic HSP70 and seemed to alter antioxidant signaling, feeding RPM may help cows maintain homeostasis in mTOR, insulin signaling, and 1-carbon metabolism. Feeding RPM also may help maintain whole-blood antioxidant response during HS, which is an important aspect of innate immune function.

Unnecessary caesarean section delivery in rural China: exploration of relationships with full-term gestational age and early childhood development.

INTRODUCTION: Gestational age at delivery is reportedly associated with cognitive and non-cognitive development in early childhood. Delivery at an earlier full-term gestational age has been associated with an increased rate of caesarean section (C-section) delivery; the high rate of C-section delivery in China implies that the rate of medically unnecessary C-section delivery is also high. This study investigated the relationships of medically unnecessary C-section delivery with full-term gestational age and early childhood development in rural China. METHODS: We conducted a survey of 2765 children (aged 5-24 months) who resided in 22 national designated poverty counties. Primary caregivers were interviewed to collect information regarding child and household characteristics (including the child's gestational age), each child's delivery method, and reasons for C-section delivery (if applicable). The children were assessed using the Bayley Scales of Infant Development. Developmental outcomes were compared among gestational age-groups; regression analyses were used to assess relationships among medically unnecessary C-section delivery, gestational age, and developmental outcomes. RESULTS: Overall, 56.2% of children were born at ≤39 weeks of gestation. Among C-section deliveries, 13.1% were medically necessary and >40% could clearly be classified as medically unnecessary. Repeat C-section was the most common reason given for medically unnecessary C-section delivery. For each 1-week increase in full-term gestational age, cognition scale scores increased by 0.62 points (P<0.01), language scale scores increased by 0.84 points (P<0.01), and motor scale scores increased by 0.55 points (P<0.05). Medically unnecessary Csection delivery was significantly associated with lower full-term gestational age. CONCLUSION: Higher full-term gestational age was significantly associated with better childhood developmental outcomes, indicating that medically unnecessary C-section delivery may negatively influence early childhood development.

Effects of phenylpyruvate on the growth performance and intestinal microbiota in broiler chicken.

1. The purpose of this study was to see how dietary supplementation with phenylpyruvate affected broiler growth, slaughter performance, gut health microbiota and immunity. This information can be used to develop alternative approaches to antibiotic replacement in modern poultry production and health.2. A total of 288, one-day-old broiler chickens were randomly assigned to one of four groups (six replicates each replicate has 12 chickens). A control basal diet (NC), basal diet plus antibiotic virginiamycin 15ppm (PC), basal diet plus phenylpyruvate 1 kg/t or 2 kg/t, respectively (LCP and HCP).3. Results showed that the birds in the PC group had higher ADFI during the first 21 d, and better FCR than the NC group. The HCP-fed group had a higher all-eviscerated ratio than the NC group and less abdominal fat than the birds fed LCP. The birds fed HCP had increased villus length and crypt depth in the ileum compared to the NC group.4. The bursa index was lower in the HCP group whereas the thymus index was lower in LCP and PC groups. In contrast, birds fed HCP has lower pro-inflammatory cytokine IL-1, as well as lower TLR4. Phenylpyruvate improved number in the Selenomonadaceae, genus Megamonas bacteroides spp., which are known for their beneficial effects on the maintenance of the cell surface structure, regulating aromatic amino acids and Clostridia jejuni-suppressive treatment respectively.5. It was concluded that phenylpyruvate can be utilised in feed to improve growth performance and positively modulate gut microbiota. However, this was less efficient than antibiotics in improving growth performance, although more efficient in improving productive performance and gut morphology. Moreover, a high dose of phenylpyruvate is more effective than a low dose.

[Association between fluid balance and clinical outcomes in sepsis patients with identified subtypes].

Objective: To identify clinical subphenotypes of sepsis by clinical variables, and the association between fluid balance (FB) and outcomes in sepsis patients with different subphenotypes. Methods: Data were derived from China Critical Care Sepsis Trial. A total of 2 075 patients were included in the study, with a mean age of (62.5±17.4) years, 1 362 (65.6%) were male, 713 (34.3%) were female. In-hospital mortality was the primary outcome. Clinical variables were entered into the latent profile analysis (LPA) model which was used to identify the subphenotypes of sepsis. Multivariable logistic regression model was used to explore the association of FB on the first 2 days admitted to ICU and in-hospital mortality. Results: Total of 687 (33.1%) patients died in the hospital. Four subphenotypes of sepsis were identified by the PLA model: 1 421 (68.5%) patients were identified as profile 1, which was characterized by the lowest in-hospital mortality (28.3%, 402/1 421) and was considered as the baseline subphenotype; profile 2 was characterized by multiple organ dysfunction(232, 11.2%); profile 3 was characterized by respiratory dysfunction (196, 9.4%) and profile 4 was characterized by kidney injury/failure (226, 10.9%). Profile 2 showed the highest in-hospital mortality (54.3%, 126/232), followed by profile 4 (39.4%, 89/226), profile 3 (35.7%, 70/196). Profile 2 had the highest FB of 68.5(34.7, 89.4)ml/kg on day 1 and decreased rapidly to 29.4(13.6, 49.8) ml/kg on day 2. Multivariable analysis showed that for every 10 ml/kg of FB increased on the first 48 hours admitted to ICU, the risk of in-hospital mortality decreased 14% (OR=0.86, 95%CI: 0.81-0.97) in profile 2, and increased 4% (OR=1.04, 95%CI:1.02-1.07) in profile 4. However, there were no significant association between FB on the fist 2 days admitted to ICU and the risk of in-hospital mortality in profile 1 (OR=1.06, 95%CI: 0.94-1.19)and in profile 3 (OR=0.99, 95%CI: 0.94-1.05). Conclusions: Four subphenotypes of sepsis were identified according to the clinical variables, which showed different characteristics, distributions, outcomes and responses to fluid balance.

[Some HBeAg-negative chronic hepatitis B patients treated with nucleos(t)ide analogue can achieve HBsAg loss after drug withdrawal: stop-to-cure may be coming].

Nucleoside/Nucleotide analogues (NAs) are widely used for the antiviral treatment of chronic hepatitis B (CHB), however, it is difficult to achieve serum hepatitis B surface antigen (HBsAg) loss with NAs therapy. In recent years, several prospective trails have reported that HBsAg loss (functional cure or clinical cure) also occurs in a small number of hepatitis B e antigen (HBeAg) negative CHB patients who discontinued long-term treatment with NAs. Accordingly, the "stop-to-cure" strategy is proposed. Although the mechanism has not been fully elucidated, the known factors related to serum HBsAg loss with NAs withdrawal include HBV genotype, duration of NAs treatment, serum HBsAg and HBV RNA levels at end-of-treatment, and ethnic differences. In the review, we discuss the best time to stop NAs therapy, the potential markers for predicting relapse after cessation of NAs and the possible mechanism of "stop-to-cure" in HBeAg-negative CHB patients, and propose some suggestions on the time of retreatment.

[Evaluation of the level of carotid bifurcation and the morphology of extracranial internal carotid artery in patients with carotid stenosis by color doppler ultrasound and digital subtraction angiography].

Objective: To evaluate the value of color Doppler ultrasound and digital subtraction angiography (DSA) in evaluating the level of carotid bifurcation and the morphology of extracranial internal carotid artery in patients with atherosclerotic carotid stenosis. Methods: The carotid artery examination data of 186 patients with atherosclerotic carotid stenosis who underwent carotid DSA and color Doppler ultrasound in Shanghai Changzheng Hospital from July 2017 to June 2019 were retrospectively analyzed, including 154 males and 32 females, with ages ranging from 36 to 84 (66±8) years old. The correlation between the position of carotid bifurcation and the level of cervical spine, the distance from the position of carotid bifurcation to mandibular angle, the correlation of the level of bifurcation with the length of neck, and the incidence of carotid distortion were analyzed. Results: DSA showed that the most common position of carotid bifurcation was at C3 level on the left [37.3% (56/150)], and at C3-C4 level on the right [33.6% (42/125)], and the highest position was at C2 level on the left, and at C2-C3 levels on the right, while the lowest level on both sides was at C5 level. The incidence of high bifurcation of left carotid artery (C3 and above) was 46% (69/150), which was higher than that of right carotid artery [21.6% (27/125), P<0.001]. The incidence of high carotid bifurcation in men and women was 33.2% (76/229) and 43.5% (20/46), respectively, with no significant difference (P = 0.182). Carotid ultrasound showed that the distance between the left carotid bifurcation and the mandibular angle was (3.0±1.3) cm, which was shorter than that on the right [(3.4±1.2) cm] (P<0.001). The distance between carotid bifurcation and mandibular angle in men and women was (3.2±1.2) cm and (3.3±1.0) cm, respectively, with no significant difference (P = 0.093). There was no significant correlation between carotid bifurcation level and carotid length (right: r = 0.02, P = 0.091; left: r = 0.01, P = 0.927). The incidence of carotid artery distortion was 28.1% (9/32) in women and 15.6% (24/154) in men, with no significant difference (P = 0.091). The incidence of right carotid artery distortion in high bifurcation group was 59.3% (16/27), which was higher than that in non-high bifurcation group [3.1% (3/98)] (P<0.001). Likewise, the incidence of left carotid artery distortion in high bifurcation group was 30.4% (21/69), which was higher than that in non-high bifurcation group [2.5% (2/81)] (P<0.001). Conclusions: The bifurcation position of left carotid artery in patients with atherosclerotic carotid stenosis is higher than that of the right. Patients with high bifurcation of carotid artery are more likely to be complicated with carotid distortion. Preoperative color doppler ultrasound combined with DSA can evaluate the distortion of extracranial carotid artery, thereby providing reference for the selection of surgical methods.

[Characteristics and regulatory mechanisms of lipid metabolism remodeling after malignant transformation of glioma-associated macrophages].

Objective: To observe the lipid metabolism characteristics of tumor-associated macrophages (TAM) after malignant transformation in the glioma micro-environment, and analyze the biological phenotype changes and regulatory mechanisms after inhibiting the lipid metabolism remodeling. Methods: Twelve male Balb/c mice of 6-8 weeks were used in the study. Macrophages (Mφ) were derived from mouse bone marrow, and malignantly transformed macrophages (tMφ1 and tMφ2) were cloned from the model of glioma stem cell (GSC) through interaction with Mφ in vivo and in vitro. Intracellular lipid droplet formation and cellular cholesterol content were measured respectively in Mφ, tMφ1 and tMφ2. qRT-PCR was performed to detect the genes expression level related with lipid metabolism, including sterol regulatory element binding protein (SREBP), fatty acid synthase (FASN), and 3-hydroxy-3-methylglutarate monoacyl coenzyme A reductase (HMG-CoA). Simvastatin (SIM) was used to analyze the proliferation, immigration and invasiveness ability in tMφ1 and tMφ2 after inhibition of the lipid metabolism. Differential expression profiles of miRNAs after SIM treatment were constructed in t-Mφ1 and bio-informatics analysis was screened and verified for miR449a and its target gene sorting micro-tubule connectin 17 (SNX17) associated with lipid metabolism remodeling. The effect on SNX17 by up-regulated miR-449a were analyzed by qRT-PCR and Western blot, meanwhile, the biological phenotype and cholesterol content were observed after up-regulation of miR449a. Low-density lipoprotein receptor (LDLR) protein levels after SNX17 knockdown and intracellular cholesterol content after LDLR knockdown were detected respectively. Results: The numbers of intracellular lipid droplet formation in tMφ1 and tMφ2 were more than that in Mφ (P<0.001). Likewise, the relative contents of cholesterol (3.89±0.68 and 3.56±0.53), SREBP (4.78±0.60 and 2.84±0.41), FASN (4.65±0.70 and 3.01±0.45), and HMG-CoA (5.74±0.55 and 2.97±0.34) were significantly higher in tMφ1 and tMφ2 than those of Mφ (1.01 wel, 1.02 wel and 0.99 wel, respectively) (all P<0.001). The proliferation rates of tMφ1 and tMφ2 decreased from (47.06±5.88) % and (45.29±5.64)% to (23.53±4.70)% and (18.74±5.76)%, respectively after treatment with SIM (both P<0.05). The numbers of migrated cells decreased from 1 025±138 and 350±47 to 205±63 and 99±25, respectively (both P<0.001). And the numbers of invasiveness cells decreased from 919±45 and 527±34 to 220±23 and 114±21, respectively (both P<0.001). While the relative intracellular cholesterol content decreased to 0.52±0.08 and 0.58±0.07 (both P<0.05), respectively. MiR-449a was screened from tMφ1 by SIM, and the target gene was analyzed and verified to be SNX17. SNX17 expression was down-regulated, and the proliferation rate, the number of migration and invasiveness was significantly decreased after miR-449a over-expression (all P<0.05). Low-density lipoprotein receptor (LDLR) expression was down-regulated after knock-down of SNX17, while the cholesterol content was decreased after knock-down of LDLR in tMφ1 and tMφ2 (all P<0.05). Conclusions: Malignantly transformed TAMs undergo lipid metabolism remodeling characterized with enhanced lipid metabolism. MiR-449a regulates the LDLR by targeting SNX17, thereby affecting the lipid metabolism of malignantly transformed macrophages, and subsequently inhibiting its proliferation, migration, and invasion ability. Precise intervention with miR-449a/SNX17/LDLR axis could provide an experimental basis for reversing its tumor-promoting micro-environment remodeled by GSC through metabolic intervention.

[Tuberculosis screening in respiratory department inpatients in comprehensive medical institutions].

Objective: To explore the effect of screening tuberculosis patients in the respiratory department of general hospitals, and to provide a basis for the development of patient screening strategy. Methods: Clinical information and sputum samples of inpatients in the respiratory department of a general hospital in Longhua District, Shenzhen from December 2018 to December 2020 were collected. Sputum samples were sent to the tuberculosis laboratory of the Shenzhen Longhua Center for Chronic Disease Control (designated tuberculosis diagnosis and treatment institution) for sputum smear, liquid culture and Gene-Xpert test. Results: A total of 407 sputum samples (23 cases of suspected tuberculosis by chest imaging and 384 by clinical manifestations) were collected from 3 724 hospitalized patients. A total of 88 patients with positive etiology were detected by the three methods, and the positive rate was 21.6% (88/407), among which 15 patients with suspected tuberculosis were detected by imaging reports, and the positive rate of etiology was 19.0% (73/384) in the reported patients without imaging reports. At least 1.96% (73/3 724) of the hospitalized patients were estimated to be tuberculosis positive during the study. Pneumonia (30.1%,22/73), cough (15.1%,11/73) and pulmonary infection (15.1%,11/73) were the main characteristics in the patients with positive pathogens. Conclusions: Screening for tuberculosis among inpatients in the respiratory department of general hospitals is an effective way to detect patients who were radiographically reported to have probable tuberculosis. It is of great significance to carry out active screening in key departments of general hospitals for tuberculosis detection and control.

[Efficacy and safety of endothelin receptor antagonists combined with phosphodiesterase 5 inhibitor in the treatment of pulmonary arterial hypertension: a network meta-analysis].

Objective: To examine the efficacy and safety of endothelin receptor antagonists (ERA) combined with phosphodiesterase 5 inhibitors (PDE5i) in the treatment of pulmonary artery hypertension (PAH). Methods: Computer-based retrieval was performed on PubMed, Cochrane Library, CNKI, Wanfang, and VIP database (up to February 12th, 2021). Randomized controlled trials about endothelin receptor antagonists (ERAs) or PDE5i in patients with PAH were collected. The change of 6-minute walking distance (6MWD) in 12-16 weeks was used as primary outcome index. Case fatality rate, worsening clinical events, WHO functional class (FC) improvement, adverse events (AEs), serious adverse events (SAE) were the key secondary outcomes indicators. STATA 16.0 software was used for network meta-analysis, and the pooled estimates of odds ratios (ORs) or weighted mean differences (WMDs) and 95% confidence intervals (CIs) of the results were shown. To help explain ORs and WMDs, we used the surface under the cumulative ranking curve (SUCRA) to calculate the probability of each intervention. Results: We included 29 trials with 5 949 participants. In network meta-analysis, Bosentan combined with Sildenafil (WMD=53.93, 95%CI=6.19-101.66) had shown the greatest improvement in 6MWD compared with placebo, followed by Bosentan combined with Tadalafil (WMD=50.84, 95%CI=7.05-94.62), Ambrisentan combined with Tadalafil (WMD=46.67, 95%CI=15.88-77.45), Bosentan (WMD=29.44, 95%CI=5.86-53.02), Ambrisentan (WMD=23.90, 95%CI=0.31-47.48) and Macitentan (WMD=21.57, 95%CI=2.45-40.69). According to SUCRA, the effects of different intervention measures on improving 6MWD in patients with arterial pulmonary hypertension were as follows: Bosentan+Sildenafil (82.9%)>Bosentan+Tadalafil (78.4%)>Ambrisentan+Tadalafil (77.1%)>Bosentan (49.2%)>Sildenafil (48.5%)>Ambrisentan (40.3%)>Macitentan (37.3%)>Tadalafil (33.0%)>Placebo (3.3%). For the WHO functional class, Sildenafil (OR=2.90, 95%CI=1.04-8.08) was optimal compared with placebo, followed by Bosentan (OR=2.15, 95%CI=1.15-4.04), and there was no significant difference in the rest. For clinical worsening, Bosentan combined with Tadalafil (OR=0.08, 95%CI=0.01-0.49) performed best compared with placebo, followed by Bosentan (OR=0.20, 95%CI=0.11-0.38), Bosentan combined with Sildenafil (OR=0.21, 95%CI=0.09-0.46), Ambrisentan combined with Tadalafil (OR=0.27, 95%CI=0.15-0.50), Sildenafil (OR=0.33, 95%CI=0.17-0.66) and Tadalafil (OR=0.44, 95%CI=0.21-0.90). There was no statistical difference between all interventions and placebo in terms of the incidence of adverse events and serious adverse events. For case fatality rate, Ambrisentan (OR=0.28, 95%CI=0.11-0.74) was statistically superior to placebo and there was no statistics difference in the rest. Conclusions: The combination therapy of ERAs and PDE5i performed well in the short-term improvement of motor function. Furthermore, there was no significant difference with monotherapy in terms of safety. However, it is worth emphasizing that the choice of treatment should be based on the patient's individualized situation and the patient's requirements.

[Clinical effect of minimally invasive duodenum preserving pancreatic head resection for benign and pre-malignant lesions of pancreatic head].

Objective: To examine the clinical effect of minimally invasive duodenum preserving pancreatic head resection(DPPHR) for benign and pre-malignant lesions of pancreatic head. Methods: The clinical data of patients with diagnosis of benign or pre-malignant pancreatic head tumor were retrospectively collected and analyzed,all of them underwent laparoscopic or robotic DPPHR between October 2015 and September 2021 at Division of Gastrointestinal and Pancreatic surgery,Zhejiang Provincial People's Hospital. Thirty-three patients were enrolled with 10 males and 23 females. The age(M(IQR)) was 54(32) years old(range: 11 to 77 years old) and the body mass index was 21.9(2.9)kg/m2(range: 18.1 to 30.1 kg/m2). The presenting symptoms included abdominal pain(n=12), Whipple triad(n=2), and asymptomatic(n=19). There were 7 patients with hypertension and 1 patient with diabetes mellitus. There were 19 patients who were diagnosed as American Society of Anesthesiologists class Ⅰ and 14 patients who were diagnosed as class Ⅱ. The student t test,U test, χ2 test or Fisher exact test was used to compare continuous data or categorized data,respectively. All the perioperative data and metabolic morbidity were analyzed and experiences on minimally invasive DPPHR were concluded. Results: Fourteen patients underwent laparoscopic DPPHR,while the rest of 19 patients received robotic DPPHR. Indocyanine green fluorescence imaging was used in 19 patients to guide operation. Five patients were performed pancreatico-gastrostomy and the rest 28 patients underwent pancreaticojejunostomy. Pathological outcomes confirmed 9 solid pseudo-papillary neoplasms, 9 intraductal papillary mucinous neoplasms, 7 serous cystic neoplasms, 6 pancreatic neuroendocrine tumors, 1 mucous cystic neoplasm, 1 chronic pancreatitis. The operative time was (309.4±50.3) minutes(range:180 to 420 minutes),and the blood loss was (97.9±48.3)ml(range:20 to 200 ml). Eighteen patients suffered from postoperative complications,including 3 patients experienced severe complications(Clavien-Dindo Grade ≥Ⅲ). Pancreatic fistula occurred in 16 patients,including 8 patients with biochemical leak,7 patients with grade B pancreatic fistula and 1 patient with grade C pancreatic fistula. No one suffered from the duodenal necrosis and none perioperative death was occurred. The length of hospital stay was 14(7) days (range:6 to 87 days). The follow-up was 22.6(24.5)months(range:2 to 74 months). None suffered from recurrence or metastasis. During the follow-up,all the patients were free of refractory cholangitis. Moreover,in the term of endocrine dysfunction,no postoperative new onset of diabetes mellitus were observed in the long-term follow-up. However,in the view of exocrine insufficiency,pancreatic exocrine insufficiency and non-alcoholic fatty liver disease (NAFLD) was complicated in 2 and 1 patient,respectively,with the supplement of pancreatic enzyme,steatorrhea and weight loss relieved,but NAFLD was awaited to be seen. Conclusions: Minimally invasive DPPHR is feasible and safe for benign or pre-malignant lesions of pancreatic head. Moreover,it is oncological equivalent to pancreaticoduodenectomy with preservation of metabolic function without refractory cholangitis.

[Determination of creatinine and 2-thiothiazolidine-4-carboxylic acid in urine by ultra high performance liquid chromatography tandem mass spectrometry].

Objective: To establish an ultrahigh performance liquid chromatography tandem mass spectrometry method for the determination of creatinine (Cre) and 2-thiothiazolidine-4-carboxylic acid (TTCA) in urine. Methods: In October 2020, the end-of-shift urine samples of the monitored subjects were taken, and the filtrate was prepared by centrifugation. After separated by ultra high performance liquid chromatography C18 column, acetonitrile and 0.2% acetic acid aqueous solution were used as mobile phases for gradient elution, the three quadrupole tandem mass spectrometry adopted an electrospray ion source (ESI) , the ion source temperature was 500 ℃ , and the air curtain gas flow rate was 31.4 L/min, qualitative and quantitative analysis of Cre and TTCA were carried out under the multiple reaction monitoring mode. Results: The linear range of Cre was 1.0-1 000.0 µg/L, the linear equation was y=947.3x-1605.6, and the correlation coefficient was 0.9994. The detection limit and the limit of quantitation were 0.3, 1.0 µg/L. When the addition concentrations were 50.0, 150.0 and 450.0 µg/L, the recovery rates were 92.8%-94.6% , the intra assay precisions were 3.6%-5.7% , and the inter assay precisions were 3.4%-5.4%. The linear range of TTCA was 0.1-200.0 µg/L, the linear equation was y=1164.7x-2243.9, and the correlation coefficient was 0.9991. The detection limit and the limit of quantitation were 0.03, 0.1 µg/L. When the addition concentrations were 10.0, 40.0 and 160.0 µg/L, the recovery rates were 90.8%-93.6%, the intra assay precisions were 4.6%-7.4%, and the inter assay precisions were 4.4%-6.9%. Conclusion: The sample pretreatment process of the ultra high performance liquid chromatography tandem mass spectrometry method for the determination of Cre and TTCA in urine is simple, and the continuous determination of Cre and TTCA in urine can be realized only by switching mass spectrometry parameters under the same chromatographic conditions, which is accurate and efficient, and each performance index of the method meets the determination requirements.