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Screening serum biomarkers for acute and subacute pain is important for precise pain management. This study aimed to examine serum levels of angiogenic factors in patients with acute and subacute pain as potential biomarkers. Serum samples were collected from 12 healthy controls, 20 patients with postherpetic neuralgia (PHN), 4 with low back pain (LBP), and 1 with trigeminal neuralgia (TN). Pain intensity in these patients was evaluated using the visual analog scale (VAS). The serum concentrations of 11 angiogenic biomarkers were examined by Milliplex Map Human Angiogenesis Magnetic Bead Panel 2. The pain assessment from VAS showed that all patients showed moderate and severe pain. Among 11 angiogenic factors, osteopontin (OPN), thrombospondin-2 (TSP-2), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble urokinase-type plasminogen activator receptor (suPAR), and soluble epidermal growth factor receptors (sErbB2) were up-regulated and soluble interleukin-6 receptor α (sIL-6Rα) were down-regulated in patients with pain compared to the healthy participants (all P -values were < 0.005). Moreover, a linear regression model showed that the serum OPN concentration was correlated with pain intensity in patients with PHN ( P = 0.03). There was no significant difference between the serum concentration of soluble epidermal growth factor receptors, sErbB3, soluble AXL, tenascin, and soluble neuropilin-1 in patients with acute and subacute pain and that of healthy controls. The results of this study provided new valuable insights into our understanding of angiogenic factors that may contribute to as mechanistic biomarkers of pain, and reveal the pathophysiological mechanism of pain. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200061775., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Yuan, Wang, Wang, Liu, Li and Zhang.)

Sex reversal in insects, amphibians, reptiles, and fishes is a complicated and interesting biological phenomenon. Sex reversal changes the sex ratio of populations and may complicate breeding schemes. In the Chinese tongue sole (Cynoglossus semilaevis), genetic females may change into pseudomales, thereby increasing aquaculture costs because of the lower growth rate of the males than that of the females. Here we identify a new locus associated with sex reversal; this single nucleotide polymorphism (SNP) is located in the third intron of the doublesex and mab-3 related transcription factor 1 (Dmrt1) gene on the Z chromosome (named Cyn&#95;Z&#95;8564889) and has two alleles, A and G. Cyn&#95;Z&#95;8564889 regulates sex reversal interactively with our previously detected SNP (Cyn&#95;Z&#95;6676874), with the genetic females simultaneously carrying the T allele of Cyn&#95;Z&#95;6676874 and the A allele of Cyn&#95;Z&#95;8564889 changing into pseudomales. Other Dmrt1 polymorphisms were detected, which formed two haplotypes. Two SNPs in the second exon of Dmrt1 result in amino acid changes, suggesting that Dmrt1 is essential in sex reversal. We also verified that pseudomales produce no or little W sperm. The interaction and linkage between Cyn&#95;Z&#95;6676874 and Cyn&#95;Z&#95;8564889 and the absence of W sperm from pseudomales unravel the genetic architecture of sex reversal in C. semilaevis.

Background: Cerebrovascular risk is increased in people living with HIV infection compared with age-matched uninfected individuals. Cerebrovascular endothelial dysfunction related to antiretroviral therapy (ART) and inflammation may contribute to higher stroke risk in HIV infection., Methods: We compared cerebral vasoreactivity-a measure of cerebrovascular endothelial function assessed by the breath-holding index (BHI) using transcranial Doppler ultrasound-between virologically suppressed Chinese HIV-infected individuals followed in an HIV clinic in Beijing, China, and uninfected controls. We constructed mixed-effects models to evaluate the association of HIV, ART, and inflammatory markers with cerebral vasoreactivity., Results: In an unadjusted model, HIV infection was associated with a trend toward lower cerebral vasoreactivity (BHI 1.08 versus 1.26, P = 0.079). In multivariable analyses, cholesterol modified the association between HIV infection and cerebral vasoreactivity (P = 0.015 for interaction). At a lower total cholesterol of 4.15 mmol/L, HIV was associated with lower cerebral vasoreactivity (BHI -0.28, P = 0.019), whereas at a cholesterol of 5.15 mmol/L, the reduction in cerebral vasoreactivity associated with HIV was no longer statistically significant (BHI -0.05, P = 0.64). Among HIV-infected individuals, use of lopinavir/ritonavir compared with efavirenz was associated with lower cerebral vasoreactivity (BHI -0.24, P = 0.040). We did not find a significant association between inflammatory markers and cerebral vasoreactivity., Conclusions: Cerebrovascular endothelial dysfunction associated with HIV infection may be most relevant for individuals with less traditional vascular risk, such as those with lower cholesterol. Further study of the impact of ART on cerebrovascular endothelial function is warranted to aid with ART selection in individuals at high cerebrovascular risk., Competing Interests: No authors report any relevant conflicts of interest.

Interleukin-6 (IL-6) is one of the most important multifunctional cytokines, playing essential roles in mediating the innate and adaptive immune responses. In this study, il-6 gene and its promoter from blunt snout bream, Megalobrama amblycephala, were characterized, and its expression at the transcript level in healthy fish and after bacterial infection was determined by quantitative real-time PCR. The results showed that the M. amblycephala il-6 (Mamil-6) cDNA had an ORF of 699 bp, encoding 232 amino acids, and contained 9 instable motifs in the 3' UTR. The deduced MamIL-6 possessed a 24-amino acid signal peptide and was located in the cytoplasm. Although sequence alignment and phylogenetic analysis revealed that IL-6 is poorly conserved in vertebrates, the protein and genomic structure of il-6 gene was well conserved. Analysis of the Mamil-6 promoter revealed the presence of a conserved TATA box and six major cis-regulatory elements, including C/EBPβ (NF-IL6), AP-1, CRE, GRE, GATA and NF-κB binding sites. In healthy fish, Mamil-6 was the most abundant in the spleen. After Aeromonas hydrophila infection, Mamil-6 was significantly up-regulated in all 6 immune-related tissues examined, suggesting that Mamil-6 plays an important role in the blunt snout bream immune system.

Background: Although combination antiretroviral therapy (cART) including tenofovir (TDF)+lamivudine (3TC) or emtricitabine (FTC) is recommended for treatment of HIV/HBV coinfected patients, TDF is unavailable in some resource-limited areas. Some data suggest that 3TC monotherapy-based cART may be effective in patients with low pretreatment HBV DNA., Methods: Prospective study of 151 Chinese HIV/HBV coinfected subjects of whom 60 received 3TC-based cART and 91 received TDF+3TC-based cART. Factors associated with HBV DNA suppression at 24 and 48 weeks, including anti-HBV drugs, baseline HBV DNA, and baseline CD4 cell count, were evaluated overall and stratified by baseline HBV DNA using Poisson regression with a robust error variance., Results: Baseline HBV DNA ≥20,000 IU/mL was present in 48.3% and 44.0% of subjects in the 3TC and TDF groups, respectively (P = 0.60). After 48 weeks of treatment, HBV DNA suppression rates were similar between these 2 groups (96.8% vs. 98.0% for 3TC and TDF+3TC, P > 0.999) in subjects with baseline HBV DNA <20,000 IU/mL; whereas in those with baseline HBV DNA ≥20,000 IU/mL, TDF+3TC was associated with higher suppression rates (34.5% vs. 72.5% in 3TC and TDF+3TC groups, respectively, P = 0.002). In stratified multivariate regression, TDF use (RR 1.98, P = 0.010) and baseline HBV DNA (per 1 log increase in International Units Per Milliliter, RR 0.74, P < 0.001) were associated with HBV DNA suppression only when baseline HBV DNA ≥20,000 IU/mL., Conclusion: This study suggests that 3TC monotherapy-based cART is efficacious for HBV treatment through 48 weeks in HIV/HBV coinfection when baseline HBV DNA <20,000 IU/mL. Studies with long-term follow-up are warranted to determine if this finding persists.

Objective: To better understand the clinical characteristics and predisposing factors in non-pregnant patients with Listeria monocytogenes (Listeria) sepsis., Methods: Clinical data were collected at Peking Union Medical College Hospital between January 2002 and December 2014. A case with non-pregnant Listeria sepsis is defined as a non-pregnant person with clinically compatible illness and from whom Listeria was isolated from his/her blood culture. We define an underlying condition if a patient has been diagnosed of and/or has been treated for a concurrent baseline disease within 1 month prior to the onset of Listeria sepsis., Results: A total of 35 patients were enrolled. The age of all patients was (49.1 ± 17.0) years. The male to female ratio was 2: 3. Most patients were combined with at least 1 underlying condition (33, 94.3%), including 42.9% patients with an autoimmune disease, 34.3% with malignancies. The majority (91.4%) represented an acute onset (<1 week) with median time of 3 days. Clinical manifestations included fever (34/35, 97.1%), central nervous system (CNS) symptoms (17/35, 48.6%), gastrointestinal tract symptoms (13/35, 37.1%). Fourteen patients had undergone lumber puncture and cerebral spinal fluid (CSF) tests, which revealed abnormalities comparable of Listeria meningitis. Listeria was isolated from CSF in 11 of 14 patients (78.6%). There were 34 patients receiving empiric antibiotics including 54.3% cephalosporins which are resistant to Listeria. Twenty five (71.4%) patients were switched to the target antimicrobials according to positive blood culture. Of the 35 patients with Listeria sepsis, 21 (60.0%) recovered or were cured, however the rest (40.0%) had dismal outcome. Six patients died in hospital, 8 critical patients were discharged and died after transferring to local hospitals., Conclusions: Listeria sepsis is commonly associated with non-pregnant patients with compromised immune function. Clinical presentations include acute fever, CNS symptoms and gastrointestinal symptoms etc. Empiric antibiotics covering Listeria should be considered when sepsis is suspected among susceptible hosts.

Objective: To summarize the clinical characteristics and outcome of maternal listeriosis so as to improve the understanding of disease and the level of diagnosis and treatment., Methods: Retrospectively, 16 cases of maternal listeriosis, who were treated at Peking Union Medical College Hospital between March 2007 and December 2014 were reviewed. Maternal listeriosis is defined when a pregnant woman presents with symptoms as listeriosis, meanwhile Listeria monocytogenes is isolated from sterile tissue or peripheral blood, or from a non-sterile site (uterus swab) or pathological evidence of chorioamnionitis. The neonatal listeriosis is diagnosed as acute listeria sepsis., Results: The mean age of these 16 patients was (30.0 ± 3.9) years old. There were 1, 8, 7 patients with listeriosis diagnosed in the first, second and third trimester of pregnancy, respectively. All had an acute onset of illness (≤ 2 weeks), the median time from onset to presentation was 2.5 days. Clinical manifestations included fever (93.8%, 15/16), leukocytosis (78.6%, 11/14), chorioamnionitis (77.8%, 7/9), gastrointestinal symptoms (37.5%, 6/16) and fetal movement decrease (31.3%, 5/16). Listeria monocytogenes were isolated from blood (6 cases), uterus swab (6 cases), blood plus uterus swab (1 case), and neonates (3 cases). All maternal cases recovered well after the termination of pregnancy, even none of them had received empiric antibiotics sensitive to listeria. A very high proportion of adverse pregnancy outcomes occurred (15/16, 93.8%). There were 8 fetal losses. Seven neonates were complicated with listeria sepsis and treated successfully., Conclusions: The patients with maternal listeriosis commonly presented with acute fever and an extremely high incidence of adverse pregnancy outcomes, however empiric antibiotics can hardly cover this pathogenic bacterium. So both pregnant women and clinicians should maintain a high level of vigilance against listeriosis and pay more attention to dietetic hygiene.

Background: As life expectancy increases, HIV-infected patients are facing a wide array of metabolic complications, including diabetes mellitus (DM) and impaired fasting glucose (IFG). However, little is known about the incidence of and risk factors for glycemic disorders in Chinese HIV-infected patients., Methods: Longitudinal data were pooled from a multicenter clinical trial of combination antiretroviral regimens between 2009 and 2010 across Mainland China. DM was defined as fasting glucose level ≥7.0 mmol/L and IFG as between 5.6 and 6.9 mmol/L on 2 separate measurements. We calculated the incidence densities of DM and IFG. Risk factors for DM and IFG were also identified., Results: Four hundred fifteen patients contributed 457.35 person-years of follow-up. The incidence densities of DM and IFG were 2.62 and 35.64 per 100 person-years, respectively. In a multivariate analysis, advanced age [adjusted hazard ratio (HR): 1.03, 95% confidence interval (CI): 1.01 to 1.04], hepatitis B virus coinfection (adjusted HR: 1.59, 95% CI: 1.06 to 2.38), and baseline fasting glucose (adjusted HR: 1.28, 95% CI: 1.00 to 1.63) were associated with DM and IFG., Conclusions: A high incidence of DM and IFG was detected in Chinese HIV-infected patients receiving combination antiretroviral therapy. Clinicians should be aware of the potential for an increased risk of glycemic disorders in Chinese HIV-infected patients, particularly those of advanced age, with hepatitis B virus coinfection or high baseline fasting glucose.

Background: Distribution of HIV-1 subtypes, transmitted drug resistance (TDR)/drug resistance mutation (DRM), and their impact on response to combination antiretroviral therapy remain poorly understood in China., Methods: We analyzed data from our multicenter cohort study with 444 antiretroviral-naive participants recruited between 2008 and 2010. HIV-1 subtype and tropism were determined by V3 sequencing, and TDR/DRM was determined by Pol sequencing. Virologic and immunologic responses were monitored over 96 weeks of follow-up. The initial combination antiretroviral therapy regimen for all patients was nevirapine + lamivudine + zidovudine or stavudine. Analysis 1 included patients who finished 96 weeks of follow-up (n = 379), and analysis 2 included all 444 patients., Results: Subtype B/B' was associated with higher prevalence of TDR/DRM to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors. Median time to HIV-1 suppression was 18 weeks in all 3 subtype groups. In Cox proportional models for viral suppression, neither viral tropism nor HIV-1 subtypes had any impact on viral suppression; however, subtypes CRF01&#95;AE and C/CRF07&#95;BC/CRF08&#95;BC were associated with lower risk of virologic failure compared with subtype B/B', with adjusted hazard ratio of 0.11 (P = 0.032) and 0.06 (P = 0.036), respectively in analysis 1, 0.42 (P = 0.047) and 0.22 (P = 0.008), respectively in analysis 2. This association was attenuated by adding DRM profiles to multivariate regression models. Neither subtype nor HIV-1 tropism affected immunologic response., Conclusions: HIV-1 subtype tended to be associated with virologic but not immunologic response; this effect could be ascribed to baseline DRM.

Objective: To evaluate the clinical diagnostic contribution of (18)F-FDG PET/CT in giant cell arteritis with initial presentation as fever of unknown origin (FUO) ., Methods: Eight cases with initial presentation as FUO diagnosed with the contribution of PET/CT were retrospectively studied in Peking Union Medical College Hospital. The radiologic manifestations of PET/CT were analyzed., Results: Eight patients (4 men and 4 women) with average (63 ± 7) years (range from 55-75 years) were included in our study based on the criteria.Non-specific clinical symptoms were common in these patients, including fatigue, night sweat and weight loss. They all suffered from anemia of chronic disease.Not surprisingly, the inflammatory parameters were elevated significantly in all patients. The medical history, physical examination and routine lab and radiologic examinations couldn't reveal the causes of fever. PET/CT was performed in all of them, which demonstrated intense (18)F-FDG uptake in the area of aorta and its major branches with maximal standard uptake value (SUVmax) 2.1- 4.6 (3.6 ± 0.9).Immunosuppressive agents were effective to control the inflammation activity. The SUV decreased significantly after treatment in the follow-up PET/CT., Conclusions: PET/CT has demonstrated high yield of diagnostic contribution in giant cell arteritis with initial presentation as fever of unknown origin. As to elderly FUO patients presenting with prominent inflammatory reaction, PET/CT may provide potential value to differentiate diagnosis from maligancies.

Objective: To determine the clinical characteristics of HIV infected patients in China in order to improve early recognition and diagnosis of AIDS., Methods: A total of 297 newly diagnosed HIV/AIDS patients were enrolled in Peking Union Medical College Hospital (PUMCH) from January 2001 to December 2012, including 19 patients of primary phase, 115 of asymptomatic phase and 163 of AIDS phase. Clinical characteristics of these patients were retrospectively analyzed., Results: Two hundred and nineteen out of 297 patients reported clinical symptoms with variety. The main systemic symptoms included fever (100 cases, 33.7%), weight loss (50 cases, 16.8%) and fatigue (38 cases, 12.8%). Organ involvement included mucocutaneous (67 cases, 22.6%), respiratory (62 cases, 20.9%), gastrointestinal (40 cases, 13.5%) systems. Patients in AIDS phase were more symptomatic. Seventy-three out of 173 (42.2%)patients have been referred by 2 healthcare providers at least before the diagnosis of HIV infection was confirmed. Initial diagnoses were made in Departments of Infectious Diseases (36.9%), Gastroenterology (16.4%), and Emergency (13.7%). Opportunistic infections accounted for most AIDS defining conditions (ADC), including pneumocystis jiroveci pneumonia (PCP) (36 cases, 22.1%), cytomegalovirus infection (25 cases, 15.3%) and tuberculosis (22 cases, 13.5%). Median peripheral CD(+)4 T lymphocyte count in patients with ADC were 36 cells/µl., Conclusions: Common clinical presentations of HIV/AIDS included fever, weight loss, diarrhea, short of breath and mucocutaneous lesions. Opportunistic infections mainly affected respiratory and gastrointestinal system, with PCP the most common one. The diagnosis of HIV infection was delayed in most cases, suggesting that more efforts are required especially in universal education of clinicians and accurate viral detection.

Objective: To improve the diagnosis and treatment of Q fever endocarditis., Methods: From 2008 to 2013, four cases of Q fever endocarditis were diagnosed in Peking Union Medical College Hospital. Clinical features, laboratory test, management and prognosis were analyzed with literature review., Result: All four cases had long period of fever and heart murmur. Two patients represented with respiratory symptom and one with non-specific rash. General laboratory tests including complete blood cell count, ESR, C-reactive protein(CRP), liver function and radiology of lung did not show specific abnormalities. Signs of endocarditis were shown by ultrasound and important for diagnosis. Repeated blood culture was negative. All of the diagnoses were confirmed by serum antibody detection and the patients recovered well with treatment based on doxycycline or minocycline., Conclusions: Endocarditis is the most common form of chronic Q fever, which is easily misdiagnosed because its blood culture is negative and may accompanied with varied manifestation such as pneumonia and liver injury. For the patients with chronic fever and blood culture negative endocarditis, chronic Q fever should be considered as differential diagnosis. The confirmatory method for diagnosis is serum antibody detection. Early and sufficient treatment may improve the prognosis.

Objectives: Nevirapine (NVP), a still widely used nonnucleoside reverse transcriptase inhibitor, can cause severe hepatotoxicity. Previous studies suggest that CD4 cell counts more than 250 cells per microliter in women and more than 400 cells per microliter in men are risk factors for NVP-related hepatotoxicity. These studies have informed Chinese national treatment guidelines. We evaluate whether current Chinese guidelines for NVP use are appropriate., Methods: Longitudinal data were pooled from 2 clinical trials between 2005 and 2009 across mainland China. Five hundred sixty-six antiretroviral therapy-naive Chinese patients were given NVP-containing antiretroviral therapy for 24 weeks. Hepatotoxicity was defined as alanine aminotransferase, aspartate transaminase, or total bilirubin level greater than 1.25 times the upper limit of normal range. Severe hepatotoxicity was defined as greater than 5 times the upper limit of normal range., Results: One hundred ninety-seven (36.1%) patients developed hepatotoxicity during treatment, including 42 (7.7%) patients with severe hepatotoxicity. CD4 cell count more than 250 cells per microliter was an independent predictor for hepatotoxicity both in men [relative risk = 1.22 (95% confidence interval: 1.04 to 1.44)] and in women [relative risk = 1.72 (95% confidence interval: 1.20 to 2.46)]. Severe hepatotoxicity was also more common among all persons with CD4 >250 cells per microliter., Conclusions: Hepatotoxicity was a common adverse effect of NVP among men and women with CD4 >250 cells per microliter. Chinese treatment guidelines should be considered to reflect this risk.

Objective: To evaluate the influence of hepatitis B virus (HBV) coinfection on immunological, virological and clinical responses to lamivudine (3TC)-based combined antiretroviral therapy (cART) in Chinese patients., Design and Methods: This prospective, multicenter cohort study recruited 529 antiretroviral-naive participants (aged 18–65 years, both sexes) between 2008 and 2010.They were grouped by HBV serostatus. Virological and immunological responses were monitored at baseline and week 4, 8, 12, 24, 36 and 48. cART for all patients was nevirapine, 3TC with either zidovudine or stavudine., Results: First, HIV/HBV coinfection rate in our cohort was 14.6%. Second, among 508 patients with complete baseline information, median CD4 level was significantly lower in the chronic HBV-infected (CHB) group and isolated core group. In the CHB group,hepatitis B e antigen positivity rather than HBV DNA level was associated with lower CD4 cell count. Third, in the isolated core group, occult infection rate was 9.5%.Fourth, at week 48, rate of HIV suppression below 40 copies/ml was 74.2%. Median increase in the CD4 cell count at week 48 was 127 cells/ml. Of note, HBV serostatus did not influence virological and immunological response to cART at each follow-up time point. Although HBV serostatus was associated with different alanine aminotransferase levels during follow-up, hepatitis and hyperbilirubinemia rates were not significantly different. Fifth, the 3TC-based regimen was efficacious against HBV replication, with median decrease in HBV DNA of 2.87 log copies/ml. However, hepatitis B e antigen positivity was associated with poorer HBV DNA suppression., Conclusion: In our cohort, CHB infection and isolated hepatitis B core antibody positivity were related to faster HIV progression. Despite of this, virological and immunological responses were not affected by HBV serostatus.