Globally 37.9 million people are living with HIV/AIDS, and with mortality rates declining, there is an increasing focus on comorbidities including musculoskeletal (MSK) disorders. Therefore, the aim of this scoping review was to generate and summarize an overview of the existing scientific literature dealing with MSK complaints in people living with HIV/AIDS (PLWHAs).

This scoping review followed the five-stage methodological framework proposed by Arksey and O’Malley. We searched PubMed, EMBASE, CINAHL, and the Cochrane Library from inception to June 1, 2020. Two reviewers independently reviewed the articles for eligibility. A data extraction form was used to chart information such as author, year of publication, data source, sample size, country of origin, ethnicity, age, gender, antiretroviral therapy, MSK condition prevalence, and anatomical location.

The search identified 10 522 articles. Of these, 27 studies were included after full-text screening for data extraction. Studies were conducted in thirteen different countries with diverse data sources such as outpatient clinic files, hospital records, primary care clinic files, and AIDS Service Organization files. PLWHAs have a variety of MSK conditions. Most studies reported spinal pain such as lower back or neck pain, but pain in the extremities and osteoarthritis (OA) were also represented. However, the frequencies of pain at various anatomical sites were highly variable.

There is a lack of knowledge regarding MSK conditions in PLWHAs. Future studies designed to specifically study MSK complaints and disabilities are needed to gain a better picture of the impact of these conditions in PLWHAs and to inform prevention and treatment strategies globally in this often-underserved population.

The systemic inflammatory response is regarded as the major cause of endotoxin-induced coagulopathy, which is a strong predictor of mortality in patients with severe sepsis. Simvastatin plays an important role in reducing inflammation. In addition, the gut has long been hypothesized to be the “motor” of critical illness, driving or aggravating sepsis by the increased intestinal permeability and bacterial translocation. Whether simvastatin plays a role in severe endotoxin-induced coagulopathy through the gut is unclear.

In this study, mice were administered 20 mg/kg simvastatin by gavage for 2 weeks and then intraperitoneally injected with 50 mg/kg endotoxin. Twelve h later, cytokine release, coagulation dysfunction, organ damage, and survival were assessed. Besides, the intestinal barrier, permeability, bacteria abundance, and translocation were evaluated.

We found that the severity of endotoxin-induced coagulopathy was significantly improved in simvastatin-pretreated mice, who showed attenuated depletion of coagulation factors and platelets, decreased plasminogen activator inhibitor-1 (PAI-1) expression, reduced organ fibrin deposition, and improved survival time. Also, simvastatin reduced epithelial apoptosis and improved intestinal barrier function by upregulating antimicrobial peptides, lysozyme, and mucins. Simvastatin increased Lactobacillales counts, while the lipopolysaccharide group showed increased Desulfovibrio and Mucispirillum, which can produce harmful toxins. Finally, the decreased intestinal permeability in the simvastatin group caused reduced bacterial translocation in the organs and blood, both in terms of quantity and species.

Simvastatin improves the prognosis of severe endotoxemia, and the intestinal microenvironment participates in this process.

Angelica (A.) sinensis is used as a traditional medical herb for the treatment of neurodegeneration, aging, and inflammation in Asia. A. sinensis optimal formula (AOF) is the best combination in A. sinensis that has been screened to rescue the cognitive ability in β-amyloid peptide (Aβ_25–35)-treated Alzheimer’s disease (AD) rats. The objective of this study was to investigate the effect of AOF on the learning and memory of AD rats as well as to explore the underlying mechanisms.

Male Wistar rats were infused with Aβ_25–35 for AD model induction or saline (negative control). Five groups of AD rats were fed on AOF at 20, 40, or 80 mL/kg every day, donepezil at 0.9 mg/kg every day (positive control), or an equal volume of water (AD model) intragastrically once a day for 4 weeks, while the negative control rats were fed on water. The Morris water maze test was used to evaluate the cognitive function of the rats. The Aβ accumulation, cholinergic levels, and antioxidative ability were detected by ELISA. Additionally, the candidate mechanism was determined by gene sequencing and quantitative real-time polymerase chain reaction.

The results showed that AOF administration significantly ameliorated Aβ_25–35-induced memory impairment. AOF decreased the levels of amyloid-β precursor protein and Aβ in the hippocampus, rescued the cholinergic levels, increased the activity of superoxide dismutase, and decreased the malondialdehyde level. In addition, AOF inhibited the expression of IL1b, Mpo, and Prkcg in the hippocampus.

These experimental findings illustrate that AOF prevents the decrease in cognitive function and Aβ deposits in Aβ_25–35-treated rats via modulating neuroinflammation and oxidative stress, thus highlighting a potential therapeutic avenue to promote the co-administration of formulas that act on different nodes to maximize beneficial effects and minimize negative side effects.

The nuclear factor erythroid 2 (NFE2)-related factor 2 (Nrf2) is associated with doxorubicin (DOX)-induced cardiac injury. It has been reported that microRNA-24-3p (miR-24-3p) may regulate the Keapl by mRNA degradation, whereas Keapl can suppress the activation of Nrf2. However, the role of miR-24-3p in DOX-related cardiotoxicity remains unclear.

The mice receiving DOX were used as cardiac injury model. In this study, an adenoassociated virus 9 system was used to deliver miR-24-3p or miR-scramble to mice hearts. The echocardiographic and hemodynamic analyses were used to evaluate the effects of miR-24-3p on cardiac function under DOX stimulation. ELISA and RT-PCR were used to detect protein or mRNA expressions associated with cardiac injury, inflammation response, apoptosis and oxidative stress. Western Blot were used for quantitative analysis of the roles of miR-24-3p in regulating Nrf2 expression. H9C2 cells used to verify the role of miR-24-3p in vitro.

We found that miR-24-3p mRNA was significantly decreased in DOX-treated mice and cardiomyocytes. Overexpression of miR-24-3p blocked cardiac injury caused by DOX injection, as reflected by the reduction in the levels of cardiac troponin I, creatinine kinase isoenzyme MB and the N-terminal pro brain natriuretic peptide. Furthermore, miR-24-3p reduced oxidative stress and cell loss without affecting the inflammation response. As expected, we found that Nrf2 was upregulated by miR-24-3p supplementation, and that the protective efforts of miR-24-3p supplementation were abolished when Nrf2 was silenced.

The results from this study suggest that miR-24-3p protects cardiomyocytes against DOX-induced heart injury via activation of the Nrf2 pathway. miR-24-3p supplementation may be a novel strategy to counteract the cardiac side effects of DOX treatment.

The clinical characteristics and microbiological data of patients with K. pneumoniae bloodstream infections (BSI) from January 2018 to December 2020 were retrospectively analyzed to study the molecular epidemiology of Carbapenem-resistant Klebsiella pneumoniae (CRKP). We also aimed to identify the risk factors for the development of CRKP BSI.

This retrospective study was conducted at Renmin Hospital of Wuhan University from January 2018 to December 2020. The date of non-duplicate K. pneumoniae isolates isolated from blood samples was identified using the microbiology laboratory database. The data from patients diagnosed with K. pneumoniae BSI were collected and analyzed.

From 2018 to 2020, there were 510 non-duplicated K. pneumoniae blood isolates, mainly distributed in the intensive care unit (ICU) (28.4%), that were identified in our research. These cases included 77 strains of CRKP and 433 strains of carbapenem-susceptible K. pneumoniae (CSKP). The resistance rate of K. pneumoniae to meropenem and imipenem increased from 11.2% in 2018 to 27.1% in 2020. Moreover, Compared with CSKP, all CRKP isolates showed multi-resistance to tested antibiotics. The phylogenetic analysis showed that the CRKP isolates could be grouped into four major clades, and multilocus sequence typing revealed that the isolates had considerable clonality. Overall, 8 sequence types (STs) of CRKP were detected, of which ST11 comprised the majority and clustered into clade 3. The most prevalent carbapenemase gene was bla_KPC (87%) among the CRKP isolates, followed by bla_NDM (9.1%) and bla_IMP (1.3%). A total of 74 (16.6%) patients with CRKP BSI and 373 (83.4%) patients with CSKP BSI were categorized as the case and control groups. The mortality in the CRKP group was 44.6%, and 11.5% in CSKP group (P<0.001). A multivariate analysis that a long hospital stay before BSI (OR=1.42, 95% CI 1.02–4.31, P=0.011), ICU hospitalization history (OR=3.30, 95% CI 1.35–8.05, P=0.002), and prior use of carbapenems (OR=3.33, 95% CI 1.29–7.27, P=0.001) and antifungals (OR=2.81, 95% CI 1.24–6.04, P<0.001) were independent risk factors for CRKP BSI.

ST11 is the predominant type of CRKP mediating inter-hospital transmission, and bla_KPC is the main carbapenemase gene harboured by CRKP blood isolates. ICU stay, prolonged hospitalization before BSI, and prior use of carbapenems and antifungals were independent risk factors for acquiring CRKP BSI. Our study may provide insights into early infection control practices.

Although the effect of decitabine on myelodysplastic syndrome (MDS) has been demonstrated, merely a proportion of patients respond to therapy, and no well-recognized predictors have been identified. This study was conducted to investigate the effectiveness of decitabine in real-world clinical practice, and determine the predictive factors of response and overall survival (OS) in MDS patients.

Clinical and pathological data were collected from 94 patients and analyzed. These patients were reclassified according to the 2016 World Health Organization classification criteria, and restratified by International Prognostic Scoring System prognostic scores. The response evaluation was performed according to the 2006 modified International Working Group response criteria.

In this study, 62% of patients responded to decitabine. Among these patients, 15 patients (16%) obtained complete remission (CR), 15 patients (16%) obtained marrow CR with hematologic improvement (HI), 20 patients (21%) obtained marrow CR without HI, and 8 patients (9%) only obtained HI, and no patient botained partial remission. The OS of the responders was significantly longer than that of non-responders (67 months vs. 7 months, P<0.001). The OS in patients with and without platelet doubling was significantly different in both the low/intermediate and high/very high risk groups (P=0.0398 and P=0.0330). The multivariate analysis revealed that platelet doubling after the first decitabine cycle is an independent predictor of response and OS in MDS patients (P=0.002 and P=0.008).

Decitabine is effective for treating MDS patients in real-world clinical practice. Furthermore, platelet doubling after the first decitabine cycle can be used as a predictor of response and survival in MDS patients.

Several studies indicated that tonsillectomy can improve the prognosis of patients with immunoglobulin A nephropathy (IgAN). However, the relationship between tonsillar immunity and IgAN is still unclear.

A total of 14 IgAN patients were recruited in the current study from May 2015 to April 2016 in Tongji Hospital. B cells, dendritic cells (DCs), and IgA1 positive cells in human tonsils were detected using immunofluorescence and immunohistochemistry. Correlations between these cells and clinicopathologic features were evaluated.

CD19⁺CD5⁺ B cells were predominantly located in germinal centers and mantle zones of lymphoid follicles, the CD208+ DCs were distributed in the interfollicular and subepithelial area, and IgA1-positive cells were predominantly detected in mantle zones of lymphoid follicles and subepithelial tissues. The numbers of CD19⁺CD5⁺ B cells, CD208⁺ DCs, and IgA1-positive cells in tonsillar tissues from IgAN patients were significantly higher than those in the normal controls (P<0.01, respectively). CD19⁺CD5⁺ B cells, CD208⁺ DCs, and IgA1-positive cells in tonsillar tissues were significantly associated with 24-h proteinuria levels and tubular atrophy/interstitial fibrosis of IgAN.

CD19⁺CD5⁺ B cells, CD208⁺ DCs, and IgA1-positive cells in tonsillar tissues might be involved in the pathogenesis of IgAN.

The eukaryotic release factor 3a (eRF3a), a member of the eukaryotic peptide chain release factor family, is overexpressed in several types of cancer. This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer.

Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer. Western blotting and RT-qPCR were used to detect the expression level of eRF3a in normal liver cells and liver cancer cells. The cell transfection experiments were performed to overexpress eRF3a levels in liver cancer cells HCCLM9 and Huh7, and then cell cycle and apoptosis experiments, Cell Counting Kit-8 (CCK8), plate cloning, and Transwell experiments were done to evaluate the function of eRF3a in the progression of liver cancer. The Western blotting was done to explore the mechanism of eRF3a promoting the development of liver cancer.

eRF3a was significantly highly expressed in liver cancer cells, and its expression level was negatively correlated with the clinical prognosis of patients. In addition, in vitro experiments showed that eRF3a could promote the proliferation and migration of liver cancer cells through the ERK and JNK signaling pathways.

This study suggests that eRF3a may be a potential prognostic marker for liver cancer and act as an oncogene by activating JNK and ERK signaling; therefore, eRF3a may be a new target for the treatment of liver cancer.

To investigate the feasibility and safety of achieving total enteroscopy by consecutive bidirectional double-balloon enteroscopy (DBE) procedures.

The demographic data, indication, initial insertion route, examination time for each insertion and the entire procedure, total enteroscopy rate, diagnostic yield and adverse events of patients who attempted to achieve total enteroscopy by consecutive bidirectional DBE procedures from January 2014 to December 2019 were retrospectively analyzed.

A total of 189 patients were included, and the total enteroscopy rate was 87.3%. Initiating the DBE procedure via the retrograde approach as the initial insertion route achieved a higher total enterosocpy rate (90.9% vs. 78.9%, P=0.023), with shorter overall examination time (134.2±36.2 vs. 156.9±47.6 min, P=0.017) and shorter examination time for the opposite insertion route (23.8±19.9 vs. 53.1±27.6 min, P=0.000) compared with anteograde approach as the initial insertion route. The overall diagnostic yield was 37.6%. The diagnostic yield for successfully achieving total enteroscopy was higher, when compared to the yield for not successfully achieving total enteroscopy (39.4% vs. 25%, P=0.029). The overall rate of adverse events was 2.1% (4/189). There was no significant difference in adverse event rate between the overall examination time ≥2 h group and <2 h group (2.1% vs. 2.0%, P=0.593).

Consecutive bidirectional DBE procedure is an effective and safe strategy for achieving total enteroscopy with a considerable success rate. This may be a promising option and alternative to traditional methods, and helpful to more promptly establish a definite diagnosis. The retrograde approach, as the initial insertion route, is preferred in clinical practice.

To investigate the value of routine intraoperative ultrasound (IU) and intraoperative contrast-enhanced ultrasound (ICEUS) in the surgical treatment of brain tumors, and to explore the utilization of ICEUS for the removal of the remnants surrounding the resection cavity.

In total, 51 patients who underwent operations from 2012 to 2018 due to different tumors in the brain were included in this study. The clinical data were evaluated retrospectively. IU was performed in all patients, among which 28 patients underwent ICEUS. The effects of IU and ICEUS on tumor resection and recurrence were evaluated. Semiquantitative analysis was performed to compare ICEUS parameters of the brain tumor with those of the surrounding tissue.

In total, 36 male and 15 female patients were included in this study. The average age was 43 years (range: 14–68 years). The follow-up period was from 7 to 74 months (mean follow-up 32 months). IU was used in all patients, and no lesion was missed. Among them, 28 patients underwent ICEUS. The rate of total removal of the ICEUS group (23/28, 82%) was significantly higher than that of the IU group (11/23, 48%) (P<0.05). The recurrence rate of ICEUS and IU was 18% (5/23), and 22% (5/28), respectively, and the difference did not reach statistical significance (P>0.05). The semiquantitative analysis showed that the intensity and the transit time of microbubbles reaching the lesions were significantly different from the intensity and the transit time of microbubbles reaching the surrounding tissue (P<0.05) and reflected indirectly the volume and the speed of blood perfusion in the lesions was higher than those in the surrounding tissue.

ICEUS is a useful tool in localizing and outlining brain lesions, especially for the resection of the hypervascular lesions in the brain. ICEUS could be more beneficial for identifying the remnants and improving the rate of total removal of these lesions than routine intraoperative ultrasound.

Childhood obesity is a major health concern worldwide. Previous studies have explored the relationship between obesity and gut microbiota. However, the results from such studies remain contradictory.

In the present nested case-control study, based on a twin birth cohort study, the relationship between gut microbiota diversity and overweight/obesity in 1- and 6-month-old infants was explored. Twins were enrolled when one child had normal weight and the other child was overweight/obese at six months old. For both infants, stool samples were collected at 1 and 6 months of age. Finally, 12 twins were enrolled in the study. The gut microbiota was identified by 16S rRNA gene sequencing in the V3–V4 area. Six of the twins were monozygotic.

The results revealed that the microbiota communities of monozygotic twins were similar to those of dizygotic twins. The relative abundance (RA) of microbiota of 1-month-old twins was significantly higher than that of 6-month-old twins. However, the microbiota diversity of 1-month-old twins was significantly lower than that of 6-month-old twins. In addition, 6-month-old twins had significantly higher RA levels of Bifidobacterium and Lachnospiracea incertae sedis than 1-month-old twins. The 6-month-old group had significantly lower RA levels of Veillonella, Klebsiella, Akkermansia, Streptococcus, or Staphylococcus than the 1-month-old group. At six months, the RA level of Clostridium sensu stricto was higher in the overweight/obesity group than the normal-weight group.

These findings imply that changes in gut microbiota diversity during infancy may contribute to the development of obesity in early infancy.

The objective of this study was to investigate the application of unenhanced computed tomography (CT) texture analysis in differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC).

Preoperative CT images of 112 patients (31 with PASC, 81 with PDAC) were retrospectively reviewed. A total of 396 texture parameters were extracted from AnalysisKit software for further texture analysis. Texture features were selected for the differentiation of PASC and PDAC by the Mann-Whitney U test, univariate logistic regression analysis, and the minimum redundancy maximum relevance algorithm. Furthermore, receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the texture feature-based model by the random forest (RF) method. Finally, the robustness and reproducibility of the predictive model were assessed by the 10-times leave-group-out cross-validation (LGOCV) method.

In the present study, 10 texture features to differentiate PASC from PDAC were eventually retained for RF model construction after feature selection. The predictive model had a good classification performance in differentiating PASC from PDAC, with the following characteristics: sensitivity, 95.7%; specificity, 92.5%; accuracy, 94.3%; positive predictive value (PPV), 94.3%; negative predictive value (NPV), 94.3%; and area under the ROC curve (AUC), 0.98. Moreover, the predictive model was proved to be robust and reproducible using the 10-times LGOCV algorithm (sensitivity, 90.0%; specificity, 71.3%; accuracy, 76.8%; PPV, 59.0%; NPV, 95.2%; and AUC, 0.80).

The unenhanced CT texture analysis has great potential for differentiating PASC from PDAC.

The annual influenza epidemic is a heavy burden on the health care system, and has increasingly become a major public health problem in some areas, such as Hong Kong (China). Therefore, based on a variety of machine learning methods, and considering the seasonal influenza in Hong Kong, the study aims to establish a Combinatorial Judgment Classifier (CJC) model to classify the epidemic trend and improve the accuracy of influenza epidemic early warning.

The characteristic variables were selected using the single-factor statistical method to establish the influencing factor system of an influenza outbreak. On this basis, the CJC model was proposed to provide an early warning for an influenza outbreak. The characteristic variables in the final model included atmospheric pressure, absolute maximum temperature, mean temperature, absolute minimum temperature, mean dew point temperature, the number of positive detections of seasonal influenza viruses, the positive percentage among all respiratory specimens, and the admission rates in public hospitals with a principal diagnosis of influenza.

The accuracy of the CJC model for the influenza outbreak trend reached 96.47%, the sensitivity and specificity change rates of this model were lower than those of other models. Hence, the CJC model has a more stable prediction performance. In the present study, the epidemic situation and meteorological data of Hong Kong in recent years were used as the research objects for the construction of the model index system, and a lag correlation was found between the influencing factors and influenza outbreak. However, some potential risk factors, such as geographical nature and human factors, were not incorporated, which ideally affected the prediction performance to some extent.

In general, the CJC model exhibits a statistically better performance, when compared to some classical early warning algorithms, such as Support Vector Machine, Discriminant Analysis, and Ensemble Classfiers, which improves the performance of the early warning of seasonal influenza.