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Background Lumbar disc herniation (LDH) has emerged as one of the most common causes of low back pain. The routine treatment approach involves chemonucleolysis therapy, discectomy by percutaneous endoscopy, and percutaneous laser disc decompression. Unfortunately, all of these methods carry inherent risk of causing harm to the patient and, as such, there is an unmet but urgent need for an effective and safe noninvasive treatment for LDH. The purpose of this report is to describe a non-invasive method for re-absorption of LDH. Case summary A 34-year-old woman was admitted with a complaint of waist pain that she reported as having become acutely aggravated over the past 3 d and accompanied by discomfort in the right lower limb. Her self-reported medical history included persistent postpartum low back pain from 7 years prior. Physical exam showed positivity for neck flexion test (Lindner sign) and supine abdomen test; the straight leg-raising test showed right 60(+) and left 80(-). Findings from standard imaging (magnetic resonance) and collective physical examinations indicated a L5/S1 herniated lumbar disc. Treatment consisted of three-dimensional (balanced regulating) spinal manipulation and acupuncture, upon which the LDH resolved by retraction. Conclusion Following L5/S1 herniated lumbar disc diagnosis, three-dimensional (balanced regulating) spinal manipulation combined with acupuncture therapy is an effective treatment.

The world is experiencing an ongoing pandemic of coronavirus disease-2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In attempts to control the pandemic, a range of nonpharmaceutical interventions (NPIs) has been implemented worldwide. However, the effect of synchronized NPIs for the control of COVID-19 at temporal and spatial scales has not been well studied. Therefore, a meta-population model that incorporates essential nonlinear processes was constructed to uncover the transmission characteristics of SARS-CoV-2 and then assess the effectiveness of synchronized NPIs on COVID-19 dynamics in China. Regional synchronization of NPIs was observed in China, and it was found that a combination of synchronized NPIs (the travel restrictions, the social distancing and the infection isolation) prevented 93.7% of SARS-CoV-2 infections. The use of synchronized NPIs at the time of the Wuhan lockdown may have prevented as much as 38% of SARS-CoV-2 infections, compared with the unsynchronized scenario. The interconnectivity of the epicenter, the implementation time of synchronized NPIs, and the number of regions considered all affected the performance of synchronized NPIs. The results highlight the importance of using synchronized NPIs in high-risk regions for the control of COVID-19 and shed light on effective strategies for future pandemic responses. Supplementary Information The online version contains supplementary material available at 10.1007/s11071-021-06505-0.

The purpose of this study was to analyze the acute effect of ambient temperature on hospitalization due to acute exacerbation of chronic obstructive pulmonary disease (AECOPD), stroke, and myocardial infarction (MI) in Shenyang, China. We used the distributed delayed nonlinear model to evaluate the impact of ambient temperature on respiratory and cardiovascular diseases. The study population was divided into four groups: < 65 group and ≥ 65 age groups, female and male groups. The < 65 age group of AECOPD patients was more likely to be affected by high ambient temperature, while the ≥ 65 age group of AECOPD patients was more sensitive to low ambient temperature. The hospitalization risk of MI admission increased in the ≥ 65 age group at 1–8 days delay under low ambient temperature conditions. Supplementary Information The online version contains supplementary material available at 10.1007/s11356-020-11934-2.

Abiotic stress factors can significantly affect insects. In particular, the stressful effects of exposure to ultrasound on insects are considered important. In the present study, we investigated the effects of ultrasound on the important global pest Monochamus alternatus (Coleoptera: Cerambycidae), which is the main vector of the pinewood nematode. We exposed M. alternatus adults (aged 1 day, 3 days, and 5 days) to ultrasound at different frequencies (using two ultrasonic devices, i.e., LHC20 with a mixture of frequencies at 35 kHz, 70 kHz, and 105 kHz; and GFG-8016G at two separate frequencies of 30 kHz and 60 kHz) for different periods of time (1 h, 12 h, and 24 h), before evaluating the juvenile hormone III (JHIII) titers. All of the ultrasound treatments significantly decreased the JHIII titers in M. alternatus adults. The decreases in the JHIII titers due to ultrasound exposure did not differ according to sex, but the effects on beetles of different ages differed significantly depending on the duration of exposure. The decreases in the JHIII titers were highest in male and female beetles after exposure to ultrasound for 12 h. Following exposure to ultrasound for any time period, the decreases in the JHIII titers were lower in adults aged 3 days than those aged 1 day and 5 days. The different ultrasonic frequencies led to variable decreases in the JHIII titers in M. alternatus adults, where the greatest decreases occurred in beetles exposed to ultrasound at 60 kHz. Our results indicate that ultrasound can negatively affect the normal JHIII levels and it may further disrupt sexual maturation by M. alternatus adults.

Proliferation is one of the significant hallmarks of gallbladder cancer, which is a relatively rare but fatal malignance. Aim of this study was to examine the biological impact and molecular mechanism of the candidate hub-gene on the proliferation and tumorigenesis of gallbladder cancer. We analyzed the differentially expressed genes and the correlation between these genes with MKI67, and showed that KIF11 is one of the major upregulated regulators of proliferation in gallbladder cancer (GBC). The Gene Ontology, Gene Sets Enrichment Analysis and KEGG Pathway analysis indicated that KIF11 may promote GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. Gain-of-function and loss-of-function assay demonstrated that KIF11 regulated GBC cell cycle and cancer cell proliferation in vitro. GBC cells exhibited G2M phase cell cycle arrest, cell proliferation and clone formation ability reduction after treatment with Monastrol, a specific inhibitor of KIF11. Xenograft model showed that KIF11 promotes GBC growth in vivo. Rescue experiments showed that KIF11-induced GBC cell proliferation dependented on ERBB2/PI3K/AKT pathway. Moreover, we found that H3K27ac signals are enriched among the promoter region of KIF11 in the UCSC Genome Browser Database. Differentially expressed analysis showed that EP300, a major histone acetyltransferase modifying H3K27ac signal, is highly expressed in gallbladder cancer and correlation analysis illustrated that EP300 is positively related with KIF11 in almost all the cancer types. We further found that KIF11 was significantly downregulated in a dose-dependent and time-dependent manner after histone acetylation inhibitor treatment. The present results highlight that high KIF11 expression promotes GBC cell proliferation through the ERBB2/PI3K/AKT signaling pathway. The findings may help deepen our understanding of mechanism underlying GBC cancer development and development of novel diagnostic and therapeutic target.

BACKGROUND Results from previous studies evaluating the effects of remote ischemic preconditioning (RIPC) on morbidity and mortality after cardiac surgery are inconsistent. This meta-analysis of randomized controlled trials (RCTs) aims to determine whether RIPC improves cardiac and renal outcomes in adults undergoing cardiac surgery. METHODS PubMed, EMBASE, and Cochrane Library were comprehensively searched to identify RCTs comparing RIPC with control in cardiac surgery. The coprimary outcomes were the incidence of postoperative myocardial infarction (MI) and the incidence of postoperative acute kidney injury (AKI). Meta-analyses were performed using a random-effect model. Subgroup analyses were conducted according to volatile only anesthesia versus propofol anesthesia with or without volatiles, high-risk patients versus non-high-risk patients, and Acute Kidney Injury Network (AKIN) or Kidney Disease Improving Global Outcomes (KDIGO) criteria versus other criteria for AKI diagnosis. RESULTS A total of 79 RCTs with 10,814 patients were included. While the incidence of postoperative MI did not differ between the RIPC and control groups (8.2% vs 9.7%; risk ratio [RR] = 0.87, 95% confidence interval [CI], 0.76-1.01, P = .07, I2 = 0%), RIPC significantly reduced the incidence of postoperative AKI (22% vs 24.4%; RR = 0.86, 95% CI, 0.77-0.97, P = .01, I2 = 34%). The subgroup analyses showed that RIPC was associated with a reduced incidence of MI in non-high-risk patients, and that RIPC was associated with a reduced incidence of AKI in volatile only anesthesia, in non-high-risk patients, and in the studies using AKIN or KDIGO criteria for AKI diagnosis. CONCLUSIONS This meta-analysis demonstrates that RIPC reduces the incidence of AKI after cardiac surgery. This renoprotective effect of RIPC is mainly evident during volatile only anesthesia, in non-high-risk patients, and when AKIN or KDIGO criteria used for AKI diagnosis.

We aimed to investigate the circRNA–miRNA regulatory network in atrial fibrillation (AF) by using Cytoscape and HMDD v3.0. Finally, 120 differentially expressed circRNAs in peripheral blood monocytes of 4 AF patients were preliminarily screened by circRNA microarray. circRNA_4648, circRNA_4631, and circRNA_2875 were the first four circRNAs with the most binding nodes in the circRNA–miRNA network. The top three most frequent miRNAs for up-regulated circRNAs were hsa-miR-328 that interacted with 5 up-regulated circRNAs, hsa-miR-4685-5p with 4 up-regulated circRNAs, hsa-miR-3150a-3p, hsa-miR-4649-5p, hsa-miR-4783-3p, and hsa-miR-8073 with 3 up-regulated circRNAs,, while the top three most frequent miRNAs for down-regulated circRNAs were hsa-miR-328 that interacted with 14 down-regulated circRNAs, hsa-miR-4685-5p with 11 down-regulated circRNAs and hsa-miR-661 with 9 down-regulated circRNAs. According to HMDD v3.0, five up-regulated and eleven down-regulated circRNAs were found to interact with AF related miRNAs. These results indicated the possible regulatory network between circRNAs and miRNAs in the pathogenesis of AF.

The aim of this study was to investigate the safety and clinical efficacy of mini-laparoscopic pyeloplasty in treating ureteropelvic junction obstruction (UPJO) in infants.We retrospectively analysed the clinical data of 66 infants with UPJO from January 2013 to August 2018 at our hospital. They were divided into the laparoscopic surgery group (group A) and the open surgery group (group B), depending on the surgical method.The bleeding volume, analgesia duration, postoperative hospitalization duration, and incision length in group A were significantly less than those in group B (Mini-laparoscopic pyeloplasty to treat UPJO in infants has the same early clinical efficacy and safety as open surgery, and this procedure has the advantages of fewer incisions, less pain, quicker recovery, and better cosmetic outcomes.

Background and objectives Patients with femoral neck fractures often suffer severe pain. This randomized controlled clinical study compared the effect of femoral nerve block (FNB) and fascia iliaca compartment block (FICB) in this population. Patients and methods Forty-six patients were randomly assigned to one of the two groups: FNB group (femoral nerve block, n=23) or FICB group (fascia iliaca compartment block, n=23). Before positioning for spinal anesthesia, patients received FNB with 15 mL of 0.5% ropivacaine or FICB with 40 mL of 0.5% ropivacaine. Pain was evaluated using a visual analogue scale (VAS) at rest and during hip flexion after admission to the operation room; at 3, 5, 8, and 10 min after analgesia intervention; and during positioning for spinal anesthesia. Positioning was attempted after 10 min of analgesia intervention in each group. Time required to perform spinal anesthesia, quality of positioning, and patient satisfaction were documented. Results The VAS scores in the FNB group were significantly lower than those in FICB group at 3 and 5 min after analgesia intervention (P=0.000). However, there were no significant differences in VAS between groups at 8 or 10 min or during positioning. Conclusion FNB and FICB produce similar analgesic effects in patients with femoral neck fractures, but FNB has a more rapid onset of pain relief.

Background: The role of miR-1 and miR-133 in regulating the expression of potassium and calcium ion channels, and mediating cardiomyocyte apoptosis in mice with viral myocarditis (VMC) is investigated herein. Methods: Male Balb/c mice were randomly divided into groups: control group, VMC group, VMC + miR-1/133 mimics group, or VMC + miR-1/133 negative control (NC) group. VMC was induced with coxsackievirus B3 (CVB3). MiR-1/133 mimics ameliorated cardiac dysfunction in VMC mice and was compared to the VMC+NC group. Results: Hematoxylin and eosin staining showed a well-arranged myocardium without inflammatory cell infiltration in the myocardial matrix of the control group. However, in the VMC and VMC+NC groups, the myocardium was disorganized and swollen with necrosis, and the myocardial matrix was infiltrated with inflammatory cells. These changes were alleviated by miR-1/133 mimics. TUNEL staining revealed decreased cardiomyocyte apoptosis in the VMC + miR-1/133 mimics group compared with the VMC group. In addition, miR-1/133 mimics up-regulated the expression of miR-1 and miR-133, the potassium channel genes Kcnd2 and Kcnj2, as well as Bcl-2, and down-regulated the expression of the potassium channel suppressor gene Irx5, L-type calcium channel subunit gene a 1c (Cacna1c), Bax, and caspase-9 in the myocardium of VMC mice. MiR-1/133 also up-regulated the protein levels of Kv4.2 and Kir2.1, and down-regulated the expression of CaV1.2 in the myocardium of VMC mice. Conclusions: MiR-1 and miR-133 decreased cardiomyocyte apoptosis by mediating the expression of apoptosis-related genes in the hearts of VMC mice.

Purpose: The purpose of this study was to summarize the clinical experience with laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle for inguinal hernias in girls.Material and methods: A total of 462 girls with inguinal hernias participated in this study from January 2013 to June 2019. Laparoscopic percutaneous extraperitoneal closure of the internal ring via an epidural needle was used to treat these patients.Results: All 462 girls with an inguinal hernia successfully underwent laparoscopic surgery. The operative times for unilateral and bilateral inguinal hernias were 15 (11-25) minutes and 23 (18-33) minutes, respectively. All patients were discharged 1-2 days after the operations. During the hospitalization and follow-up periods, none of the following complications were observed: hernia recurrence, umbilical hernia, abdominal wall vascular injury, intestinal injury or bladder injury. However, there were six patients with complications: two cases of poor healing of the umbilical incision, three cases of suture granulomas and one case of groin traction pain and discomfort.Conclusion: Laparoscopic percutaneous extraperitoneal closure of the internal ring using an epidural needle is a safe and feasible method for the treatment of inguinal hernias in girls. This method has the advantages of limited trauma, no scarring and a good cosmetic effect.

Few systemic studies of psychotic depression (PD) have been conducted in first-episode and drug-naïve (FEDN) patients. This study was to examine the prevalence of PD and its clinical correlates in a large sample of FEDN outpatients with major depressive disorder (MDD) in a Chinese Han population, which to our best knowledge has not been studied.In this cross-sectional study, a total of 1718 FEDN MDD outpatients were recruited. All patients were rated on the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) for psychotic symptoms, the 17-item Hamilton Depression Rating Scale (HAMD-17) for depression and Hamilton Anxiety Rating Scale (HAMA) for anxiety.The prevalence of PD was 10.0% (171/1718) in MDD patients. Compared to the non-PD patients, PD patients had significantly older age, lower educational levels, higher anxiety symptom score and were more likely to attempt suicide. Further logistic regression analysis indicated that PD was associated with older age, suicide attempt and comorbid anxiety (all p 0.05). Multiple regression analyses showed that both HAMD and HAMA total scores were significantly associated with PANSS positive symptom subscale score.Our cross-sectional study design does not show a direct causal relationship between psychiatric symptoms and related factors in patients with MDD.Our results suggest a high prevalence of PD in MDD patients in the acute early stage in a Chinese Han population, which is associated with demographic variables and clinical symptoms.

Background In recent years, there have been increasing calls for integrating late-life mental health services into primary care in China, but data on the epidemiology of depressive disorders in older adults receiving primary care are very limited. This study examined prevalence, correlates and recognition of depressive disorders among Chinese older adults receiving primary care. Methods A total of 752 older patients (65+ years) were consecutively recruited from 13 primary care clinics in Wuhan, China, and interviewed with the Chinese Mini-international Neuropsychiatric Interview 5.0. Results One–fifth (20.3%) of the older adults met DSM-IV criteria for depressive disorders during the month prior to the interview: 10.2% had major depression, 4.8% had dysthymia, and 5.3% had minor depressive disorder. The recognition rate of older patients with depressive disorders was 1.3% only. In multiple logistic regression analysis, factors significantly associated with depressive disorders included female gender (OR = 1.61), an education of primary school and below (OR = 1.69), poor financial status (OR = 2.44), poor or fair family relationship (OR = 1.66), loneliness (OR = 1.77), hypertension (OR = 1.91), heart disease (OR = 2.02), chronic gastric ulcer (OR = 6.01), and arthritis (OR = 3.55). Limitations Older adults from primary care clinics of economically underdeveloped regions of China were not included. Conclusions Depressive disorders are prevalent but poorly recognized in Chinese older adults receiving treatment in primary care clinics. In order to improve the emotional well-being and health of older adults, it is time to integrate the management of common mental disorders into primary healthcare in China.

This study examines binaural response properties and sensitivity to interaural level difference of single neurons in the primary auditory cortex (AC) of the big brown bat, Eptesicus fuscus under earphone stimulation conditions. Contralateral sound stimulation always evoked response from all 306 AC neurons recorded but ipsilateral sound stimulation either excited, inhibited or did not affect their responses. High best frequency (BF) neurons typically had high minimum threshold (MT) and low BF neurons had low MT. However, both BF and MT did not correlate with their recording depth. The BF of these AC neurons progressively changed from high to low along the anteromedial-posterolateral axis of the AC. Their number of impulses and response latency varied with sound level and inter-aural level differences (ILD). Their number of impulses typically increased either monotonically or non-monotonically to a maximum and the latency shortened to a minimum at a specific sound level. Among 205 AC neurons studied at varied ILD, 178 (87%) and 127 (62%) neurons discharged maximally and responded with the shortest response latency at a specific ILD, respectively. Neurons sequentially isolated within an orthogonal electrode puncture shared similar BF, MT, binaurality and ILD curves. However, the response latency of these AC neurons progressively shortened with recording depth. Species-specific difference among this bat, the mustached bat and the pallid bat is discussed in terms of frequency and binaurality representation in the AC.

Background While many studies have assessed the predictive value of secreted phosphoprotein (SPP) genes in cancer, the findings have been inconsistent. To resolve these inconsistencies, we systematically analyzed the available data to determine whether SPP1 and SPP2 are prognostic markers in the context of human cancer. Methods The expression of SPP1 and SPP2 was assessed by Oncomine analysis. The PrognoScan database was used to assess the prognostic value of SPP1 and SPP2, with cBioPortal used to assess copy number variations. The STRING database was used to generate a Protein - Protein Interaction (PPI) network for SPP genes. Results SPP1 was more likely to be over-expressed in breast, bladder, colorectal, head, neck, liver, lung, and esophageal cancers. SPP2 was expressed at lower levels in colorectal cancer, leukemia, liver cancer and pancreatic cancer. In addition, SPP1 and SPP2 mutations mainly occurred in cutaneous melanoma and endometrial cancer. Conclusions Our results suggest that SPP1 and SPP2 may be effective therapeutic or diagnostic targets in certain cancers. Further research is required to confirm these results and verify the value of SPP1 and SPP2 as clinical markers of cancer prognosis.

Proper development of mammalian skeletal muscle relies on precise gene expression regulation. Our previous studies revealed that muscle development is regulated by both mRNA and long non-coding RNAs (lncRNAs). Accumulating evidence has demonstrated that N6-methyladenosine (m6A) plays important roles in various biological processes, making it essential to profile m6A modification on a transcriptome-wide scale in developing muscle. Patterns of m6A methylation in lncRNAs in developing muscle have not been uncovered. Here, we reveal differentially expressed lncRNAs and report temporal m6A methylation patterns in lncRNAs expressed in mouse myoblasts and myotubes by RNA-seq and methylated RNA immunoprecipitation (MeRIP) sequencing. Many lncRNAs exhibit temporal differential expression, and m6A-lncRNAs harbor the consensus m6A motif “DRACH” along lncRNA transcripts. Interestingly, we found that m6A methylation levels of lncRNAs are positively correlated with the transcript abundance of lncRNAs. Overexpression or knockdown of m6A methyltransferase METTL3 alters the expression levels of these lncRNAs. Furthermore, we highlight that the function of m6A genic lncRNAs might correlate to their nearby mRNAs. Our work reveals a fundamental expression reference of m6A-mediated epitranscriptomic modifications in lncRNAs that are temporally expressed in developing muscle.

PurposeThis study aimed to investigate the effect of essential ingredients of licorice on the chronic obstructive pulmonary disease (COPD).MethodThe ingredients information were obtained fromPubChem(https://pubchem.ncbi.nlm.nih.gov/), related genes about COPD was collected fromgeneCards(http://www.genecards.org/).Networkpharmacology was utilized in this study.ResultThe intersection data set contains 20 molecular targets between COPD and liquorice. Protein-protein interaction network showed that there are a total of 58 nodes and 137 edges involved. The link number of AKT1 in PPI network was 39, which is the highest level of interaction. MAPK1 is an important target of Licorice on COPD.ConclusionMAPK signaling pathway could be the important key target of main ingredients of licorice on COPD.

Background Accurate preprocedural measurements is important for left atrial appendage closure (LAAC). However, there were limited data comparing tomography angiography (CTA), trans-esophageal echocardiography (TEE) and digital subtraction angiography (DSA) for diagnostic accuracy and the utility for LAAC. This study aimed to compare the results of CTA, TEE and DSA measurements and analyze their accuracy, correlation and consistency in patients who successfully underwent LAAC.Methods 157 non-valvular atrial fibrillation (AF) patients who underwent LAAC were included. The maximum diameter and depth of LAA were recorded by CTA, TEE and DSA. Correlations and agreements were compared. Results All patients were successfully performed LAAC with Watchman device. There was no significant difference in the diameter measurement of LAA ostium between DSA and TEE. Meanwhile, The diameter of LAA ostium obtained by CTA was greater than that of DSA and TEE. There were good correlations between the LAA ostium measured by TEE, CTA, DSA and the Watchman device. DSA measurements and the actual device size were the widest limits of agreement, followed by TEE, CTA measurements were the narrowest limits of agreement. For the LAA depth measurements, mean CTA measurements was higher than that of TEE and DSA. There was no significant difference in the depth measurement among the three imaging modalities. Conclusions CTA, TEE and DSA measurements had good correlations with WATCHMAN device. The ostium diameter and depth of the LAA measured by CTA were greater than those measured by TEE and DSA. The relevance and concordance of CTA measurements were the best.

Children with repeated inhalational anesthesia may develop cognitive disorders. This study aimed to investigate the transcriptome-wide response of hippocampus in young mice that had been exposed to multiple sevoflurane in the neonatal period. Mice received 3% sevoflurane for 2 h on postnatal day (PND) 6, 8, and 10, followed by arterial blood gas test on PND 10, behavioral experiments on PND 31-36, and RNA sequencing (RNA-seq) of hippocampus on PND 37. Functional annotation and protein-protein interaction analyses of differentially expressed genes (DEGs) and quantitative reverse transcription polymerase chain reaction (qPCR) were performed. Neonatal sevoflurane exposures induced cognitive and social behavior disorders in young mice. RNA-seq identified a total of 314 DEGs. Several enriched biological processes (ion channels, brain development, learning, and memory) and signaling pathways (oxytocin signaling pathway and glutamatergic, cholinergic, and GABAergic synapses) were highlighted. As hub-proteins, Pten was involved in nervous system development, synapse assembly, learning, memory, and behaviors, Nos3 and Pik3cd in oxytocin signaling pathway, and Cdk16 in exocytosis and phosphorylation. Some top DEGs were validated by qPCR. This study revealed a transcriptome-wide profile in mice hippocampus after multiple neonatal exposures to sevoflurane, promoting better understanding of underlying mechanisms and investigation of preventive strategies.

Key Points Leukemic blasts of a female carrier of an ATRX germline mutation have persistently skewed inactivation of the X chromosome. Germline mutation in leukemia needs to be interpreted with caution because it is not always pathologic.

Background Prior studies showed that tumor glycolysis and tumor immune evasion are interdependent. However, a systematic investigation of the association between tumor glycolysis and tumor immunity in various cancers remains lacking. Methods Using the Cancer Genome Atlas (TCGA) datasets, we explored the association between glycolytic activity and immune signatures in 14 cancer types. We also explored the associations between glycolytic activity and tumor immunity associated genetic features, including PD-L1 expression, tumor mutation burden (TMB), and tumor aneuploidy. Moreover, we performed in vitro experiments to verify some findings from bioinformatics analysis. Furthermore, we explored the association between tumor glycolytic activity and immunotherapy response. Findings Glycolytic activity was likely correlated with active immune signatures in various cancers and highly glycolytic tumors presented an immune-stimulatory tumor microenvironment. Compared to TMB and aneuploidy, glycolytic activity was a stronger and more consistent predictor for immune signatures in diverse cancers. Both computational and experimental analyses showed that glycolysis could increase PD-L1 expression in tumor. Glycolytic activity had a strong correlation with apoptosis which was a strong positive predictor for immune signatures, suggesting that apoptosis could be an important medium connecting glycolytic activity with immune activity in cancer. Finally, highly glycolytic tumors exhibited a better immunotherapy response and a favorable survival in the immunotherapy setting. Interpretation Tumor glycolysis may increase tumor immunity in diverse cancers. Glycolytic activity enhances PD-L1 expression on tumor cells and thus promotes anti-PD-1/PD-L1 immunotherapy response. Thus, the tumor glycolytic activity could be a predictive biomarker for immunotherapy response in diverse cancers. Fund This work was supported by the China Pharmaceutical University (grant numbers 3150120001 , 2632018YX01 to XW).

This paper presents test results of fifteen reinforced engineered cementitious composite (ECC)-concrete beams. The main parameters investigated were the amount and type of reinforcement, and ECC thickness. All reinforced ECC-concrete composite beams tested were classified into four groups according to the amount and type of main longitudinal reinforcement used; three groups were reinforced with FRP, steel and hybrid FRP/steel bars, respectively, having similar tensile capacity, whereas the fourth group had a larger amount of only FRP reinforcement. In each group, four height replacement ratios of ECC to concrete were studied. The test results showed that the moment capacity and stiffness of concrete beams are improved and the crack width can be well controlled when a concrete layer in the tension zone is replaced with an ECC layer of the same thickness. However, the improvement level of ECC-concrete composite beams was controlled by the type and amount of reinforcement used. Based on the simplified constitutive relationships of materials and plane section assumption, three failure modes and their discriminate formulas are developed. Furthermore, simplified formulas for moment capacity calculations are proposed, predicting good agreement with experimental results.

Acoustic communication signals are inevitably challenged by ambient noise. In response to noise, many animals adjust their calls to maintain signal detectability. However, the mechanisms by which the auditory system adapts to the adjusted pulses are unclear. Our previous study revealed that the echolocating bat, Hipposideros pratti, increased its pulse intensity in the presence of background white noise. In vivo single-neuron recording demonstrated that the auditory midbrain neurons tuned to the second harmonic (H2 neurons) increased their minimal threshold (MT) to a similar degree as the increment of pulse intensity in the presence of the background noise. Furthermore, the H2 neurons exhibited consistent spike rates at their best amplitudes and sharper intensity tuning with background white noise compared with silent conditions. The previous data indicated that sound intensity analysis by auditory midbrain neurons was adapted to the increased pulse intensity in the same noise condition. This study further examined the echolocation pulse frequency and frequency analysis of auditory midbrain neurons with noise conditions. The data revealed that H. pratti did not shift the resting frequency in the presence of background noise. The auditory midbrain neuronal frequency analysis highly linked to processing the resting frequency with the presence of noise by presenting the constant best frequency (BF), frequency sensitivity, and frequency selectivity. Thus, our results suggested that auditory midbrain neuronal responses in background white noise are adapted to process echolocation pulses in the noise conditions.

The 2019 novel coronavirus (SARS-CoV-2) has spread rapidly worldwide and was declared a pandemic by the WHO in March 2020. The evolution of SARS-CoV-2, either in its natural reservoir or in the human population, is still unclear, but this knowledge is essential for effective prevention and control. We propose a new framework to systematically identify recombination events, excluding those due to noise and convergent evolution. We found that several recombination events occurred for SARS-CoV-2 before its transfer to humans, including a more recent recombination event in the receptor-binding domain. We also constructed a probabilistic mutation network to explore the diversity and evolution of SARS-CoV-2 after human infection. Clustering results show that the novel coronavirus has diverged into several clusters that cocirculate over time in various regions and that several mutations across the genome are fixed during transmission throughout the human population, including D614G in the S gene and two accompanied mutations in ORF1ab. Together, these findings suggest that SARS-CoV-2 experienced a complicated evolution process in the natural environment and point to its continuous adaptation to humans. The new framework proposed in this study can help our understanding of and response to other emerging pathogens.

Dengue is a significant public health issue, affecting hundreds of millions of people worldwide. As it is spreading from tropical and subtropical zones, some regions previously recognised as non-endemic are at risk of becoming endemic. However, the global circulation of dengue is not fully understood and quantitative measurements of endemicity levels are lacking, posing an obstacle in the precise control of dengue spread. In this study, a sequence-based pipeline was designed based on random sampling to study the transmission of dengue. The limited intercontinental transmission was identified, while regional circulation of dengue was quantified in terms of importation, local circulation and exportation. Additionally, hypo- and hyper-endemic regions were identified using a new metric, with the former characterised by low local circulation and increased importation, whereas the latter by high local circulation and reduced importation. In this study, the global circulation pattern of dengue was examined and a sequence-based endemicity measurement was proposed, which will be helpful for future surveillance and targeted control of dengue.

Background Gastric cancer is a common but lethal cancer owing to deficient in effective treatment. Substantial evidences have proved that immune infiltration plays a key role in progression of gastric cancer. This study aimed to establish a signature based on immune related genes that can predict clinical outcomes and therapeutic efficacy. Methods The expression data from The Cancer Genome Atlas database and 4617 immune related genes from previously published 160 immune gene sets were collected for development and validation of the signature. Cox proportional hazard regression model was used to construct the signature. The reliability and forecasting ability were evaluated by two independent datasets from GEO. Results A gene model consisting of 47 immune related genes was used as our signature. Risk scores were calculated based on the coefficient and the expression level of each gene in this model. The low risk score group had an obviously favorable prognosis than the other group in all cohorts. Both of univariate and multivariate analysis suggested that our immune gene signature was an independent prognostic factor. Single sample gene Set Enrichment Analysis (ssGSEA) revealed that high risk score was associated with high Th17 cell infiltration, low mast cell and pro- angiogenesis immune cell infiltration. More importantly, patients with high risk score presented high tumor mutation burden (TMB), which is an essential element for predicting therapeutic efficacy of immune check point inhibitor. Conclusion This signature is a promising tool to predict prognosis and screen out population who can get benefit from immune check point inhibitor.

Multiple exposures to anesthesia may increase the risk of cognitive impairment in young children. However, the mechanisms underlying this neurodevelopmental disorder remain elusive. In this study, we investigated alteration of the gut microbiota after multiple neonatal exposures to the anesthetic sevoflurane and the potential role of microbiota alteration on cognitive impairment using a young mice model. Multiple neonatal sevoflurane exposures resulted in obvious cognitive impairment symptoms and altered gut microbiota composition. Fecal transplantation experiments confirmed that alteration of the microbiota was responsible for the cognitive disorders in young mice. Microbiota profiling analysis identified microbial taxa that showed consistent differential abundance before and after fecal microbiota transplantation. Several of the differentially abundant taxa are associated with memory and/or health of the host, such as species of Streptococcus, Lachnospiraceae, and Pseudoflavonifractor. The results reveal that abnormal composition of the gut microbiota is a risk factor for cognitive impairment in young mice after multiple neonatal exposures to sevoflurane and provide insight into a potential therapeutic strategy for sevoflurane-related neurotoxicity.

Background The progress of green credit in China is accelerating, but its development is uneven and insufficient in different regions. And whether the issuance of green credit can effectively promote the improvement of the environment and economy is not well understood. Objective Previous research has found that green credit promotes economic growth through improvement of the industrial structure and green technological innovation. However, these studies have not considered the positive externality of environmental improvement even though environmental improvement and economic growth are requirements of the sustainable development concept. Methods We use the chain-mediated model to estimate the impact of green credit issuance on the economic growth of different provinces since the large-scale implementation of green credit in China with data from 2008 to 2016. Results and conclusion This paper shows that the issuance of green credit can improve labor supply rather than labor productivity through the improvement of air quality to achieve regional economic growth. Such a chain-mediated path is different from the economic growth caused by industrial structural adjustment and green technology innovation. At the national level, every 1% increase in green credit issuance relative to industrial loans will increase the per capita gross domestic product (GDP) by approximately 4.6 yuan, or 0.012%, through air quality and labor supply, accounting for 2.875% of the total effect. Heterogeneity analysis indicates that due to regional industrial structure differences and diminishing marginal effects, the impact of green credit is stronger in the western region than in the eastern and central regions. For every 1% increase in the proportion of green credit issuance relative to industrial loans, the per capita GDP growth achieved through the chain-mediated path is approximately 30.17 yuan in the western region, approximately 6.6 times greater than that at the national level. Within a 95% confidence interval of 5000 bootstrap samples, this path is found to be true, and the chain-mediated effect accounts for approximately 12.96% of the total indirect effect. Limitations The limitation of this paper is the measurement of green credit. Although green credit has a large volume, it remains underdeveloped, and there is a lack of perfect indicators. Most existing studies have adopted only alternative or reverse indicators to measure the issuance of green credit. For example, this paper takes the interest expenditure of six high-energy-consuming enterprises as the reverse indicator, which may to a certain extent lead to the overestimation of the issuance of green credit and its impact on the environment and economy. Future research can accurately explore the performance of green credit on the basis of its mature development.

Introduction/Background Various biomarkers have been investigated to identify patients likely to respond to PARP inhibition. PARP inhibitor olaparib plus bevacizumab is approved by the US FDA as maintenance therapy for homologous recombination deficiency (HRD)–positive advanced ovarian cancer; the FDA contemporaneously approved a commercial assay as a companion diagnostic for HRD assessment that includes a genomic instability biomarker. Other genomic platforms measuring HRD are available or in development, including single-nucleotide polymorphism (SNP) genotyping arrays designed to measure tumour-related copy number changes. We evaluated the performance of OncoScan™ (ThermoFisher) and Infinium CytoSNP-850K (CytoSNP; Illumina) for assessing HRD genomic instability. Methodology DNA extracted from pretreatment archival tumour samples (N=126 across 20 indications) was evaluated with Oncoscan™, CytoSNP and an FDA-approved HRD test. ASCAT (v2.5.1), using log R ratio and B-allele frequency of autosomal markers with GC wave correction, was used to evaluate copy number variation (CNV) and loss of heterozygosity (LOH). The genomic metrics were further generated with default parameters using previously reported algorithms1 for LOH,2 number of telomeric-allelic imbalance (NTAI)3 and large-scale state transition (LST)4; the aggregate HRD metric was the sum of the three components. The association between genomic metrics (with BRCA deleterious alterations) and an FDA-approved HRD test metric (dichotomised at clinical cutoff) was calculated using AUROC. Correlations among continuous metrics were assessed using Spearman rank correlation coefficients. Results CNV segmentation and genomic metrics were successfully calculated for 120 (Oncoscan™), 106 (CytoSNP) and 126 (FDA-approved test) samples. Assessed by SNP genotyping arrays, the genomic metric as a continuous variable demonstrated good association with deleterious BRCA alterations (AUROC of HRD: Oncoscan™, 0.87; CytoSNP, 0.75) (table 1) and the FDA-approved test at cutoff 42 (AUROC of HRD: Oncoscan™, 0.92; CytoSNP, 0.91) (table 2). The genomic metric as a continuous variable showed good correlation with the FDA-approved HRD test metric (Spearman correlation of HRD: Oncoscan™, 0.82; CytoSNP, 0.81). The Spearman correlation of genomic metrics with the FDA-approved HRD test metric was 0.68 (LOH), 0.76 (TAI), 0.78 (LST) and 0.82 (HRD) for Oncoscan™ and 0.59 (LOH), 0.77 (TAI), 0.82 (LST) and 0.81 (HRD) for CytoSNP. Conclusion HRD as a continuous variable assessed by SNP genotyping arrays showed good correlation with an FDA-approved HRD test metric; SNP assays may potentially be able to identify most HRD-positive tumours if appropriate clinically relevant cutoffs can be determined. Disclosures This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Razvan Cristescu is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and has stock ownership interests in Merck & Co., Inc., Kenilworth, NJ, USA. Xiao Qiao Liu is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Gladys Arreaza is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and has stock ownership interests in Merck & Co., Inc., Kenilworth, NJ, USA. Cai Chen is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Andrew Albright is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and has stock ownership interests in Merck & Co., Inc., Kenilworth, NJ, USA. Ping Qiu is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and has stock ownership interests in Merck & Co., Inc., Kenilworth, NJ, USA. Matthew Marton is an employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and has stock ownership interests in Merck & Co., Inc., Kenilworth, NJ, USA.

The coronavirus disease 2019 (COVID-19) pandemic is still ongoing and has become an important public health threat. This disease is caused by a new coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, and so far, little is known about this virus. In this study, by using plaque purification, we purified two SARS-CoV-2 virus strains from the same specimen, one named F8 containing a 12-bp deletion in the E gene and the other named 8X containing the wild-type E gene. There was no significant difference in the viral titer and infectivity of these two strains. The S protein content of the F8 viral culture was 0.39 μg/ml, much higher than that of 8X. An inactivated vaccine made from the F8 strain could trigger high levels of the IgG titer and neutralizing antibody titer, which could last for at least 6 weeks and were significantly higher than those from the 8X strain at 1 and 3 weeks post vaccination, respectively. In conclusion, we reported that both the E gene mutant and wild-type SARS-CoV-2 strains were isolated from the same clinical sample by plaque purification. A 12-bp deletion in the E gene was important for SARS-CoV-2 replication and immunogenicity.

Background. A growing number of studies have suggested that microRNAs exert an essential role in the development and occurrence of multiple tumours and act as crucial regulators in various biological processes. However, the expression and function of miRNA-140 in hepatocellular carcinoma (HCC) cells are not yet adequately identified and manifested. Methods. The expression of miRNA-140 was determined in HCC tissues and adjacent nontumour tissues by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan–Meier survival analysis and Cox regression analysis were performed to explore the correlation between miRNA-140 expression level and the survival rate of patients with HCC. Additionally, overexpression experiments were conducted to investigate the biological role of miRNA-140 in HCC cells. Bioinformatics was used to predict the related target genes and pathways of miRNA-140. Results. QRT-PCR results signified that the expression level of miRNA-140 in HCC was lower than that of adjacent normal tissues ( P < 0.0001 ). Compared with the control group, the SMMC-7721 HCC cells in the miRNA-140 mimic group had a decrease in proliferation, migration, and invasion ( P < 0.05 ), whereas those in the miRNA-140 inhibitor group had an increase in proliferation, migration, and invasion ( P < 0.05 ). Cell cycle arrest occurred in the G0/1 phase. Prognosis analysis showed that the expression level of miRNA-140 was not related to the prognosis of HCC. Furthermore, the Kaplan–Meier test revealed that patients with lower miRNA-140 expression levels in liver cancer tissue had significantly shorter disease-free survival (DFS, P = 0.004 ) and overall survival (OS) times ( P = 0.010 ) after hepatectomy. Cox regression analysis further indicated that miRNA-140 was an independent risk factor that may affect the DFS ( P = 0.004 ) and OS times ( P = 0.014 ) of patients after hepatectomy. Our results suggested that miRNA-140 might be a crucial regulator involved in the HCC progression and is thus considered a potential prognostic biomarker and therapeutic target for HCC.

BackgroundInterleukin-12 (IL-12) is considered to be a risk factor for cancer; however, its role in hepatocellular carcinoma (HCC) remains unknown. This study aimed to explore the impacts of the IL-12 rs3212227 and rs568408 gene polymorphisms on HCC.MethodsWe searched PubMed, Embase, Web of Science, and Chinese Knowledge Infrastructure databases for studies on the associations between HCC and IL-12 rs568408 and rs3212227 polymorphisms published prior to 1 May 2020. The effects of the polymorphisms on HCC susceptibility were presented as odds ratios (ORs) and associated 95% confidence intervals.ResultsSeven studies were ultimately included, including 2375 cases and 3445 controls. The rs3212227 polymorphism was significantly associated with the risk of HCC in both the dominant model (CC+AC vs. AA, OR=1.22) and the allele model (C vs. A, OR=1.12). Combined analysis of rs568408 yielded a significant relative risk for HCC in the dominant (AA+AG vs. GG, OR=1.13), recessive (AA vs. AG+GG, OR=1.72), allele (A vs. G, OR=1.29), heterozygote (AG vs. GG, OR=1.27), and homozygote models (AA vs. GG, OR 1.17).ConclusionThe IL-12 rs3212227 and rs568408 gene polymorphisms are associated with an increased risk of HCC.

The COVID-19 virus has infected more than 38 million people and resulted in more than one million deaths worldwide as of October 14, 2020. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, economic inequality enhanced the risk of COVID-19 transmission. The per capita hospital beds correlated negatively with COVID-19 deaths. Blood types B and AB were protective factors for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV and influenza and pneumonia was associated with reduced COVID-19 risk. Increased intake of vegetables, edible oil, protein, vitamin D, and vitamin K was associated with reduced COVID-19 risk, while increased intake of alcohol was associated with increased COVID-19 risk. Other factors included age, sex, temperature, humidity, social distancing, smoking, health investment, urbanization level, and race. High temperature is a more compelling factor mitigating COVID-19 transmission than low temperature. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread., Graphical abstract Unlabelled Image, Highlights • High temperature is more compelling in mitigating COVID-19 than low temperature. • Economic inequality promotes the risk of COVID-19 transmission. • Major sports events facilitate COVID-19 transmission in European countries. • Blood types B and AB are protective factors for COVID-19. • The per capita hospital beds correlate inversely with COVID-19 deaths.

BACKGROUND The aim of this study was to assess the safety and clinical effectiveness of laparoscopic disconnected pyeloplasty in treating ureteropelvic junction obstruction (UPJO) in children. MATERIAL AND METHODS We retrospectively analyzed the clinical data of 122 young children with UPJO treated from February 2015 to February 2018 at our hospital. According to the surgery type, the patients were divided into 2 groups: a laparoscopic surgery group (group A, n=69) and a traditional open surgery group (group B, n=53). RESULTS The success rate of laparoscopic disconnected pyeloplasty was 100%, and none of the patients were converted to open surgery. The mean duration of use of painkillers was 27.6±11.3 h in group A and 58.2±18.2 h in group B (p=0.012), the postoperative hospital stay was 7.8±1.5 days in group A and 11.5±2.6 days in group B (p=0.041), and the length of the incision was 1.5±0.4 cm in group A and 5.2±1.1 cm in group B (p=0.007). The incidence rate of poor surgical wound healing was 0% in group A and 7.5% in group B (p=0.020). The incidence rate of ureteral stricture was 4.3% in group A and 3.8% in group B (p=0.874) during follow-up. The 1-year follow-up showed that both the anterior and posterior diameters and glomerular filtration rate were significantly improved from the preoperation period. CONCLUSIONS Laparoscopic disconnected pyeloplasty to treat UPJO in young children has the same early clinical effectiveness and safety as open surgery, and this procedure has the advantages of minimal trauma, quick recovery, and good cosmetic effect.

BACKGROUND Loneliness is a significant public health concern among older adults (OA) given its association with a wide range of adverse health outcomes. Primary care is an opportune setting to manage loneliness. However, the epidemiology of loneliness in Chinese OA treated in primary care remains unclear. The present study investigated the prevalence and correlates of loneliness in OA treated in Chinese primary care. METHODS A total of 744 OA patients (65+ years) were consecutively recruited from 13 primary care clinics in Wuhan, China, and interviewed with a standardized questionnaire, concerning sociodemographic characteristics, lifestyle, relationships with family and others, physical health, and sensory impairments. Consistent with prior research on the construct, loneliness was measured with a single-item self-report question. Logistic regression was used to identify correlates of loneliness. RESULTS Of primary care OA patients, 26.2% endorsed loneliness. Factors significantly and independently associated with loneliness included 75+ age group (odds ratio [OR]: 1.61, 95% confidence interval [CI]: 1.07, 2.44, P: 0.023), being illiterate (OR: 2.07, 95%CI: 1.26, 3.42, P: 0.004), unmarried (OR: 2.30, 95%CI: 1.40, 3.78, P: 0.001), living alone (OR: 4.37, 95%CI: 2.27, 8.41, P

14-3-3ζ is overexpressed in several cancers, including esophageal squamous cell carcinoma (ESCC), and plays an important role in tumorigenesis. However, the mechanisms underlying its tumorigenesis remain unclear. Here we report that 14-3-3ζ was upregulated in ESCC tumors, compared with adjacent normal tissues; 14-3-3ζ levels were positively correlated with ESCC lymph node metastasis and recurrence. Overexpression of 14-3-3ζ promoted the tumor growth and invasion of ESCC in vitro and in vivo, whereas depletion of 14-3-3ζ suppressed these effects. Moreover, 14-3-3ζ reduces expression of genes mediating S1P/S1PR2 signaling, and this effect is mediated through activation of NF- κ B. Taken together, 14-3-3ζ contributes to ESCC tumorigenesis and progression through repressing S1PR2 signaling and may act as a new therapeutic target for ESCC.

Insulin-like growth factor (IGF-I) is an important growth factor in mammals, but the functions of the local muscle-specific isoform of insulin-like growth factor 1 (mIGF-1) to skeletal muscle development have rarely been reported. To determine the effect of pig mIGF-1 on body development and muscle deposition in vivo and to investigate the molecular mechanisms, the transgenic mouse model was generated which can also provide experimental data for making transgenic pigs with pig endogenous IGF1 gene. We constructed a skeletal muscle-specific expression vector using 5′- and 3′-regulatory regions of porcine skeletal α-actin gene. The expression cassette was flanked with Sleeping Beauty transposon (SB)-inverted terminal repeats. The recombinant vector could strongly drive enhanced green fluorescence protein (EGFP) reporter gene expression specifically in mouse myoblast cells and porcine fetal fibroblast cells, but not in porcine kidney cells. The EGFP level driven by α-actin regulators was significantly stronger than that driven by cytomegalovirus promoters. These results indicated that the cloned α-actin regulators could effectively drive specific expression of foreign genes in myoblasts, and the skeletal muscle-specific expression vector mediated with SB transposon was successfully constructed. To validate the effect of pig mIGF-1 on skeletal muscle growth, transgenic mice were generated by pronuclear microinjection of SB-mediated mIGF-1 skeletal expression vector and SB transposase-expressing plasmid. The transgene-positive rates of founder mice and the next-generation F1 mice were 30% (54/180) and 90.1% (64/71), respectively. The mIGF-1 gene could be expressed in skeletal muscle specifically. The levels of mRNA and protein in transgenic mice were 15 and 3.5 times higher, respectively, than in wild-type mice. The body weights of F1 transgenic mice were significantly heavier than wild-type mice from the age of 8 weeks onwards. The paraffin-embedded sections of gastrocnemius from 16-week-old transgenic male mice showed that the numbers of myofibers per unit were increased in comparison with those in the wild-type mice. mIGF-1 overexpression in mice skeletal muscle may promote myofibers hypertrophy and muscle production, and increased the average body weight of adult mice. Transgenic mice models can be generated by the mediation of SB transposon with high transgene efficiency.

Bariatric surgery effectively treats morbid obesity. However, the negative effect of this surgery on the bone is concerning. The aim of this meta-analysis was to investigate the fracture risk associated with bariatric surgery in morbidly obese subjects. Relevant studies published from database inception to September 2017 were identified in PubMed, Embase and the Cochrane Library. The Newcastle-Ottawa Scale was used to evaluate the quality of the observational studies, and the Jadad score evaluated randomized controlled trials. Among the 1003 studies initially identified, five observational trials and one randomized controlled trial were eligible for inclusion. All studies included in the meta-analysis were considered high quality. Risk for any type of fracture was higher in the surgical group than in the non-surgical group (risk ratio [RR] 1.29, 95% confidence interval [CI] 1.18-1.42). After surgery, the fracture risk in non-vertebral sites was significantly increased, especially in the upper limbs (RR 1.42, 95% CI 1.08-1.87; and RR 1.68, 95% CI 1.15-2.45). Compared with those with restrictive procedures, subjects who underwent mixed restrictive and malabsorptive procedures tended to have an increased fracture risk (RR 1.54, 95% CI 0.96-2.46). To conclude, bariatric surgery is associated with an increased risk of total and non-vertebral fractures, especially in the upper limbs.

Chloroform is a common contaminant in the drinking water. Exposure of human to chloroform leads to severe hepatotoxicity. In the present study, chloroform-induced acute liver injury was investigated in mice using 3-methyadenine (3-MA), a common autophagy inhibitor. At 24 h after intraperitoneal injection of 0.5 mL/kg chloroform, serum alanine aminotransferase (ALT) levels were increased significantly; extensive necrosis and inflammation occurred as identified by histological examinations. Moreover, chloroform induced an increase in lipid peroxidation as demonstrated by increased formation of malondialdehyde (MDA) in the liver tissues. Hepatic antioxidants including glutathione (GSH) and superoxide dismutase (SOD) were decreased by chloroform treatment. All these changes were significantly inhibited by 3-MA treatment. Further mechanistic insights demonstrated that chloroform up-regulated pro-inflammatory cytokine, IL-1β, in the livers and blood, which was suppressed by 3-MA. Surprisingly, Western blots results showed that after 24-hours of chloroform treatment 3-MA activated autophagy as indicated by decreased levels of LC3B II and p62 protein. Co-treatment of chloroquine with 3-MA to inhibit autophagy would abrogate the hepatoprotection of 3-MA in chloroform hepatotoxicity. Taken together, findings in the present study suggested that a widely-used autophagy inhibitor, 3-MA, significantly reduced chloroform hepatotoxicity in mice via autophagy activation. Findings in this study also suggested that caution should be exercised when using 3-MA to modulate autophagy in vivo.