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Rui Deng,* Juan Lu,* Xiong Liu, Xiao-Hong Peng, Jie Wang, Xiang-Ping Li Department of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiang-Ping LiDepartment of Otolaryngology-Head and Neck Surgery, Nanfang Hospital, 1838 North of Guangzhou Avenue, Guangzhou, People’s Republic of ChinaTel +86-20-61642001Fax +86-20-87703645Email li321162@qq.comPurpose: Tumour-associated macrophages (TAMs) are the most abundant immune cells in the tumor microenvironment and provide a barrier against the cytotoxic effector functions of T cells and natural killer (NK) cells. Recently, TAMs have become increasingly recognised as an attractive target in combination therapy with PD-1/PD-L1 immuno-checkpoint blockades (ICBs). However, the relationship between PD-L1 expression and TAMs remains unknown in nasopharyngeal carcinoma (NPC).Patients and Methods: A total of 212 NPC patients from Nanfang hospital were collected in this study. We evaluated the expression of PD-L1 in tumor cells, CD68 (pan-macrophages), and CD163 (M2-like macrophage) in NPC tissues using immunohistochemical (IHC) staining.Results: The positivity of PD-L1 on tumor cells was 61.3% (130/212). The infiltration densities of CD68+ cells and CD163+ cells in PD-L1-positive NPC tissues were significantly higher than those in PD-L1-negative NPC tissues (P=0.0012 for CD68; P< 0.0001 for CD163). Logistic regression analysis showed that high densities of CD68+ macrophages and CD163+ TAMs were significantly associated with increased PD-L1 expression. Subgroup analyses demonstrated that a positive PD-L1 expression on tumor cells in combination with lower CD163+ TAMs density was significantly associated with favorable prognosis, whereas negative PD-L1 expression on tumor cells with higher CD163+ TAMs density was associated with worse prognosis.Conclusion: The PD-L1 expression in tumor cells was positively correlated with TAMs density in tumor microenvironment of NPC, suggesting TAMs as a new target for combination therapy to improve the response rate of ICBs in NPC treatment.Keywords: nasopharyngeal carcinoma, PD-L1, tumor-associated macrophage, prognosis, tumor microenvironment

Phytochemical studies on the leaves and twigs of Garcinia oligantha Merr. led to the isolation of twelve previously undescribed depsidone derivatives (oliganthdepsidones A-L, 1-12). Their structures were elucidated by extensive spectroscopic analysis including 1 H and 13 C NMR, HSQC, HMBC and NOESY along with HRESIMS. The structures of oliganthdepsidones G and J were finally determined using DFT-NMR chemical shift calculations and DP4+ methods. Cytotoxicity test in four human cancer cell lines indicated that oliganthdepsidone F had relatively strong cytotoxic effect against A375 (melanoma), A549 (lung cancer), HepG2 (liver cancer), and MCF-7 (breast cancer) cell lines with IC 50 of 18.71, 15.44, 10.92, and 15.90 μM, respectively. The dose- and time-dependent antiproliferative effects of oliganthdepsidone F on these cell lines were also observed by CCK-8 test. As determined by fluorescent microscopy and flow cytometry in these cell lines, oliganthdepsidone F could promote cell apoptosis, leading to the inhibition of cell proliferation. The results of wound healing assay and transwell assay showed that oliganthdepsidone F could inhibit the migration and invasion of A549 and MCF-7 cell lines in a concentration-dependent manner., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Conventionally, octahedral ( O h ) coordination symmetry of lanthanide centers is not ideal for constructing high-performance single-molecule magnets (SMMs). However, introducing a strong ligand field in the axial direction to increase crystal field splitting can potentially overcome this limitation. Herein, we successfully obtained two dysprosium(III) single-molecule magnets, [Dy(OC t Bu 3 )X 2 (py) 3 ] (X = Cl (1), I (2), py = pyridine), in O h coordination symmetry. The two complexes differ only in the coordinating anions on the equatorial plane, yet their magnetic performances are distinctly different. When chloride is replaced by a weaker donor iodide, the energy barrier is dramatically improved from 29 cm -1 (1) to 860 cm -1 (2), highlighting the importance of weakening the transverse ligand field and maximizing the axial ligand field for high-performance SMMs.

Somatostatin (SOM)-expressing neurons in the central lateral amygdala (CeL) are responsible for fear memory learning, but the circuit and molecular mechanisms underlying this biology remain elusive. Here, we found that glutamatergic neurons in the lateral parabrachial nucleus (LPB) directly dominated the activity of CeL SOM neurons, and that selectively inhibiting the LPB Glu →CeL SOM pathway suppressed fear memory acquisition. By contrast, inhibiting CeL-projecting glutamatergic neurons in the paraventricular thalamic nucleus (PVT) interfered with consolidation-related processes. Notably, CeL SOM -innervating neurons in the LPB were modulated by presynaptic cannabinoid receptor 1 (CB1R), and knock down of CB1Rs in LPB glutamatergic neurons enhanced excitatory transmission to the CeL and partially rescued the impairment in fear memory induced by CB1R activation in the CeL. Overall, our study reveals the mechanisms by which CeL SOM neurons mediate the formation of fear memories during fear conditioning in mice, which may provide a new direction for the clinical research of fear-related disorders., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Sensorineural hearing loss (SNHL), characterized by damage to the inner ear or auditory nerve, is a prevalent auditory disorder. This study explores the potential of Castanopsis echinocarpa (CAE) as a therapeutic agent for SNHL. In vivo experiments were conducted using zebrafish and mouse models. Zebrafish with neomycin-induced ototoxicity were treated with CAE, resulting in otic hair cell protection with an EC 50 of 0.49 µg/mL and a therapeutic index of 1020. CAE treatment improved auditory function and protected cochlear sensory cells in a mouse model after noise-induced hearing loss (NIHL). RNA sequencing of NIHL mouse cochleae revealed that CAE up-regulates genes involved in neurotransmitter synthesis, secretion, transport, and neuronal survival. Real-time qPCR validation showed that NIHL decreased the mRNA expression of genes related to neuronal function, such as Gabra1 , Gad1 , Slc32a1 , CaMK2b , CaMKIV , and Slc17a7 , while the CAE treatment significantly elevated these levels. In conclusion, our findings provide strong evidence that CAE protects against hearing loss by promoting sensory cell protection and enhancing the expression of genes critical for neuronal function and survival.

Collective excitations including plasmons, magnons, and layer-breathing vibration modes emerge at an ultralow frequency (<1 THz) and are crucial for understanding van der Waals materials. Strain at the nanoscale can drastically change the property of van der Waals materials and create localized states like quantum emitters. However, it remains unclear how nanoscale strain changes collective excitations. Herein, ultralow-frequency tip-enhanced Raman spectroscopy (TERS) with sub-10 nm resolution under ambient conditions is developed to explore the localized collective excitation on monolayer semiconductors with nanoscale strains. A new vibrational mode is discovered at around 12 cm -1 (0.36 THz) on monolayer MoSe 2 nanobubbles and it is identified as the radial breathing mode (RBM) of the curved monolayer. The correlation is determined between the RBM frequency and the strain by simultaneously performing deterministic nanoindentation and TERS measurement on monolayer MoSe 2 . The generality of the RBM in nanoscale curved monolayer WSe 2 and bilayer MoSe 2 is demonstrated. Using the RBM frequency, the strain of the monolayer MoSe 2 on the nanoscale can be mapped. Such an ultralow-frequency vibration from curved van der Waals materials provides a new approach to study nanoscale strains and points to more localized collective excitations to be discovered at the nanoscale., (© 2024 Wiley‐VCH GmbH.)

Background: Bitter taste receptors (Tas2rs) are generally considered to sense various bitter compounds to escape the intake of toxic substances. Bitter taste receptors have been found to widely express in extraoral tissues and have important physiological functions outside the gustatory system in vivo., Methods: To investigate the physiological functions of the bitter taste receptor cluster Tas2r106/Tas2r104/Tas2r105/Tas2r114 in lingual and extraoral tissues, multiple Tas2rs mutant mice and Gnat3 were produced using CRISPR/Cas9 gene-editing technique. A mixture containing Cas9 and sgRNA mRNAs for Tas2rs and Gnat3 gene was microinjected into the cytoplasm of the zygotes. Then, T7EN1 assays and sequencing were used to screen genetic mutation at the target sites in founder mice. Quantitative real-time polymerase chain reaction (qRT-PCR) and immunostaining were used to study the expression level of taste signaling cascade and bitter taste receptor in taste buds. Perception to taste substance was also studied using two-bottle preference tests., Results: We successfully produced several Tas2rs and Gnat3 mutant mice using the CRISPR/Cas9 technique. Immunostaining results showed that the expression of GNAT3 and PLCB2 was not altered in Tas2rs mutant mice. But qRT-PCR results revealed the changed expression profile of mTas2rs gene in taste buds of these mutant mice. With two-bottle preference tests, these mutant mice eliminate responses to cycloheximide due to genetic mutation of Tas2r105. In addition, these mutant mice showed a loss of taste perception to quinine dihydrochloride, denatonium benzoate, and cucurbitacin B (CuB). Gnat3-mediated taste receptor and its signal pathway contribute to CuB perception., Conclusions: These findings implied that these mutant mice would be a valuable means to understand the biological functions of TAS2Rs in extraoral tissues and investigate bitter compound-induced responses mediated by these TAS2Rs in many extraoral tissues., (© 2023 The Author(s). Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Objective: To understand the changes in pain and its effects in patients with the diagnosis of herpes zoster. Methods: A total of 3 487 patients diagnosed with herpes zoster (HZ) for the first time at the outpatient department of Miyun District Hospital from January 1, 2017, to December 31, 2019, were included in the study. The information of patients was registered and issued with a record card. Patients were required to record the time of pain and rash by themselves. Telephone follow-up was conducted at 21, 90, 180 and 365 days after the onset of rashes, including hospitalization, location of rash and pain, and the time of start and end. The impact of pain on life was evaluated by the Zoster Brief Pain Inventory (ZBPI). Results: The age of 2 999 HZ patients included in the analysis were (53±16) years old, including 1 377 (45.91%) males and 1 903 (63.45%) patients aged 50 years and older. After 21 days of rash, mild, moderate and severe pain accounted for 20.87% (626 cases), 37.98% (1 139 cases) and 33.81% (1 014 cases), respectively. Only 5.07% (152 cases) had no pain or discomfort, and 2.27% (68 cases) had no pain but discomfort. Most of the pain sites were consistent with the rash sites. The chest and back and waist and abdomen were the most common, accounting for 35.58% (1 067 cases) and 29.18% (875 cases), respectively, followed by the limbs and face and neck, accounting for 16.74% (502 cases) and 16.40% (492 cases), respectively. The M ( Q 1 , Q 3 ) of pain days in the HZ patients was 14 (8, 20) days, and the incidence of post-herpetic neuralgia (PHN) was 6.63% (171/2 580) (excluding 419 patients who refused to visit or lost to visit on 90 days after the onset of rash). The pain score of HZ patients within 21 days after the rash was (5.19±2.73) points, and the pain score of PHN patients was (7.61±2.13) points, which was significantly higher than that of non-PHN patients [(5.04±2.69) points] ( P <0.001). Daily activities, emotions, walking ability, work, social interaction, sleep and recreation were affected for 21 days after the rash in HZ patients, ranging from 60.79% to 83.83%, with sleep being the most affected (83.83%). The impact scores of pain and life dimensions in PHN patients ranged from 4.59 to 7.61 points on the ZBPI scale, which were higher than those in non-PHN patients (2.49-5.04) ( t values ranged from 8.86 to 11.67, all P values <0.001). Conclusion: The proportion of pain in HZ patients after the diagnosis is high, and the pain is more obvious in patients with PHN and HZ patients aged 50 and older, which has a greater impact on their daily lives.

Chemical tagging via possible derivatization reagents alters metabolites' retention times, leading to different retention behavior during liquid chromatography-mass spectrometry (LC-MS) analysis. Incorporation of the retention time dimension can dramatically reduce false-positive structural elucidation in chemical-tagging-based metabolomics. However, few studies predict the retention times of chemically labeled metabolites, especially requiring a simple, easy-to-access, accurate, and universal predictor or descriptor. This pilot study demonstrates the application of volume-corrected free energy (VFE) calculation and region mapping as a new criterion to describe the retention time for structure elucidation in chemical-tagging-based metabolomics. The universality of VFE calculation is first evaluated with four different types of submetabolomes including hydroxyl-group-, carbonyl-group-, carboxylic-group-, and amino-group-containing compounds and oxylipins with similar chemical structures and complex isomers on reverse-phase LC. Results indicate a good correlation ( r > 0.85) between VFE values and their corresponding retention times using different technicians, instruments, and chromatographic columns, describing retention behavior in reverse-phase LC. Finally, the VFE region mapping is described for identifying 1-pentadecanol from aged camellia seed oil using three proposed steps, including public database searching, VFE region mapping for its 12 isomers, and chemical standard matching. The possibility of VFE calculation of nonderivatized compounds in retention time prediction is also investigated, demonstrating its effectiveness on retention times with different influence factors.

Background: There are remarkable genetic differences between animal major histocompatibility complex (MHC) systems and the human leukocyte antigen (HLA) system. HLA transgenic humanized mouse model systems offer a much better method to study the HLA-A-related principal mechanisms for vaccine development and HLA-A-restricted responses against infection in human., Methods: A recombinant gene encoding the chimeric HLA-A30 monochain was constructed. This HHD molecule contains the following: α1-α2 domains of HLA-A30, α3 and cytoplasmic domains of H-2D b , linked at its N-terminus to the C-terminus of human β2m by a 15-amino-acid peptide linker. The recombinant gene encoding the chimeric HLA-A30 monochain cassette was introduced into bacterial artificial chromosome (BAC) CH502-67J3 containing the HLA-A01 gene locus by Red-mediated homologous recombination. Modified BAC CH502-67J3 was microinjected into the pronuclei of wild-type mouse oocytes. This humanized mouse model was further used to assess the immune responses against influenza A virus (H1N1) pdm09 clinically isolated from human patients. Immune cell population, cytokine production, and histopathology in the lung were analyzed., Results: We describe a novel human β2m-HLA-A30 (α1α2)-H-2D b (α3 transmembrane cytoplasmic) (HHD) monochain transgenic mouse strain, which contains the intact HLA-A01 gene locus including 49 kb 5'-UTR and 74 kb 3'-UTR of HLA-A01*01. Five transgenic lines integrated into the large genomic region of HLA-A gene locus were obtained, and the robust expression of exogenous transgene was detected in various tissues from A30-18# and A30-19# lines encompassing the intact flanking sequences. Flow cytometry revealed that the introduction of a large genomic region in HLA-A gene locus can influence the immune cell constitution in humanized mice. Pdm09 infection caused a similar immune response among HLA-A30 Tg humanized mice and wild-type mice, and induced the rapid increase of cytokines, including IFN-γ, TNF-α, and IL-6, in both HLA-A30 humanized Tg mice and wild-type mice. The expression of HLA-A30 transgene was dramatically promoted in tissues from A30-9# line at 3 days post-infection (dpi)., Conclusions: We established a promising preclinical research animal model of HLA-A30 Tg humanized mouse, which could accelerate the identification of novel HLA-A30-restricted epitopes and vaccine development, and support the study of HLA-A-restricted responses against infection in humans., (© 2022 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Investigation of proteins in their native state is the core of proteomics towards better understanding of their structures and functions. Surface-enhanced Raman spectroscopy (SERS) has shown its unique advantages in protein characterization with fingerprint information and high sensitivity, which makes it a promising tool for proteomics. It is still challenging to obtain SERS spectra of proteins in the native state and evaluate the native degree. Here, we constructed 3D physiological hotspots for a label-free dynamic SERS characterization of a native protein with iodide-modified 140 nm Au nanoparticles. We further introduced the correlation coefficient to quantitatively evaluate the variation of the native degree, whose quantitative nature allows us to explicitly investigate the Hofmeister effect on the protein structure. We realized the classification of a protein of SARS-CoV-2 variants in 15 min, which has not been achieved before. This study offers an effective tool for tracking the dynamic structure of proteins and biomedical research., Competing Interests: The authors declare no competing financial interest., (This journal is © The Royal Society of Chemistry.)

Background: Radical resection remains the most effective treatment for hilar cholangiocarcinoma (HCCA). However, due to the complex anatomy of the hilar region, the tumor is prone to invade portal vein and hepatic arteries, making the surgical treatment of HCCA particularly difficult. Successful laparoscopic radical resection of HCCA(IIIA, IIIB) requires excellent surgical skills and rich experience. Furthermore, the safety and effectiveness of this operation are still controversial., Aim: To retrospectively analyze and compare the efficacy and safety of laparoscopic and open surgery for patients with HCCA., Methods: Clinical imaging and postoperative pathological data of 89 patients diagnosed with HCCA (IIIA, IIIB) and undergoing radical resection in our center from January 2018 to March 2022 were retrospectively analyzed. Among them, 6 patients (4 were lost to follow-up and 2 were pathologically confirmed to have other diseases after surgery) were ruled out, and clinical data was collected from the remaining 83 patients for statistical analysis. These patients were divided into an open surgery group (n=62) and a laparoscopic surgery group (n=21) according to the surgical methods used, and after 1:2 propensity score matching (PSM), 32 and 16 patients respectively in the open surgery group and laparoscopic surgery group were remained. The demographic data, Bismuth type, perioperative data, intraoperative data, postoperative complications, pathological findings, and long-term survivals were compared between these two groups., Results: After 1:2 PSM, 32 patients in the open surgery group and 16 patients in the laparoscopic surgery group were included for further analysis. Baseline characteristics and pathological outcomes were comparable between the two groups. Statistically significant differences between the two groups were observed in intraoperative blood loss and operative time, as it were 400-800 mL vs 200-400 mL (P=0.012) and (407.97 ± 76.06) min vs (489.69 ± 79.17) min (P=0.001) in the open surgery group and laparoscopic surgery group, respectively. The R0 resection rate of the open group was 28 cases (87.5%), and the R0 resection rate of the laparoscopic group was 15 cases (93.75%). The two groups showed no significant difference in terms of surgical approach, intraoperative blood transfusion, incidence of postoperative complications, and short- and long-term efficacy (P>0.05)., Conclusions: Laparoscopic radical resection of HCCA has comparable perioperative safety compared to open surgery group, as it has less bleeding and shorter operation time. Although it is a promising procedure with the improvement of surgical skills and further accumulation of experience, further investigations are warranted before its wider application., 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 He, Huang, Ren, Li, Yang, Deng, Li, Peng, Tang, Zheng, Huang and Li.)

Background: Multiple studies have demonstrated that neoadjuvant chemotherapy (NACT) can prolong the overall survival of pancreatic ductal adenocarcinoma (PDAC) patients. However, most studies have focused on open surgery following NACT., Aim: To investigate the efficacy and safety of laparoscopic radical resection following NACT for PDAC., Methods: We retrospectively analyzed the clinical data of 15 patients with pathologically confirmed PDAC who received NACT followed by laparoscopic radical surgery in our hospital from December 2019 to April 2022. All patients underwent abdominal contrast-enhanced computed tomography (CT) and positron emission tomography-CT before surgery to accurately assess tumor stage and exclude distant metastasis., Results: All 15 patients with pancreatic cancer were successfully converted to surgical resection after NACT, including 8 patients with pancreatic head cancer and 7 patients with pancreatic body and tail cancer. Among them, 13 patients received the nab-paclitaxel plus gemcitabine regimen (gemcitabine 1000 mg/m 2 plus nab-paclitaxel 125 mg/m 2 on days 1, 8, and 15 every 4 wk) and 2 patients received the modified FOLFIRINOX regimen (intravenous oxaliplatin 68 mg/m 2 , irinotecan 135 mg/m 2 , and leucovorin 400 mg/m 2 on day 1 and fluorouracil 400 mg/m 2 on day 1, followed by 46-h continuous infusion of fluorouracil 2400 mg/m 2 ). After each treatment cycle, abdominal CT, tumor markers, and circulating tumor cell counts were reviewed to evaluate the treatment efficacy. All 15 patients achieved partial remission. The surgical procedures included laparoscopic pancreaticoduodenectomy (LPD, n = 8) and laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS, n = 7). None of them were converted to a laparotomy. One patient with pancreatic head carcinoma was found to have portal vein involvement during the operation, and LPD combined with vascular resection and reconstruction was performed. The amount of blood loss and operation times of L-RAMPS vs LPD were 435.71 ± 32.37 mL vs 343.75 ± 145.01 mL and 272.52 ± 49.14 min vs 444.38 ± 68.63 min, respectively. The number of dissected lymph nodes was 16.87 ± 4.10, and 3 patients had positive lymph nodes. One patient developed grade B postoperative pancreatic fistula (POPF) after L-RAMPS, and one patient experienced jaundice after LPD. None of the patients died after surgery. As of April 2022, progressive disease was noted in 4 patients, 2 patients had liver metastasis, and one had both liver metastasis and lymph node metastasis and died during the follow-up period., Conclusion: Laparoscopic radical resection of PDAC after NACT is safe and effective if it is performed by a surgeon with rich experience in LPD and in a large center of pancreatic surgery., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Historic and protected buildings are increasingly valued due to their valuable historical and cultural value. The assessment of the safety state of historic buildings has received more attention. Emerging machine learning algorithms, with their excellent computational performance, provide new ideas and new means to solve practical problems in various fields. Therefore, this paper proposes a method for assessing the safety state of historic buildings based on machine learning techniques. Firstly, based on the analysis of the characteristics of historical buildings and common security problems, the application of wireless sensor networks to the security monitoring of historical buildings is proposed in order to improve the automation of monitoring. Then, in order to improve the accuracy of the assessment, a combination of kernel canonical correlation analysis (KCCA) and support vector machine (SVM) is used to establish the security monitoring model. The experimental results show that by choosing a suitable KCCA function, the redundant features of the data can be reduced while the comprehensiveness of the building structure identification features can be retained, thus effectively improving the prediction accuracy of the SVM. The KCCA-SVM model can accurately predict the physical quantities such as relative structural displacement of historical buildings with good reliability., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (Copyright © 2022 Xiao-Hong Peng and Zi-Hao Zhang.)

Background: Thyroid dysfunction has been reported in severe liver diseases. The aim of this study was to analyze the impact of serum thyroid-stimulation hormone (TSH) levels on the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF)., Methods: This retrospective cohort study included 1,862 patients with HBV-related ACLF. Risk factors associated with 30-day and 90-day survival, hazard ratios (HRs), and 95% confidence intervals (CIs) for TSH were estimated using Cox proportional hazards regression. The Area Under the ROC curve (AUROC) analysis was carried out, and the cut-off values were calculated. After grouping by the cut-off value, survival was compared between the groups using the log-rank test. This study data is from the "Survival Cohort Study (SCS)", which has been registered at ClinicalTrials.gov (NCT03992898)., Results: Multivariate analysis indicated that an elevated TSH level was a highly significant predictor for 30-day survival (HR = 0.743, 95% CI: 0.629-0.878, P < 0.001) and 90-day survival (HR = 0.807, 95% CI: 0.717-0.909, P < 0.001). The AUROC of TSH level for 30-day and 90-day mortality were 0.655 and 0.620, respectively, with the same best cut-off values of 0.261 µIU/mL. Log-rank test showed that the group with higher TSH level had higher 30-day (78.5%, 95% CI: 76.1%-80.9% vs. 56.9%, 95% CI: 53.4%-60.4%; P < 0.001) and 90-day survival rate (61.5%, 95% CI: 58.6%-64.4% vs. 42.8%, 95% CI: 39.3%-46.3%; P < 0.001). Similar findings were observed in subgroups analysis. After adjusting for age and other risk factors, the higher level of TSH remained associated with 30-day survival (HR = 0.602, 95% CI: 0.502-0.721, P < 0.001) and 90-day survival (HR = 0.704, 95% CI, 0.609-0.814, P < 0.001)., Conclusions: Serum TSH level significantly correlate with HBV-related ACLF patients' survival and may be of value for predicting 30-day and 90-day survival of patients with HBV-related ACLF., (© 2022. The Author(s).)

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a severe and life-threatening complication, characterised by multi-organ failure and high short-term mortality. However, there is limited information on the impact of various comorbidities on HBV-ACLF in a large population. This study aimed to investigate the relationship between comorbidities, complications and mortality. In this retrospective observational study, we identified 2166 cases of HBV-ACLF hospitalised from January 2010 to March 2018. Demographic data from the patients, medical history, treatment, laboratory indices, comorbidities and complications were collected. The mortality rate in our study group was 47.37%. Type 2 diabetes mellitus was the most common comorbidity, followed by alcoholic liver disease. Spontaneous bacterial peritonitis, pneumonia and hepatic encephalopathy (HE) were common in these patients. Diabetes mellitus and hyperthyroidism are risk factors for death within 90 days, together with gastrointestinal bleeding and HE at admission, HE and hepatorenal syndrome during hospitalisation. Knowledge of risk factors can help identify HBV-ACLF patients with a poor prognosis for HBV-ACLF with comorbidities and complications.

Objective: To explore the association between a modified Blumgart anastomosis technique and the operative time and surgical complications., Methods: This is a retrospective cohort study that analyzed the data of patients who underwent laparoscopic pancreaticoduodenectomy from January 2015 to March 2021. The primary outcome was to explore the association between the modified Blumgart anastomosis technique and operative time., Results: A total of 282 patients were enrolled. There were 177 cases of pancreatic duct-to-mucosa anastomosis in the traditional surgery group, and 105 cases of the modified three-step Blumgart anastomosis in the modified group. There were no statistically significant differences in the general and intraoperative characteristics found between the two groups ( P  > 0.05). The surgical method was an independent predictor of operative time. Overall complications postsurgery were less common in the modified group than in the traditional group. The incidence of postoperative pancreatic fistula was higher in the traditional group than in the modified group (45 cases (25.4%) and 11 cases (10.5%), respectively). Fourteen cases (7.9%) in the traditional group and four case (3.8%) in the modified group had postoperative pancreatic fistula of grades B + C. The two groups had statistically significant differences ( P  < 0.05). The results of the linear regression showed that the type of surgical method was associated with operation time (95% CI, -73.074 to -23.941, β: -0.438, P  < 0.001)., Conclusion: This modified three-step Blumgart pancreaticojejunostomy was associated with the operation time., 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 He, Yang, Peng, Li, Huang, Jian, Wu, Tang, Wang and Huang.)

Soil acidification along with base cations loss degrades soil quality and is a major environmental problem, especially in agroecosystems with extensive nitrogen (N) fertilization. So far, the rates of proton (H + ) production and real soil acidification (loss of base cations) remain unclear in subtropical agricultural watersheds. To assess the current status and future risk of soil acidification in subtropical red soil region of China, a two-year monitoring was conducted in a typical agricultural watershed with upland, paddy fields, and orchards where high N fertilizers are applied (320 kg N ha -1 yr -1 ). H + production, neutralization and base cations losses were quantified based on the inputs (rainwater, inflow of water, and fertilizer) and outputs (outflow of water, groundwater drainage, and plant uptake) of major elements (K + , Ca 2+ , Na + , Mg 2+ , Al 3+ , NH 4 + , NO 3 - , SO 4 2- , Cl - , and H + ). The result showed that total H + production in the watershed was 5152 mol c ha -1 yr -1 . N transformation was the most important H + source (68%), followed by excess plant uptake of cations (25%) and H + deposition (7%). Base cations exchange and weathering of minerals (3842 mol c ha -1 yr -1 ) dominated H + neutralization, followed by SO 4 2- adsorption (1081 mol c ha -1 yr -1 ), while H + and Al 3+ leaching amounted to 431 mol c ha -1 yr -1 , only. These results state clearly that despite significant soil acidification, the acidification of surface waters is minor, implying that soils have buffered substantially the net H + addition. As a result of soil buffering, there was abundant loss of base cations, whose rate is significantly higher than the previously reported weathering rate of minerals in red soils (3842 vs 230-1080 mol c ha -1 yr -1 ). This suggests that the pool of exchangeable base cations is being depleted in the watershed, increasing the vulnerability of the watershed, and posing a serious threat to future recovery of soils from acidification., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Six alkaloids peharmalines F-K, along with 14 known ones, were isolated from the aerial part of Peganum harmala L.. The structures of the isolated compounds were determined based on their HR-ESI-MS data, extensive NMR spectroscopic analyses, and ECD calculations. 3-(4-Hydroxyphenyl)quinoline exhibited potent antiproliferative activity against the HepG-2 cell lines with an IC 50 value of 3.05 μM. Norharmane displayed a moderate inhibition against A549 and HepG-2 cells with IC 50 values of 16.45 μM and 17.27 μM, respectively., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

To set the cultivation goal with adaptation to rural order-oriented medical students, the teaching mode of Human Parasitology was reformed in the context of curriculum ideological and political education. The new teaching mode not only enables students to harvest medical knowledge during the school education stage, but also plays a guiding role in cultivation of humanistic qualities and professional spirit, which provides a basis for cultivating general practitioners serving for grassroots healthcare.

Ethnopharmacological Relevance: Hanchuan Zupa Granule (HCZP) is a classic prescription of Uyghur medicine, that is used for cough and abnormal mucinous asthma caused by a cold and "Nai-Zi-Lai"., Aim of the Study: This study aimed to explore the possible molecular mechanism of HCZP in the treatment of asthma, using a network pharmacology method and in vivo experiments., Materials and Methods: First, we conducted qualitative analysis of the chemical composition of HCZP as a basis for network pharmacology analysis. Using network pharmacology tools, the possible signaling pathways of HCZP in the treatment of asthma were obtained. An OVA-sensitized asthma model was established, and HCZP was continuously administered for one week. BALF was collected for cell counting, and serum and lung tissues were collected to analyze the expression of IgE, IL-4, IL-5, IL-13 and IFN-γ. Hematoxylin & eosin (H&E) staining was performed to assess the pathological changes in the lung tissues. Related protein expression in the lung tissues was analyzed by Western blotting for molecular mechanism exploration., Results: Fifty-six chemical compounds were identified by UPLC Q-TOF MS. According to the network pharmacology results, 18 active compounds were identified among the 56 compounds, and 68 target genes of HCZP in the treatment of asthma were obtained. A total of 19 pathways were responsible for asthma (P < 0.05) according to KEGG pathway analysis. In vivo results showed that OVA sensitivity induced increased respiratory system resistance and inflammatory responses, which included inflammatory cell infiltration and high levels of IgE, IL-4, IL-5 and IL-13 in serum and lung tissues. Furthermore, OVA upregulated p-PI3K, p-JNK and p-p38 expression in lung tissues. Moreover, HCZP treatment significantly downregulated respiratory system resistance, and the expression of IL-4, IL-5, IL-13 and IgE, as well as significantly improved inflammatory cell infiltration in lung tissues. Moreover, the protein expression of p-PI3K, p-JNK and p-p38 in lung tissues decreased after HCZP treatment., Conclusion: HCZP significantly inhibited the OVA-induced inflammatory response via the PI3K-Akt and Fc epsilon RI signaling pathways., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Endoscopic retrograde pancreatic drainage (ERPD) and stent implantation has become the major treatment method for pancreatic pseudocysts. However, it is associated with a high recurrence rate and infection., Aim: To manage pancreatic pseudocysts by sequential therapy with endoscopic naso-pancreatic drainage (ENPD) combined with ERPD and evaluate the treatment outcome., Methods: One hundred and sixty-two cases of pancreatic pseudocyst confirmed by endoscopic examination at our hospital between January 2014 and January 2020 were retrospectively analyzed. There were 152 cases of intubation via the duodenal papilla, of which 92 involved pancreatic duct stent implantation and 60 involved sequential therapy with combined ENPD and ERPD (two-step procedure). The success rate of the procedure, incidence of complications (infection, bleeding, etc .), recurrence, and length and cost of hospitalization were compared between the two groups., Results: The incidence of infection was significantly higher in the ERPD group (12 cases) than in the two-step procedure group (2 cases). Twelve patients developed infection in the ERPD group, and anti-infection therapy was effective in five cases but not in the remaining seven cases. Infection presented as fever and chills in the two-step procedure group. The reoperation rate was significantly higher in the ERPD group with seven cases compared with zero cases in the two-step procedure group ( P < 0.05). Similarly, the recurrence rate was significantly higher in the ERPD group (19 cases) than in the two-step procedure group (0 cases)., Conclusion: Sequential therapy with combined ENPD and ERPD is safe and effective in patients with pancreatic pseudocysts., Competing Interests: Conflict-of-interest statement: The authors declare that there is no conflict of interest to disclose., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To establish a reference range and compare differences among three methods, and then to construct Z-score reference ranges in normal fetuses from the three methods to provide an extra tool for fetal conduction time assessment., Methods: A total of 227 echocardiographic examinations were finally included. Fetal atrioventricular (AV) time and ventriculoatrial (VA) time intervals were measured by three methods: superior vena cava/ascending aorta (SVC/AAO), pulmonary artery/pulmonary vein (PA/PV) and tissue Doppler imaging (TDI). Regression analysis of the mean and standard deviation was performed to establish Z-scores., Results: With the three methods, positive correlations of intervals with gestational age (GA) and fetal heart rate (FHA) were observed, while intervals were negatively correlated with fetal heart rate (FHR). Correlations between VA/AV and GA, FHA and FHR were weak. The general trend of all intervals was towards an increase. In AV intervals, PA/PV revealed the longest mean AV time interval and SVC/AAO showed the shortest interval. In addition, PA/PV revealed the shortest VA interval., Conclusion: This study presents not only the reference range of AV and VA intervals with the three methods but also the Z-score reference ranges for these indices against GA and FHA in normal fetuses. Each method has a different reference range, and appropriate application can facilitate diagnosis and treatment., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Conventional prognostic models do not fully reflect the severity of hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). This study aimed to establish an effective and convenient nomogram for patients with HBV-related ACLF. Methods: A nomogram was developed based on a retrospective cohort of 1,353 patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016. The predictive accuracy and discriminatory ability of the nomogram were determined by a concordance index (C-index) and calibration curve, and were compared with current scoring systems. The results were validated using an independent retrospective cohort of 669 patients consecutively treated at the same institution from July 2016 to March 2018. This study is registered at ClinicalTrials.gov (NCT03992898). Results: Multivariable analysis of the derivation cohort found that independent predictors of 90-day survival were age, white blood cell (WBC) count, hemoglobin (Hb), aspartate aminotransferase (AST), total bilirubin (TBil), international normalized ratio, serum creatinine (Cr), alpha fetoprotein (AFP), serum sodium (Na), hepatic encephalopathy (HE), pre-existing chronic liver disease(PreLD), and HBV DNA load. All factors were included in the nomogram. The nomogram calibration curve for the probability of 90-day survival indicated that nomogram-based predictions were in good agreement with actual observations. The C-index of the nomogram was 0.790, which was statistically significantly greater than those for the current scoring systems in the derivation cohort ( P < 0.001). The results were confirmed in the validation cohort. Conclusions: The proposed nomogram is more accurate in predicting the 90-day survival of patients with HBV-related ACLF than current commonly used methods., 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 © 2021 Chen, Weng, Huang, Peng, He, Zhang, Xiong, Zhang, Cao, Gao, Lin, Gao, Gao and Lin.)

Background: Women with postpartum psychiatric disorders are prone to severe anorexia. Clinical studies have revealed the efficacy of 919 syrup, a traditional Chinese medicine mixture against postpartum illnesses, such as in regulating maternal mood and improving postpartum anorexia., Aim: This study investigated the mechanisms through which 919 syrup improved anorexia induced by postpartum stress, focussing on the combined peroxisome proliferator-activated receptor gamma (PPARγ) and leptin signalling pathway, and its effects on the structure of the gut flora., Methods: Mice were randomly divided into five groups-control group, immobilisation stressed (IS) group (normal saline), pioglitazone (Piog; western medicine control) group, 919 syrup low-dose (TJD; 13.5 g/kg) group, and 919 syrup high-dose (TJG; 27.0 g/kg) group. The control group was housed normally. The other groups received IS for 3 h daily for 21 days. The treatments were initiated following the first postnatal day and were administered by gastric gavage. All mice were sacrificed under anaesthesia on postnatal day 22. Blood, hypothalamus, stomach, and faecal specimens were collected. Gene and protein expression levels of components of the PPARγ-leptin signalling pathway in the serum, hypothalamus, and stomach were determined. Immunofluorescence staining for proopiomelanocortin (POMC), phosphorylated signal transducer and activator of transcription 3 (pSTAT3), and leptin was performed to observe their spatial distributions in the hypothalamus and stomach. 16s rRNA gene sequencing and bioinformatics analysis of fecal specimens were performed., Results: After IS, postpartum mice showed significantly reduced appetite and body weight, accompanied by abnormalities in the structure of the gut flora. Treatment with 919 syrup (27.0 g/kg) downregulated malondialdehyde and upregulated catalase, glutathione peroxidase, and superoxide dismutase by activating PPARγ, thereby affecting the expression of leptin signalling pathway components (leptin, leptin receptor, pSTAT3, POMC, and cocaine and amphetamine-related transcript and neuropeptide Y), and modulated the gut flora in stressed mice., Conclusion: 919 syrup improved appetite in mice with postnatal stress by activating PPARγ to induce crosstalk with the leptin signalling pathway, this mechanism was similar to that of PPARγ agonists. 919 syrup also improved gut flora structure, and the changes in the relative abundances of the gut flora strongly correlated with the expression levels of PPARγ and leptin pathway components., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Postpartum depression is one of the most common mental diseases that occur in women after childbirth; this disorder is extremely painful for women and represents a major burden on the society. Therefore, we designed this study to explore the possible material basis of the disease, and provide potential novel antidepressants therapy using a mouse model. We established a postpartum immobilization stress model. Maternal body weight changes and food intake were recorded for half a month after delivery, and levels of ghrelin and its receptor, growth hormone secretagogue receptor (GHSR) were measured. The mice in the immobilization stress group showed stress activity as well as low body weight and low feeding status. Ghrelin expression was elevated in blood whereas ghrelin or GHSR expression decreased in the hippocampus and prefrontal cortex of the immobilization stress mice, and the number of ghrelin-active and GHSR cells reduced., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Long-term morphine use is associated with serious side effects, such as morphine-induced hyperalgesia and analgesic tolerance. Previous investigations have documented the association between dopamine (DA) neurons in the ventral tegmental area (VTA) and pain. However, whether VTA DA neurons are implicated in morphine-induced hyperalgesia and analgesic tolerance remains elusive., Methods: Initially, we observed behavioural effects of lidocaine administration into VTA or ablation of VTA DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance. Subsequently, c-Fos expression in nucleus accumbens (NAc) shell-projecting and medial prefrontal cortex (mPFC)-projecting VTA DA neurons after chronic morphine treatment was respectively investigated. Afterwards, the effects of chemogenetic manipulation of NAc shell-projecting or mPFC-projecting DA neurons on morphine-induced hyperalgesia and anti-nociceptive tolerance were observed. Additionally, effects of chemogenetic manipulation of VTA GABA neurons on c-Fos expression in VTA DA neurons were investigated., Results: Lidocaine injection into VTA relieved established hyperalgesia and anti-nociceptive tolerance whereas ablation of VTA DA neurons prevented the development of morphine-induced hyperalgesia and anti-nociceptive tolerance. Chronic morphine treatment increased c-Fos expression in NAc shell-projecting DA neurons, rather than in mPFC-projecting DA neurons. Chemogenetic manipulation of NAc shell-projecting DA neurons had influence on morphine-induced hyperalgesia and tolerance. However, chemogenetic manipulation of mPFC-projecting DA neurons had no significant effects on morphine-induced hyperalgesia and anti-nociceptive tolerance. Chemogenetic manipulation of VTA GABA neurons affected the c-Fos expression in VTA DA neurons., Conclusions: These findings revealed the involvement of NAc shell-projecting VTA DA neurons in morphine-induced hyperalgesia and anti-nociceptive tolerance, and may shed new light on the clinical management of morphine-induced hyperalgesia and analgesic tolerance., Perspective: This study demonstrated that NAc shell-projecting DA neurons rather than mPFC-projecting DA neurons in the VTA were implicated in morphine-induced hyperalgesia and anti-nociceptive tolerance. Our findings may pave the way for the discovery of novel therapies for morphine-induced hyperalgesia and analgesic tolerance.

Background: Human leukocyte antigen (HLA)-DP is much less studied than other HLA class II antigens, that is, HLA-DR and HLA-DQ, etc. However, the accumulating data have suggested the important roles of DP-restricted responses in the context of cancer, allergy, and infectious disease. Lack of animal models expressing these genes as authentic cis -haplotypes blocks our understanding for the role of HLA-DP haplotypes in immunity., Methods: To explore the potential cis -acting control elements involved in the transcriptional regulation of the HLA-DPA1/DPB1 gene, we performed the expression analysis using bacterial artificial chromosome (BAC)-based transgenic humanized mice in the C57BL/6 background, which carried the entire HLA-DP401 gene locus. We further developed a mouse model of Staphylococcus aureus pneumonia in HLA-DP401 humanized transgenic mice, and performed the analysis on the expression pattern of HLA-DP401 and immunological responses in the model., Results: In this study, we screened and identified a BAC clone spanning the entire HLA-DP gene locus. DNA from this clone was analyzed for integrity by pulsed-field gel electrophoresis and then microinjected into fertilized mouse oocytes to produce transgenic founder animals. Nine sets of PCR primers for regional markers with an average distance of 15 kb between each primer were used to confirm the integrity of the transgene in the five transgenic lines carrying the HLA-DPA1/DPB1 gene. Transgene copy numbers were determined by real-time PCR analysis. HLA-DP401 gene expression was analyzed at the mRNA and protein level. Although infection with S aureus Newman did not alter the percentage of immune cells in the spleen and thymus from the HLA-DP401-H2-Aβ1 humanized mice. Increased expression of HLA-DP401 was observed in the thymus of the humanized mice infected by S aureus ., Conclusions: We generated several BAC transgenic mice, and analyzed the expression of HLA-DPA1/DPB1 in those mice. A model of S aureus -induced pneumonia in the HLA-DP401-H2-Aβ1 -/- humanized mice was further developed, and S aureus infection upregulated the HLA-DP401 expression in thymus of those humanized mice. These findings demonstrate the potential of those HLA-DPA1/DPB1 transgenic humanized mice for developing animal models of infectious diseases and MHC-associated immunological diseases., (© 2021 The Authors. Animal Models and Experimental Medicine published by John Wiley & Sons Australia, Ltd on behalf of The Chinese Association for Laboratory Animal Sciences.)

Background: The COVID-19 outbreak has affected people's health worldwide. For college students, web-based physical education is a challenge, as these course are normally offered outdoors., Objective: The aim of this study was to use data from a web-based survey to evaluate the relationship between the mental health status of college students and their sports-related lifestyles. Problems related to web-based physical education were also examined., Methods: A web-based survey was conducted by snowball sampling from May 8 to 11, 2020. Demographic data, mental health status, and sports-related lifestyles of college students in Wuhan as well as issues related to web-based physical education were collected. Mental health status was assessed by the Depression, Anxiety, and Stress Scale (DASS-21)., Results: The study included 1607 respondents from 267 cities. The average scores of the DASS-21 subscales (2.46 for depression, 1.48 for anxiety, and 2.59 for stress) were significantly lower in our study than in a previous study (P<.05). Lower DASS-21 scores were significantly correlated with regular exercise, maintaining exercise habits during the outbreak of COVID-19, exercising more than 1 to 2 times a week, exercise duration >1 hour, and >2000 pedometer steps (all P<.05). None of the three forms of web-based physical education was preferred by more than 50% of respondents. Frequent technical problems were confronted by 1087/1607 students (67.6%). Shape-up exercises (846/1607, 52.6%), a designed combination of exercises (710/1607, 44.2%), and Chinese kung fu (559/1607, 34.8%) were suggested sports for web-based physical education., Conclusions: Mental status was significantly correlated with regular exercise and sufficient exercise duration. Professional physical guidance is needed for college students in selected sports. Exercises not meeting students' preferences, frequent technical problems, and the distant interaction involved in web-based physical education were the main problems that should be solved in future., (©Cheng-Hu Deng, Jing-Qiang Wang, Li-Ming Zhu, He-Wang Liu, Yu Guo, Xue-Hua Peng, Jian-Bo Shao, Wei Xia. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 05.10.2020.)

Background: Visceral hypersensitivity is a common occurrence of gastrointestinal diseases such as irritable bowel syndrome (IBS), wherein early-life stress (ELS) may have a high predisposition to the development of visceral hypersensitivity in adulthood, with the specific underlying mechanism still elusive. Herein, we assessed the potential effect of small-conductance calcium-activated potassium channel subtype 2 (SK2) in the spinal dorsal horn (DH) on the pathogenesis of visceral hypersensitivity induced by maternal separation (MS) in mice., Methods: Neonatal mice were subjected to the MS paradigm, an established ELS model. In adulthood, the visceral pain threshold and the abdominal withdrawal reflex (AWR) were measured with an inflatable balloon. The elevated plus maze, open field test, sucrose preference test, and forced swim test were employed to evaluate the anxiety- and depression-like behaviors. The expression levels of SK2 in the spinal DH were determined by immunofluorescence and western blotting. The mRNA of SK2 and membrane palmitoylated protein 2 (MPP2) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Electrophysiology was applied to evaluate the neuronal firing rates and SK2 channel-mediated afterhyperpolarization current ( I AHP ). The interaction between MPP2 and SK2 was validated by coimmunoprecipitation., Results: In contrast to the naïve mice, ethological findings in MS mice revealed lowered visceral pain threshold, more evident anxiety- and depression-like behaviors, and downregulated expression of membrane SK2 protein and MPP2 protein. Moreover, electrophysiological results indicated increased neuronal firing rates and decreased I AHP in the spinal DH neurons. Nonetheless, intrathecal injection of the SK2 channel activator 1-ethyl-2-benzimidazolinone (1-EBIO) in MS mice could reverse the electrophysiological alterations and elevate the visceral pain threshold. In the naïve mice, administration of the SK2 channel blocker apamin abated I AHP and elevated spontaneous neuronal firing rates in the spinal DH neurons, reducing the visceral pain threshold. Finally, disruption of the MPP2 expression by small interfering RNA (siRNA) could amplify visceral hypersensitivity in naïve mice., Conclusions: ELS-induced visceral pain and visceral hypersensitivity are associated with the underfunction of SK2 channels in the spinal DH., Competing Interests: All authors declare no financial competing interests., (Copyright © 2020 Ke Wu et al.)

Background: The clinical management of coronavirus disease 2019 (COVID-19) is dependent on understanding the underlying factors that contribute to the disease severity. In the absence of effective antiviral therapies, other host immunomodulatory therapies such as targeting inflammatory response are currently being used without clear evidence of their effectiveness. Because inflammation is an essential component of host antiviral mechanisms, therapies targeting inflammation may adversely affect viral clearance and disease outcome., Objective: To understand whether the persistent presence of the virus is a key determinant in the disease severity during COVID-19 and to determine whether the viral reactivation in some patients is associated with infectious viral particles., Methods: The data for patients were available including the onset of the disease, duration of viral persistence, measurements of inflammatory markers such as IL-6 and C-reactive protein, chest imaging, disease symptoms, and their durations among others. Follow-up tests were performed to determine whether the viral negative status persists after their recovery., Results: Our data show that patients with persistent viral presence (>16 days) have more severe disease outcomes including extensive lung involvement and requirement of respiratory support. Two patients who died of COVID-19 were virus-positive at the time of their death. Four patients demonstrated virus-positive status on the follow-up tests, and these patient samples were sent to viral culture facility where virus culture could not be established., Conclusions: These data suggest that viral persistence is the key determining factor of the disease severity. Therapies that may impair the viral clearance may impair the host recovery from COVID-19., (Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

An efficient and convenient iridium(iii) catalyzed ortho -C-H bond amidation of weakly coordinating benzamides treated with readily available sulfonyl azides as the amino source has been described. In this transformation, ionic liquids represents an ideal reaction medium, giving rise to a broad range of amidation products under mild conditions in the open air. This protocol offers moderate to excellent chemical yields, exclusive regioselectivities, and good functional group tolerance., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

The application of resting state functional MRI (RS-fMRI) in Parkinson's disease (PD) was widely performed using standard statistical tests, however, the machine learning (ML) approach has not yet been investigated in PD using RS-fMRI. In current study, we utilized the mean regional amplitude values as the features in patients with PD (n = 72) and in healthy controls (HC, n = 89). The t-test and linear support vector machine were employed to select the features and make prediction, respectively. Three frequency bins (Slow-5: 0.0107-0.0286 Hz; Slow-4: 0.0286-0.0821 Hz; conventional: 0.01-0.08 Hz) were analyzed. Our results showed that the Slow-4 may provide important information than Slow-5 in PD, and it had almost identical classification performance compared with the Combined (Slow-5 and Slow-4) and conventional frequency bands. Similar with previous neuroimaging studies in PD, the discriminative regions were mainly included the disrupted motor system, aberrant visual cortex, dysfunction of paralimbic/limbic and basal ganglia networks. The lateral parietal lobe, such as right inferior parietal lobe (IPL) and supramarginal gyrus (SMG), was detected as the discriminative features exclusively in Slow-4. Our findings, at the first time, indicated that the ML approach is a promising choice for detecting abnormal regions in PD, and a multi-frequency scheme would provide us more specific information., (Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.)

Objectives: To establish Z-score models for early diastolic blood flow widths of mitral and tricuspid valves in normal fetuses and compare Z-scores and other blood flow dynamic parameters between normal fetuses and fetuses with dilated coronary sinus (CS). This study seeks to assess whether dilated CS affects cardiac structure or hemodynamics. Methods: One hundred twenty-nine normal fetuses (Group I) and 15 fetuses with dilated CS connected to persistent left superior vena cava (PLSVC) (Group II) were included in this study. Noncardiac biometrical parameters, including gestation age (GA), biparietal diameter (BPD), femoral length (FL), and heart area (HA), were obtained. Hemodynamic parameters, such as the early diastolic blood flow widths of mitral and tricuspid valves (MV-CDFI-Width, TV-CDFI-Width), velocity and time integral of blood flow (VTI), peak early and late diastolic velocity of mitral and tricuspid valves [peak early diastolic velocity of the mitral valve (MVE), peak late diastolic velocity of the mitral valve (MVA), peak early diastolic velocity of the tricuspid valve (TVE), peak late diastolic velocity of the tricuspid valve (TVA)], were measured. Results: Z-score models for MV-CDFI-Width and TV-CDFI-Width against noncardiac biometrical parameters were best described by linear regression analysis. The mean equations of MV-CDFI-Width against noncardiac biometrical parameters were 0.066 + (0.025 × GA), 0.169 + (0.084 × BPD), 0.213 + (0.106 × FL) and 0.533 + (0.028 × HA). The SD for MV-CDFI-Width against FL was estimated based on values from the following equation: -0.006 + (0.02 × FL). Other SDs were constants estimated as the standard deviations of the unscaled residuals. Z-scores and other blood flow dynamic parameters exhibited no statistically significant differences between Group I and Group II. Conclusions: This study demonstrated that dilated CS did not affect fetal hemodynamics of the mitral or tricuspid valves or cardiac structures. We also suggested that the causes of diminutive left heart or coarctation of the aorta might not be associated with dilated CS in fetuses with PLSVC.

Objectives: To evaluate the performance of fetal intelligent navigation echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volumes in generating 3 specific abnormal cardiac views (left ventricular outflow tract, right ventricular outflow tract, and 3-vessel and trachea) used to screen for d-transposition of the great arteries (d-TGA)., Methods: In this prospective study, 1 or more STIC volumes were obtained from the 4-chamber view in 34 second- and third-trimester fetuses with d-TGA. Each appropriate STIC volume was evaluated by STICLoop (Samsung Medison, Seoul, Korea) before applying the FINE method. One optimal volume per fetus was selected by observers. The visualization rates of the 3 specific abnormal cardiac views of d-TGA and their diagnostic elements were calculated, and the reliability between 2 observers was verified by the intraclass correlation coefficient., Results: Fetal intelligent navigation echocardiography applied to STIC volume data sets of fetuses with d-TGA successfully generated the 3 specific abnormal cardiac views in the following manner for 2 observers: 75.0% (n = 21) for the left ventricular outflow tract, 89.2% (n = 25) for the right ventricular outflow tract, and 85.7% (n = 24) for the 3-vessel and trachea view. Twenty-four (85.7%) of the STIC volume data sets showed 2 or 3 of the abnormal cardiac views. The interobserver intraclass correlation coefficients between the 2 observers ranged from 0.842 to 1.000 (95% confidence interval), indicating almost perfect reliability for the 2 observers., Conclusions: In cases of d-TGA, the FINE method has a high success rate in generating 3 specific abnormal cardiac views and therefore can be performed to screen for this congenital defect., (© 2019 by the American Institute of Ultrasound in Medicine.)

Intracellular polyphosphate (poly-P) plays important roles in Enhanced biological phosphorus removal (EBPR) process, but an effective and reliable protocol for extracting intracellular P and its poly-P in EBPR sludge without hydrolysis of poly-P has not been setup yet. In the study, it was revealed that the severe hydrolysis of intracellular poly-P occurred during the different extraction processes, such as acid (i.e., HClO 4 , H 2 SO 4 and HCl), basic (i.e., NaOH and KOH) and freezing-grind (under different solid-liquid ratios), but it did not occur during ultrasonic extraction process. The optimal extraction process of the ultrasonic protocol was 10 w/mL of ultrasonic power density and 15 min of ultrasonic time, when the extraction efficiency of intracellular P was 88.24 ± 1.56%. In addition, the extraction efficiency of intracellular P could be furtherly improved by that the 0.75 mol/L LiCl solution was used to resuspend the bacterial cell before ultrasonic extraction (i.e., LiCl-ultrasonic protocol). The ultrasonic protocol was more suitable to extract the intracellular P and its poly-P of EBPR sludge than the other 4 protocols (i.e., PCA-NaOH, EDTA-NaOH, freezing-grind and LiCl-ultrasonic), which had the technical characteristics of (i) with relatively high extraction efficiency of intracellular P, (ii) without hydrolysis of intracellular poly-P, (iii) with weak noise signal in 31 P NMR spectrum and (iv) with simple extraction process and short extraction time. It was founded by the ultrasonic protocol that there was the high content (82.88%-89.79% of intracellular P content) of intracellular poly-P with long average chain length (376.4-383.2) in the EBPR sludges. Importantly, it was confirmed that the EBPR process was related to the combined action of extracellular and intracellular poly-P using a new fractionation method of P in EBPR sludge, which included the ultrasonic protocol at high power density for extracting the intracellular P and its poly-P., (Copyright © 2019. Published by Elsevier B.V.)

Inspired by the intriguing structures and bioactivities of polyprenylated xanthones, ten previously undescribed polyprenylated xanthones, nujiangxanthones G-P (1-10), and fifteen known ones (11-25) were isolated from the twigs and leaves of Garcinia nujiangensis. The structures of these compounds were established on the basis of spectroscopic data as well as comparison with the literature. Most of the isolates showed potent cytotoxicity against selected cancer cells. Compound 8 showed the highest effects against MDA-MB-231 and A549 cell lines with IC 50 values of 4.12 and 2.67 μM and 16 demonstrated the most potent activity against MCF-7 cell line with an IC 50 value of 3.36 μM., (Copyright © 2019 Elsevier Inc. All rights reserved.)

To evaluate the anesthetic effect of ultrasound-guided (USG) ilioinguinal/iliohypogastric nerve (II/IHN) block combined with genital branch of genitofemoral nerve (GFN) block in the elderly undergoing inguinal hernia repair, 54 old patients (aged 60-96years, ASA I-III) with indirect hernia were enrolled and scheduled for unilateral tension-free herniorrhaphy. Patients were grouped randomly to receive either USG II/IHN plus GFN block (Group G) or USG II/IHN block alone (Group I). The intraoperative visual analogue scale (VAS) scores were recorded at skin incision, at spermatic cord/round ligament traction and at sac ligation. The resting and dynamic VAS scores were recorded postoperatively. The requirements of extra sedatives and analgesics for intra- and postoperative analgesia were assessed. Occurrence of complications of the block, postoperative nausea and vomiting and femoral nerve palsy was also reported. Both groups showed similar sensory block. When stretching spermatic cord/round ligament, the patients in group G had significantly lower VAS scores than in group I. And group G used much fewer adjuvant sedatives and analgesics to achieve adequate anaesthesia. In addition, group G was presented with better intraoperative anaesthesia and lower postoperative dynamic VAS scores at all time points tested. No significant difference was found in the postoperative requirement of rescue medication. Both groups showed no complications related to the block and group G reported no femoral nerve palsy. The addition of GFN block to II/IHN block improves the quality of perioperative anesthesia and analgesia in the elderly and reduces the consumption of extra sedatives and analgesics during the surgery.

Peri-operative dexmedetomidine can reduce rates of delirium immediately after surgery. We aimed to assess the effect of dexmedetomidine on cognition up to six postoperative months and its association with changes in serum concentrations of brain-derived neurotrophic factor on the third and seventh postoperative days. We randomly allocated 535 patients aged 65 years or more undergoing scheduled gastro-intestinal laparotomy to: intra-operative dexmedetomidine, 0.5 μg.kg -1 bolus followed by 0.4 μg.kg -1 .hr -1 infusion (n = 269), or placebo (n = 266). Dexmedetomidine reduced the rate of cognitive impairment: on the third postoperative day, 40/269 vs. 65/266, p = 0.006; on the seventh postoperative day, 31/269 vs. 49/266, p = 0.03 and at one postoperative month, 42/250 vs. 61/248, p = 0.04. Cognitive impairment at seven postoperative days was associated with changes in brain-derived neurotrophic factor concentrations on the third and seventh postoperative days; area under the receiver operating characteristic curve 0.63, p < 0.001 and 0.58, p = 0.016, respectively. Intra-operative dexmedetomidine reduced cognitive decline up to one postoperative month in elderly patients undergoing scheduled laparotomy, which was associated with changes in serum brain-derived neurotrophic factor., (© 2019 Association of Anaesthetists.)

Objective: To investigate right aortic arches (RAA) quantitatively and risk-stratify fetuses with RAA prenatally., Method: A total of 143 singleton fetuses were enrolled. Four measurements were studied, including the angle and distance between the aortic arch (AO) and ductal arch (DA), the diameters of the AO and DA, and the distance growth rate (DGR)., Result: A significant increase in mean distance was observed in the study group (4.89 ± 1.07 mm) compared to the control group (1.62 ± 0.33 mm, p<.01). The distance increased from the second (1.52 ± 0.35 mm, p<.01, 4.06 ± 0.78 mm, p<.01) to third trimester (1.71 ± 0.29 mm, p<.01, 5.13 ± 1.10 mm, p<.01) in the normal and study groups. Fetuses with abnormalities in addition to RAAs had significantly lower growth rates (12.4 ± 5.2%) than those with an isolated RAA (33.7 ± 12.0%)., Conclusion: Parameters, especially DGR, may be clinically significant. DGR may be restricted when an RAA exists with other malformations. Decreasing DGR in fetuses with RAAs suggests the presence of other malformations.

Objective: Using data of health information system (HIS) of medical institutions to study the incidence and hospitalization of herpes zoster in three districts of Beijing. Methods: According to the different level of economic development and geographical features in Beijing, 3 districts of Xicheng, Changping and Miyun were chosen and all 110 medical institutions of the first level and above in the 3 districts are included in the survey. All the outpatient and inpatient herpes zoster cases in 2015 were retrospectively reviewed by HIS system. After distinguishing the reduplicated cases, Using the first outpatient case as a molecule and the resident population as denominator to estimate the annual incidence rate, as well as the annual hospitalization rate was estimated based on primary diagnostic hospitalized cases as molecule and the resident population as denominator. Results: A total of 32 313 primary visit outpatient cases were investigated, of which 18 360 cases (56.8%) were women and 20 923 cases (64.8%) were ≥50 years old. The overall estimated incidence of the 3 districts was 8.8‰ with an increase trends with age and reached to the highest in ≥80 years old (30.5/1 000). The incidence of Xicheng, Changping and Miyun districts are respectively 16.2‰, 4.0‰ and 5.7‰. A total of 701 primary visit inpatient cases were identified, of which 366 cases (52.2%) were women and 651 cases (92.9%) were ≥50 years old. The estimated annual hospitalization rate was 19.4/100 000, with the primary and secondary diagnostic hospitalization rate are respectively 5.9/100 000 (212 cases) and 13.5/100 000 (489 cases). The disease types of secondary diagnostic inpatient herpes zoster cases were as follows: cardiovascular disease (19.0%, 93 cases), stroke (14.5%, 71 cases), pneumonia/chronic obstructive pulmonary disease (14.1%, 69 cases), tumor (12.5%, 61 cases) and diabetes (5.7%, 28 cases). Conclusion: Most of the herpes zoster cases in Beijing are over 50 years old, and the incidence of female is slightly higher than male. This disease should become a public health issue of great concern.