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Now cancer-related fatigue is gradually being emphasized, which is a common symptom in cancer patients. During long-term radiotherapy, the emotion of patients will be affected directly, and inevitably produce cancer-caused fatigue needle symptoms. Moreover, the weakness and fatigue are always produced simultaneously, which are harmful to patients’ prognosis level of their overall survival quality. The acupuncture has a helpful effect on improving the Chinese medical evidence of side effects caused by radiotherapy and chemotherapy in tumor patients. In this paper, we model the effect of acupuncture on cancer fatigue after chemotherapy in gynecologic oncology patients through data analysis, so as to effectively analyze the degree of cancer fatigue after chemotherapy in patients.

Lung cancer is the most common cancer and one of the main causes of cancer-related deaths, presenting in most cases as metastatic disease. Given the frequent gene mutation and/or signaling deregulation in lung adenocarcinoma, identifying novel factors or agents that target these signaling pathways may be promising strategies for lung adenocarcinoma therapy. Herein, we identified inhibitor of DNA binding 2 (ID2) as an aberrantly downregulated gene in lung adenocarcinoma. ID2 overexpression not only suppressed the viability, colony formation ability, and migration ability of lung adenocarcinoma cells but also decreased the protein levels of N-cadherin, MMP2, MMP9 and the phosphorylation levels of AKT and mTOR. The effects of PI3K/AKT/mTOR signaling agonist on lung adenocarcinoma cells were opposite to those of ID2 overexpression, partially reversing the effects of ID2 overexpression. In these experimental tissue samples, ID2 protein levels and mRNA expression were also down-regulated compared with those in adjacent non-cancerous tissues. Altogether, these findings indicated that ID2 exerts its tumor-suppressive effects on the malignant behavior of lung adenocarcinoma cells by inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. Restoration of ID2 expression in lung adenocarcinoma cells may improve the therapeutic efficacy of lung adenocarcinoma therapies.

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 μM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 μM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 μM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 μM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 μM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 μM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe

Because the recovery of genitourinary function after total mesorectal excision (TME) is affected by multiple factors, the role of robot-assisted TME technology in postoperative function in previous studies is still controversial. Our study aimed to evaluate the impact of robotic technology on the recovery of genitourinary function after TME for rectal cancer by analysing the correlations between influencing factors of genitourinary function and robotic surgery.Between January 2017 and January 2020, patients with rectal cancer (cT1-3NxM0) were registered. Genitourinary function was assessed by the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) test, Female Sexual Function Index (FSFI) and urodynamic examination before surgery and 1, 3, 6, and 12 months postoperatively. Genitourinary function was compared between the laparoscopic total mesorectal excision (L-TME) and robotic total mesorectal excision (R-TME) groups, and the correlative factors associated with postoperative genitourinary function were analysed using the generalized estimated equation (GEE).Compared with L-TME, R-TME showed a superior IPSS, voiding volume, residual urine volume and IIEF score during the early postoperative period. According to the GEE analysis, postoperative genitourinary function was positively correlated with laparoscopic anterior resection/abdomen perineal resection (LAR/APR) but negatively correlated with tumour size, tumour distance to anus, TNM, adjuvant chemotherapy, adjuvant radiotherapy, complete TME, circumferential resection margin (CRM), blood loss, diverting stoma, conversion, and anastomotic leakage.Due to the important role of robotic surgical technology on the influential factors of postoperative genitourinary function and the superiority of identifying and preserving autonomic nerves, robotic technology is conducive to the early recovery of postoperative urogenital function while adhering to oncological dissection principles. No significant difference was found between the da Vinci R-TME and MicroHand R-TME groups.

Thermoelectric materials (TMs) can uniquely convert waste heat into electricity, which provides a potential solution for the global energy crisis that is increasingly severe. Bulk Cu2Se, with ionic conductivity of Cu ions, exhibits a significant enhancement of its thermoelectric figure of merit zT by a factor of ~3 near its structural transition around 400 K. Here, we show a systematic study of the electronic structure of Cu2Se and its temperature evolution using high-resolution angle-resolved photoemission spectroscopy. Upon heating across the structural transition, the electronic states near the corner of the Brillouin zone gradually disappear, while the bands near the centre of Brillouin zone shift abruptly towards high binding energies and develop an energy gap. Interestingly, the observed band reconstruction well reproduces the temperature evolution of the Seebeck coefficient of Cu2Se, providing an electronic origin for the drastic enhancement of the thermoelectric performance near 400 K. The current results not only bridge among structural phase transition, electronic structures, and thermoelectric properties in a condensed matter system, but also provide valuable insights into the search and design of new generation of thermoelectric materials., Comment: To appear in Science Bulletin

In this paper, 4H-SiC planar MOSFETs were designed and fabricated. By using TCAD tool, the trade-off between on-resistance and maximum gate oxide electric field was optimized. With optimized gate oxide growth process, the gate oxide’s critical electric field of 9.8 MV/cm and the effective barrier height of 2.57 eV between SiO2 and 4H-SiC were obtained. The field effective mobility with different p-body doping was compared and studied. The MOS interface state density of 1.12E12 cm-2eV-1 at EC - EIT = 0.21 eV and channel mobility of 19.3 cm2/Vs at VGS = 20 V were obtained. The fabricated MOSFET’s on-resistance of 6.4 mΩcm2 was obtained with hexagonal cell structure which is very consistent with the simulation results.

Type-II iron-based superconductors (Fe-SCs), the alkali-metal-intercalated iron selenide AxFe2−ySe2 (A = K, Tl, Rb, etc.) with a superconducting transition temperature of 32 K, exhibit unique properties such as high Néel temperature, Fe-vacancies ordering, antiferromagnetically ordered insulating state in the phase diagram, and mesoscopic phase separation in the superconducting materials. In particular, the electronic and structural phase separation in these systems has attracted intensive attention since it provides a platform to unveil the insulating parent phase of type-II Fe-SCs that mimics the Mott parent phase in cuprates. In this work, we use spatial- and angle-resolved photoemission spectroscopy to study the electronic structure of superconducting KxFe2−ySe2. We observe clear electronic phase separation of KxFe2−ySe2 into metallic islands and insulating matrix, showing different K and Fe concentrations. While the metallic islands show strongly dispersive bands near the Fermi level, the insulating phase shows an energy gap up to 700 meV and a nearly flat band around 700 meV below the Fermi energy, consistent with previous experimental and theoretical results on the superconducting K1−xFe2Se2 (122 phase) and Fe-vacancy ordered K0.8Fe1.6Se2 (245 phase), respectively. Our results not only provide important insights into the mysterious composition of phase-separated superconducting and insulating phases of KxFe2−ySe2, but also present their intrinsic electronic structures, which will shed light on the comprehension of the unique physics in type-II Fe-SCs.

BACKGROUND The sleep quality of patients with postoperative glioma at home has not been reported worldwide. In this study, the sleep quality of postoperative glioma patients at home was explored through telephone interviews. AIM To investigate the sleep quality of patients with postoperative glioma. METHODS Glioma patients who were treated and operated on at Nanjing Brain Hospital from May 2012 to August 2019 were selected as participants via convenience sampling. A total of 549 patients were recruited by telephone, and 358 of those patients responded to the Pittsburgh Sleep Quality Index (PSQI). RESULTS The total PSQI score was 5.19 ± 3.39 in all patients with postoperative glioma, which was higher than that of the normal group. There were 135 patients with poor sleep quality (PSQI > 7), which accounted for 37.7% of all respondents. The scores of the seven dimensions of the PSQI were sleep latency (1.22 ± 1.05), sleep disturbance (1.12 ± 0.98), subjective sleep quality (1.03 ± 0.92), habitual sleep efficiency (1.02 ± 0.91), daytime dysfunction (0.95 ± 0.43), sleep persistence (0.83 ± 0.76), and use of sleeping medication (0.25 ± 0.24). The results showed that the subjective sleep quality of the patients who underwent an operation 1-2 years ago was worse than that of the patients who underwent an operation more than 2 years ago (P < 0.05). Older patients had worse sleep latency and sleep duration scores than younger patients (P < 0.05). Sleep disturbance and daytime dysfunction were worse in patients who received postoperative radiotherapy/ chemotherapy (P < 0.05). CONCLUSION The sleep quality of patients with postoperative glioma at home is worse than that of normal adults. Moreover, difficulty falling asleep and sleep disorders are common complications among these patients, and age, postoperative duration, and postoperative chemoradiotherapy could affect sleep quality.

0.67CaTiO3–0.33LaAlO3 (CTLA) microwave dielectric ceramic materials with the additives of H3BO3, Li2CO3 or H3BO3–Li2CO3 were prepared by a conventional solid-state reaction method. The effects of the sintering additives on the densification behavior, phase compositions, microstructures, and microwave dielectric properties of the CTLA ceramic samples were investigated. It was found that the binary additive of H3BO3–Li2CO3 effectively promoted the densification and lowered the sintering temperature of the CTLA ceramic samples without a significant decrease in their Q × f values. For example, with an addition of 0.2 wt% H3BO3–0.1 wt% Li2CO3, the optimal microwave dielectric properties of er = 45.5, Q × f = 31,771 GHz and a near-zero τf of 2.43 ppm/℃ were obtained in the CTLA ceramic sample sintered at only 1175 ℃, which is significantly lower (~ 225 ℃) compared to the sintering temperatures of conventionally sintered CTLA ceramics.

The purpose of this study was to investigate whether TXA can effectively reduce blood loss after HTO and related complications and to evaluate its safety.From March 2016 to March 2018, 100 patients who underwent medial opening wedge HTO in the Department of Orthopedics, the second affiliated hospital of xi'an jiaotong university, with an average age of 52.8 ± 3.2 years, were randomly divided into the TXA group (using intravenous TXA) and the control group (using the same amount of normal saline), with 50 patients in each group. The postoperative wound drainage volume, decrease in hemoglobin and hematocrit value, total blood loss, wound healing, blood transfusion, deep venous thrombosis (DVT) and pulmonary embolism (PE) were compared between the two groups.The drainage volume on the first postoperative day and the total drainage volume of the TXA group were significantly lower compared with those of the control group (145.7 vs 264.5 ml, 282.3 vs 413.2 ml, P 0.05). The decreases in the hemoglobin and hematocrit values on the postoperative first, second and fifth days were lower in the TXA group than those in the control group (1.4 VS 3.5, 2.6 vs 3.3, 1.9 vs 2.9 g, P 0.05; 3.3 vs 5.5, 5.0 vs 9.1, 3.8 vs 7.2%, P 0.05), and the mean total blood loss was also lower in the TXA group than that in the control group (477.9 vs 834.6 ml, P 0.05). In the control group, 1 patient had wound hematoma requiring additional paracentesis and pressure dressing, 1 patient had superficial wound infection requiring additional debridement, and 1 patient had postoperative blood transfusion compared to none in the TXA group (P 0.05). There was no symptomatic DVT or PE in either of the groups.Intravenous TXA can effectively and safely reduce blood loss and bleeding-related complications after HTO and was beneficial for the blood management of HTO.

Cold sintered, Li2MoO4‐based ceramics have recently been touted as candidates for electronic packaging and low temperature co‐fired ceramic (LTCC) technology but MoO3 is an expensive and endangered raw material, not suited for large scale commercialisation. Here, we present cold sintered temperature‐stable composites based on LiMgPO4 (LMP) in which the Mo (and Li) concentration has been reduced, thereby significantly decreasing raw material costs. Optimum compositions, 0.5LMP‐0.1CaTiO3‐0.4K2MoO4 (LMP‐CTO‐KMO), achieved 97% density at

Ovarian cancer (OC) is a common gynecological malignant carcinoma worldwide. Accumulating research has revealed that multiple microRNAs (miRNAs) are abnormally expressed at different levels in various malignancies, playing vital roles in tumorigenesis. This study investigated the regulatory functions and potential mechanism of miR-126 in OC proliferation, invasion and migration. It was found that miR-126 was prominently downregulated in OC. Moreover, the decrease of miR-126 promoted the aggressive phenotypes and indicated poor prognosis of OC patients. Functional assays demonstrated that restoration of miR-126 dramatically repressed OC cell proliferation, migration and invasion. Furthermore, luciferase reporter assay was conducted to verify putative binding sites of miR-126 in the epidermal growth factor-like domain 7 (EGFL7) 3 untranslated region (3′UTR), indicating that EGFL7 was a target gene of miR-126 in OC cells. It was further discovered that miR-126 exerts its function on regulating ERK/MAPK pathway and epithelial-to-mesenchymal transition (EMT) in OC cells. The above findings suggested that miR-126 served as a cancer suppressor in OC, suggesting a promising application of miR-126 in the clinical diagnosis and therapeutics of OC.

Background EDP‐305 is a novel and potent farnesoid X receptor (FXR) agonist, with no/minimal cross‐reactivity to TGR5 or other nuclear receptors. Herein we report therapeutic efficacy of EDP‐305, in direct comparison with the first‐in‐class FXR agonist obeticholic acid (OCA), in mouse models of liver disease. Methods EDP‐305 (10 and 30 mg/kg/day) or OCA (30mg/kg/day) was tested in mouse models of pre‐established biliary fibrosis (BALBc.Mdr2‐/‐, n = 9‐12/group) and steatohepatitis induced by methionine/choline‐deficient diet (MCD, n = 7‐12/group). Effects on biliary epithelium were evaluated in vivo and in primary EpCAM + hepatic progenitor cell (HPC) cultures. Results In a BALBc.Mdr2‐/‐ model, EDP‐305 reduced serum transaminases by up to 53% and decreased portal pressure, compared to untreated controls. Periportal bridging fibrosis was suppressed by EDP‐305 at both doses, with up to a 39% decrease in collagen deposition in high‐dose EDP‐305. In MCD‐fed mice, EDP‐305 treatment reduced serum ALT by 62% compared to controls, and profoundly inhibited perisinusoidal ‘chicken wire’ fibrosis, with over 80% reduction in collagen deposition. In both models, treatment with 30mg/kg OCA reduced serum transaminases up to 30%, but did not improve fibrosis. The limited impact on fibrosis was mediated by cholestasis‐independent worsening of ductular reaction by OCA in both disease models; OCA but not EDP‐305 at therapeutic doses promoted ductular proliferation in healthy mice and favoured differentiation of primary HPC towards cholangiocyte lineage in vitro. Conclusions EDP‐305 potently improved pre‐established liver injury and hepatic fibrosis in murine biliary and metabolic models of liver disease, supporting the clinical evaluation of EDP‐305 in fibrotic liver diseases including cholangiopathies and non‐alcoholic steatohepatitis.

Background Gossypium hirsutum is highly susceptible to Verticillium wilt, and once infected Verticillium wilt, its yield is greatly reduced. But G. barbadense is highly resistant to Verticillium wilt. It is possible that transferring some disease-resistant genes from G. barbadense to G. hirsutum may contribute to G. hirsutum resistance to Verticillium wilt. Result Here, we described a new gene in G. barbadense encoding AXMN Toxin Induced Protein-11, GbAt11, which is specifically induced by Verticillium dahliae in G. barbadense and enhances Verticillium wilt resistance in G. hirsutum. Overexpression in G. hirsutum not only significantly improves resistance to Verticillium wilt, but also increases the boll number per plant. Transcriptome analysis and real-time polymerase chain reaction showed that GbAt11 overexpression can simultaneously activate FLS2, BAK1 and other genes, which are involved in ETI and PTI pathways in G. hirsutum. Conclusion These data suggest that GbAt11 plays a very important role in resistance to Verticillium wilt in cotton. And it is significant for improving resistance to Verticillium wilt and breeding high-yield cotton cultivars.

Low-loss (1−x)Li2TiO3–xLi3Mg2NbO6 (LT-LMN, 0.02 ≤ x ≤ 0.08) microwave dielectric ceramics (MDCs) with rock salt structures were fabricated via a traditional solid-state reaction route. Li3Mg2NbO6 was used as a Li2TiO3 compensator to improve temperature stability. Scanning electron microscope observations and X-ray diffraction analyses were used to investigate the microstructures and crystalline structures of the ceramics, respectively. We demonstrated a correlation between macroscopic “dark hole” phenomena and the microwave dielectric properties (MDPs) of LT-LMN ceramics by analysing the valence states of Ti ions and the content of oxygen vacancies using X-ray photoelectron spectra. We continuously added Li3Mg2NbO6 to pure Li2TiO3 to form MDCs, and found that at x = 0.04, (1−x)Li2TiO3–xLi3Mg2NbO6 ceramics achieved a near-zero resonance-frequency temperature coefficient (τf). 0.96Li2TiO3–0.04Li3Mg2NbO6 ceramics sintered at 1250 °C had excellent MDP values: appropriate permittivity (ϵr) = 19.12, high quality factors (Q × ƒ) = 70814 GHz (at 6.105 GHz), and τf = 2.6 ppm/°C. This indicates that LT-LMN ceramics are promising materials for high-selectivity microwave ceramic dielectric substrates.

In this work, Ba4Nd9.33Ti18O54 (BNT) microwave dielectric ceramic materials fabricated by a conventional solid-state reaction method was compositionally modified via the replacement of Ti4+ by (Al0.5Nb0.5)4+ and the addition of NdAlO3 to enhance the temperature stability ( τ f ) and quality factor (Q×f) of the BNT ceramic materials. In the ceramic samples of Ba4Nd9.33(Al0.5Nb0.5)xTi18-xO54 (BNANT), an increase in the concentration of (Al0.5Nb0.5)4+ (i.e., x from 0 to 1.6) effectively improved both the τ f (from 67.5 to 12.6 ppm/°C) and the Q×f (from 9260 to 10245 GHz) despite the fact that the excessively high concentration of (Al0.5Nb0.5)4+ (i.e., x = 1.6) severely deteriorated the Q×f, and the τ f was still not at a near-zero level. Therefore, NdAlO3 was introduced into the BNANT ceramic materials as a τ f compensator. In the binary system of (1-y)Ba4Nd9.33(Al0.5Nb0.5)1.2Ti16.8O54-yNdAlO3, a near-zero τ f level of −2.06 ppm/°C with Q×f = 13680 GHz and dielectric constant ( e r ) = 70 was achieved at y = 0.55.

An approach for the construction of furo[3,2-b]quinolines and furo[2,3-b:4,5-b′]diquinolines is developed through a metal-free [4 + 2] cycloaddition of easily available in situ generated aza-o-quinone methides and furans. The reaction tolerates a wide range of aza-o-quinone methides and substituted furans to afford the corresponding dihydro- or tetrahydrofuroquinolines in good to excellent yields. Mechanistic studies reveal that the reaction involves a concerted [4 + 2] cycloaddition pathway and shows a high regioselectivity of cycloaddition for a furan ring. The present method features mild reaction conditions, dearomatization of furans, high regio- and diastereoselectivity, gram-scalable preparations, and diversity of furoquinolines.

In this work, a novel additive-free microwave dielectric ceramic (MWDC) system of (1 − x)CaWO4−x(Li0.5Sm0.5)WO4 (CW-LSW, 0.12 ≤ x ≤ 0.20) for low temperature co-fired ceramic (LTCC) applications was successfully fabricated by a solid-state reaction route. The sintering temperature and composition effects on the microwave dielectric (MWD) properties, microstructures, and crystalline phases were investigated. The optimal sintering temperatures of the CW-LSW ceramics are ranging from 875 to 950 °C. When sintered at 900 °C for 3 h, the sample of 0.86CW-0.14LSW exhibited excellent MWD properties: er = 10.76, Q × f = 28,754 GHz, and τf = − 0.54 ppm/°C. Furthermore, it is found that the CW-LSW ceramics are well compatible with Ag electrode during the sintering process. Therefore, the findings suggest that CW-LSW ceramic materials are promising for LTCC applications.

Introduction: Ultrasound-guided thoracic paravertebral block (US-TPVB) is generally used for postoperative analgesia. We hypothesized that single-injection US-TPVB could be used as the principal anesthetic technique for a peritoneal dialysis catheter (PDC) procedure (implantation or removal). The anesthetic effect and venous ropivacaine level after a TPVB would be compared with that after local anesthetic infiltration (LAI). Methods: Patients undergoing PDC procedures were randomized into Group LAI or TPVB. In Group LAI, 40 mL of 0.25% ropivacaine were used. In Group TPVB, single-injection of US-TPVB at T10–T11 level was performed with 20 mL of 0.25% ropivacaine. The quality of anesthesia, visual analogue scale of pain, and venous total plasma ropivacaine level were compared between the 2 groups. Results: Seventy-four eligible patients were enrolled and 38 in Group TPVB. Thirty patients in Group TPVB and 26 patients in Group LAI underwent PDC procedures successfully. Higher satisfaction rates by nephrologists and patients (76.3 and 78.9%) were reported in Group TPVB (44.4 and 44.4% in Group LAI, respectively). The peak venous total plasma ropivacaine concentrations were below the reported toxic threshold in the 2 groups. Conclusions: A single-injection US-TPVB with 20 mL of 0.25% ropivacaine at T10–T11 could be the principal anesthetic technique for PDC procedures, which provided a comparable anesthetic effect to that of LAI with 40 mL ropivacaine. Higher satisfaction rates by nephrologists and patients were observed in Group TPVB. The 20 mL dose of 0.25% ropivacaine used for an US-TPVB was safe in end-stage renal diseases patients.

A recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a “turning point”. The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.

Fingerprints of 18 batches of substance benchmark of Shentong Zhuyu Decoction(SZD) were established by UPLC under the following conditions: Waters Sun Fire C_(18) column(3.0 mm×150 mm, 3.5 μm), column temperature of 35 ℃, gradient elution with mobile phase of acetonitrile(A)-0.1% phosphoric acid aqueous solution(B) at the flow rate of 0.4 mL·min~(-1), and detection by wavelength switching. A total of 16 common peaks were identified. The similarities among the fingerprints were calculated by Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 Edition) and the result showed they were in the range of 0.911-0.988. Based on the 16 common peaks, cluster analysis(CA), principal component analysis(PCA), and partial least square discriminant analysis(PLS-DA) all categorized the 18 batches of samples into two groups(S1, S2, S5-S8, S14, and S17 in one group, and S1, S2, S5-S8, S14, and S17 in another), and 11 most influential components were screened. Five known components with great difference among samples(hydroxysafflor yellow A, ferulic acid, benzoic acid, ecdysone, and ammonium glycyrrhizinate) were determined. The combination of multi-component content determination and fingerprints can reflect the overall cha-racteristics of the primary standards of SZD, which is simple, feasible, reproducible, and stable. This study can serve as a reference for the quality control of the primary standards of SZD.

Background. Rhein is the main extract of Rheum palmatum L., which has been proved to improve the renal function of chronic kidney disease, but its mechanism is not clear. Therefore, this experiment explored the potential pharmacological effect of rhein on renal interstitial fibrosis rats. Methods. This study explores the potential pharmacological action of rhein. In this work, we investigate the potential pharmacological action of rhein in unilateral urethral obstruction (UUO) rats. Thirty Sprague Dawley rats were randomly divided into three groups: sham, UUO, and rhein (rhein-treated UUO rats) groups. The left ureters of the UUO group rats were exposed and bluntly dissected. The rhein group rats were administered an intragastric gavage of rhein (2 mg·kg−1·d−1) for 14 d. Kidney function-related indicators were monitored in these rats, while indexes of pathologic aspects were determined histologically. The expression of α-SMA, TGF-β1, SHH, Gli1, and Snail was quantified using real-time polymerase chain reaction and western blotting. The NRK-49F cells were incubated with and without SHH (100 ng·ml−1) for 48 hours. The SHH-activated NRK-49F cells were incubated with cyclopamine (CNP, 20 umol L−1) or rhein (1 ng·ml−1). The Gli1 and Snail mRNA and protein level were detected. Results. In the in vivo experiment, the results exhibited that UUO caused renal pathological damages. However, these changes could be significantly reversed by the administration of rhein. Compared with the untreated UUO group, the rhein group showed reduced kidney tubular atrophy and necrosis, interstitial fibrosis, hyperplasia, and abnormal deposition of extracellular matrix. Rhein reduced the RNA and protein expression of SHH, Gli1, and Snail of the UUO rats. In the in vitro experiment, CNP or rhein treatment decreased the expression of Gli1 and Snail on mRNA and protein levels in SHH-induced NRK-49F cells, suggesting that CNP or rhein suppresses SHH-induced NRK-49F activation. Taken together, these results demonstrated that rhein suppresses SHH-Gli1-Snail signal pathway activation, with potential implications for the treatment of renal fibrosis. Conclusions. Treatment with rhein remarkably ameliorated renal interstitial fibrosis in UUO rats by regulating the SHH-Gli1-Snail signal pathway.

Radiation therapy, especially the development of linear accelerators, plays a key role in cancer management. The fast-rotating coplanar O-ring Halcyon Linac has demonstrated many advantages. The previous literature has mainly focused on the machine parameters and plan quality of Halcyon, with a lack of relevant research on its clinical application.To evaluate the clinical performance of the O-ring Halcyon treatment system in a real-world application setting.Data from sixty-one patients who were treated with the Halcyon system throughout the entire radiotherapy process in Peking Union Medical College Hospital between August 2019 and September 2020 were retrospectively reviewed. We evaluated the target tumour response to radiotherapy and irradiation toxicity from 1 to 3 mo after treatment. Dosimetric verification of Halcyon plans was performed using a quality assurance procedure, including portal dosimetry, ArcCHECK and point dose measurements for verification of the system delivery accuracy.Of the 61 patients in the five groups, 16, 12, 7 and 26 patients had complete response, partial response, progressive disease and stable disease, respectively. No increase in the irradiated target tumour volume was observed when separately evaluating the local response. Regarding irradiation toxicity, no radiation-induced deaths were observed. Thirty-eight percent (23/61 patients) had no radiation toxicity after radiotherapy, 56% (34/61 patients) experienced radiation toxicity that resolved after treatment, and 6% (4/61 patients) had irreversible adverse reactions. The average gamma passing rates with a 2% dose difference and 2-mm distance to agreement for IMRT/VMAT/SRT plans were ArcCHECK at 96.4% and portal dosimetry at 96.7%, respectively. All of the validated clinical plans were within 3% for point dose measurements, and Halcyon's ArcCHECK demonstrated a high pass rate of 99.1% ± 1.1% for clinical gamma passing criteria of 3%/3 mm.The O-ring Halcyon Linac could achieve a better therapeutic effect on the target volume by providing accurate treatment delivery plans with tolerable irradiation toxicity.

Alzheimer's disease (AD) remains a medical and social challenge worldwide. Magnesium (Mg) is one of the most frequently evaluated essential minerals with diverse biological functions in human body. However, the association between circulating Mg levels and AD remains controversial. We conducted a meta-analysis of 21 studies published between 1991 and 2021 to determine whether the Mg levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data without language limitations. A pooled subject sample including 1,112 AD patients and 1,001 healthy controls (HCs) was available to assess Mg levels in serum and plasma; 284 AD patients and 117 HCs were included for Mg levels in CSF. It was found that serum and plasma levels of Mg were significantly reduced in AD patients compared with HCs (standardized mean difference [SMD] = −0.89; 95% confidence interval [CI] [−1.36, −0.43];P= 0.000). There was statistically non-significant for Mg level in CSF between AD and HCs, whereas a decreased tendency were detected (SMD = −0.16; 95% CI [−0.50, 0.18];P= 0.364). .In addition, when we analyzed the Mg levels of serum, plasma and CSF together, the circulating Mg levels in AD patients was significantly lower (SMD = −0.74, 95% CI [−1.13; −0.35];P= 0.000). These results indicate that Mg deficiency may be a risk factor of AD and Mg supplementation may be a potentially valuable adjunctive treatment for AD.Systematic Review Registration:www.crd.york.ac.uk/PROSPERO/, registration number CRD42021254557.

When studying intelligent community and property management system, network service has an important impact on intelligent community construction and property management service. How to use machine learning and other technologies to improve the network service of intelligent community and integrate it into real estate property management is worthy of further research. This paper introduces the basic model of machine learning and proposes a network data prediction model based on time series. For the time dimension, an improved prediction algorithm model of machine learning is proposed. For mobile data allocation, from the perspective of ensuring the current and future continuity of the spectrum after spectrum allocation, this paper proposes a spectrum allocation algorithm based on the joint measurement of time domain and frequency domain. In addition, the VP-tree algorithm is used to construct the spatial vector relationship of the intelligent community. At the same time, in the time trend and periodicity of the mobile data in the intelligent community network, the attention mechanism is introduced to realize the distribution of mobile data and traffic prediction in the intelligent community by machine learning. This paper analyzes the requirements of the property management system, designs the property management information system including the field subsystem layer, data acquisition layer, and cloud service layer, introduces the property management module and customer service module in detail, and carries out the system test. The test results show that the system runs well. Finally, aiming at the problems existing in the property management industry, this paper puts forward the development strategy of property management.

Objective. To investigate the effect of a home care model on coping style and quality of life of patients with postcranial surgery complicated by epilepsy. Methods. One hundred and forty-four patients with postcranial surgery complicated by epilepsy admitted to our hospital from July 2017 to April 2018 were selected as study subjects and randomly divided into 63 cases each in the observation group and the control group. The control group was given nursing interventions including health education, psychological intervention, medication guidance, complication prevention, and follow-up management, while the observation group was jointly given collaborative family nursing interventions. At a follow-up of 6 months, indicators such as coping style, treatment compliance, and quality of life were compared between the two groups. Results. Patients in the observation group had significantly higher problem solving, help seeking, and rationalization scores and significantly lower self-blame scores than the control group ( P < 0.01 ); significantly higher treatment compliance than the control group ( P < 0.01 ); and significantly higher social functioning, emotional well-being, and energy/fatigue scores than the control group ( P < 0.01 ). Conclusion. The home care model helps to promote the development of positive coping styles, improve treatment compliance, and improve the quality of life of patients after cranial surgery.

To evaluate the prognostic value of DNAJB6, KIAA1522, and p-mTOR expression for colorectal cancer (CRC) and to develop effective prognostic models for CRC patients.The expression of DNAJB6, KIAA1522, and p-mTOR (Ser2448) was detected using immunohistochemistry in 329 CRC specimens. The prognostic values of the three proteins in the training cohort were assessed using Kaplan-Meier curves and univariate and multivariate Cox proportional hazards models. Prediction nomogram models integrating the three proteins and TNM stage were constructed. Subsequently, calibration curves, receiver operating characteristic (ROC) curves, the concordance index (C-index), and decision curve analysis (DCA) were used to evaluate the performance of the nomograms in the training and validation cohorts.The three proteins DNAJB6, KIAA1522, and p-mTOR were significantly overexpressed in CRC tissues (each P 0.01), and their expression was an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) (each P 0.05). The area under the ROC curves (AUC) and C-index values were approximately 0.7. Additionally, the calibration curves showed that the predicted values and the actual values fit well. Furthermore, DCA curves indicated that the clinical value of the nomogram models was higher than that of TNM stage. Overall, the novel prediction models have good discriminability, sensitivity, specificity and clinical utility.The nomograms containing DNAJB6, KIAA1522, and p-mTOR may be promising models for predicting postoperative survival in CRC.

Objective: To analyze the value of serum miRNA-122 expression in the diagnosis, severity, and prognosis of Acute Cerebral Infarction (ACI) and the correlation mechanism of serum miRNA-122 on the proliferation and apoptosis of vascular endothelial cells in ACI. Method: A total of 60 patients with ACI who were admitted to the emergency department of the Taizhou People’s Hospital from January 1, 2019, to December 30, 2019, and 30 healthy controls during the same period were selected. General clinical data of all patients at admission were collected. Including age, sex, medical history, and inflammatory factors (C-Reactive Protein [CRP], Interleukin-6 [IL-6], Procalcitonin [PCT], Neutrophil Gelatinase-Associated Lipid carrier protein [NGAL]). The National Institutes of Health Stroke Scale (NIHSS) score at admission and short-term prognosis (the Modified Rankin Score [mRS]) score at 3 months after onset were recorded. The expression level of miRNA-122 in the serum of patients with ACI and normal controls was detected by reverse-transcription quantitative Real-Time Polymerase Chain Reaction (RT-QPCR), and the correlation between the expression level of miRNA-122 in the serum of patients with ACI and the level of inflammatory factors, NIHSS and mRS scores were analyzed. The expression levels of miRNA-122 in the serum of patients with ACI, normal people, and Human Umbilical cord Endothelial Cells (HUVECs) cultured in a blank control group were detected by RT-QPCR and statistically analyzed. MTT and flow cytometry was used to compare the proliferation and apoptosis of vascular endothelial cells in the miRNA-122 mimics and inhibitors transfection groups and the corresponding negative control group. The mRNA and protein levels of apoptosis-related factors Bax, Bcl-2, Caspase-3, and angiogenesis-related proteins Hes1, Notch1, Vascular Endothelial Growth Factors (VEGF), and CCNG1 were detected by RT-QPCR and Western blot. Bioinformatics methods predicted CCNG1 to be the target of miRNA-122, and the direct targeting relationship between CCNG1 and miRNA-122 was verified by a dual-luciferase reporting assay. Result: Serum miRNA-122 expression in patients with ACI was significantly higher than that in healthy controls, with an area under the receiver operating characteristic curve of 0.929, 95% Confidence Interval of 0.875‒0.983, and an optimal cut-off value of 1.397. The expression levels of CRP, IL-6, and NGAL in patients with ACI were higher than those in healthy control groups, p < 0.05; miRNA-122 was positively correlated with CPR, IL-6, NIHSS score, and mRS score. At 48h and 72h, the proliferation rate of HUVECs cells in the miRNA-122 mimics group decreased and the apoptosis rate increased. Cell proliferation rate increased, and apoptosis rate decreased significantly in the groups transfected with miRNA-122 inhibitors. The mRNA and protein levels of pro-apoptotic factors Bax and caspase-3 were significantly increased in the miRNA-122 mimics transfection group, while those of anti-apoptotic factor Bcl-2 were significantly decreased compared to those of the control group. The expression of Bax and Caspase-3 decreased, and the expression of anti-apoptotic factor Bcl-2 increased in the transfected miRNA-122 inhibitors group. mRNA expression levels of Hes1, Notch1, VEGF, and CCNG1 in the miRNA-122 mimic transfected group were significantly decreased, while mRNA expression levels in the miRNA-122 inhibitors transfected group were significantly increased. Bioinformatics showed that there was a miRNA-122 binding site in the 3′UTR region of CCNG1, and dual luciferase assay confirmed that CCNG1 was the target of miRNA-122.

Sedum emarginatum Migo (Aoyejingtian) is a perennial succulent herb of the sedum genus in the family Crassulaceae, which has the fountion of treating furuncle, swelling and haematemesis, hematochezia, menorrhagia and hepatitis. Preliminary studies of our research group had showed that the ethyl acetate extract of Sedum emarginatum Migo could inhibit the proliferation of liver cancer HepG2 cells. The establishment of a reasonable and feasible quality evaluation method for the effective parts of Sedum emarginatum Migo can provide a scientific basis for the further development and utilization of Sedum emarginatum Migo. In this study, a multi-wavelength conversion method was used to establish high-performance liquid chromatography (HPLC) fingerprints of the ethyl acetate extract of Sedum emarginatum Migo, and the method was also used to simultaneously determine the gallic acid, protocatechuic acid, caffeic acid, and ferulic acid, isoquercitrin and luteolin in the ethyl acetate extract of Sedum emarginatum Migo. The similarity of the fingerprints of the ethyl acetate extract of Sedum emarginatum Migo from different origins and the content of 6 components were compared. The established method was simple, accurate, table and reliable, which could provide a fast, accurate and reliable method for comprehensive evaluation of the quality of Sedum emarginatum Migo.

BACKGROUND: In recent years, a series of clinical trials have explored the application of neoadjuvant immunotherapy or chemoimmunotherapy in non-small cell lung cancer (NSCLC). However, no randomized control trials comparing neoadjuvant immunotherapy with chemoimmunotherapy have yet been reported. This study aimed to summarize and compare the efficacy and safety of neoadjuvant immunotherapy and chemoimmunotherapy in NSCLC. METHODS: Literature focusing on the efficacy and safety of neoadjuvant immunotherapy or chemoimmunotherapy in NSCLC published before June 2021 was retrieved from PubMed, Embase, and the Cochrane Library. Study endpoints included major pathological response (MPR), complete pathological response (pCR), treatment-related adverse events (TRAEs), severe adverse events (SAEs), resection rate, surgical delay rate, and conversion to thoracotomy. The risk of bias was assessed using the Cochrane bias risk assessment tool. Subgroup and sensitivity analyses were further performed. RESULTS: A total of 988 patients from 16 studies were included in this meta-analysis. For patients who received neoadjuvant immunotherapy with single/combined ICIs or chemoimmunotherapy, the pooled MPR rate was 43.5% and the pooled pCR rate was 21.9%. The pooled incidence of TRAEs and SAEs were 54.8% and 15.3%, respectively. The pooled resection rate was 85.8%, the surgical delay rate was 7.4%, and the conversion rate was 17.4%. Patients who received neoadjuvant chemoimmunotherapy had remarkably improved pathological response (MPR rate: 53.3% vs. 28.6%; pCR rate: 28.6% vs. 9.9%) compared with those receiving neoadjuvant single-agent immunotherapy, while the incidence of SAEs (18.0% vs. 12.3%) and surgical delay rate (3.8% vs. 7.4%) did not significantly increase. Neoadjuvant nivolumab combined with ipilimumab also achieved a high pCR rate (28.6%) with tolerable toxicity. Nivolumab- and pembrolizumab-based neoadjuvant therapy showed a higher MPR rate (nivolumab 51.5%, pembrolizumab 46.8%) and pCR rate (nivolumab 29.1%, pembrolizumab 31.5%). Besides, patients with positive programmed death-ligand 1 (PD-L1) expression [tumor proportion score (TPS) ≥1%] exhibited favorable pathological responses than PD-L1 negative patients. DISCUSSION: Overall, neoadjuvant immunotherapy or chemoimmunotherapy is effective and safe in NSCLC. Compared with single-agent immunotherapy, neoadjuvant chemoimmunotherapy provides a significant improvement in pathological response without increasing the incidence of SAEs or surgical delay. These results need further confirmation by more large-scale randomized controlled trials.

The authors have requested that this preprint be removed from Research Square.

We perform a study of the $$D_s^+ \rightarrow a_0(980)(f_0(980)) e^+ \nu _e$$ D s + → a 0 ( 980 ) ( f 0 ( 980 ) ) e + ν e reactions investigating the different sources of isospin violation which make the production of the $$a_0(980)$$ a 0 ( 980 ) possible. We find that loops involving kaons in the production mechanism provide a source of isospin violation since they do not cancel due to the different mass of charged and neutral kaons, but we also find that the main source comes from the breaking of isospin in the meson-meson transition T matrices, which contain information on the nature of the low lying scalar mesons. The reaction is thus very sensitive to the nature of the $$a_0(980)$$ a 0 ( 980 ) and $$f_0(980)$$ f 0 ( 980 ) resonances. Our results are consistent with the present upper bound for $$a_0(980)$$ a 0 ( 980 ) production and only a factor three smaller, indicating that future runs with more statistics should find actual numbers for this reaction from where we can learn more about the origin of the scalar resonances and their nature.

Members of the R2R3-MYB4 subgroup are well-known negative regulatory transcription factors of phenylpropane and lignin pathways. In this study, we found that transgenic tobacco plants overexpressing a R2R3-MYB4 subgroup gene from Camellia sinensis (CsMYB4a) showed inhibited growth that was not regulated by phenylpropane and lignin pathways, and these plants exhibited altered sensitivity to synthetic auxin 1-naphthaleneacetic acid (α-NAA) treatment. An auxin/indole-3-acetic acid 4 (AUX/IAA4) gene from Camellia sinensis (CsIAA4) participating in the regulation of the auxin signal transduction pathway was screened from the yeast two-hybrid library with CsMYB4a as the bait protein, and tobacco plants overexpressing this gene showed a series of auxin-deficiency phenotypes, such as dwarfism, small leaves, reduced lateral roots, and a shorter primary root. CsIAA4 transgenic tobacco plants were less sensitive to exogenous α-NAA than control plants, which was consistent with the findings for CsMYB4a transgenic tobacco plants. The knockout of the endogenous NtIAA4 gene (a CsIAA4 homologous gene) in tobacco plants alleviated growth inhibition in CsMYB4a transgenic tobacco plants. Furthermore, protein–protein interaction experiments proved that domain II of CsIAA4 is the key motif for the interaction between CsIAA4 and CsMYB4a and that the degradation of CsIAA4 is prevented when CsMYB4a interacts with CsIAA4. In summary, our results suggest that CsMYB4a is a multifunctional transcription factor that regulates the auxin signaling pathway, phenylpropane and lignin pathways. This study provides new insights into the multiple functions of R2R3-MYB4 subgroup members as a group of well-known negative regulatory transcription factors.One-sentence summaryCsMYB4a act as multifunctional transcription factor that regulates the auxin signaling pathway, phenylpropane and lignin pathways.

Background: Lung cancer is the most common cancer and one of the main causes of cancer-related deaths, and it manifests as metastatic disease in most cases. Considering frequent gene mutation and/or signaling deregulation in lung adenocarcinoma, identifying novel factors or agents targeting these signaling pathways might be promising strategies for lung adenocarcinoma therapy. Methods: GEO datasets were analyzed to identify differentially expressed genes (DEGs) in lung adenocarcinoma. The specific effects of candidate gene overexpression or knockdown on lung adenocarcinoma cell phenotypes were examined. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) are used to connect the genomic and functional information of DEGs. The dynamic effects of candidate gene and signaling pathway agonist on lung adenocarcinoma malignant behaviors were investigated. Finally, clinical lung adenocarcinoma and adjacent non-cancerous tissues were collected and the levels of candidate gene were examined in tissue samples.Results: Inhibitor of DNA binding 2 (ID2) was identified as an aberrantly downregulated gene in lung adenocarcinoma. ID2 overexpression suppressed lung adenocarcinoma cell viability, colony formation capacity, and migration. ID2 overexpression also reduced the protein levels of N-cadherin, MMP2, MMP9, and the phosphorylation of AKT and mTOR. The PI3K/AKT/mTOR signaling agonist exerted opposite effects on lung adenocarcinoma cells to those of ID2 overexpression, and partially reversed the effects of ID2 overexpression. In tissue samples, ID2 protein levels and mRNA expression were also downregulated compared with those in adjacent non-cancerous tissues. Conclusion: ID2 exerts its tumor-suppressive effects on lung adenocarcinoma cell malignant behaviors through inhibiting the activation of the PI3K/AKT/mTOR signaling pathway. Restoring ID2 expression in lung adenocarcinoma cells might improve the curative effect of lung adenocarcinoma therapies.

Juan Jiang,1,2 Xia Wang,3 Jian He,3 Donglei Liao,3 Xiaolu Deng3 1Department of Respiratory Medicine (National Key Clinical Specialty), Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Hunan Provincial Clinical Research Center for Respiratory Diseases, Changsha, People’s Republic of China; 3Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Xiaolu DengDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of ChinaTel +86 13786113654Email dengxiaolu1019@163.comBackground: Pneumocystis jirovecii pneumonia (PCP) is a serious opportunistic infection in immunocompromised children. Real-time polymerase chain reaction (PCR) is widely used for the diagnosis of PCP due to its good accuracy. However, the diagnostic performance of multiplex real-time PCR on sputum in children with PCP has never been explored.Methods: Medical records of 63 consecutive pediatric patients were analyzed retrospectively, including 13 cases with PCP and 50 with non-PCP pneumonia. Pneumocystis jirovecii (P. jirovecii) and other co-pathogens detected by multiplex real-time PCR in sputum samples were summarized. Using clinical composite diagnosis as the reference standard, we further compared the diagnostic performance of multiplex real-time PCR to combined serological markers (1,3)-β-D-glucan plus lactate dehydrogenase. Additionally, modifications of antimicrobial treatment for pediatric PCP patients after the report of multiplex real-time PCR results were reviewed.Results: In children with PCP, nonproductive cough and shortness of breath were more common, lymphocyte count in peripheral blood was markedly lower, and serum levels of (1,3)-β-D-glucan and lactate dehydrogenase were much higher than non-PCP group. Multiplex real-time PCR reached a sensitivity of 100% in diagnosing PCP, which was better than serum (1,3)-β-D-glucan plus lactate dehydrogenase (76.9%). Its specificity (98.0%) significantly surpassed serum (1,3)-β-D-glucan plus lactate dehydrogenase (84.4%). Furthermore, multiplex real-time PCR showed a good performance in identifying co-pathogens in sputum of pediatric PCP patients. Cytomegalovirus, Epstein–Barr virus and Streptococcus pneumoniae were the most common co-pathogens in these patients. Initial antimicrobial treatment was modified in 76.9% of children with PCP after the report of PCR results.Conclusion: Multiplex real-time PCR on sputum is a diagnostic tool with good performance for the identification of P. jirovecii as well as co-pathogens in children with PCP. Sputum may be an alternative to bronchoalveolar lavage fluid for PCR assay in children when bronchoscopic examination is not feasible.Keywords: immunocompromised population, children, Pneumocystis jirovecii pneumonia, multiplex real-time polymerase chain reaction, sputum

Weiling Leng,1,* Juan Jiang,2,* Bing Chen,1 Qinan Wu3 1Endocrinology Department, The First Affiliated Hospital of the Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Endocrinology and Nephrology Department, Chongqing University Cancer Hospital and Chongqing Cancer Institute and Chongqing Cancer Hospital, Chongqing, People’s Republic of China; 3Endocrinology Department, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qinan WuEndocrinology Department, Dazu Hospital of Chongqing Medical University, The People’s Hospital of Dazu, Chongqing Email wqn11@126.com View the original paper by Dr Leng and colleagues This is in response to the Letter to the Editor

To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36)-"Sanyinjiao"(SP6) on glucose and lipid metabolism and insulin resistance (IR) in obese diabetic rats, so as to explore its mechanism underlying improvement of obesity diabetes.SPF male rats were randomly divided into normal control, model, meridian-acupoint EA (acupoint), non-meridian non-acupoint EA (non-acupoint), and medication (metformin) groups, with 10 rats in each group. The diabetes model was established by feeding the rats with high-fat diet for 8 weeks. EA (1.5 mA, 10 Hz/100 Hz) was applied to unilateral ST36 and SP6 for 20 min, once daily (except Sundays) for 4 weeks. Rats of the medication group were treated by gavage of metformin (300 mg/kg) once daily for 4 weeks (except Sundays). The body weight and length were measured and the Lee's index was calculated. The contents of total cholesterol (TC), triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C) in the plasma were detected by using a full-automatic biochemical analyzer. The content of fasting serum insulin (FINS) was assayed by using radioimmunoassay, the fasting blood glucose (FBG) was measured, and serum superoxide dismutase (SOD) activity by using xanthine oxidase method, serum malondialdehyde (MDA) by color method, serum glutathione peroxidase (GSH-Px) activity by indirect method, reactive oxygen species (ROS) by Dithio-bis-nitrobenzoic acid (DTNB) direct method, and the homeostasis model assessment of IR (HOMA-IR) and insulin sensitive index (ISI) were calculated. The expression levels of pancreatic tissue P66shc mRNA and PKCβ mRNA were detected by using RT-PCR, and the histopathological changes of the liver and adipose tissues were observed after H.E. staining.Compared with the normal control group, the Lee's index, levels of FBG, FINS, HOMA-IR, TC, TG, LDL-C, MDA, ROS, and P66shc mRNA and PKCβ mRNA expressions were significantly increased (EA of ST36 and SP6 can improve glucose and lipid metabolism and IR in obese diabetic rats, which may be related to its function in suppressing PKCβ/P66shc signaling and oxidative stress.

IntroductionEpidermal growth factor receptor (EGFR) 19del and L858R mutation are known as “common mutations” in non-small cell lung cancer (NSCLC) and predict sensitivities to EGFR tyrosine kinase inhibitors (TKIs), whereas 20ins and T790M mutations confer drug-resistance to EGFR-TKIs. The role of the remaining uncommon EGFR mutations remains elusive.MethodsWe retrospectively screened a group of NSCLC patients with uncommon EGFR mutations other than 20ins and T790M. The mutation patterns, use of different generations of EGFR-TKIs, and concurrent genetic alterations were analyzed. Meanwhile, a cohort of patients with single 19del or L858R were included for comparison.ResultsA total of 180/1,300 (13.8%) patients were identified. There were 102 patients with advanced or recurrent NSCLC that received first-line therapy of gefitinib/erlotinib/icotinib and afatinib and were eligible for analysis. The therapeutic outcomes among patients with common mutations (EGFRcm, n = 97), uncommon mutation plus common mutations (EGFRum+EGFRcm, n = 52), complex uncommon mutations (complex EGFRum, n = 22), and single uncommon mutations (single EGFRum, n = 28) were significantly different (ORRs: 76.3%, 61.5%, 54.5%, and 50.0%, respectively, p = 0.023; and mPFS: 13.3, 14.7, 8.1, and 6.0 months, respectively, p = 0.004). Afatinib showed superior efficacy over gefitinib/erlotinib/icotinib in EGFRcm (ORR: 81.0% vs. 75.0%, p = 0.773; mPFS: 19.1 vs. 12.0m, p = 0.036), EGFRum+EGFRcm (ORR: 100% vs. 54.5%, p = 0.017; mPFS: NE vs. 13.6m, p = 0.032), and single EGFRum (ORR: 78.6% vs. 21.4%, p = 0.007; mPFS: 10.1 vs. 3.0m, p = 0.025) groups. Comprehensive genomic profiling by Next Generation Sequencing encompassing multiple cancer-related genes was performed on 51/102 patients; the mPFS of patients without co-mutation (n = 16) and with co-mutations of tumor-suppressor genes (n = 31) and driver oncogenes (n = 4) were 31.1, 9.2, and 12.4 months, respectively (p = 0.046). TP53 mutation was the most common co-alteration and showed significantly shorter mPFS than TP53 wild-type patients (7.0 vs. 31.1m, p < 0.001). Multivariate analysis revealed that concurrent 19del/L858R and tumor-suppressor gene alterations independently predicted better and worse prognosis in patients with uncommon mutations, respectively.ConclusionsUncommon EGFR mutations constitute a highly heterogeneous subgroup of NSCLC that confer different sensitivities to EGFR-TKIs with regard to the mutation patterns. Afatinib may be a better choice for most uncommon EGFR mutations. Concurrent 19del/L858R and tumor-suppressor gene alterations, especially TP53, can be established as prognostic biomarkers.

Shank3 is a postsynaptic scaffolding protein of excitatory synapses. Mutations or variations of SHANK3 are associated with various psychiatric and neurological disorders. We set to determine its normal expression pattern in the human brain, and its change, if any, with age and Alzheimer’s disease (AD)-type β-amyloid (Aβ) and Tau pathogenesis. In general, Shank3 immunoreactivity (IR) exhibited largely a neuropil pattern with differential laminar/regional distribution across brain regions. In youth and adults, subsets of pyramidal/multipolar neurons in the cerebrum, striatum, and thalamus showed moderate IR, while some large-sized neurons in the brainstem and the granule cells in the cerebellar cortex exhibited light IR. In double immunofluorescence, Shank3 IR occurred at the sublemmal regions in neuronal somata and large dendrites, apposing to synaptophysin-labeled presynaptic terminals. In aged cases, immunolabeled neuronal somata were reduced, with disrupted neuropil labeling seen in the molecular layer of the dentate gyrus in AD cases. In immunoblot, levels of Shank3 protein were positively correlated with that of the postsynaptic density protein 95 (PSD95) among different brain regions. Levels of Shank3, PSD95, and synaptophysin immunoblotted in the prefrontal, precentral, and cerebellar cortical lysates were reduced in the aged and AD relative to youth and adult groups. Taken together, the differential Shank3 expression among brain structures/regions indicates the varied local density of the excitatory synapses. The enriched Shank3 expression in the forebrain subregions appears inconsistent with a role of this protein in the modulation of high cognitive functions. The decline of its expression in aged and AD brains may relate to the degeneration of excitatory synapses.

The mechanism of the enhanced superconductivity in monolayer FeSe/SrTiO3 has been enthusiastically studied and debated over the past decade. One specific observation has been taken to be of central importance: the replica bands in the photoemission spectrum. Although suggestive of electron-phonon interaction in the material, the essence of these spectroscopic features remains highly controversial. In this work, we conduct angle-resolved photoemission spectroscopy measurements on monolayer FeSe/SrTiO3 using linearly polarized photons. This configuration enables unambiguous characterization of the valence electronic structure with a suppression of the spectral background. We consistently observe high-order replica bands derived from various Fe 3d bands, similar to those observed on bare SrTiO3. The intensity of the replica bands is unexpectedly high and different between dxy and dyz bands. Our results provide new insights on the electronic structure of this high-temperature superconductor and the physical origin of the photoemission replica bands., The origin of the photoemission replica bands in monolayer FeSe/SrTiO3 remains controversial. Here, the authors perform angle-resolved photoemission spectroscopy with polarized photon on FeSe/SrTiO3 and observe high-order replica bands with high intensity from various Fe 3d bands, suggesting a mixed mechanism.

Dehydrocostus lactone (DHL), a natural sesquiterpene lactone isolated from the traditional Chinese herbs Saussurea lappa and Inula helenium L., has important anti-inflammatory properties used for treating colitis, fibrosis, and Gram-negative bacteria-induced acute lung injury (ALI). However, the effects of DHL on Gram-positive bacteria-induced macrophage activation and ALI remains unclear. In this study, we found that DHL inhibited the phosphorylation of p38 MAPK, the degradation of IκBα, and the activation and nuclear translocation of NF-κB p65, but enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of Nrf2 and HO-1 in lipoteichoic acid (LTA)-stimulated RAW264.7 cells and primary bone-marrow-derived macrophages (BMDMs). Given the critical role of the p38 MAPK/NF-κB and AMPK/Nrf2 signaling pathways in the balance of M1/M2 macrophage polarization and inflammation, we speculated that DHL would also have an effect on macrophage polarization. Further studies verified that DHL promoted M2 macrophage polarization and reduced M1 polarization, then resulted in a decreased inflammatory response. An in vivo study also revealed that DHL exhibited anti-inflammatory effects and ameliorated methicillin-resistant Staphylococcus aureus (MRSA)-induced ALI. In addition, DHL treatment significantly inhibited the p38 MAPK/NF-κB pathway and activated AMPK/Nrf2 signaling, leading to accelerated switching of macrophages from M1 to M2 in the MRSA-induced murine ALI model. Collectively, these data demonstrated that DHL can promote macrophage polarization to an anti-inflammatory M2 phenotype via interfering in p38 MAPK/NF-κB signaling, as well as activating the AMPK/Nrf2 pathway in vitro and in vivo. Our results suggested that DHL might be a novel candidate for treating inflammatory diseases caused by Gram-positive bacteria.