Interferon subverts an AHR-JUN axis to promote CXCL13+ T cells in lupus.

Systemic lupus erythematosus (SLE) is prototypical autoimmune disease driven by pathological T cell-B cell interactions1,2. Expansion of T follicular helper (TFH) and T peripheral helper (TPH) cells, two T cell populations that provide help to B cells, is a prominent feature of SLE3,4. Human TFH and TPH cells characteristically produce high levels of the B cell chemoattractant CXCL13 (refs. 5,6), yet regulation of T cell CXCL13 production and the relationship between CXCL13+ T cells and other T cell states remains unclear. Here, we identify an imbalance in CD4+ T cell phenotypes in patients with SLE, with expansion of PD-1+/ICOS+ CXCL13+ T cells and reduction of CD96hi IL-22+ T cells. Using CRISPR screens, we identify the aryl hydrocarbon receptor (AHR) as a potent negative regulator of CXCL13 production by human CD4+ T cells. Transcriptomic, epigenetic and functional studies demonstrate that AHR coordinates with AP-1 family member JUN to prevent CXCL13+ TPH/TFH cell differentiation and promote an IL-22+ phenotype. Type I interferon, a pathogenic driver of SLE7, opposes AHR and JUN to promote T cell production of CXCL13. These results place CXCL13+ TPH/TFH cells on a polarization axis opposite from T helper 22 (TH22) cells and reveal AHR, JUN and interferon as key regulators of these divergent T cell states.

Bifonazole caffeate: The first molecular salt of bifonazole with enhanced biopharmaceutical property based on experiments and quantum chemistry research.

In order to make novel breakthroughs in molecular salt studies of BCS class-IV antifungal medication bifonazole (BIF), a salification-driven strategy towards ameliorating attributes and aiding augment efficiency is raised. This strategy fully harnesses structural characters together attributes and benefits of caffeic acid (CAF) to concurrently enhance dissolvability and permeability of BIF by introducing the two ingredients into the identical molecular salt lattice through the salification reaction, which, coupled with the aroused potential activity of CAF significantly amplifies the antifungal efficacy of BIF. Guided by this route, the first BIF-organic molecular salt, BIF-CAF, is directionally designed and synthesized with satisfactorily structural characterizations and integrated theoretical and experimental explorations on the pharmaceutical properties. Single-crystal X-ray diffraction resolving confirms that there is a lipid-water amphiphilic sandwich structure constructed by robust charge-assistant hydrogen bonds in the salt crystal, endowing the molecular salt with the potential to enhance both dissolvability and permeability relative to the parent drug, which is validated by experimental evaluations. Remarkably, the comprehensive DFT-based theoretical investigations covering frontier molecular orbital, molecular electrostatic potential, Hirshfeld surface analysis, reduced density gradient, topology, sphericity and planarity analysis strongly support these observations, thereby allowing some positive relationships between macroscopic properties and microstructures of the molecular salt can be made. Intriguingly, the optimal properties, together with the stimulated activity of CAF markedly augment in vitro antifungal ability of the molecular salt, with magnifying inhibition zones and reducing minimum inhibitory concentrations. These findings fill in the gaps on researches of BIF-organic molecular salt, and adequately exemplify the feasibility and validity by integrating theoretical and experimental approaches to resolve BIF's problems via the salification-driven tactic.

Enhancement of zinc-ion storage capability by synergistic effects on dual-ion adsorption in hierarchical porous carbon for high-performance aqueous zinc-ion hybrid capacitors.

Aqueous zinc-ion capacitors (AZICs) are considered potential energy storage devices thanks to their ultrahigh power density, high safety, and extended cycling life. Carbon-based materials widely used as cathodes in AZICs face challenges, such as inappropriate pore sizes, poor electrolyte-electrode wettability, and insufficient vacancy defects and active sites. These limitations hinder efficient energy storage capacity and long-term stability. To address these issues, the B and F co-doped hierarchical porous carbon cathode materials (BFPC) are constructed through a facile annealing treatment process. The BFPC-2//Zn device exhibited high capacities of 222.4 and 118.3 mAh g-1 at current densities of 0.2 and 10 A g-1, respectively. Notably, the BFPC-2//Zn device demonstrated long-term cycling stability with a high capacity retention of 96.9 % after 20,000 cycles at 10 A g-1. Additionally, the assembled BFPC-2 based AZICs displayed a maximum energy density of 175.8 Wh kg-1 and an ultrahigh power density of 17.3 kW kg-1. Mechanism studies revealed that the exceptional energy storage ability and charge-transfer process of the BFPC cathode are attributed to the synergistic effect of B and F heteroatoms and the coupling effect between vacancy defects and pore size. This work presents a novel design strategy by incorporating B and F active sites into hierarchical porous carbon materials, providing enhanced energy storage capabilities for practical application in AZICs.

Effect of ginger and P6 acupressure on chemotherapy-induced nausea and vomiting: a randomized controlled study.

OBJECTIVE: To evaluate the effect of ginger with P6 acupressure in preventing and treating chemotherapy-induced nausea and vomiting (CINV) in cancer patients. METHOD: A total of 172 participants were randomly divided into the control, ginger, acupressure, and joint groups, who were hospitalized in the Affiliated Hospital of Xuzhou Medical University from February and September 2022. The baseline characteristics, nausea, vomiting, and retching, benefit finding, functional living index-emesis, treatment satisfaction, and adverse reaction, were used in data collection. RESULTS: No significant difference was found in benefit finding and adverse reactions among the four groups (P > 0.05). Ginger significantly improved delayed CINV and function living index-nausea (P < 0.05) but had no significant effect on acute CINV, retching, and delayed vomiting, functional living index-emesis, and treatment satisfaction (P>0.05). Acute nausea and retching, delayed nausea, vomiting, and retching, functional living index-emesis, and treatment satisfaction were effectively improved in the acupressure and joint groups (P < 0.05). CONCLUSION: Ginger with P6 acupressure may contribute to improving CINV in patients undergoing chemotherapy.

First-line penpulimab combined with paclitaxel and carboplatin for metastatic squamous non-small-cell lung cancer in China (AK105-302): a multicentre, randomised, double-blind, placebo-controlled phase 3 clinical trial.

BACKGROUND: Penpulimab is a novel programmed death (PD)-1 inhibitor. This study aimed to establish the efficacy and safety of first line penpulimab plus chemotherapy for advanced squamous non-small-cell lung cancer. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial enrolled patients with locally advanced or metastatic squamous non-small-cell lung cancer from 74 hospitals in China. Eligible participants were aged 18-75 years, had histologically or cytologically confirmed locally advanced (stage IIIb or IIIc) or metastatic (stage IV) squamous non-small-cell lung cancer, were ineligible to complete surgical resection and concurrent or sequential chemoradiotherapy, had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, did not have previous systemic chemotherapy for locally advanced or metastatic non-small-cell lung cancer, and had one or more measurable lesions according to RECIST (version 1.1). Participants were randomly assigned (1:1) to receive intravenous penpulimab 200 mg or placebo (excipient of penpulimab injection), plus paclitaxel 175 mg/m2 and carboplatin AUC of 5 intravenously on day 1 every 3 weeks for four cycles, followed by penpulimab or placebo as maintenance therapy. Stratification was done according to the PD-L1 tumour proportion score (<1% vs 1-49% vs ≥50%) and sex (male vs female). The participants, investigators, and other research staff were masked to group assignment. The primary outcome was progression-free survival assessed by the masked Independent Radiology Review Committee in the intention-to-treat population and patients with a PD-L1 tumour proportion score of 1% or more (PD-L1-positive subgroup). The primary analysis was based on the intention-to-treat analysis set (ie, all randomly assigned participants) and the PD-L1-positive subgroup. The safety analysis included all participants who received at least one dose of study drug after enrolment. This trial was registered with ClinicalTrials.gov (NCT03866993). FINDINGS: Between Dec 20, 2018, and Oct 10, 2020, 485 patients were screened, and 350 participants were randomly assigned (175 in the penpulimab group and 175 in the placebo group). Of 350 participants, 324 (93%) were male and 26 (7%) were female, and 347 (99%) were of Han ethnicity. In the final analysis (June 1, 2022; median follow-up, 24·7 months [IQR 0-41·4]), the penpulimab group showed an improved progression-free survival compared with the placebo group, both in the intention-to-treat population (median 7·6 months, 95% CI 6·8--9·6 vs 4·2 months, 95% CI 4·2-4·3; HR 0·43, 95% CI 0·33-0·56; p<0·0001) and in the PD-L1-positive subgroup (8·1 months, 5·7-9·7 vs 4·2 months, 4·1-4·3; HR 0·37, 0·27-0·52, p<0·0001). Grade 3 or worse treatment-emergent adverse events occurred in 120 (69%) 173 patients in the penpulimab group and 119 (68%) of 175 in the placebo group. INTERPRETATION: Penpulimab plus chemotherapy significantly improved progression-free survival in patients with advanced squamous non-small-cell lung cancer compared with chemotherapy alone. The treatment was safe and tolerable. Penpulimab combined with paclitaxel and carboplatin is a new option for first-line treatment in patients with this advanced disease. FUNDING: The National Natural Science Foundation of China, Shanghai Municipal Health Commission, Chia Tai Tianqing Pharmaceutical, Akeso.

Atomic observation and structural evolution of covalent organic framework rotamers.

Dynamic 3D covalent organic frameworks (COFs) have shown concerted structural transformation and adaptive gas adsorption due to the conformational diversity of organic linkers. However, the isolation and observation of COF rotamers constitute undergoing challenges due to their comparable free energy and subtle rotational energy barrier. Here, we report the atomic-level observation and structural evolution of COF rotamers by cryo-3D electron diffraction and synchrotron powder X-ray diffraction. Specifically, we optimize the crystallinity and morphology of COF-320 to manifest its coherent dynamic responses upon adaptive inclusion of guest molecules. We observe a significant crystal expansion of 29 vol% upon hydration and a giant swelling with volume change up to 78 vol% upon solvation. We record the structural evolution from a non-porous contracted phase to two narrow-pore intermediate phases and the fully opened expanded phase using n-butane as a stabilizing probe at ambient conditions. We uncover the rotational freedom of biphenylene giving rise to significant conformational changes on the diimine motifs from synclinal to syn-periplanar and anticlinal rotamers. We illustrate the 10-fold increment of pore volumes and 100% enhancement of methane uptake capacity of COF-320 at 100 bar and 298 K. The present findings shed light on the design of smarter organic porous materials to maximize host-guest interaction and boost gas uptake capacity through progressive structural transformation.

Ash1L ameliorates psoriasis via limiting neuronal activity-dependent release of miR-let-7b.

BACKGROUND AND PURPOSE: Psoriasis is a common autoimmune skin disease that significantly diminishes patients' quality of life. Interactions between primary afferents of the somatosensory system and the cutaneous immune system mediate the pathogenesis of psoriasis. This study aims to elucidate the molecular mechanisms of how primary sensory neurons regulate psoriasis formation. EXPERIMENTAL APPROACH: Skin and total RNA were extracted from wild-type (WT) and ASH1-like histone lysine methyltransferase (Ash1l+/- ) mice in both naive and imiquimod (IMQ)-induced psoriasis models. Immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR) and fluorescence-activated cell sorting (FACS) were then performed. Microfluidic chamber coculture was used to investigate the interaction between somatosensory neurons and bone marrow dendritic cells (BMDCs) ex vivo. Whole-cell patch clamp recordings were used to evaluate neuronal excitability after Ash1L haploinsufficiency in primary sensory neurons. KEY RESULTS: The haploinsufficiency of ASH1L, a histone methyltransferase, in primary sensory neurons causes both neurite hyperinnervation and increased neuronal excitability, which promote miR-let-7b release from primary afferents in the skin in a neuronal activity-dependent manner. With a 'GUUGUGU' core sequence, miR-let-7b functions as an endogenous ligand of toll-like receptor 7 (TLR7) and stimulates the activation of dermal dendritic cells (DCs) and interleukin (IL)-23/IL-17 axis, ultimately exacerbating the symptoms of psoriasis. Thus, by limiting miR-let-7b release from primary afferents, ASH1L prevents dermal DC activation and ameliorates psoriasis. CONCLUSION AND IMPLICATIONS: Somatosensory neuron ASH1L modulates the cutaneous immune system by limiting neuronal activity-dependent release of miR-let-7b, which can directly activate dermal DCs via TLR7 and ultimately lead to aggravated psoriatic lesion.

Study of the mechanism of acupuncture and moxibustion in protecting the intestinal mucosal barrier in DSS-induced UC rats based on the IL-9/IL-9R pathway / 针灸推拿医学（英文版）

Objective:To observe the effects of acupuncture and moxibustion on interleukin(IL)-9/IL-9 receptor(IL-9R)in the colon tissue of rats with ulcerative colitis(UC)and investigate the protective mechanism of acupuncture and moxibustion on the intestinal mucosal barrier in UC rats. Methods:Male Sprague-Dawley rats were randomly divided into a normal control(NC)group and a modeling group.UC models were prepared by giving 4%dextran sulfate sodium(DSS)water for 7 d.After the successful construction of the UC rat model,the modeling group was randomly divided into a UC group,a herb-insulated moxibustion(HM)group,and an electroacupuncture(EA)group.HM and EA interventions at bilateral Tianshu(ST25)were performed once a day for 7 d.Hematoxylin-eosin(HE)staining was used to observe the histopathological changes in the colon.The serum concentrations of IL-9,IL-6,IL-1β,and hemoglobin-H(HbH)were determined by enzyme-linked immunosorbent assay.The protein expression levels of IL-9,IL-9R,claudin-2,zonula occludens-1(ZO-1),and occludin in the colon tissue were measured by Western blotting or immuno-histochemistry.Immunofluorescence was used to detect the co-expression of PU.1 and CD4 with the IL-9 protein. Results:Compared with the NC group,the colon tissue of UC rats was severely damaged and ulcerated with congestion and edema,and the colonic histopathological score increased significantly(P<0.01).The serum HbH concentration decreased significantly(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β increased(P<0.01).The protein expression of colonic ZO-1 and occludin decreased significantly(P<0.01),while the protein expression of colonic IL-9 and IL-9R increased(P<0.05).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 increased in the colon tissue(P<0.05).Compared with the UC group,the colonic mucosal structures were gradually repaired in both HM group and EA group,and healed ulcers could be observed,the colonic histopathological score decreased significantly(P<0.05).The serum concentration of HbH increased(P<0.01),while the serum concentrations of IL-9,IL-6,and IL-1β decreased(P<0.05).The protein expression levels of ZO-1 and occludin increased(P<0.05),while the protein expression levels of IL-9 and IL-9R decreased(P<0.01).The positive co-expression levels of IL-9/PU.1 and IL-9/CD4 decreased in the colon tissue(P<0.05). Conclusion:Both HM and EA can inhibit the protein expression levels of IL-9 and IL-9R in the UC colon by regulating the transcription factor PU.1,promote the repair of intestinal mucosal barrier,and down-regulate protein contents of proinflammatory factors IL-9,IL-6,and IL-1β in the serum,which may be one of the key mechanisms of acupuncture and moxibustion in reducing the inflammation of UC colonic mucosa and protecting the intestinal mucosal barrier.

Study on preoperative bedside ultrasonography-assessed perioperative reflux and aspiration risk in surgical colon cancer patients with incomplete intestinal obstruction / 肿瘤研究与临床

Objective:To investigate the correlation between preoperative incomplete intestinal obstruction and the risk of perioperative reflux and aspiration assessed by preoperative bedside ultrasonography in patients with colon cancer.Methods:A prospective case series study was conducted. A total of 300 patients with colon cancer who underwent elective surgery from March 2020 to January 2022 in the First Hospital of Shanxi Medical University were prospectively selected for the study. According to whether there was incomplete intestinal obstruction before operation, the patients were divided into obstruction group and non-obstruction group. All patients underwent preoperative ultrasound examination of the gastric antrum, measuring the cross-sectional area of the gastric antrum in the right lateral position, and calculating the gastric volume and unit body mass gastric volume (GV/W), which were all expressed as M ( Q1, Q3). The differences in cross-sectional area of the gastric antrum, gastric volume and GV/W in the right lateral position between the two groups were compared, as well as the risk of reflux and aspiration (the risk of reflux and aspiration was extremely low at GV/W<0.8 ml/kg, the risk was low at GV/W 0.8-1.5 ml/kg, and the risk was high at GV/W >1.5 ml/kg). Multivariate logistic regression was used to analyze the influencing factors of high risk of reflux and aspiration. Results:Of 300 patients, 7 patients were excluded because of blurred images on ultrasonography, and a total of 293 patients were finally included. The age [ M ( Q1, Q3)] of obstruction group (146 cases) was 58.0 years old (55.0 years old, 67.0 years old), including 80 males and 66 females; the age of non-obstruction group (147 cases) was 55.0 years old (53.5 years old, 64.0 years old), including 64 males and 83 females. The age and body mass index (BMI) of the patients in the obstructin group were higher than those in the non-obstruction group, and the differences were statistically significant (both P < 0.05), and there were no significant differences in gender, duration of dietary abstinence, comorbid hypertension, comorbid diabetes mellitus, smoking status, sedentariness, and alcoholism between the two groups (all P > 0.05). Compared with the non-obstruction group, patients in the obstruction group had a higher cross-sectional area of the gastric antrum [5.83 cm 2 (5.25 cm 2, 6.70 cm 2) vs. 5.13 cm 2 (4.43 cm 2, 5.79 cm 2), P < 0.001], gastric volume [43.00 ml (37.07 ml, 52.74 ml) vs. 32.78 ml (25.52 ml, 39.85 ml), P < 0.001] and GV/W [0.70 ml/kg (0.65 ml/kg, 0.82 ml/kg) vs. 0.55 ml/kg (0.46 ml/kg, 0.62 ml/kg), P < 0.001] in the right lateral position. The proportion of patients at high risk of reflux and aspiration in the obstruction group was higher than that in the non-obstruction group [22.6% (33/146) vs. 12.2% (18/147), χ2 = 4.59, P = 0.032]. Multivariate logistic regression analysis showed that combination of incomplete intestinal obstruction (combined vs. uncombined, OR = 2.145, 95% CI: 1.096-4.198, P = 0.026), and males (females vs. males, OR = 0.415, 95% CI: 0.199-0.867, P = 0.019) were the independent risk factors for a high risk of perioperative reflux and aspiration assessed by preoperative bedside ultrasonography. Conclusions:Colon cancer patients combined with incomplete intestinal obstruction have significantly larger preoperative cross-sectional area of the gastric antrum, gastric volume and GV/W in the right lateral position, and have gastric retention, which may contribute to a higher risk of perioperative reflux and aspiration.

Comprehensive evaluation of TCM resource allocation in Guangzhou community using TOPSIS and RSR / 实用医学杂志

Objective To comprehensively evaluate the current situation of traditional Chinese medicine resource allocation in grassroots community health service centers in Guangzhou in 2022.Methods Based on the index system of traditional Chinese medicine resource allocation(community health service center)in Guangzhou,MATLAB R2021a and SPSS 27 software were used to comprehensively evaluate the current situation of traditional Chinese medicine resource allocation in 116 community health service centers in Guangzhou by TOPSIS method and RSR method.Results The allocation of TCM resources in 5 communities,including Xiaoguwei Street Community Health Service Center in Panyu District,Guangzhou City,Dadong Street Community Health Service Center in Yuexiu District,Guangzhou City,Fengyuan Street Community Health Service Center in Leiwan District,Guangzhou City,was evaluated as"excellent",and the allocation of TCM resources in 4 communities was rated as"poor".In addition,27,53 and 27 community health service centers were rated as"upper middle","medium"and"lower middle"respectively.Analysis of variance showed that the difference was statistically significant(F = 231.268,P<0.001).Conclusion TOPSIS method combined with RSR method can better evaluate the allocation of TCM resources in grass-roots communities:The allocation of TCM resources in grass-roots communities in Guangzhou is generally good,but there are still significant differences among different communities.In the future,health administrative departments at all levels in Guangzhou can rationally allocate resources according to the differences of different com-munities and better improve the capacity building of traditional Chinese medicine service in grassroots communities.

Active ingredients of Panax notoginseng regulate signaling pathways related to steroid-induced necrosis of the femoral head / 中国组织工程研究

BACKGROUND:Steroid-induced osteonecrosis of the femoral head is a refractory disease in the field of orthopedics.There is no definitive idea to fully explain its pathogenesis.With the increased research on the active ingredients of Panax notoginseng interfering with the signaling pathways related to various diseases,the active ingredients of Panax notoginseng that treat steroid-induced necrosis of the femoral head via the regulation of relevant signaling pathways have gradually become a hot research topic. OBJECTIVE:To systematically summarize the literature on the pathological mechanism of steroid-induced osteonecrosis of the femoral head and the regulation of signaling pathways by the active ingredients of Panax notoginseng in recent years,thereby providing a reference for the follow-up study on the active ingredients of Panax notoginseng in the treatment of this disease. METHODS:CNKI,WanFang,and PubMed were searched for relevant literature with the key words of"glucocorticoid,steroid-induced osteonecrosis of the femoral head,pathological mechanism,signaling pathway,Panax notoginseng,active ingredient"in Chinese and English.Documents related to the pathological mechanism of steroid-induced osteonecrosis of the femoral head as well as related to the intervention of active ingredients of Panax notoginseng on the signaling pathway of steroid-induced osteonecrosis of the femoral head were retrieved.A total of 63 documents were finally included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The main ingredients of Panax notoginseng include Panax notoginseng saponins,ginsenoside,Panax notoginseng saponins,quercetin,kaempferol,etc.Panax notoginseng saponins,ginsenoside Rb1 and quercetin can promote bone repair and angiogenesis by acting on the transforming growth factor-β/bone morphogenetic protein pathway.Panax notoginseng saponins,ginsenoside CK and kaempferol can promote osteogenic differentiation and lipid metabolism by acting on the Wnt/β-catenin pathway.Panax notoginseng saponins and Panax notoginseng saponins R1/R2 act on the MAPK pathway to inhibit osteoclastogenesis and promote bone repair.Panax notoginseng saponins,ginsenoside Rb2 and quercetin can inhibit osteoclast proliferation and promote osteoblastic differentiation by acting on the RANKL/RANK/OPG pathway.Panax notoginseng saponins,quercetin and kaempferol can repair vascular injury and promote osteogenesis by acting on the hypoxia-inducible factor-1α pathway.Panax notoginseng saponins R1,quercetin combined with hydroxyapatite nanoparticles,Panax notoginseng saponins combined with polyethylene-L-lactic acid and other biomaterials have good research prospects in the treatment of steroid-induced osteonecrosis of the femoral head.The active ingredients of Panax notoginseng can regulate the signaling pathways related to steroid-induced osteonecrosis of the femoral head through various mechanisms,and play an active intervention role in the disease.However,the depth and breadth of relevant research are insufficient at present,and the future research should be based on the existing mechanism to explore the specific mechanism of Panax notoginseng regulating different pathways and the interaction between pathways,which will be beneficial to the multi-development of the active ingredients of Panax notoginseng in the treatment of steroid-induced osteonecrosis of the femoral head.

Clinical Characteristics of Mycoplasma Pneumoniae Infection and Factors Associated with Co-infections in Children / 医学研究杂志

Objective To analyze the clinical characteristics of mycoplasma pneumoniae pneumonia(MPP)in children with atopic constitution and exploring the predictors of disease conditions.Methods A total of 250 children diagnosed with MPP in the Department of Pediatric Respiratory Medicine,Xinhua Hospital,Shanghai Jiaotong University School of Medicine from September 2019 to September 2022 were selected and divided into atopic group(n=149)and non-atopic group(n=101)according to whether they were atopic,to explore the clinical characteristics of MPP in children with atopic constitution and the risk factors of severe mycoplasma pneumoniae pneu-monia(SMPP).The efficacy of the combined test of lactate dehydrogenase(LDH),immunoglobulin E(IgE)and serum amyloid A(SAA)in predicting the development of SMPP in MPP children with atopic constitution was evaluated by the receiver operating character-istic(ROC)curve.Results Children in the atopic group had more pronounced symptoms of cough,wheezing,nasal congestion,croup,combined pleural effusion with severe pneumonia and the proportion requiring hormone therapy than those in the non-atopic group,and the differences were statistically significant(P＜0.05).Logistic regression analysis showed that serum IgE,SAA and LDH levels were in-dependent risk factors for the development of SMPP in MPP children with atopic constitution(P＜0.05);ROC curve analysis showed that the combined test of IgE,LDH and SAA could be used to predict the development of SMPP in MPP children with atopic constitution,with an area under the curve(AUC)of 0.881,sensitivity of 81.0％,and specificity of 85.0％.Conclusion MPP children with atopic con-stitution are more likely to develop SMPP and require hormone therapy.The combined detection of serum IgE,SAA and LDH can effec-tively predict the occurrence of SMPP in MPP children with atopic constitution.

Clinical observation of camrelizumab combined with sorafenib in the treatment of advanced liver cancer / 中国药房

OBJECTIVE To observe the clinical efficacy and safety of camrelizumab combined with sorafenib in the treatment of advanced liver cancer. METHODS Sixty patients with advanced liver cancer who were treated in our hospital from March 2020 to November 2021 were selected as the study subjects， and then were randomly divided into study group and control group， with 30 cases in each group. The control group was treated with Sorafenib tosylate tablets orally （0.4 g，bid）， and the study group was additionally given Camrelizumab for injection intravenously （200 mg， every 3 weeks） based on the control group； for all patients， the treatment was stopped until disease progression or intolerable side effects occurred. The clinical efficacy， progression-free survival （PFS）， total survival （OS） and 1-year survival rate of the two groups were compared， and the incidence of adverse reactions in two groups， and immune-related adverse reactions in the study group during treatment were recorded. RESULTS The objective remission rate of the study group was significantly higher than the control group （36.7% vs. 13.3%， P＜0.05）， and the median OS and median PFS were significantly longer than the control group （OS： 12.6 months vs. 7.9 months； PFS： 8.2 months vs. 5.3 months， P＜0.05）. There was no significant difference in the 1-year survival rate and the incidence of elevated aspartate aminotransferase and alanine aminotransferase， rash or pruritus， anorexia， diarrhea， fatigue and hypertension between the two groups （P＞0.05）. The adverse events immune-related in the study group mainly included 21 cases of reactive capillary hyperplasia （70.0%）， 6 cases of hypothyroidism （20.0%）， and 1 case of immune-associated pneumonia （3.3%）， which were improved or tolerable after symptomatic treatment. CONCLUSIONS Camrelizumab combined with sorafenib in the treatment of advanced liver cancer can effectively control and delay the disease progression， prolong the survival period of patients， and the adverse reactions can be tolerated.

A Bibliometric and Visual Analysis of the Current Status and Trends of Foren-sic Mixed Stain Research / 法医学杂志

Objective To explore the context and hotspot changes of forensic mixed stain research through bibliometric approach.Methods The literature of forensic mixed stain included in the core col-lection of Web of Science database from 2011 to 2022 were collected as the study object,and the an-nual publication number,countrie(region),institution,journal,keywords,etc.were bibliometrically and visually analyzed using the R-based Bibliometrix 1.1.6 package and VOSviewer 1.6.18 software.Re-sults A total of 732 articles on forensic mixed stain were included from 2011 to 2022,with the an-nual number of articles published and the annual citation frequency showing a steady increase year by year.Among the 59 countries(regions)with the most published articles,the United States ranked first with 246 articles,followed by China with 153 articles.The literature came from 104 journals,and the total number of articles published in the top 10 journals was 633.FORENSIC SCI INT GENET ranked first with 307 articles.Visual analysis using VOSviewer software showed that keywords could be divided into four research clusters,namely the genetic marker development group(blue),the mixed stain typing analysis theory group(red),the sequencing analysis group(yellow),and the case sample research group(green).It can be divided into four development stages in terms of different time peri-ods:early development(2011-2013),middle development(2014-2016),rapid development(2017-2020)and latest development(2021-2022).Conclusion The number of publications by domestic and foreign scholars in the study of mixed stain in forensic science is showing a relatively stable trend.Machine learning,next generation sequencing and other research have been the hottest topics that have attracted the most attention in recent years,which is expected to further develop the theory of mixed stain typing and sequencing analysis in forensic mixed stain research.

Study on mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy based on proteomics / 中国药理学通报

Aim To explore the mechanism of hydroxy-a-sanshool in the treatment of diabetic cardiomyopathy ( DCM) based on label-free quantitative proteomics detection technique. Methods DCM model was established by high fat diet and intraperitoneal injection of streptozotocin ( STZ) . They were divided into control group ( CON group ) , diabetic cardiomyopathy group (DCM group) and hydroxy-a-sanshool treatment group ( DCM + SAN group) . The cardiac function of mice was evaluated by echocardiography, the myocardial morphology was observed by pathology staining, the protective mechanism of hydroxy-a-sanshool on diabetic cardiomyopathy was speculated by proteomic technique , and the expression level of cAMP/PKA signaling pathway and key proteins were verified by Western blotting. Results Cardiac ultrasound and pathology staining showed that hydroxy-a-sanshool had protective effect on the heart of DCM mice. Label-free quantitative proteomic analysis was carried out between DCM + SAN group and DCM group, and 160 differential pro-teins were identified by proteomics, in which 127 proteins were up-regulated and 33 proteins were down regulated ; GO secondary functional annotations showed the biological process, molecular function and cellular component; KEGG enrichment analysis showed that cAMP signaling pathway was the most abundant; protein interaction network showed that PKA as the central node interacted with many proteins in the cAMP signaling pathway. Western blot showed that the relative expression of с AMP, PKA protein in DCM group was significantly lower than that in CON group ( P < 0. 05 ) , while the relative expression of cAMP, PKA protein in DCM + SAN group was significantly higher than that in DCM group ( P < 0. 05 ) . Conclusions Hydroxy-a-sanshool has protective effect on heart function of mice with diabetes, which plays a role through cAMP signaling pathway.

Singlet oxygen induces cell wall thickening and stomatal density reducing by transcriptome reprogramming.

Singlet oxygen (1O2) has a very short half-life of 10-5 s; however, it is a strong oxidant that causes growth arrest and necrotic lesions on plants. Its signaling pathway remains largely unknown. The Arabidopsis flu (fluorescent) mutant accumulates a high level of 1O2 and shows drastic changes in nuclear gene expression. Only two plastid proteins, EX1 (executer 1) and EX2 (executer 2), have been identified in the singlet oxygen signaling. Here, we found that the transcription factor abscisic acid insensitive 4 (ABI4) binds the promoters of genes responsive to 1O2-signals. Inactivation of the ABI4 protein in the flu/abi4 double mutant was sufficient to compromise the changes of almost all 1O2-responsive-genes and rescued the lethal phenotype of flu grown under light/dark cycles, similar to the flu/ex1/ex2 triple mutant. In addition to cell death, we reported for the first time that 1O2 also induces cell wall thickening and stomatal development defect. Contrastingly, no apparent growth arrest was observed for the flu mutant under normal light/dim light cycles, but the cell wall thickening (doubled) and stomatal density reduction (by two-thirds) still occurred. These results offer a new idea for breeding stress tolerant plants.

Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial.

Importance: Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. Objective: To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions: Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. Main Outcomes and Measures: The primary end point was overall survival time from randomization. Results: Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%). Conclusions and Relevance: Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03745170.

Spatio-temporal variation and environmental drivers of chlorophyll a concentration and diatom community in four small urban lakes of Kunming, China.

Chlorophyll a (Chla) and diatom community structure are two indicators of lake water quality. In this study, we investigated the environmental parameters, chlorophyll a, and diatom community of four small urban lakes in Kunming (Beitan, Beihu, Nanhu and Longtan lakes in the campus of Yunnan Normal University) between March 2017 and December 2019. The results showed that the concentrations of total nitrogen (TN), total phosphorus (TP), and Chla in the four lakes showed significant seasonal fluctuation. The Chla concentration in Nanhu Lake, which had the highest nutrient level among the four lakes, was significantly higher than that in the other three lakes and largely affected by TN. In comparison, water temperature significantly contributed to the increases in Chla concentration in the other three lakes. Water temperature and TN were significantly correlated with Chla across the four lakes. Diatom assemblages in Beitan, Nanhu, and Longtan lakes were dominated by planktonic diatoms, and benthic diatoms were dominant in the shallowest lake Beihu, suggesting that water depth significantly affected the proportion of planktonic diatoms and dominant taxa. Water depth, TN, TP, transparency, and water temperature affected the spatio-temporal changes of diatom community structure, with water temperature as the major factor in causing the seasonal variation in diatom community, and TN and TP as the major drivers for community variation among lakes within the same season.