LECT2, a Ligand for Tie1, Plays a Crucial Role in Liver Fibrogenesis.

Liver fibrosis is a very common condition seen in millions of patients with various liver diseases, and yet no effective treatments are available owing to poorly characterized molecular pathogenesis. Here, we show that leukocyte cell-derived chemotaxin 2 (LECT2) is a functional ligand of Tie1, a poorly characterized endothelial cell (EC)-specific orphan receptor. Upon binding to Tie1, LECT2 interrupts Tie1/Tie2 heterodimerization, facilitates Tie2/Tie2 homodimerization, activates PPAR signaling, and inhibits the migration and tube formations of EC. In vivo studies showed that LECT2 overexpression inhibits portal angiogenesis, promotes sinusoid capillarization, and worsens fibrosis, whereas these changes were reversed in Lect2-KO mice. Adeno-associated viral vector serotype 9 (AAV9)-LECT2 small hairpin RNA (shRNA) treatment significantly attenuates fibrosis. Upregulation of LECT2 is associated with advanced human liver fibrosis staging. We concluded that targeting LECT2/Tie1 signaling may represent a potential therapeutic target for liver fibrosis, and serum LECT2 level may be a potential biomarker for the screening and diagnosis of liver fibrosis.

A strategy of vascular-targeted therapy for liver fibrosis.

BACKGROUND AND AIMS: No effective treatments are available for liver fibrosis. Angiogenesis is deeply involved in liver fibrogenesis. However, current controversial results suggest it is difficult to treat liver fibrosis through vascular targeting. There are three different microvessels in liver: portal vessels, liver sinusoids, and central vessels. The changes and roles for each of the three different vessels during liver fibrogenesis are unclear. We propose that they play different roles during liver fibrogenesis, and a single vascular endothelial cell (EC) regulator is not enough to fully regulate these three vessels to treat liver fibrosis. Therefore, a combined regulation of multiple different EC regulatory signaling pathway may provide new strategies for the liver fibrosis therapy. Herein, we present a proof-of-concept strategy by combining the regulation of leukocyte cell-derived chemotaxin 2 (LECT2)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 signaling with that of vascular endothelial growth factor (VEGF)/recombinant VEGF (rVEGF) signaling. APPROACH AND RESULTS: The CCl4 -induced mouse liver fibrosis model and NASH model were both used. During fibrogenesis, vascular changes occurred at very early stage, and different liver vessels showed different changes and played different roles: decreased portal vessels, increased sinusoid capillarization and the increased central vessels the increase of portal vessels alleviates liver fibrosis, the increase of central vessels aggravates liver fibrosis, and the increase of sinusoid capillarization aggravates liver fibrosis. The combinational treatment of adeno-associated viral vector serotype 9 (AAV9)-LECT2-short hairpin RNA (shRNA) and rVEGF showed improved therapeutic effects, but it led to serious side effects. The combination of AAV9-LECT2-shRNA and bevacizumab showed both improved therapeutic effects and decreased side effects. CONCLUSIONS: Liver vascular changes occurred at very early stage of fibrogenesis. Different vessels play different roles in liver fibrosis. The combinational treatment of AAV9-LECT2-shRNA and bevacizumab could significantly improve the therapeutic effects on liver fibrosis.

Predictors of post-stroke depression: the perspective from the social convoy model.

BACKGROUND: Post-stroke depression (PSD) as one of the most common neuropsychiatric disorders after a stroke and is caused by many factors. However, the relationships among different factors and their potential contributions to PSD remain unclear. METHODS: Two hundred and seventy-six patients were recruited into this study. The general information questionnaire, the Patient Health Questionnaire-9, the Perceived Social Support Scale, the Family Assessment Device, the General Well-Being Scale, the Barthel Index, and the modified Rankin Scale were used to assess the condition of patients. Subsequently, we identify the main causes associated with the PSD and then performed a path analysis to clarify the direct, indirect and total effects among the variables. RESULTS: We found that age, stroke with coronary heart disease, neurological function, family function, social support, and general well-being had a significant impact on PSD (P < 0.05). Of these, neurological function had the largest total effect on PSD (ß = 0.451), social support contributed the most as a direct effect (ß = -0.306), and family function showed the largest indirect effect (ß = -0.264). CONCLUSION: Individual, disease, and social-psychological factors all contributed to the development of PSD. We should pay more attention to comprehensive assessment, especially for those with poor neurological function, and lacking family or social support. In addition, it would be preferable to provide them with necessary support and care strategies to reduce the incidence of PSD.

Methylation of ERß 5'-untranslated region attenuates its inhibitory effect on ERα gene transcription and promotes the initiation and progression of papillary thyroid cancer.

Normal thyroid tissue displays a prevalent expression of ERß than ERα, which drastically turns upside down in the initiation and progression of papillary thyroid cancer (PTC). The underlying molecular mechanism of this phenomenon remains unclear. Here, we demonstrated that ERα and ERß were coexpressed in human thyroid tissues and cells. ERα mRNA (A-1) and ERß mRNA (0N-1), transcribed from Promoter A of ERα gene and Promoter 0N of ERß gene, respectively, were the major mRNA isoforms which mainly contributed to total ERα mRNA and total ERß mRNA in human thyroid-derived cell lines and tissues. The expression levels of ERα mRNA (A-1) and total ERα mRNA were gradually increased, and those of ERß mRNA (0N-1) and total ERß mRNA were decreased by degree in the initiation and progression of PTC. No aberrant DNA methylation of ERα 5'-untranslated region was involved in its up-regulation; however, aberrant DNA methylation in Promoter 0N and Exon 0N of ERß gene was found to be involved in its down-regulation in the initiation and progression of PTC. ERß can repress ERα gene transcription via recruitment of NCoR and displacement of RNA polymerase II at the Sp1 site in ERα Promoter A-specific region in thyroid-derived cells. It is suggested that DNA methylation of CpG islands in Promoter 0N and Exon 0N of ERß gene leads to a decreased ERß gene expression, which attenuates its inhibitory effect on ERα gene transcription and results in an increased ERα gene expression, cell proliferation, initiation, and progression of PTC.

Proposal for modified inguinofemoral lymphadenectomy derived from investigation of anatomic distribution of sentinel and metastatic nodes in vulvar cancer.

OBJECTIVE: We aimed to develop a less invasive inguinofemoral lymphadenectomy (IFL) approach for vulvar cancer based on the investigation of the anatomic distribution of sentinel and metastatic nodes. METHODS: Patients with vulvar cancer treated by surgery between 1995 and 2019 were retrospectively reviewed. A seven-field method was adopted to assign the anatomic locations for lymph nodes removed via IFL or sentinel node biopsy. Only patients with nodal metastasis or sentinel nodes were included. RESULTS: A total of 102 patients with eligible data were analyzed. Nodal metastasis was confirmed in 118 groins undergoing IFL; sentinel node detection succeeded in 46 groins. The medial-inguinal field had the highest rate of nodal metastasis involvement (59.3%, 70/118) and sentinel nodes present (73.9%, 34/46). The inferior-femoral field was involved only in one groin with quadruple-field metastases. The lateral-inguinal field was not involved in any groin. Neither the lateral-inguinal nor the inferior-femoral field presented sentinel nodes. CONCLUSION: The lateral-inguinal and inferior-femoral fields of the groins have a low risk of developing nodal metastasis. Therefore, a modified IFL preserving these fields can be established to reduce surgical morbidity without sacrificing its therapeutic effect.

Matrine involves in the progression of gastric cancer through inhibiting miR-93-5p and upregulating the expression of target gene AHNAK.

Matrine, also known as oxymatrine, is an important active ingredient of traditional Chinese herb Sophora flavescens. Recent studies have found that matrine may inhibit multiple tumors through inhibiting the tumor cell proliferation, inducing cell apoptosis, blocking cell cycle, suppressing cell invasion and migration and assisting in the synergy, and attenuation of radiotherapy and chemotherapy. This study mainly investigated the role of matrine in gastric cancer and its possible mechanism. The real-time fluorescence quantitative polymerase chain reaction technique showed that matrine inhibited the proliferation and migration of gastric tumor cells and significantly suppressed the expression of miR-93-5p. The dual-luciferase reporter gene assay indicated that AHNAK was a target gene of miR-93-5p and regulated by miR-93-5p and matrine. The torsion test demonstrated that matrine exerted its role via miR-93-5p while miR-93-5p played a role by targeting AHNAK. Thus, this study found that matrine affected the progression of gastric cancer by inhibiting the function of gastric cancer cells through the possible mechanism of inhibiting miR-93-5p expression to increase the expression level of the downstream target gene AHNAK.

[Effects of UHRF1 on Estrogen Receptor and Proliferation, Invasion and Migration of BCPAP Cells in Thyroid Papillary Carcinoma].

OBJECTIVE: To investigate the effects of ubiquitin-like PDH and ring finger domain 1 (UHRF1) on the expression ratio of estrogen receptor (ER) α/ERß, and to explore the experimental mechanism of UHRF1 affecting the proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma. METHODS: The protein and mRNA expressions of UHRF1, ERα and ERß in normal thyroid Nthy-ori3-1 cells and thyroid papillary carcinoma BCPAP cells were detected by Western blot and qRT-PCR. BCPAP cells were treated with Scrambled siRNA and UHRF1 siRNA, respectively. The expressions of ER α and ER ß mRNAs were detected by qRT-PCR. MTT and Transwell were used to determine the proliferation, invasion and migration in each group of BCPAP cells. RESULTS: Compared with Nthy-ori3-1 cells, the expressions of UHRF1 and ERα proteins and mRNAs in BCPAP cells were significantly up-regulated ( P<0.05), while the expressions of ERß protein and mRNA were significantly down-regulated ( P<0.05). Compared with the control group and Scrambled siRNA group, the expression of ER α mRNA in BCPAP cells transfected with UHRF1 siRNA was significantly decreased ( P<0.05), while the expression of ER ß mRNA was significantly increased ( P<0.05). The proliferation, invasion and migration of BCPAP cells transfected with UHRF1 siRNA were significantly decreased ( P<0.05). CONCLUSION: UHRF1 upregulates ERα/ERß expression ratio and promotes proliferation, invasion and migration of BCPAP cells in papillary thyroid carcinoma.

Multiresponsive UV-One-Photon Absorption, Near-Infrared-Two-Photon Absorption, and X/γ-Photoelectric Absorption Luminescence in One [Cu4I4] Compound.

A new Cu4I4-cluster-based compound is constructed to show multifaceted photoluminescent attributes: (1) ultraviolet (UV)-excited thermo-, mechano-, and rigido-chromic phosphorescence by the OPA (one-photon absorption) pathway, due to the interchanging emissions from cluster-centered (3CC) and halide-to-ligand charge-transfer (3XLCT) excited triplet states, (2) the ability to convert X/γ-ray and near-infrared (NIR) radiation to visible-light emission, in which the heavy Cu4I4 cores serve as the efficient X/γ-PEA (photoelectric absorption) or NIR-TPA (two-photon absorption) trapper and convertor to photons in the visible spectrum from the same emissive triplet states as those produced by UV excitation. This all-in-one compound affords a highly integrated nanolab for understanding and exploiting a wide range of photophysical phenomena simultaneously and is further fabricated into fiber-coupled long-range, in situ cryogenic thermometer and poly(methyl methacrylate) (PMMA)-embedded monolith gel, providing access to advanced applications in multifunctional optical materials and devices.

[Resources and usage status of Tibetan medicinal plant "Bangga"].

The study is aimed to clarify the actual original plant, find out the usage status and the resource distribution of the Tibetan medicinal plant "Bangga". By using the way of the literatures survey, interview and investigation, it found out that the actual original plant of the Tibetan medicinal plant "Bangga" were the whole dried plant or the aerial part of Aconitum tanguticum or A. naviculare of Ranunculaceae, among which A. tanguticummainly distributed in Sichuan, Gansu, Qinghai, Tibet (Qamdo), and A. naviculare mainly distributed in Tibet. Sichuan, Gansu, Qinghai and other Tibetan areas mainly used the resources of A. tanguticum, Tibet (except the Qamdo area) mainly uses the A. naviculare, which resource was imminent in danger. Other species described in the literature were not used. It showed that the use of herbs related to their resources, it is recommended to strengthen the protection and guide the market.

Concomitant high expression of BRAFV600E, P-cadherin and cadherin 6 is associated with High TNM stage and lymph node metastasis in conventional papillary thyroid carcinoma.

CONTEXT AND OBJECTIVE: BRAFV600E mutation is the most common activating mutation associated with aggressive behaviours in human tumours including conventional papillary thyroid carcinoma (cPTC). P-cadherin and cadherin 6 have been shown to be mesenchymal-associated cadherins and promote cancer cell invasion and metastasis. The purpose of this study was to examine BRAFV600E, P-cadherin and cadherin 6 expressions in cPTC and to assess the association of their expression with clinicopathological indicators. METHODS: BRAFV600E, P-cadherin and cadherin 6 protein expressions in 80 cPTCs, 61 nodular hyperplasia and 76 normal thyroid tissues were examined by immunohistochemistry. The correlation of their protein expression with clinicopathological indicators of cPTC was statistically analysed. RESULTS: Protein expression of BRAFV600E, P-cadherin and cadherin 6 was upregulated in cPTC. High protein expression of BRAFV600E, P-cadherin and cadherin 6 was significantly correlated with high TNM stage and lymph node metastasis (LNM) (P < 0·001). Furthermore, BRAFV600E, P-cadherin and cadherin 6 protein expressions were correlated with one another. BRAFV600E high expression combined with both P-cadherin and cadherin-6 high expressions had stronger correlation with high TNM stage and LNM when compared with BRAFV600E high expression combined with either P-cadherin or cadherin-6 high expression (P = 0·042, 0·017 for TNM stage and P = 0·003, 0·006 for LNM, respectively) and only BRAFV600E high expression (P < 0·001 for both TNM stage and LNM). CONCLUSIONS: Concomitant high expression of BRAFV600E, P-cadherin and cadherin 6 is strongly associated with high TNM stage and LNM in cPTC.

[Discrimination of Honey Varieties Based on Amino Acid Derivative Fluorescence Method Combining with Multilinear Pattern Recognition].

Assessing the authenticity about the botanical and geographical origins of food is an important content for food safety research. Amino acids are the most important nutrients of honey. The types and contents of amino acids are different in various honey samples. Thus they can be used as one of the important parameters to discriminate the honey variety and quality. In this article, amino acids in honey were first derived with formaldehyde and acetyl acetone solution. In the following step, three-dimensional fluorescence spectrums combing with multidimensional pattern recognition methods were used to distinguish the kinds of honey. Five kinds of honey (total 150 honey samples) from different botanicals were studied in this research. Before fluorescence detection, the effect of the amount of derivation reagent, the time of reaction, temperature and pH to the derivation progress of honey samples were first studied. Research showed that the fluorescence intensity of derivatives of honey was the strongest when the amount of derivation reagent was 4.0 mL, the time of reaction being 2 h, pH being 4 and the temperature being 100 ℃. The derivatives of honey were then scanned with three-dimensional fluorescence spectrometry. The collection of fluorescence intensity values occurred within excitation-emission ranges of 300~500 and 380~580 nm. A 150×41×101 cube matrix data sets can be acquired. The three-dimensional fluorescence data sets were decomposed with multilinear pattern recognition methods, such as multilinear principal components analysis (M-PCA), self-weight alternative trilinear decomposition (SWATLD) and multilinear partial least squares discriminant analysis (N-PLS-DA) methods. All of these multilinear pattern recognition methods showed the clustering tendency for five different kinds of honey. Compared with the other two methods, N-PLS-DA got more accurate and reliable classification results because it made full use of all the fluorescence information of the derivative honey samples. Its total recognition rate reached 88%. The result is acceptable for the complexity of the honey samples. It showed this method could be applied to identify the varieties of honey. Compared with the chromatographic analysis method, this method is relatively simpler and more sensitivity. It avoided the chromatographic separation and reduced the consumption of organic solvent. Thus it can be regarded as a kind of relatively green honey classification method. This research will provide a new idea to directly fluorescence analyze for no or weak fluorescence natural substances.

Regression of fragmented QRS complex: a marker of electrical reverse remodeling in cardiac resynchronization therapy.

BACKGROUND: Fragmented QRS (fQRS) marks inhomogeneous activation and asynchronous cardiac contraction. It has been proved that cardiac resynchronization therapy (CRT) could reverse geometrical remodeling as well as correct electrical dyssynchrony. We aimed to investigate whether fQRS changed corresponding to the therapeutic response to CRT. METHODS: Patients who underwent de novo CRT implantation previously and had ≥1 follow-up between August 2012 and September 2013 in our hospital were investigated. Intrinsic electrocardiogram was recorded and fQRS in any lead was calculated. Response to CRT was defined as absolute improvement in left ventricular ejection fraction by ≥10% or by improvement >1 New York Heart Association class and without heart failure hospitalization. RESULTS: A total of 75 patients (48 male, mean ages, 61 ± 9 years) were included in this study. At a median follow-up of 13 months, 57 patients had response to CRT. Responders had narrowed QRS (from 167 ± 23 ms to 158 ± 19 ms, P = 0.003) and reduced fQRS post-CRT. Nonresponders had QRS prolonging (from 151 ± 26 ms to 168 ± 16 ms, P = 0.033) and increase in fQRS. Eleven of 12 patients with reduced fQRS were responders and 8 of 12 with increased fQRS were nonresponders. Both changes in QRS and fQRS correlated strongly with CRT response (r = 0.389, P = 0.001 and r = 0.403, P = 0.000, respectively). Reduction of fQRS in ≥1 leads had high specificity (95%) in association to responders, though in low sensitivity (19%). CONCLUSIONS: The changes in fQRS associated with therapeutic response to CRT. Regression of fQRS could be a maker of electrical reverse remodeling following CRT.

Follow-up Study of Retreatment TB Patients with Sputum Smear and/or Culture Positive Two Years after They were Declared Cured with First-line Anti-TB Drugs in Shandong Province.

This study aimed to learn the recurrence rate in the retreatment TB patients with sputum smear and/or culture positive (ss+ and/or c+) two years after they were declared cured, and to explore causes of recurrence in order to improve long-time treatment outcome. 5 cities were selected as research locations. Recurrence of TB was judged by chest X-ray examination together with sputum smear and culture examination. Questionnaire was carried out to collect data on treatment history, demographics and possible risk factors. Chi-square test and logistic regression were conducted using SPSS in this study. As the result, 99 active TB patients were identified and the recurrence rate was 16.67% and irregular medicine and smoking were the causes of the recurrence. The retreatment TB patients with sputum smear and/or culture positive in this study had higher recurrence rate and health education work on regular medication and smoking should be strengthened.

[Toxic effect of formaldehyde on mouse different brain regions].

The aim of this study was to explore the mechanism of the nervous system lesions induced by formaldehyde (FA). Male Balb/c mice were exposed to gaseous formaldehyde for 7 days (8 h/d) with three different concentrations (0, 0.5 and 3.0 mg/m(3)). A group of animals injected with the nitric oxide synthase inhibitor L-NMMA (0.01 mL/g) was also set and exposed to 3.0 mg/m(3) FA. The concentrations of cAMP, cGMP, NO and the activity of NOS in cerebral cortex, hippocampus and brain stem were determined by corresponding assay kits. The results showed that, compared with the control (0 mg/m(3) FA) group, the cAMP contents in cerebral cortex and brain stem were significantly increased in 0.5 mg/m(3) FA group (P < 0.05), but decreased in 3.0 mg/m(3) FA group (P < 0.05); The concentration of cAMP in hippocampus was significantly decreased in 3.0 mg/m(3) FA group (P < 0.05). In comparison with the control group, L-NMMA group showed unchanged cAMP contents and NOS activities in different brain regions, but showed increased cGMP contents in hippocampus and NO contents in cerebral cortex (P < 0.05). In addition, compared with 3.0 mg/m(3) FA group, L-NMMA group showed increased contents of cAMP and reduced NOS activities in different brain regions, as well as significantly decreased cGMP contents in cerebral cortex and brain stem and NO content in brain stem. These results suggest that the toxicity of FA on mouse nervous system is related to NO/cGMP and cAMP signaling pathways.

Heterojunction of ZnO nanoparticle/PMMA and its ultraviolet electroluminescence.

A ZnO nanoparticle layer was synthesized by the sol-gel method on ITO glass. Devices with a ZnO nanoparticle layer/polymethylmethacrylate (PMMA) heterojunction structure were then fabricated and the room temperature electroluminescence (EL) spectra were studied. Under DC bias, ultraviolet (UV) EL at 390 nm from the ZnO band edge emission was observed, and defect-related emission of ZnO at 600 and 760 nm were also detected. The EL mechanisms are discussed in terms of the carrier tunneling process.

Association of body mass index with cardiac reverse remodeling and long-term outcome in advanced heart failure patients with cardiac resynchronization therapy.

BACKGROUND: The effect of adiposity on response to cardiac resynchronization therapy (CRT) and long-term outcome in patients undergoing CRT has not been previously reported. This study assessed the impact of baseline body mass index (BMI) on cardiac reverse remodeling and prognosis following CRT. METHODS AND RESULTS: A total of 247 CRT patients were included and divided into 4 groups according to baseline BMI. During 6-month follow-up, overweight and obese patients (BMI, 24-28 kg/m(2), ≥28 kg/m(2), respectively) were inclined to have better clinical and echocardiographic improvements (P<0.05) as well as higher response rate (P<0.001) than underweight and normal weight patients (BMI, <18.5 kg/m(2), 18.5-24 kg/m(2), respectively). During long-term follow-up, overweight and obese patients had lower all-cause mortality (P=0.015) and combined endpoint of death or HF hospitalizations (P=0.001) than underweight and normal weight patients. Compared with normal weight patients, underweight patients had a 2.29-fold increase in risk of combined endpoint events whereas overweight and obese patients had a reduction in the risk of death (66% and 58%, respectively) and combined endpoint events (52% and 38%, respectively). CONCLUSIONS: Patients with obesity and overweight derived more benefit from CRT. Higher BMI was independently associated with better clinical outcome in CRT patients.

Achieving a new controllable male contraception by the photothermal effect of gold nanorods.

During the process of human civilization, owning household pets has become increasingly popular. However, dogs and cats may be reservoirs or vectors of transmissible diseases to humans. Confronted with the overpopulation of pets, traditional contraception methods, surgical methods of sterilization, for animals are used, namely, ovariohysterectomy and orchidectomy. Therefore, a simple, nonsurgical, controllable, more effective and less expensive contraception method is highly desirable. In this study, we show that in situ testicular injection of methoxy poly(ethylene glycol)-modified gold nanorods with near-infrared irradiation in male mice can achieve short-lived or permanent male infertility. In a lower hyperthermia treatment, the morphology of testes and seminiferous tubules is only partly injured, and fertility indices are decreased to 10% at day 7, then recovered to 50% at day 60. In a higher hyperthermia treatment, the morphology of testes and seminiferous tubules are totally destroyed, and fertility indices are decreased to 0 at day 7. Overall, our results indicate a potential application of plasmonic nanomaterials for male contraception.

[Discussing the basic ecological relations of sand dune vegetation process]. / è®ºæ²™ä¸˜æ¤è¢«è¿‡ç¨‹çš„åŸºæœ¬ç”Ÿæ€å ³ç³».

Dune is often considered as a degraded ecosystem. Natural vegetation restoration and stable artificial vegetation construction are the basic means restoring dune ecosystem. Based on long-term study of dune ecosystem, by taking into consideration both the philosophical principles of unity of opposites and dynamic change, and related ecological theories, we put forward some ecological relations that should be paid attention to in the study of vegetation assembly from the perspective of the uniqueness of dune ecosystem. We discussed the necessity of coupling relationships of scale-pattern-process and the transformation of synergy-tradeoff relationships, interpreted the importance of distinguishing sand dune stabilized and shifting phases, disturbance and stress, wind erosion and sand burial in the study of vegetation process. We further explored the applied value of niche law or neutral law in the study of dune vegetation process. Finally, we discussed the issues that should be paid attention to in the study of dune vegetation process from the aspects of adaptability to aeolian activities and drought tolerance, physiological and reproductive process, sexual and asexual reproduction of plants. This study would provide theoretical supports for vegetation restoration and stable vegetation construction of dune ecosystem.

[Shelterbelt construction in the scenario of coordinated development of mountain, river, forest, farmland, lake, grassland, and sandy land ecosystems in semi-arid wind-sand areas: Principles and methods]. / 半干旱风沙区"山水林田湖草沙"建设中防护林营建的原理与方法.

We established the systematic concept framework of shelterbelt construction, with "shelterbelts" as the core concern in the construction of integrated ecosystems including mountain, river, forest, farmland, lake, grassland and sandy-land in semi-arid wind-sand areas. In the construction of shelterbelts, it is necessary to adhere to the principles of scientific coordination and systematic management, considering the carrying capacity of water resources, the demand for dust control, the greening and beautification effects, as well as the principle of improving economic benefits. In practice, the construction methods should base on the types and temporal-spatial distribution of shelterbelts, following the shelterbelts construction theory and technology to form different structure and service functions, achieving the functional goals of shelterbelts. By focusing on the key elements including people, forests, grass, fields, water, and sand, we put forward the timeliness, practicality, and scientificity of shelterbelt construction, proposing construction methods for farmland shelterbelts, pastureland shelterbelts, windbreak and sand-fixing forests and protective forest around village (city), which might provide production technical support for the high-quality construction of green ecological barrier in northern China.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .