Objective To evaluate the effects of the project of ditching for drain on Oncomelania hupensis snail control and flood prevention security and explore the optimal engineering design plan in Dongting Lake region. Methods A retrospective study was performed on the previous studies about the project of ditching for drain. The reference values of project indices were determined. The outside levee of Nanhu New Distinct of Yueyang City in Dongting Lake region was selected as the study area , and the cross section of marshland perpendicular to the center line of the levee was extracted to research. According to the situa?tions of various water levels,a dynamic simulation was performed on the effect and security of the project of ditching for drain through the software FLAC3D. Results The retrospective study showed that the project would be effective when the relatively subsoil water level decreased by 0.35 m,and the soil water content decreased correspondingly. The dynamic simulation by FLAC3D showed that the minimum safe distances between transverse ditch 1,vertical ditch and levee toe should be 25 m and 13 m respectively. The digging depth of transverse ditch and vertical ditch should be 1.2 m and 1.0 m respectively. If the width of marshland in drought period was less than 500 m,one transverse ditch was efficient. Otherwise,more transverse ditches should be set with the intervals of 300 m. Conclusions The project of ditching for drain is an effective ecological snail elimination method. Optimizing the digging depth of ditches and distances between transverse ditches,vertical ditch and levee toe will en?sure the effects and security of the project.

Objective To investigate the clinical efficacy of endoscopic surgery for extensive osteoradionecrosis (ORN) of skull base in patients with nasopharyngeal carcinoma (NPC) after radiotherapy.Methods Seventeen patients diagnosed as ORN of skull base after radiotherapy for NPC and underwent endoscopic surgery were retrospectively studied with their clinic data.Results Based on the CT and endoscopic examination,all patients had large skull base defects with bone defects averaged 7.02 cm2 (range,3.60-14.19 cm2).Excepting for curetting the sequestra,endoscopic surgery was also used to repair the wound or to protect the internal carotid artery with flap in 12 patients.No bone reconstructions were conducted in all patients with the bone defects of skull base.CT examinations were taken after endoscopic surgery when required.The postoperative follow-up ranged from 8 months to 6 years (average,14 months).Aside from 1 patient with delayed cerebrospinal fluid (CSF),others had no related complications.Conclusions The patients with extensive ORN can be treated with endoscopic surgery to curette the necrotic bone of skull base,and endoscopic reconstruction provides an alternative technique.It may not be necessary to reconstruct the bone defects at skull base,however,the exposed important structures of skull base,such as internal carotid artery,need to repair with soft tissue such as flap.

Immune checkpoint inhibitors （ICIs） have shown good efficacy in tumor treatment and have changed the landscape of tumor treatment. However， some patients treated with ICIs have not only failed to achieve the desired therapeutic effect， but also developed an atypical response pattern of abnormally accelerated tumor growth， namely hyperprogressive disease （HPD）. The pathogenesis of HPD is still unclear and it is difficult to diagnose， which poses a challenge for clinical identification and treatment decisions. Exploring the underlying mechanism of HPD is important to improve the effect of immunotherapy. Based on the theory of "Yang deficiency and toxic knot"， this paper discussed the mechanism of HPD in immunotherapy from the perspective of "spleen and kidney Yang deficiency and hefty toxic pathogens". It was concluded that the inactivation of p53 oncogene and immunosuppressive microenvironment were the manifestations of the deficiency of healthy qi in the body and declined yang in the spleen and kidney， serving as an important basis for the occurrence of HPD. Adverse reactions caused by ICIs belong to the category of "drug toxicity". The occurrence and development of murine double minute 2 （MDM2）/murine double minute 4 （MDM4） activation， epidermal growth factor receptor （EGFR） mutation， and tumor inflammatory microenvironment are the manifestations of the hyperactivity of pathogenic Qi， conflict of cancer toxicity and drug toxicity， and being hefty by virtue of deficiency， which can promote the abnormal proliferation of tumor cells， and they are the core pathogenic elements of HPD and are closely related to disease prognosis. In terms of treatment， under the guidance of the theory of "five views on differentiation and treatment" （time-space view， core view， symptom view， precision view， and disease-before-onset view）， which was summarized according to the clinical practice of this research team， this paper， taking the prevention and treatment of HPD as the entry point， formulated traditional Chinese medicine （TCM） compounds to reinforce healthy Qi and warm Yang and realize the dynamic management of the whole spatiotemporal cycle， and removed toxins and resisted cancer to realize the all-round systemic intervention of the specimen. Additionally， targets were enriched in the macro-clinical manifestations and microscopic pathological changes of HPD to improve the targeting of drug selection and the precision of prevention and treatment， giving full play to the unique therapeutic advantages of TCM， and providing new ideas for the clinical application of TCM in the prevention and treatment of HPD.

As an important concept in Chinese medicine theory， "qi sinking" is the inheritance and extension of the thought core of sinking of qi in whole body. This article explored the concept of sinking of pectoral qi， center qi， and kidney qi in the theory of qi sinking， and believed that sinking of pectoral qi， stagnation and sinking of center qi， deficiency and sinking of kidney qi were the core pathogenesis of postoperative injury in malignant tumours. Anchored to the method of reinforcing healthy qi and lifting the sunken， this article recommended to identify pattern and treat by guiding supplement and lifting the sunken. For lung gold impairment， heart yang depletion， and pectoral qi sinking， the treatment is to warm and supplement heart and lung， lift pectoral qi， and restore the respiratory function by modified Shengxian Decoction （升陷汤） plus Guizhi Decoction （桂枝汤）； for spleen depletion and pathways blockage， liver failing to act freely， and center qi stagnation and sinking， the treatment is to warm and supplement center qi， raise yang and lift the sunken， and restore the digestive function by modified Buzhong Yiqi Decoction （补中益气汤）； for source exhausted and essence deficiency， liver qi hiding， and kidney qi deficiency to inward invasion， the treatment is to nourish the kidney and astringe the liver， consolidate the original qi and lift qi， improve the pelvic floor dysfunction， and protect the kidney function by modified Liuwei Dihuang Pill （六味地黄丸） plus Shengma Chaihu Decoction （升麻柴胡汤）. Modification need base on different disease patterns and stages， and new ideas for postoperative traditional Chinese medicine treatment and rehabilitation of malignant tumours were provided.

Coding regions have complex interactions among multiple selective forces, which are manifested as biases in nucleotide composition. Previous studies have revealed a decreasing GC gradient from the 5′-end to 3′-end of coding regions in various organisms. We confirmed that this gradient is universal in eukaryotic genes, but the decrease only starts from the～25th codon. This trend is mostly found in nonsynonymous (ns) sites at which the GC gradient is universal across the eukaryotic genome. Increased GC contents at ns sites result in cheaper amino acids, indicating a universal selection for energy efficiency toward the N-termini of encoded proteins. Within a genome, the decreasing GC gradient is intensified from lowly to highly expressed genes (more and more protein products), further supporting this hypothesis. This reveals a conserved selective constraint for cheaper amino acids at the translation start that drives the increased GC contents at ns sites. Elevated GC contents can facilitate transcription but result in a more stable local secondary structure around the start codon and subsequently impede translation initiation. Conversely, the GC gradients at four-fold and two-fold synonymous sites vary across species. They could decrease or increase, suggesting different constraints acting at the GC contents of different codon sites in different species. This study reveals that the overall GC contents at the translation start are consequences of complex interactions among several major biological processes that shape the nucleotide sequences, especially efficient energy usage.

We present GranatumX, a next-generation software environment for single-cell RNA sequencing (scRNA-seq) data analysis. GranatumX is inspired by the interactive webtool Granatum. GranatumX enables biologists to access the latest scRNA-seq bioinformatics methods in a web-based graphical environment. It also offers software developers the opportunity to rapidly promote their own tools with others in customizable pipelines. The architecture of GranatumX allows for easy inclusion of plugin modules, named Gboxes, which wrap around bioinformatics tools written in various programming languages and on various platforms. GranatumX can be run on the cloud or private servers and generate reproducible results. It is a community-engaging, flexible, and evolving software ecosystem for scRNA-seq analysis, connecting developers with bench scientists. GranatumX is freely accessible at http://garmiregroup.org/granatumx/app.

An effective therapeutic regimen for hepatic fibrosis requires a deep understanding of the pathogenesis mechanism. Hepatic fibrosis is characterized by activated hepatic stellate cells (aHSCs) with an excessive production of extracellular matrix. Although promoted activation of HSCs by M2 macrophages has been demonstrated, the molecular mechanism involved remains ambiguous. Herein, we propose that the vitamin D receptor (VDR) involved in macrophage polarization may regulate the communication between macrophages and HSCs by changing the functions of exosomes. We confirm that activating the VDR can inhibit the effect of M2 macrophages on HSC activation. The exosomes derived from M2 macrophages can promote HSC activation, while stimulating VDR alters the protein profiles and reverses their roles in M2 macrophage exosomes. Smooth muscle cell-associated protein 5 (SMAP-5) was found to be the key effector protein in promoting HSC activation by regulating autophagy flux. Building on these results, we show that a combined treatment of a VDR agonist and a macrophage-targeted exosomal secretion inhibitor achieves an excellent anti-hepatic fibrosis effect. In this study, we aim to elucidate the association between VDR and macrophages in HSC activation. The results contribute to our understanding of the pathogenesis mechanism of hepatic fibrosis, and provide potential therapeutic targets for its treatment.
Humans ; Hepatic Stellate Cells/pathology* ; Receptors, Calcitriol ; Liver Cirrhosis/pathology* ; Macrophages/metabolism*