Cinnamomi Ramulus and Alismatis Rhizoma are commonly used in the treatment of external-contraction diseases. Cinnamomi Ramulus is pungent， sweet， and warm， with the effects of ventilating lung and dispersing cold， warming Yang and transforming Qi， and promoting water and liquid flow from Taiyang meridian to remove dampness. Alismatis Rhizoma is sweet and cold， with the effects of draining dampness and promoting urination， regulating the waterway， removing water retention in lung， and promoting urination to remove dampness and heat. Herbal pairs are extracted from the accumulated experience of medical practitioners over the ages in the use of medicines and have been proved by clinical application to be composed of simple and effective combinations for specific diseases. The herb pair Cinnamomi Ramulus-Alismatis Rhizoma is an important part in ancient classic formulas such as Wulingsan. Both herbs play a role in draining dampness and promoting urination， warming Yang and transforming Qi， being a representative herb pair used for treating external-contraction exterior syndrome and water retention inside. The review of ancient medical publications revealed that there were a large number of compound formulas containing Cinnamomi Ramulus-Alismatis Rhizoma for dispersing cold and removing dampness， which were widely used for thousands of years in clinical practice. Modern pharmacological studies have shown that the active pharmacological components of Cinnamomi Ramulus （cinnamaldehyde and cinnamic acid） and Alismatis Rhizoma （alisol A and 23-acetate alisol B） have anti-inflammatory， antiviral， and immunoregulatory effects and high safety. Qingfei Paidu decoction containing this herbal pair played an important role in fighting against COVID-19. Despite the extensive pharmacological studies on Cinnamomi Ramulus and Alismatis Rhizoma， few studies have been carried out regarding this herb pair. This paper summarizes the traditional Chinese medicine knowledge about Cinnamomi Ramulus and Alismatis Rhizoma in the treatment of external-contraction diseases and summarizes the chemical composition， pharmacological effects， toxicology and other aspects of the two herbs before and after compatibility， aiming to provide a reference for further research and clinical application.

Objective:To explore the compatibility and medication law of Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair in ancient and modern prescriptions.Methods:Ancient prescriptions and Chinese patent medicines containing Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were retrieved from the database of ancient classic famous prescriptions 1.0 and the database of listed Chinese patent medicines 1.0 developed by the Institute of Information on Traditional Chinese Medicine, China Academy of Chinese Medical Sciences. Excel 2019 was used to establish a database. The ancient and modern medical record cloud platform V2.3.5 and SPSS Modeler 18.0 software were used to perform frequency statistics, association rule analysis, clustering analysis, etc. on the data.Results:Totally 79 ancient articles with Cinnamomi Ramulus-Alismatis Rhizoma medicinal pair were obtained, including 76 ancient prescriptions, involving 250 kinds of Chinese materia medica; 25 kinds of Chinese patent medicine were obtained, involving 186 kinds of Chinese materia medica. The drug properties of ancient prescriptions and modern TCM patent medicines were both mainly warm, cold and neutral. The main tastes of ancient prescriptions and modern Chinese patent medicines were pungent, sweet and bitter. And the drugs mainly belong to spleen, lung, liver and kidney meridians. Correlation analysis suggested the same high-frequency association compatibility of ancient and modern prescriptions, Poria-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma, Atractylodis Macrocephalae Rhizoma-Cinnamomi Ramulus-Alismatis Rhizoma. Both clinical symptoms and diseases associated with medicinal compatibility of ancient prescriptions were intestinal flora, edema and vomiting. The syndrome types included bladder impoundment, dampness trapped in the guardian surface, internal retention of phlegm and morbid fluid. The clinical symptoms associated with medicinal compatibility of modern TCM patent medicine were limb joints pain and edema. The diseases included rheumatic arthritis (RA) and kidney disease. The syndrome types included wind-cold-dampness RA, stagnation of collaterals and kidney yang deficiency. High frequency drug clustering yielded 4 clustered squares.Conclusion:The core indications treated by Cinnamomi Ramulus-Alismatis Rhizoma are exogenous diseases with dampness caused by syndrome types including internal storage of water-dampness, cold-dampness obstruction and so on, which can provide reference for further in-depth research and guidance on clinical medication.

As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.

Objective:To explore the predictive value of multi-slice spiral CT (MSCT) arterial enhancement fraction (AEF) in the risk degree of gastrointestinal stromal tumors (GIST).Methods:The clinical data of 178 patients with GIST in Shanxi Province Cancer Hospital from January 2013 to May 2021 were retrospectively analyzed. According to tumor size, primary site, mitotic figure and whether the tumor was ruptured or not, the patients were divided into extremely low risk group (24 cases), low risk group (44 cases), medium risk group (48 cases), and high risk group (62 cases). One-way ANOVA was used to compare MSCT AEF value and conventional plain and enhanced scan values among the 4 groups. The receiver operating characteristics (ROC) curve was drawn to assess the predictive efficacy of AEF value, conventional plain value, enhanced scan value, Ki-67 and AEF value combined with Ki-67 for high-risk GIST.Results:Except for CT value in the venous phase and CT value in added arterial phase, the comparison of AEF value, plain scan CT value, arterial phase CT value, and added venous phase CT value of GIST patients in the 4 groups showed statistically significant differences (all P < 0.05). In the predictive efficacy evaluation of high-risk GIST, the area under the curve (AUC) of the ROC curve for AEF value was 0.753, which was higher than that for plain scan CT value (0.593), arterial phase CT value (0.592) and added venous phase CT value (0.631), lower than AEF combined with Ki-67 (0.799). Kappa consistency test showed that the AEF value, plain scan CT value and arterial phase CT value were consistent with the pathological examination results (Kappa values were 0.375, 0.168 and 0.168, respectively), however, the added venous phase CT value was inconsistent with the pathological examination results (Kappa = -0.224). The AUC of AEF value combined with Ki-67 for predicting high-risk GIST was 0.799, and the Kappar value was 0.528. Conclusions:MSCT AEF value varies in GIST with different risk degree, and its preoperative efficacy in predicting high-risk GIST is superior to that of conventional plain scan and enhanced scan; especially the combination of AEF value with Ki-67 shows a higher predictive efficacy.

Objective:To explore the elements of the diversified caring bank based on long-term care insurance system to provide a basis for the construction of diversified caring bank framework system.Methods:The phenomenological research method was adopted to conduct semi-structured interviews with 15 nursing management personnel in pension institutions in Suzhou and Suzhou long-term care insurance policy implementation management personnel in March to May 2021. NVivo 11 was used to manage interview data, and applied Colaizzi 7-step analysis to conduct inductive analysis and extract the themes.Results:The elements of the diversified caring bank based on long-term care insurance system were divided into three main modules: diversified caring personnel, diversified caring content and diversified incentive measures. The diversified caring personnel module included full-time and part-time caring personnel. Diversified caring content included six elements: daily life assistance, professional life caring, professional medical caring, communication and emotional support, emergency caring and special disease caring. Diversified incentive measures module included two elements: labor currency and "benefit" care currency.Conclusions:The diversified caring personnel provides continuous power for disabled caring; diversified caring content provides ways to meet the various needs of the disabled elderly; diverse incentives are effective ways to attract and stabilize the caring workforce.

Yuebawei refers to 8 kinds of genuine medicinal materials in south China area，namely Citri Grandis Exocarpium， Citrus reticulata， Amomum villosum， Pogostemon cablin， Morinda officinalis， Aquilaria sinensis， Citrus medica and Polygonum multiflorum. The results of this review show that， the pharmacological effects of Yuebawei are very extensive. It has significant effects in relieving cough and phlegm， anti-bacterial and anti-inflammatory， enhancing immunity， anti-oxidation， antidepressant， immune regulation and regulating gastrointestinal function. Its development and application prospects are broad， but most of the existing pharmacological studies stay on pharmacodynamic studies. In the aspect of the safety research of Yuebawei， there are few studies on the safety of other medicinal materials， except for the liver toxicity of P. multiflorum； at the same time， there are few comparative studies on the therapeutic advantages of Yuebawei and other local medicinal materials in clinical application. It is necessary to strengthen the research on the material basis of pharmacological action mechanism， and safety and efficacy observation of clinical medication for Yuebawei， so as to provide scientific basis for the development of new drugs and clinical promotion and application of Yuebawei.

Bivalves are species-rich mollusks with prominent protective roles in coastal ecosystems.Across these ancient lineages,colony-founding larvae anchor themselves either by byssus produc-tion or by cemented attachment.The latter mode of sessile life is strongly molded by left-right shell asymmetry during larval development of Ostreoida oysters such as Crassostrea hongkongensis.Here,we sequenced the genome of C.hongkongensis in high resolution and compared it to reference bivalve genomes to unveil genomic determinants driving cemented attachment and shell asymmetry.Importantly,loss of the homeobox gene Antennapedia(Antp)and broad expansion of lineage-specific extracellular gene families are implicated in a shift from byssal to cemented attachment in bivalves.Comparative transcriptomic analysis shows a conspicuous divergence between left-right asymmetrical C.hongkongensis and symmetrical Pinctada fucata in their expression profiles.Especially,a couple of orthologous transcription factor genes and lineage-specific shell-related gene families including that encoding tyrosinases are elevated,and may cooperatively govern asymmet-rical shell formation in Ostreoida oysters.

Objective:To study the efficacy and safety of Methazolamide(MTZ)for the treatment of normal pressure hydrocephalus(NPH)patients.Methods:A randomized, double-blind, placebo-controlled, prospective clinical study was conducted in Aviation General Hospital.A total of 35 NPH patients including 29 idiopathic normal pressure hydrocephalus(iNPH)and 6 secondary normal pressure hydrocephalus(sNPH)received drug treatment in our hospital from September 2019 to March 2021.All patients were unsuitable for or refused surgical treatment for some reasons.The patients were divided into drug group(n=18)and control group(n=10), taking oral MTZ or placebo 25 mg twice daily, increasing to 50 mg twice daily after 1 week if there was no discomfort.The 10 m gait score, cognitive function score, brain MRI check were completed before and 1 month after oral administration.The assessment of idiopathic normal pressure hydrocephalus scale(iNPHGS)score were performed 1 month and 3 months after oral administration.The primary efficacy endpoint was iNPHGS score for 3 months treatment and the secondary efficacy endpoint was the assessment of above scales for 1 month treatment.Results:As compared with baseline, the effect of 1 month treatment showed that MOCA scores[(16.2±8.8)and(14.8±8.7)scores, t=-2.68, P=0.02], 10 m gait scores[(22.3±11.2)and(25.6±12.9), t=2.76, P=0.02], iNPHGS scores[(7.3±3.2)and(8.1±3.5), t=4.08, P<0.01]were improved.The effect of 3 month treatment showed that the iNPHGS score(6.1±2.4)was improved compared with baseline( t=5.07, P<0.01)and 1 month( t=4.11, P<0.01). But the above scores of the control group were not significantly improved compared with the baseline(all P>0.05). After 1 month treatment, the 10 m gait score and iNPHGS score in the drug group were improved compared with those in the control group(all P<0.05). After 3 months treatment, the iNPHGS score was improved compared with the baseline level in the control group( t=-4.41, P<0.05). The above 35 patients had no serious adverse reactions such as hypokalemia and acidosis.There was no significant difference in adverse events between the two groups( χ2=0.01, P=1.00). Conclusions:The treatment of MTZ could effectively improve the clinical symptoms of NPH patients with good safety.

Pentostatin is a nucleoside antibiotics with a strong inhibitory effect on adenosine deaminase, and is widely used in the clinical treatment of malignant tumors. However, the high cost hampers its application. In the past 10 years, the biosynthesis of pentostatin were focused on strain breeding, optimization of medium composition and fermentation process. To date, there are no reviews summarizing the elucidated biosynthetic mechanism of pentostatin. This review starts by introducing the various chemical route for production of pentostatin, followed by summarizing the mechanisms of pentostatin biosynthesis in different microorganisms. Finally, challenges for biosynthesis of pentostatin were discussed, and strategies for regulating and improving the microbial synthesis of pentostatin were proposed.
Anti-Bacterial Agents ; Pentostatin

OBJECTIVE: To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock variant mice modeling bipolar disorder manic disorder. METHODS: Open field test and Elevated plus-maze test were carried out on the Clock mutant and wild-type control groups. The frontal lobe and hippocampus of Clock mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0. RESULTS: The Clock mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes. The reduced glutamine in the left frontal lobe and GABA in the right hippocampus correlated with the increased activity of Clock mutant mice. CONCLUSION Clock mutant mice showed abnormal behavior with increased activity. Reduced glutamine in the left frontal lobe and GABA in the right hippocampus were correlated with increased activity.