ObjectiveTo study the pharmacological substances and mechanisms through which sesquiterpene ZH-13 from Aquilariae Lignum Resinatum improves neuroinflammation. MethodsBV-2 microglial cells were stimulated with lipopolysaccharide （LPS） to induce neuroinflammation. The cells were divided into the normal group， the model group， and the ZH-13 low- and high-dose treatment groups （10， 20 μmol·L^-1）. The model group was treated with 1 μmol·L^-1 LPS. Cell viability was assessed using the cell proliferation and activity assay （CCK-8 kit）. Nitric oxide （NO） release in the cell supernatant was measured using a nitric oxide kit （Griess method）. The mRNA expression levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， inducible nitric oxide synthase （iNOS）， and interleukin-6 （IL-6） were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The phosphorylation of mitogen-activated protein kinase （MAPK） pathway proteins was assessed by Western blot. ResultsCompared with the model group， ZH-13 dose-dependently reduced NO release from BV-2 cells under LPS stimulation （P<0.05， P<0.01）. In the 20 μmol·L^-1 ZH-13 treatment group， the mRNA expression levels of IL-1β， TNF-α， iNOS， and IL-6 were significantly reduced compared to the model group （P<0.05， P<0.01）. In both the low- and high-dose ZH-13 groups， the expression of the inflammatory factor TNF-α and the phosphorylation of c-Jun N-terminal kinase （JNK） in the upstream MAPK pathway were significantly reduced （P<0.05）. After stimulation with the JNK agonist anisomycin （Ani）， both low- and high-dose ZH-13 treatment groups showed reduced phosphorylation of JNK proteins compared to the Ani-treated group （P<0.01）. ConclusionThe sesquiterpene compound ZH-13 from Aquilariae Lignum Resinatum significantly ameliorates LPS-induced neuroinflammatory responses in BV-2 cells by inhibiting excessive JNK phosphorylation and reducing TNF-α expression. These findings elucidate the pharmacological substances and mechanisms underlying the sedative and calming effects of Aquilariae Lignum Resinatum.

Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

AIM: To prepare a novel functionalized upconversion nanomaterial UCNPs-PEG-Tf through an improved method and observe its specific imaging phenomenon to choroidal melanoma cells(OCM-1).METHODS: NaYF4:Yb/Er(Up-conversion nanoparticles, UCNPs)was Prepared and plasma was treated to carboxylate the surface; then amino polyethylene glycol and transferrin(Tf)were respectively loaded to prepare UCNPs-PEG-Tf. Characterized them accordingly, its biocompatibility was tested accordingly, and the specific fluorescence phenomenon of OCM-1 was detected by fluorescence spectrophotometer and inverted fluorescence microscopy.RESULTS: Characterization confirmed successful synthesis of UCNPs, UCNPs-PEG, and further loading of Tf to form UCNPs-PEG-Tf. UCNPs-PEG-Tf showed excellent biocompatibility and emitted significant green fluorescence. Under the same conditions, fluorescence intensity measurement and observations from the inverted fluorescence microscope both demonstrated its significant specificity in imaging to OCM-1 cells.CONCLUSION: The synthesized novel functionalized UCNPs-PEG-Tf nanocomposite showed good biocompatibility and achieve specific imaging to OCM-1 cells.

ObjectiveTo establish a model that can quickly identify the aroma components in different parts of Nardostachys jatamansi， so as to provide a quality control basis for the market circulation and clinical use of N. jatamansi. MethodsHeadspace solid-phase microextraction-gas chromatography-mass spectrometry（HS-SPME-GC-MS） combined with Smart aroma database and National Institute of Standards and Technology（NIST） database were used to characterize the aroma components in different parts of N. jatamansi， and the aroma components were quantified according to relative response factor（RRF） and three internal standards， and the markers of aroma differences in different parts of N. jatamansi were identified by orthogonal partial least squares-discriminant analysis（OPLS-DA） and cluster thermal analysis based on variable importance in the projection（VIP） value >1 and P<0.01. The odor data of different parts of N. jatamansi were collected by Heracles Ⅱ Neo ultra-fast gas phase electronic nose， and the correlation between compound types of aroma components collected by the ultra-fast gas phase electronic nose and the detection results of HS-SPME-GC-MS was investigated by drawing odor fingerprints and odor response radargrams. Chromatographic peak information with distinguishing ability≥0.700 and peak area≥200 was selected as sensor data， and the rapid identification model of different parts of N. jatamansi was established by principal component analysis（PCA）， discriminant factor alysis（DFA）， soft independent modeling of class analogies（SIMCA） and statistical quality control analysis（SQCA）. ResultsThe HS-SPME-GC-MS results showed that there were 28 common components in the underground and aboveground parts of N. jatamansi， of which 22 could be quantified and 12 significantly different components were screened out. Among these 12 components， the contents of five components（ethyl isovalerate， 2-pentylfuran， benzyl alcohol， nonanal and glacial acetic acid，） in the aboveground part of N. jatamansi were significantly higher than those in the underground part（P<0.01）， the contents of β-ionone， patchouli alcohol， α-caryophyllene， linalyl butyrate， valencene， 1，8-cineole and p-cymene in the underground part of N. jatamansi were significantly higher than those in the aboveground part（P<0.01）. Heracles Ⅱ Neo electronic nose results showed that the PCA discrimination index of the underground and aboveground parts of N. jatamansi was 82， and the contribution rates of the principal component factors were 99.94% and 99.89% when 2 and 3 principal components were extracted， respectively. The contribution rate of the discriminant factor 1 of the DFA model constructed on the basis of PCA was 100%， the validation score of the SIMCA model for discrimination of the two parts was 99， and SQCA could clearly distinguish different parts of N. jatamansi. ConclusionHS-SPME-GC-MS can clarify the differential markers of underground and aboveground parts of N. jatamansi. The four analytical models provided by Heracles Ⅱ Neo electronic nose（PCA， DFA， SIMCA and SQCA） can realize the rapid identification of different parts of N. jatamansi. Combining the two results， it is speculated that terpenes and carboxylic acids may be the main factors contributing to the difference in aroma between the underground and aboveground parts of N. jatamansi.

ObjectiveThis study employed the scoping review method to systematically retrieve and analyze the basic information and clinical research evidence of expensive Chinese patent medicines （CPMs）， aiming to provide a basis for future related research and clinical applications. MethodsEight Chinese and English databases were systematically searched for the clinical research evidence on expensive CPMs. ResultsEleven expensive CPMs （Angong Niuhuang Wan， Jufang Zhibao Wan， Suhexiang Wan， Pien Tze Huang， Niuhuang Qingxin Wan， Qinggong Shoutao Wan， Compound Realgar Natural Indigo Tablets， Xihuang Wan， Dingkun Wan， Babao Wan， and Guilingji Capsules） were selected. A total of 365 related studies were included in this review， comprising 331 clinical studies （of which 291 were randomized controlled trials）， 30 systematic reviews and Meta-analyses， 3 expert consensus， and 1 rapid health technology assessment. Among the 11 CPMs， 2（Angong Niuhuang Wan and Jufang Zhibao Wan） had a daily price over 500 yuan. The famous and precious Chinese medicinal materials involved included Moschus （frequency of 7）， Bovisc Alculus （7）， and Borneol （5）. The dosage forms included pills， capsules， oral liquid， tablets， and lozenges. The diseases treated by these CPMs mainly included malignant tumors， cerebrovascular diseases， gynecological diseases， and hepatobiliary system diseases. The sample sizes of the clinical studies were mainly concentrated within the range of 51-100 cases， and the main control form was CPM + basic Western medicine treatment vs. basic Western medicine treatment. The 331 clinical studies reported a total of 44 adverse events occurred， of which 36 were determined to be adverse reactions. ConclusionThe scarcity of raw materials leads to the high prices of expensive CPMs. The difficulty of conducting clinical research and the critical and severe cases treated lead to a lack of clinical research evidence with large sample sizes. The uneven distribution of existing studies， incomplete information on medicine package， and non-standard clinical research designs remain to be addressed in the future.

ObjectiveTo explore the mechanism of Yishen Huashi granules in alleviating renal tubular epithelial cell injury and relieving diabetic kidney disease by regulating the mitogen-activated protein kinase （MAPK） signaling pathway. MethodsThe db/db mice of 12 weeks old were randomly assigned into model ， dapagliflozin （1.6 mg·kg^-1）， and Yishen Huashi granules （4.7 g·kg^-1）， and db/m mice were used as the control group. The general conditions of mice were observed， and fasting blood glucose and 24-h urinary protein and albumin-to-creatinine ratio （ACR） were measured at weeks 0 and 12 of administration. After 12 weeks of treatment， the levels of serum creatinine （SCr）， blood urea （UREA）， triglycerides （TG）， total cholesterol （TC）， and low density lipoprotein （LDL） were measured. The pathological changes in the renal tissue were observed by hematoxylin-eosin （HE） staining， Periodic acid-Schiff （PAS） staining， Mallory staining， and transmission electron microscopy. Real-time PCR was employed to determine the mRNA levels of monocyte chemotactic protein-1 （MCP-1） and CC chemokine receptor-2 （CCR2） in the renal tissue of mice. The immunohistochemical assay was employed to examine the expression of p38， phospho-p38 （p-p38）， MCP-1， and CCR2 in the renal tissue of mice. Western blotting was employed to measure the protein levels of p-p38， p38， MCP-1， and CCR2 in the renal tissue of mice.HK-2 cells cultured in vitro were grouped as follows： negative control， high glucose（30 mmol·L^-1）， Yishen Huashi granule-containing serum， and SB203580. After 48 h of cell culture in each group， RNA were extracted and the levels of MCP-1， and CCR2 mRNA were determined by Real-time PCR，proteins were extracted and the levels of p38， p-p38， MCP-1， and CCR2 were determined by Western blot. ResultsThe in vivo experiments showed that before treatment， other groups had higher body weight， blood glucose level， 24 h urinary protein， and ACR than the control group （P<0.05，P<0.01）. After 12 weeks of treatment， compared with the model group， the Yishen Huashi granules group showed improved general conditions， a decreasing trend in body weight， lowered levels of blood glucose， 24-h urinary protein， and ACR （P<0.01）， reduced SCr and UREA （P<0.01）， and declined levels of TC， TG， and LDL （P<0.05，P<0.01）. Compared with the model group， the Yishen Huashi granules group showed alleviated damage and interstitial fibrosis in the renal tissue as well as reductions in glomerular foot process fusion and basement membrane thickening. Moreover， the Yishen Huashi granules group showed down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01）， reduced positive expression of p-p38， MCP-1， and CCR2 （P<0.01）， and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2 （P<0.05） in the renal tissue. The cell experiment showed that compared with the high glucose group， the Yishen Huashi granule-containing serum group showcased down-regulated mRNA levels of MCP-1 and CCR2 （P<0.01） and down-regulated protein levels of p-p38/p38， MCP-1， and CCR2（P<0.05，P<0.01）. ConclusionYishen Huashi granules can regulate glucose-lipid metabolism， reduce 24 h urinary protein and ACR， improve the renal function， alleviate the renal tubule injury caused by high glucose， and protect renal tubule epithelial cells in db/db mice by reducing MCP-1/CCR2 activation via the p38 MAPK signaling pathway.

ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.

ObjectiveTo evaluate the clinical efficacy and safety of Baoshen prescription in the treatment of stage Ⅳ diabetic nephropathy （DN） in the patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction， and to explore the mechanism of this prescription delaying the disease progression. MethodsA randomized， controlled， double-blind， multicenter clinical trial was conducted， in which 94 stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction were randomly assigned into Baoshen prescription and control groups （47 cases）. The treatment lasted for 12 weeks. The primary efficacy indicators were mainly renal function indexes， including urine albumin-to-creatinine ratio （UACR）， 24-hour urine total protein （24 h-UTP）， serum creatinine （SCr）， and estimated glomerular filtration rate （eGFR）. The secondary efficacy indicators were metabolic memory of hyperglycemia， podocyte epithelial-to-mesenchymal transdifferentiation-related indexes， and TCM syndrome score. ResultsAfter 12 weeks of treatment， the Baoshen prescription group showed lowered levels of advanced glycation end products （lgAGEs）， connective tissue growth factor （CTGF）， type Ⅳ collagen （Col-Ⅳ）， receptor of AGEs （RAGE）， urinary fibroblast-specific protein-1 （FSP-1）， UACR， 24 h-UTP， and glycated hemoglobin （HbAlc） （P<0.05）， and an upward trend of miR-21 mRNA. The control group showed elevated levels of SCr and UREA and lowered levels of urinary FSP-1， eGFR， and HbAlc （P<0.05）. After treatment， the Baoshen prescription group had lower levels of lgAGEs， CTGF， urinary FSP-1， SCr， UACR， and 24 h-UTP and higher levels of Col-Ⅳ and eGFR than the control group （P<0.05）. In addition， the Baoshen prescription group showed statistically significant differences in SCr， eGFR， UACR， and 24 h-UTP before and after treatment （P<0.05）. ConclusionBaoshen prescription can effectively improve the renal function， reduce the urinary protein level， and alleviate clinical symptoms in stage Ⅳ DN patients with syndromes of Qi-Yin deficiency and kidney collateral stasis and obstruction. The mechanism may be related to the metabolic memory of hyperglycemia and epithelial-to-mesenchymal transdifferentiation of podocytes.

Liumotang comes from the Yuan dynasty's Effective Prescription Handed Down for Generations of Physicians. It is composed of six medicinal materials： Arecae Semen， Aquilariae Lignum Resinatum， Aucklandiae Radix， Linderae Radix， Rhei Radix et Rhizoma， and Aurantii Fructus. It is a classical formula for treating abdominal pain due to Qi stagnation and constipation accompanied by heat. This study systematically collated the records of Liumotang in ancient medical books and modern clinical literature and conducted in-depth analysis and textual research on its formula source， main diseases， composition， dosage， medical books， container capacity， processing， preparation method， usage， drug basis， formula meaning， and other key information， so as to provide a powerful reference for the development and clinical application of compound preparations of the classical formula Liumotang. The results show that Liumotang was first seen in Effective Prescription Handed Down for Generations of Physicians， and many medical books of the past dynasties have imitated this. In terms of drug basis， the dried and mature seeds of the palm plant Areca catechu， resin-containing wood of the Daphneaceae plant Aquilaria sinensis， the dried roots of the Asteraceae plant woody Aucklandia lappa， the dried tuber root of the Lauraceae plant Lindera aggregata， the dried roots and rhizomes of the knotweed plant， R. palmatum， R.tangutikum， and R. officinale， and the dried and unripe fruits of the citrus genus C. aurantium and its cultivated varieties from the family Rutaceae were selected. In terms of dosage， through the textual research on bowls in the Ming and Qing dynasties， combined with the conversion of medicines and bowl capacity in the Qing dynasty， it was estimated that the dosage of each drug in the Yuan dynasty was 10.86 g. In the Ming and Qing dynasties， the dosage of drugs was mostly equal， but the dosage of drugs was somewhat different. In terms of processing， preparation method， and usage， in the medical books of the past dynasties， the processing of drugs has slightly changed， but raw drugs are used in all preparations. The preparation method and usage did not change much during the Yuan， Ming， and Qing dynasties， except for certain differences in dosage. In terms of syndrome， Liumotang was first used to treat abdominal pain due to Qi stagnation and constipation accompanied by heat. Medical books of the past dynasties often omit the symptoms of heat. In modern clinical practice， Liumotang is mainly used in the digestive system and urinary system diseases and is mostly used to treat constipation-predominant irritable bowel syndrome， biliary reflux gastritis， functional constipation， slow transit constipation， and other diseases， with no adverse reactions found yet. The above results provide a reliable scientific basis for the development and clinical treatment of Liumotang compound preparations.

ObjectiveTo investigate the possible mechanism of Shenfuhuang Formula （参附黄配方） in prevention and treatment of epsis-associated encephalopathy from the perspective of brain genomics. MethodsC57BL/6 mice were randomly divided into sham surgery group， sepsis group， and Shenfuhuang group， with 20 mice in each group. The sepsis group and Shenfuhuang group were induced to develop sepsis by cecal ligation and puncture （CLP） procedure. At 4 hours after modelling， Shenfuhuang group were gavaged with 2.5 g/（kg·d） of Shenfuhuang Formula， 0.5 ml each time， at 12 hours intervals， for a total of 4 times after modelling. Sepsis group and sham surgery group were given 0.5 ml of purified water orally. At 48 hours after modeling， the transcriptome sequencing was used to explore the differential gene expression in the effects of Shenfuhuang Formula on the brain regions of septic mice， and real-time PCR and ELISA were later used to further validate the differential gene and proteins expression. ResultsA total of 4605 genes were differentially expressed in Shenfuhuang group compared with sepsis group， of which 2353 genes were up-regulated and 2252 genes were down-regulated. According to the results of previous publications， six key genes were screened， including serine/threonine-protein kinase （Nek1）， myelin-associated glycoprotein （Mag）， endothelial cell-specific tyrosine kinase receptor （Tek）， a disintegrin and metalloproteinase with thrombospondin motifs 20 （Adamts20）， lymphocyte antigen 86 （Ly86）， and E3 ubiquitin-protein ligase （Traip）. Further genetic and protein validation revealed that， compared to the sham surgery group， the mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip in the brain tissue of septic mice significantly reduced （P＜0.05）. In comparison to the sepsis group， Shenfuhuang group showed significantly increased mRNA levels and corresponding protein levels of Nek1， Mag， Tek， Adamts20， Ly86， and Traip （P＜0.05）. ConclusionThe potential therapeutic targets of Shenfuhuang Formula for treating sepsis-associated encephalopathy may be related to the Nek1， Mag， Tek， Adamts20， Ly86， and Traip genes and their encoded proteins.