Parkinson's disease （PD） is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra， abnormal aggregation of alpha-Synuclein （α-Syn）， and the formation of Lewy bodies. However， the exact mechanisms remain unclear. In recent years， the PD incidence has gradually increased， while current treatment methods are limited to symptom alleviation， incapable of halting disease progression， and prone to adverse effects， thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E₂ related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is closely related to oxidative stress， neuroinflammation， apoptosis， ferroptosis， and mitochondrial dysfunction， playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine （TCM） can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages， such as multiple targets， multiple pathways， and fewer adverse reactions， TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD， while summarizing the latest research on PD intervention by TCM monomers， active ingredients， and compounds， as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway， aiming to provide a reference for clinical medicine development to prevent and treat PD.

Objective:To prepare mesothelin-loaded paclitaxel (PTX) phase change nanoparticles and evaluate their targeting effect and therapeutic effect on ovarian cancer.Methods:PTX-loaded phase-change nanoparticles PTX-NPs were prepared by the thin-film hydration method, and targeted mesothelin-loaded PTX phase-change nanoparticles Ab-PTX-NPs were prepared by attaching anti-mesothelin antibody to the nanoparticles using the biotin-affinity method. Zeta potential and particle size were determined by applying a zeta potential and a particle size analyzer, and the encapsulation rate and the amount of drug loading of PTX was measured by applying a UV spectrophotometer. Flow cytometry was used to detect the connectivity of anti-mesothelin antibody with PTX-NPs. The phase transition of Ab-PTX-NPs was induced by low-power focused ultrasound, and its ultrasonography imaging was observed; laser scanning confocal microscopy and flow cytometry were used to detect the targeting ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells. The targeting and killing ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells was observed by in vitro targeting assay and apoptosis detection assay. The ovarian cancer model of BALB/c nude mice was constructed to observe the distribution of Ab-PTX-NPs in vivo as well as the effects on blood biochemistry and important organs of nude mice. Results:Ab-PTX-NPs were successfully prepared with a zeta potential of -(8.37±2.71) mV, a diameter of (690.46±28.75) nm, an encapsulation rate of (88.2±4.4)% for PTX, a drug loading capacity of (27.3±0.9)%, and a linkage rate of (94.9±2.8)% between anti-mesothelin antibody and PTX-NPs. Low-intensity focused ultrasound could successfully induce phase transition of Ab-PTX-NPs to realize ultrasonography imaging, and 6 W was the optimal excitation power for low-intensity focused ultrasound. Ab-PTX-NPs showed excellent targeting and killing ability to SKOV3 cells, and the apoptosis and necrosis rate of SKOV3 cells in the Ab-PTX-NPs group reached 79.6%. In vivo imaging showed that the fluorescence intensity at the tumor site of nude mice in the Ab-PTX-NPs group was significantly higher than that in the PTX-NPs group. Biosafety assay showed that 15 d after Ab-PTX-NPs administration, the serum aspartate aminotransferase, alanine aminotransferase, creatine kinase, low-density lipoprotein, blood creatinine, and urea nitrogen concentrations of nude mice were (174.163±20.596)U/L, (33.297±2.573)U/L, (1 959.978±72.212)U/L, (22.033±5.030)μmol/L, (0.393±0.058)mmol/L, and (26.405±4.957)mmol/L, which were not significantly different from those of the phosphate buffer solution (PBS) group, the NPs group, and the PTX-NPs group. The organs such as the heart, the liver, the spleen, the lungs and the kidneys remained intact, and what was seen by the naked eye and microscope was similar with those of the PBS group, NPs group and PTX-NPs group. Conclusion:Ab-PTX-NPs were successfully prepared, which had good ovarian cancer targeting ability and killing effect and effectively reduced the toxicity of PTX.

Objective To compare the efficacy and safety of stellate ganglion block(SGB)with those of conventional western medication in the treatment of insomnia.Methods A computerized retrieval of academic papers concerning the clinical randomized controlled trials of SGB versus conventional western medication in the treatment of insomnia from the databases of PubMed,Embase,Cochrane Library,CNKI,Wanfang Data knowledge service platform,VIP database and CBM database was conducted.The retrieval time period was from the establishment of the database to June 13,2023.NoteExpress v3.5 software was used to make literature screening,Stata17.0 software was used to perform meta-analysis of the obtained data,TSA0.9.5.10 beta software was used to make sequential analysis,and GRADEpro was used to perform the grade classification.Results A total of 11 articles including 875 patients with insomnia were included in this analysis.Compared with the conventional western medication,SGB showed certain advantages in the following aspects:improving total clinical effectiveness(RR total=1.24,95％CI:1.16-1.32,P＜0.01),increasing the proportion of patients who could sleep for more than 3 hours after treatment(RR total=1.24,95％CI:1.09-1.41,P=0.001),increasing total sleep time(SMD=1.53,95％CI:0.89-2.16,P＜0.01),reducing sleep latency(MD=-14.08,95％CI:-18.72--9.43,P＜0.01),decreasing PSQI score(MD=-3.54,95％CI:-4.31--2.78,P＜0.01),and reducing the recurrence rate within 6 months(RR=0.19,95％CI:0.10-0.37,P＜0.01).However,the difference in the proportion of patients who could sleep for more than 6 hours after treatment between the two groups was not statistically significant(RR=1.31,95％CI:0.97-1.76,P=0.078).The traditional SGB therapy had a certain risk of adverse events,ultrasound-guided SGB therapy was much safer.Trial sequential analysis showed that the cumulative sample size of the effective rate crossed the conventional threshold and TSA threshold,the positive results had been obtained in advance although it did not reach RIS.The quality of evidence evaluated by GRADE for the sleep latency,PSQI and recurrence rate within 6 months was medium grade,and the quality for the remaining indexes was low grade.Conclusion Compared with conventional western medication for the treatment of insomnia,the effect of SGB in increasing the total response rate,the proportion of patients who get sleeping for more than 3 hours after treatment and the total sleep duration,in reducing sleep latency,PSQI score and recurrence rate within 6 months has gained some certain evidence supports.The SGB and conventional western medication have similar efficacy in improving the proportion of patients who get sleeping for more than 6 hours after treatment.The results of this study are stable and reliable,but the current level of evidence grade is lower,therefore,large-sample randomized controlled trials need to be conducted before its clinical efficacy can get further evidence-based support.

OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.

Post-stroke limb movement disorder is a common functional disorder after stroke.Xuming Decoction in Ancient and Modern Records of the Proven is an important prescription of Zhang Zhongjing for treating"stroke prickly heat,the body cannot hold it-self".It has been modified and recorded in many later generations,among which Xiaoxuming Decoction in Important Formulas Worth a Thousand Gold Pieces for Emergency is the most commonly used.With the development of the"internal wind theory"of stroke,the pre-scriptions of Xuming Decoction were gradually criticized and even abandoned because they often used"wind drugs"and were difficult to understand the medical theory of"internal wind".Based on the viewpoints of"wind prevailing and causing movement"and"internal wind being the change of yang qi in the body",the paper proposes the theory of"inducing wind to promote movement"of Xuming De-coction and believes that"wind is qi".At the beginning of stroke,wind-yang is violently hyperactive,and wind prevails and causes movement,resulting in stroke;after stroke,yang qi is weak,wind is defeated and static,and limbs are unable to use.However,"wind drugs"such as Ephedra sinica Stapf and Cinnamomum aromaticum Nees have the functions of generating wind and promoting movement,revitalizing the decadent and the useless,exciting yang qi,harmonizing the ying and wei,and raising and lowering qi.The Xuming Decoction is mainly composed of"wind drugs",which warms the yang and replenishes the qi,generates wind to excite yang qi,and revitalizes the weak;replenishes the yang to induce wind and promote movement,replenishes qi and generates blood;relieves muscles to harmonize the ying and wei,and dredges the limbs;restores the pivot to regulate the axis of the internal organs,unblocks the qi,and promotes the recovery of limb motor function after stroke,providing a theoretical basis for the clinical application of Xuming Decoction.

Post-stroke limb movement disorder is a common functional disorder after stroke.Xuming Decoction in Ancient and Modern Records of the Proven is an important prescription of Zhang Zhongjing for treating"stroke prickly heat,the body cannot hold it-self".It has been modified and recorded in many later generations,among which Xiaoxuming Decoction in Important Formulas Worth a Thousand Gold Pieces for Emergency is the most commonly used.With the development of the"internal wind theory"of stroke,the pre-scriptions of Xuming Decoction were gradually criticized and even abandoned because they often used"wind drugs"and were difficult to understand the medical theory of"internal wind".Based on the viewpoints of"wind prevailing and causing movement"and"internal wind being the change of yang qi in the body",the paper proposes the theory of"inducing wind to promote movement"of Xuming De-coction and believes that"wind is qi".At the beginning of stroke,wind-yang is violently hyperactive,and wind prevails and causes movement,resulting in stroke;after stroke,yang qi is weak,wind is defeated and static,and limbs are unable to use.However,"wind drugs"such as Ephedra sinica Stapf and Cinnamomum aromaticum Nees have the functions of generating wind and promoting movement,revitalizing the decadent and the useless,exciting yang qi,harmonizing the ying and wei,and raising and lowering qi.The Xuming Decoction is mainly composed of"wind drugs",which warms the yang and replenishes the qi,generates wind to excite yang qi,and revitalizes the weak;replenishes the yang to induce wind and promote movement,replenishes qi and generates blood;relieves muscles to harmonize the ying and wei,and dredges the limbs;restores the pivot to regulate the axis of the internal organs,unblocks the qi,and promotes the recovery of limb motor function after stroke,providing a theoretical basis for the clinical application of Xuming Decoction.

OBJECTIVE To investigate the ameliorative effect of Pinelliae Rhizoma Praeparatum Cum Alumine and its effective components on inflammatory response in mice with acute lung injury(ALI).METHODS A mice model of acute lung injury induced by lipopolysaccharide(LPS)was used as the in vivo animal model.The levels of inflammatory factors TNF-α,IL-6,and IL-1β,the total protein concentration,the number of inflammatory cells in bronchoalveolar lavage fluid,the ratio of lung wet weight to dry weight,and the pathological damage of lung tissues were taken as the evaluation indexes.RAW264.7 macrophages induced by LPS were used as the in vitro experimental model,with the mRNA levels of intracellular inflammatory factors TNF-α,IL-1β,and IL-6 as indicators,systematic solvent extraction and silica gel column chromatography were used to separate and screen the effective parts and components of Pinelliae Rhizoma Praeparatum Cum Alumine for treating acute lung injury.The component composition of the effective fractions was analyzed by mass spectrometry,the content of cyclic dipeptide components in the effective fraction was determined,and the anti-in-flammatory activity of cyclic dipeptides was verified in vitro.RESULTS The ethyl acetate extraction fraction obtained by extracting the supernatant of water extraction and ethanol precipitation of Pinelliae Rhizoma Praeparatum Cum Alumine(referred to as the ethyl acetate fraction for short)significantly improved the inflammatory response in mice with acute lung injury and significantly reduced the mRNA levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.The Fr.1 fraction isolated from the ethyl acetate frac-tion by silica gel column chromatography had anti-inflammatory effects in vitro.Mass spectrometry determined the content of two main cyclic dipeptide components,cyclo-(Pro-Phe)and cyclo-(Pro-Val),in the Fr.1 fraction.After mixing these two cyclic dipeptide components in the molar ratio in the Fr.1 fraction and administering them in vitro,the results showed that the combination of these two cyclic dipeptide components could significantly inhibit the mRNA expression levels of TNF-α,IL-1β,and IL-6 in RAW264.7 cells induced by LPS.CONCLUSION Cyclic dipeptide component is one of the main material basis categories for the anti-inflammatory effect of Pinelliae Rhizoma Praeparatum Cum Alumine.

Objective:To prepare mesothelin-loaded paclitaxel (PTX) phase change nanoparticles and evaluate their targeting effect and therapeutic effect on ovarian cancer.Methods:PTX-loaded phase-change nanoparticles PTX-NPs were prepared by the thin-film hydration method, and targeted mesothelin-loaded PTX phase-change nanoparticles Ab-PTX-NPs were prepared by attaching anti-mesothelin antibody to the nanoparticles using the biotin-affinity method. Zeta potential and particle size were determined by applying a zeta potential and a particle size analyzer, and the encapsulation rate and the amount of drug loading of PTX was measured by applying a UV spectrophotometer. Flow cytometry was used to detect the connectivity of anti-mesothelin antibody with PTX-NPs. The phase transition of Ab-PTX-NPs was induced by low-power focused ultrasound, and its ultrasonography imaging was observed; laser scanning confocal microscopy and flow cytometry were used to detect the targeting ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells. The targeting and killing ability of Ab-PTX-NPs on ovarian cancer SKOV3 cells was observed by in vitro targeting assay and apoptosis detection assay. The ovarian cancer model of BALB/c nude mice was constructed to observe the distribution of Ab-PTX-NPs in vivo as well as the effects on blood biochemistry and important organs of nude mice. Results:Ab-PTX-NPs were successfully prepared with a zeta potential of -(8.37±2.71) mV, a diameter of (690.46±28.75) nm, an encapsulation rate of (88.2±4.4)% for PTX, a drug loading capacity of (27.3±0.9)%, and a linkage rate of (94.9±2.8)% between anti-mesothelin antibody and PTX-NPs. Low-intensity focused ultrasound could successfully induce phase transition of Ab-PTX-NPs to realize ultrasonography imaging, and 6 W was the optimal excitation power for low-intensity focused ultrasound. Ab-PTX-NPs showed excellent targeting and killing ability to SKOV3 cells, and the apoptosis and necrosis rate of SKOV3 cells in the Ab-PTX-NPs group reached 79.6%. In vivo imaging showed that the fluorescence intensity at the tumor site of nude mice in the Ab-PTX-NPs group was significantly higher than that in the PTX-NPs group. Biosafety assay showed that 15 d after Ab-PTX-NPs administration, the serum aspartate aminotransferase, alanine aminotransferase, creatine kinase, low-density lipoprotein, blood creatinine, and urea nitrogen concentrations of nude mice were (174.163±20.596)U/L, (33.297±2.573)U/L, (1 959.978±72.212)U/L, (22.033±5.030)μmol/L, (0.393±0.058)mmol/L, and (26.405±4.957)mmol/L, which were not significantly different from those of the phosphate buffer solution (PBS) group, the NPs group, and the PTX-NPs group. The organs such as the heart, the liver, the spleen, the lungs and the kidneys remained intact, and what was seen by the naked eye and microscope was similar with those of the PBS group, NPs group and PTX-NPs group. Conclusion:Ab-PTX-NPs were successfully prepared, which had good ovarian cancer targeting ability and killing effect and effectively reduced the toxicity of PTX.

Post-stroke depression is a common complication after a stroke. Based on the theory of ＂deficiency of heart qi leading to sadness＂recorded in Huangdi Neijing, our team proposes that deficiency of heart qi is the basic pathogenesis of post-stroke depression, with sadness being its main manifestation. Therefore, we advocate treating post-stroke depression from the perspective of the heart, and clinically, it can be divided into four stages: heart-liver stage, heart-lung stage, heart-spleen stage, and heart-kidney stage. Treating post-stroke depression with the principle of regulating qi and nourishing the heart, patients in the heart-liver and heart-lung stages are mainly middle-aged and young adults, with a pathological nature of qi stagnation and mild deficiency of heart qi, and therefore, the method of promoting the flow of meridians and regulating qi should be adopted. In contrast, patients in the heart-spleen and heart-kidney stages are mainly middle-aged and elderly, with a pathological nature of qi deficiency and severe deficiency of heart qi, and therefore, nourishment and tonification should be prioritized. In response to the above four stages, our team has achieved good clinical efficacy by administering Xiaoyao Powder, Baihe Dihuang Decoction, Ganmai Dazao Decoction and Jingui Shenqi Pill respectively. This study discusses the approach to treating post-stroke depression from the perspective of a "deficiency of heart qi leading to sadness" by examining three aspects: the theoretical basis of Chinese and Western medicine to treat post-stroke depression from the heart, the basic pathogenesis and staging of post-stroke depression, and the treatment principle of regulating qi and nourishing the heart. The study also briefly analyzes the clinical experience of the medications used for this condition to provide a reference for the treatment of post-stroke depression.

OBJECTIVE To investigate the variations in taste， aroma and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces derived from different sources， and to identify their origins. METHODS The flavor， odor and volatile organic compounds of Rhei Radix et Rhizoma decoction pieces from different sources were compared and analyzed by using electronic tongue， electronic nose， and gas chromatography-ion mobility spectrometry （GC-IMS）. Principal component analysis （PCA）， partial least squares-discriminant analysis （PLS-DA）， orthogonal partial least squares discriminant analysis （OPLS-DA） and Fisher discriminant analysis were employed to identify the origins of Rhei Radix et Rhizoma decoction pieces and establish the basis discrimination criteria. RESULTS The differences in taste of Rhei Radix et Rhizoma decoction pieces from 3 origins were primarily characterized by bitterness， astringency， and bitter-astringent aftertaste. In terms of smell， variations were mainly observed in inorganic sulfides， organic sulfides containing aromatic components， methane and other short-chain alkanes， alcohols， ethers， aldehydes and ketones， as well as nitrogen oxides. Differentially volatile organic compounds mainly consisted of alcohols， aldehydes and ketones. Furthermore， the samples from 8 batches could be effectively classified into 3 categories.Three types of Rhei Radix et Rhizoma decoction pieces can be effectivily identified based on the peak intensity ratio between volatile substances. For example， when the peak intensity of 2-acetylfuran was 3-19 times that of isobutyric acid [dimer]， it was considered as Rheum officinale Baill. CONCLUSIONS The discriminant models established in this study， along with the criteria for determining the origins based on the peak intensity ofcharacteristic volatile compounds， can be utilized for the identification of Rhei Radix et Rhizoma decoction pieces.