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.

Minimally conscious state （MCS） is at the edge between closed and open consciousness， but it still belongs to the category of "wind-strike block" syndrome. The basic pathogenesis of MCS is the obstruction of pathogenic qi， orifices closed and spirit hidden， with pathological factors including phlegm， fire， and blood stasis. Wind movement and water retention may also be present， and often leading to deficiency syndrome due to the exhaustion of qi， blood， yin， and yang at later stages. Treatment chooses Shexiang （Moschus） as the chief medicinal， emphasizing combination of medicinals and urgency of medication administration； the key therapeutic method is to open the orifices， with focuses on expelling pathogens and reinforcing healthy qi. For patients with severe phlegm or fire， use Xiaochengqi Decoction （小承气汤） to open the lower orifices， discharge heat and unblock the bowels， combined with Shexiang （Moschus） and Niuhuang （Bovis Calculus） to open the upper orifices， awaken the spirit and guide qi. For patients with turbid phlegm as the predominant， temporarily replace Shexiang （Moschus） with Baizhi （Angelicae dahuricae radix）， using Ditan Decoction （涤痰汤） to eliminate phlegm to open the orifices， when turbid phlegm gradually subsided， Shexiang （Moschus） could be added. For patients with blood stasis as the predominant， Tongqiao Huoxue Decoction （通窍活血汤） will be used to activate blood and open orifice， if the blood circulates， the endogenous wind will be calmed， the water will be induced， the orifices will open and the consciousness will restore. For patients with closed orifices and body deficiency， the treatment should open the orifices and reinforce healthy qi， and consider the root and branch simultaneously； qi deficiency syndrome can be addressed with Buyang Huanwu Decoction （补阳还五汤） to boost qi and reinforce healthy qi； yin deficiency syndrome can be treated with Shaoyao Gancao Decoction （芍药甘草汤） combined with Fengsui Pill （封髓丹） to nourish yin， soften sinews， and secure kidney essence； yang deficiency can be managed by using Dihuang Yinzi Decoction （地黄饮子） to enrich yin， supplement yang， and open the orifices.

ObjectiveTo establish preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients and provide a basis for standardized diagnosis and treatment of ischemic stroke. MethodsRelevant literature on the diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients was retrieved， and data were mined and extracted to form an item pool. Based on the formation of the item pool， this study used the Delphi method to initiate two rounds of questionnaire surveys with selected experts to complete the initial screening of items and the discrimination of symptom importance. A prospective clinical investigation method was adopted to collect clinical information from patients， and statistical analysis methods and data mining techniques were comprehensively used to determine their primary and secondary symptoms. Based on the clear main and secondary symptoms identified， combined with expert group discussions， the study established preliminary diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients. ResultsA total of 25 relevant syndrome differentiation standards were included. After splitting， standardizing， and screening the items， the study established a pool of 48 items. The first round of questionnaire survey consulted 30 experts， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.359. According to the item screening criteria， 26 items were retained in this round of questionnaire survey. A total of 176 cases were collected through clinical information investigation， including 94 cases with spleen and kidney deficiency syndrome and 82 cases without spleen and kidney deficiency syndrome. The statistical results were as follows： ① Descriptive statistics： The main symptoms with a frequency of ≥ 30% included mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with a frequency of ≥ 10% and ≤ 30% were lassitude and disinclination to talk， shortness of breath， etc. ② Binary logistic regression analysis： The main symptoms with an odds ratio （OR） value of ≥ 3 were mental fatigue and lack of strength， weakness of the lower back and knees， etc. The secondary symptoms with an OR value of ≥ 1 and ≤ 3 were lassitude and disinclination to talk， shortness of breath， etc. Artificial neural network： The main symptoms with a weight value（W_ij）of ≥ 0.5 and < 1 were mental fatigue and lack of strength， lassitude and disinclination to talk， etc. The secondary symptoms with W_ij of ≥ 0.3 and < 0.5 were shortness of breath， flaccid limbs， etc. In the second round of questionnaire survey， a total of 37 experts were consulted， with both the positive coefficient of experts and the effectiveness rate of the questionnaire reaching 100%. The Kendall's coefficient of concordance was 0.237. According to the criteria to determine primary and secondary symptoms based on the Delphi method， the main symptoms included in this round of the questionnaire were mental fatigue and lack of strength， lassitude and disinclination to talk， etc.， and the secondary symptoms were shortness of breath， dizziness， etc. ConclusionThe main symptoms of spleen and kidney deficiency syndrome in ischemic stroke patients are mental fatigue and lack of strength， weakness of the lower back and knees， loose stool， pale and edematous tongue texture possibly with tooth marks， and deep and thready pulse or weak pulse. The secondary symptoms include shortness of breath， dizziness， tinnitus and deafness， decreased appetite or postprandial abdominal distension， pale complexion， frequent micturition at night， dull tongue texture， and white and slippery tongue coating. The preliminarily established diagnostic criteria for spleen and kidney deficiency syndrome in ischemic stroke patients can provide a standardized and objective basis， thereby better guiding clinical diagnosis and treatment of ischemic stroke.

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 compare the clinical efficacy of percutaneous endoscopic interlaminar discectomy (PEID) and posterior small incision microdiscectomy (MD) in the treatment of recurrent lumbar disc herniation.Methods:A retrospective analysis was conducted on the data of 132 patients who underwent revision surgery for recurrent lumbar disc herniation at the same segment at Qilu Hospital of Shandong University between July 2012 and August 2022. The patients were treated with either PEID or MD. The PEID group consisted of 90 patients, including 51 males and 39 females, with a mean age of 42.7±11.3 years and a mean body mass index (BMI) of 23.7±3.4 kg/m 2. The surgical segments were L 4-5 in 38 cases and L 5S 1 in 52 cases. The primary surgeries included open discectomy in 7 cases, laminectomy with bone graft in 3 cases, MD in 35 cases, and PEID in 45 cases. The MD group consisted of 42 patients, including 30 males and 12 females, with a mean age of 41.2±12.6 years and a mean BMI of 24.3±4.7 kg/m 2. The surgical segments were L 4-5 in 19 cases and L 5S 1 in 23 cases. The primary surgeries included open discectomy in 2 cases, laminectomy with bone graft in 1 case, MD in 17 cases, and PEID in 22 cases. The visual analogue scale (VAS) scores for low back pain and leg pain, Oswestry disability index (ODI), immediate postoperative VAS score for surgical wound pain, intraoperative blood loss, surgical wound length, operation duration, length of hospital stay, and various complications before and after surgery were compared between the PEID and MD groups. Results:The operation duration in the PEID group was 81.7±11.3 min, that in the MD group was 85.2±9.5 min, but the difference was not statistically significant ( t=1.740, P=0.081). The intraoperative blood loss in the PEID group was 4.4±2.9 ml, the surgical wound length was 0.9±0.2 cm, and the length of hospital stay was 3.1±1.3 d, all significantly less than those in the MD group (26.6±10.3 ml, 3.4±1.1 cm, and 8.7±1.6 d, respectively), with statistically significant differences ( P<0.05). Both groups were followed up, with a mean follow-up duration of 24.4±5.5 months in the PEID group and 24.5±4.9 months in the MD group, and there was no statistically significant difference between the two groups ( t=0.101, P=0.920). Both the PEID and MD groups showed significant improvements in postoperative VAS scores for leg pain, VAS scores for low back pain, and ODI compared with preoperative values ( P<0.05). Additionally, the VAS score for surgical wound pain on the first postoperative day in the PEID group was 1.2±0.4, which was lower than that in the MD group (2.9±0.6), with a statistically significant difference ( t=19.261, P<0.001). The incidence rates of muscle weakness, postoperative sensory abnormalities, and dural tears in the PEID group were 12%(11/90), 27%(24/90), and 6%(5/90), respectively, significantly lower than those in the MD group [31%(13/42), 40%(17/42), and 33%(14/42), respectively], with statistically significant differences ( P<0.05). However, there were no statistically significant differences between the two groups in the incidence rates of recurrence, residual nucleus pulposus, spinal cord-like hypertension syndrome, subcutaneous wound infection, or intervertebral space infection ( P>0.05). No patients in either group developed retroperitoneal hematoma postoperatively. Conclusion:For patients with recurrent lumbar disc herniation after primary posterior surgery, PEID demonstrates equally excellent clinical efficacy compared with MD, with smaller surgical trauma and a lower incidence of complications.

Objective:To compare the outcomes of ranibizumab and conbercept adjunct for pars plana vitrectomy (PPV) in the treatment of proliferative diabetic retinopathy (PDR).Methods:A prospective randomized case-control study. From June 2022 to December 2023, 90 cases (90 eyes) of PDR patients diagnosed through ophthalmic examination at Department of Ophthalmology of Gansu Provincial Hospital were included in the study. All patients underwent the best corrected visual acuity (BCVA), intraocular pressure, B-mode ultrasound, and optical coherence tomography (OCT) examinations. The central macular thickness (CMT) was measured using an OCT instrument. The patients were randomly divided into a intravitreal injection of ranibizumab group (monoclonal-antibody group) and a intravitreal injection of conbercept group (fusion-protein group) using a random number table method, with 45 cases (45 eyes) in each group. Two groups of patients were intravitreal injected with 10 mg/ml ranibizumab or conbercept 0.05 ml, respectively. A standard 23G PPV was performed through the flat part of the ciliary body 3-7 days after intravitreal injection. Relevant examinations were performed using the same equipments and methods as before surgery at postoperative 1 week, 1, 3, 6, and 12 months. The PPV time, intraoperative use of intraocular electrocoagulation, incidence of iatrogenic retinal breaks, and sterile air or silicone oil tamponade rate in the vitreous cavity, the postoperative changes of BCVA and CMT, and incidence of complications were compared between two groups. Independent sample t test was used for inter group comparison. Results:The intraoperative utilization rate of intraocular electrocoagulation in the monoclonal-antibody group was higher than that in the fusion-protein group, and the difference was statistically significant ( χ2=3.876, P<0.05). There were no statistically significant differences in the PPV time ( t=0.152), intraoperative bleeding rate ( χ2=0.800), incidence of iatrogenic retinal breaks ( χ2=1.975), and sterile air and silicone oil tamponade rate in the vitreous cavity ( χ2=1.607, 1.553) between the two groups ( P>0.05). There were no statistically significant differences in early and late postoperative vitreous hemorrhage ( χ2=1.235, 2.355), and re-PPV ( χ2=2.355) between two groups ( P>0.05). The BCVA of the fusion-protein group was significantly better than that of the monoclonal-antibody group at postoperative 3 months, and the difference was statistically significant ( t=2.428, P<0.05). The CMT of the fusion-protein group was lower than that in the monoclonal-antibody group at postoperative 1 week, and the difference was statistically significant ( t=2.739, P<0.05). None of the patients experienced endophthalmitis, retinal artery occlusion, or severe cardiovascular events after surgery. Conclusion:Compared with intravitreal injection of ranibizumab before PPV, intravitreal injection of conbercept before PPV in PDR patients can shorten the surgical time, reduce intraoperative bleeding rate, lower the rate of electrocoagulation and intraocular tamponade, and incidence of iatrogenic retinal breaks, and improve the visual acuity.

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 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.

Neurodegenerative diseases are chronic and progressive diseases of the nervous system.Modern studies have shown that intestinal flora disorders,mitochondrial dysfunction and lipid metabolism abnormalities are closely related to the occurrence and development of neurodegenerative diseases,but the treatment methods are limited.Traditional Chinese medicine believes that spleen is the"the foundation of nurture"and the"the source of Qi and blood biochemistry",Qi deficiency leads to insufficient Qi,blood and body fluid metaplasia,brain dysplasia,leading to the occurrence of neurodegenerative diseases.This paper discusses the mechanism of treating neurodegenerative diseases by spleen from the perspective of"intestinal flora,mitochondria and lipids",and concludes that intestinal flora balance is the material basis of spleen function,mitochondrial homeostasis is an important mechanism of the function of"spleen governing transportation and transformation",and abnormal lipid metabolism is an important manifestation of spleen deficiency and phlegm stasis.Intestinal flora,mitochondria and lipid metabolism may be the potential biological basis for the treatment of neurodegenerative diseases by spleen in traditional Chinese medicine.In order to provide ideas for the clinical research and treatment of neurodegenerative diseases.