BACKGROUND:Needle-knife release of the ligamentum flavum can effectively improve symptoms in patients with lumbar degeneration,and ultrasound guidance can increase the precision of needle-knife release;however,the specific effects of needle-knife release of the ligamentum flavum on the degenerated intervertebral discs and the possible mechanisms remain to be clarified. OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife release of the ligamentum flavum. METHODS:Twenty-four New Zealand rabbits were randomized into control(n=6)and model(n=18)groups.A rabbit model of lumbar disc degeneration model was established in the model group by cutting the supraspinous and interspinous ligaments of the L5/6 and L6/7 segments to maintain a standing posture and apply axial load to the lumbar spine.After successful modeling,the model rabbits were subdivided into a control group,a model group,an ultrasonic needle-knife group,and a sham needle-knife group according to a random number table method,with six animals in each group.The ultrasonic needle-knife group underwent ultrasound-guided needle-knife release of the right yellow ligament of L7/S1,once every week,for a total of four times.The needle-knife approach in the sham needle-knife group was the same as that in the ultrasound needle-knife group,but the ligamentum flavum was not released.At 30 days after the intervention,MRI was used to observe the changes in the signal intensity of the nucleus pulposus within the L7/S1 segment.Hematoxylin-eosin staining was used to observe the morphological changes of the L7/S1 segment.Immunohistochemical staining was used to detect the expression of type I and II collagen in the nucleus pulposus of the L7/S1 segment.RT-PCR and western blot were used to detect the expression of integrin α5 and β1,p38,and nuclear factor κB in the L7/S1 segment. RESULTS AND CONCLUSION:MRI findings indicated that the nucleus pulposus of the intervertebral disc of rabbits in the model group was gray-black in color,and the gray value of the nucleus pulposus was significantly lower than that of the control group(P<0.01).The brightness of the nucleus pulposus of the intervertebral disc of the rabbits in the ultrasonic needle-knife group was elevated compared with that of the model group,and the gray value of the nucleus pulposus was higher than that of the model group(P<0.01).Results from hematoxylin-eosin staining showed that in the model group,the shape of the nucleus pulposus was irregular,the number of nucleus pulposus cells was reduced,the extracellular matrix was compressed,the fibrous ring was ruptured,the structure and boundary of the end plate were unclear,and the chondrocytes were arranged disorderly.Compared with the model group,the ultrasonic needle-knife group showed an increase in the number of the nucleus pulposus,an improvement in the rupture of the fibrous ring,and more regular arrangement of cartilage endplate cells.Results from immunohistochemical staining showed an increase in positive expression of type I collagen(P<0.01)and a decrease in positive expression of type II collagen in the nucleus pulposus of the model group compared with the control group as well as a decrease in positive expression of type I collagen and an increase in positive expression of type II collagen in the nucleus pulposus of the ultrasonic needle-knife group compared with the model group(P<0.01).RT-PCR and western blot assays showed that the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the model group were increased compared with that in the control group(P<0.01);the mRNA and protein expression of integrin α5,integrin β1,p38,and nuclear factor κB in the intervertebral discs of rabbits in the ultrasonic needle-knife group was decreased compared with that in the model group(P<0.01).To conclude,ultrasound-guided needle-knife release of the ligamentum flavum can improve the degree of lumbar disc degeneration in rabbits,which may be related to the inhibition of p38 and nuclear factor-κB expression by modulating integrin α5 and β1 expression.

Objective To investigate the protective effect of verapamil on hyperuricemia nephropathy(HN)in mice through modulating TXNIP/NLRP3 inflammasome signaling pathway.Methods Thirty-two male C57BL/6J mice(8 weeks old,weighing 18～22 g)were randomly divided into a blank control group,a model group,an allopurinol group(10 mg/kg),and a verapamil group(40 mg/kg),with 8 animals in each group.Except for the control mice,the other mice were given 10%fructose water and adenine to establish a mouse model of HN.After successful establishment of model mice,the corresponding interventions were administered to the mice of the other 3 groups for 4 consecutive weeks.The levels of serum uric acid(UA),creatinine(Cr),urea(UREA),aspartate aminotransferase(AST)and alanine aminotransferase(ALT)were measured.HE staining was used to assess the alterations in renal morphology and the infiltration of inflammatory cells,while Masson's staining was employed to evaluate renal fibrosis.Moreover,ELISA was employed to measure the contents of IL-1β and IL-6 in kidney tissue,while serum levels of malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)were detected by colorimetric assay.Furthermore,immunohistochemical staining and Western blot analysis were conducted to examine the expression of TXNIP,NLRP3,IL-1β,MMP7,FN1,CD68,and MPO proteins in the kidney.Results Compared to the control group,HN mice exhibited increased serum UA,Cr,and UREA levels(P<0.05),renal pathological changes including renal tubular regeneration,interstitial or periglomerular fibrosis and prominent infiltration of inflammatory cells,and significantly increased renal contents of IL-1β and IL-6 and serum MDA level(P<0.05),while reduced serum SOD and GSH-Px contents(P<0.05),as well as up-regulation of kidney proteins TXNIP,NLRP3,IL-1β,CD68,MPO,FN1 and MMP7(P<0.01).Verapamil treatment notably reduced serum UA and Cr levels(P<0.01),improved kidney lesions to some extents,decreased collagen volume fraction(CVF)(P<0.01),and restored pro-inflammatory cytokines and oxidative stress markers(P<0.05)when compared with the levels in the model group.Further research found that the expression of kidney proteins TXNIP,NLRP3,IL-1β,CD68,MPO,FN1,and MMP7 was significantly down-regulated by verapamil treatment(P<0.05).Conclusion Verapamil exhibits a renal protective effect on HN mice through its anti-inflammatory,antioxidant,and antifibrotic properties,and its mechanism may be related to the inhibition of the TXNIP/NLRP3 inflammasome signaling pathway.

ObjectiveBased on spatial metabolomics technology combined with pharmacological indexes， to analyze the mechanism of Fritillariae Cirrhosae Bulbus（FCB） powder in improving bleomycin-induced pulmonary fibrosis in rats. MethodSixty SD rats were randomly divided into five groups， including the blank group， the model group， and high， medium， low dosage groups of FCB. Except for the blank group， rats in all other groups were injected with bleomycin by tracheal injection to establish a pulmonary fibrosis model. Postoperatively， the high， medium and low dosage groups of FCB were administered aqueous solutions of FCB powder at doses of 0.36， 0.18， 0.09 g·kg^-1， respectively， continuously for 28 d. The blank and model groups were given an equal volume of distilled water by gavage. After the last administration， lung tissues and blood samples were collected， the pathological conditions of rat lung tissues were comprehensively evaluated by hematoxylin-eosin（HE） and Masson staining， and aerodynamic assisted desorption electrospray ionization mass spectrometry imaging（AFADESI-MSI） was used for MSI of rat lung tissues from different experimental groups. Spatial metabolomics analysis was conducted on the fibrotic areas of lung tissues in the model group and the high dosage group of FCB based on HE staining images. Differential metabolites between groups were screened by orthogonal partial least squares-discriminant analysis（OPLS-DA）， with variable importance in the projection（VIP） values>1， t-test P<0.05， and fold change analysis. Metabolic pathway analysis of the identified differential metabolites was performed using Kyoto Encyclopedia of Genes and Genomes（KEGG）. Protein expression levels of nuclear transcription factor-κB p65（NF-κB p65） and heme oxygenase-1（HO-1） in rat lung tissues were detected by Western blot. Biochemical assessments of superoxide dismutase（SOD）， malondialdehyde（MDA） and glutathione（GSH） levels in rat lung tissues were conducted. Serum levels of interleukin（IL）-1β， IL-6， nuclear factor erythroid 2 related factor 2（Nrf2）， and tumor necrosis factor-α（TNF-α） were measured by enzyme linked immunosorbent assay（ELISA）， and some of the screened signaling pathways with strong correlation were verified. ResultThe results of MSI experiment showed that after 28 d of the administration of FCB powder to rats with pulmonary fibrosis， the content of L-arginine in the fibrotic regions of lung tissues was significantly different from that of rats in the model group， and the content of phosphatidylcholine was lower than that in the fibrotic region of lung tissues of rats in the model group. Western blot results confirmed that， in comparison to the model group， oral administration of FCB powder for 28 d could inhibit the elevated expression of NF-κB p65 protein in the lung tissues of rats with pulmonary fibrosis. Furthermore， high dose of FCB powder was able to significantly inhibit the expression of HO-1 after oral administration （P<0.05）. The cytokine detection results indicated that the concentrations of IL-1β， IL-6 and TNF-α in the serum of rats from the high， medium， low dosage groups of FCB were reduced by comparing with the model group， and the high dose of Chuanbeimu powder administered by gavage could significantly inhibit the trend of decreased SOD， GSH， Nrf2 contents and increased MDA content induced by bleomycin. ConclusionOral administration of FCB powder has the potential to partially ameliorate bleomycin-induced pulmonary fibrosis in rats， and its mechanism may be related to the regulation of pathways associated with inflammation（NF-κB p65） and oxidative stress（Nrf2/HO-1）.

Gout is a metabolic disease closely associated with hyperuricemia and urate deposition. Because of the complex pathogenesis， high morbidity， multiple complications， and increasingly young patients， gout has received worldwide attention. Currently， western medicine mainly treats gout by lowering the uric acid level and reducing inflammation， which， however， causes serious adverse reactions and has contraindications. Phellodendri Chinensis Cortex （PCC） is the dried bark of Phellodendron chinense， with the effects of clearing heat， drying dampness， purging fire， detoxifying， and treating sores. Studies have shown that PCC and its active components have anti-inflammatory， pain-relieving， uric acid-lowering， and anti-gout activities， with extensive sources and high safety. PCC and its active components could prevent and treat gout through multi-targets and multi-pathways， whereas the systematic review remains to be carried out. Therefore， this paper summarized the pharmacological activities and mechanisms of PCC and its active components in the treatment of gout. The available studies have shown that PCC and its active components exert the anti-gout effect by lowering the uric acid level， reducing inflammation， alleviating oxidative stress， and regulationg intestinal flora， and protecting the kidneys. Particularly， the active components represented by alkaloids contribute obviously to the therapeutic effect of of PCC. Herein， we analyzed the problems and future development of the research on PCC， aiming to provide theoretical support and a scientific basis for the research and development of new drugs against gout.

Objective To compare the changes of the Chinese Materia Medica resources(CMMR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2011-2022).Methods Using new techniques,after field investigation,collection and identification of the specimens of the animals,plants and minerals.The data of the CMMR in Sichuan found in the 4th CMMRI were analysed and compared with the data of 3rd CMMRI.Results ①9055 species of CMMR were found in Sichuan during the 4th CMMRI,including 8272 species of medicinal plants,745 species of medicinal animals and 38 species of medicinal minerals.Compared with the 3rd CMMRI,the number of CMMR found in Sichuan have greatly increased.The number of medicinal plants increased 5018 species,the number of medicinal animals increased 637 species and the number of medicinal minerals increased 5 species,too.②The medicinal plants is the main part of the CMMR,and the higher plants(7774 species)has the absolute advantage of the CMMR.The top 20 families which have plenty of plant species include Compositae,Rosaceae,Leguminosae,Ranunculaceae,etc.③ Based on the data of the CMMR of the 183 counties in Sichuan,the reserves of 235 species of wild CMMR in Sichuan is about 36.72 million ton.There were 49 CMMR which have reserves beyond 100 thousand tons,such as Arisaematis rhizoma,Epimedii folium,Cimicifugae rhizoma,Acori tatarinowii rhizoma,Gentianae macrophyllae radix,Polygoni multiflori radix etc.④In 2021,there were 215 species of CMMR cultivated in Sichuan,the main species were Aurantii fructus,Chuanxiong rhizoma,Polygonati rhizome,Salviae miltiorrhizae radix et rhizome.The planting area was 8.17 million and the production was 1.26 million ton.⑤All 183 countries were found CMMR,the number of the species of CMMR in 30 countries exceeded 800,including 16 countries which had more than 1000 kinds of CMMR,such as Emeishan,Hongya,Muli etc.The total types of the CMMR(up 118.31%),the reserves of the wild CMMR(up 119 times)and the number of the counties(up 3 times)which had plenty of CMMR,showed a marked increase over the 3rd CMMRI.8 new species were found in the the 4th CMMRI,such as Codonopsis atriplicifolia,Tongoloa tagongensis,Allium xinlongense,etc.Conclusion The species,the reserves of the CMMR and the resource rich countries in Sichuan are the top 3 in China and Sichuan is worthy of the title of"Hometown of Traditional Chinese Medicine".The compositions and types of the family,genus and species of the CMMR in Sichuan have significantly increased.The basic information of the CMR in Sichuan was clearly found out during the 4th CMMRI,and beneficial for the sustainable development and utilization of the CMMR in Sichuan.

The establishment of a traceability system for the entire industry chain of Chinese medicinal materials can enhance regional brand building,raise the quality awareness of medicinal material producers,standardize the production processes of Chinese medicinal materials,and ensure the production of high-quality medicinal materials.Sichuan Province has successfully implemented a provincial-level Traditional Chinese Medicine(TCM)tracing system that is interconnected across provinces,cities,and counties.This system enables the complete tracking of the entire supply chain,starting from seed and seedling cultivation,through planting and breeding,harvesting and processing,and finally to the production and distribution of decoction pieces in trade and medical institutions.This research provides a comprehensive overview of the progress made in establishing the Chinese herbal medicine traceability system in Sichuan Province.It analyzes the existing challenges faced by participating enterprises,such as the hierarchy of involvement,information integrity,and the overall impact of the system.Moreover,the paper presents valuable insights and suggestions for the further development of the Chinese herbal medicine traceability system in Sichuan Province.These recommendations focus on enhancing the traceability scope,improving service capabilities,promoting data sharing,and establishing standardized norms and guidelines.

Sichuan Province is located across several major geomorphic units,such as the Qinghai Tibet Plateau,Hengduan Mountains,the Yunnan-Guizhou Plateau,Qinling Bashan Mountains,and Sichuan Basin.The complex ecological environment has created rich plant species.Based on the results of the fourth national survey of traditional Chinese medicine resources in Sichuan Province,according to the plant catalog in the,The results indicate that Sichuan has a total of 42 families,65 genera,and 116 species(including sub species)of medicinal plants under national key protection,there are 9 species such as lotus leaf fern under first level protection,and 107 species such as golden haired dog under second level protection.The distribution of rare and endangered medicinal plants in Sichuan Province has obvious regional characteristics,with the highest distribution in Leshan and Ganzi,and obvious vertical distribution.There are as many as 57 species distributed in high-altitude areas such as Ganzi Prefecture and Aba Prefecture.The endangered reasons for the key protected medicinal plants in Sichuan Province are mostly caused by human destruction and environmental damage.It is suggested to strengthen the protection of rare and endangered medicinal plant resources and develop and utilize them reasonably.

Objective To Provide basic information for the development of traditional Chinese medicine in the region by collating medicinal plant resources in Southern Sichuan Economic Zone.Methods The list was formed in Southern Sichuan Economic Zone by collecting and verifying Medicinal Plant Resources in 28 Counties(Districts)of the Southern Sichuan Economic Zone.The species composition,family structure,life type,threated degree of the medicine plants resources,the medicinal parts of key medicinal plants included,main cultivated medicinal herbs in the pharmacopoeia were statistically analysed for searching for the diversity of medicinal plant resources.Results The medicinal plant resources included 201 families,979 genera,2555 species.Herbaceous medicinal plants accounted for the largest proportion in both species and quantity.There are 270 species listed in the Chinese pharmacopoeia and 72 threatened and protected species among the medicinal plant resources.Conclusion The diversity of medicinal plant resources in the South Sichuan Economic Zone is prominent,and it can be reasonably developed,utilized,and protected.It is suggested to formulate effective protection measures for wild medicinal plant resources based on regional environmental characteristics,and rationally and sustainably develop and utilize high-quality medicinal plant resources with local characteristics.

Objective To compare the changes of the medical animal resources(MAR)in Sichuan based on the data of the 3rd Chinese Materia Medica Resource Inventory(CMMRI,1983-1986)and the 4th CMMRI(2020-2022).Methods After field investigation and identification of the photos of the animals,the data of the MAR in Sichuan found in the 4th CMMRI were analyzed and compared with the data of 3rd CMMRI.Results 745 species of MAR were found in Sichuan during the 4th CMMRI,including 212 families and 468 genera.Compared with the 108 species found in 3rd CMMRI,the number of MAR in Sichuan had greatly increased,The Aves was found to have 243 species of MAR,which is the most plenty one among the 7 classes.There were 14 families which have more than 10 species of MAR.The family,Cyprinidae had 48 species of MAR.There were 33 common Chinese medicinal herbs and 3 genuine medicinal materials including Cordyceps sinensis,musk and Venenum bufonis were found in this investigation.The new distributions of Liangshan Cordyceps and Cordyceps gunnii were found in the investigation,and the new resources of Atypus heterothecus was found in Mountain Emei.There were 140 species of key protection of wild medicinal animals,including 44 species of animals under first-class protection and 96 species of animals under second-class protection.There were 230 species of animals which had important ecological,scientific,and social values,too.Conclusion Sichuan was plenty of medical animal resources and the protection of the forest musk deer,the Cordyceps sinensis and the pangolin was need to be strengthened.

Objective Investigate the types and reserves of key Chinese medicinal materials in Sichuan Province,and provide scientific basis for the sustainable utilization of traditional Chinese medicine resources in Sichuan Province.Methods Using a combination of field sample survey,market visit survey,and cultivation visit survey,we investigated the varieties and reserves of key Chinese medicinal materials in 183 county-level administrative regions in Sichuan Province.Results Sichuan Province has included 358 key varieties in the 2020 edition of the Chinese Pharmacopoeia,including 133 key medicinal materials under market investigation and 225 key medicinal materials under field investigation.The investigation discovered 325 key plant medicinal materials,14 key animal medicinal materials,14 key mineral medicinal materials,and 5 key fungal medicinal materials.We have completed a survey on the quantity and weight of 134 key Chinese medicinal materials,and calculated the reserve information of 134 key medicinal materials through the National Traditional Chinese Medicine Resource Census Database System.Conclusion Sichuan Province has abundant types of key traditional Chinese medicine resources,accounting for 51.3%of the total number of key varieties in the country.The resource reserves are large,exceeding 20 million tons,but some varieties of resources are severely damaged and urgently need to be protected.