Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

BACKGROUND:Cartilaginous endplate stromal homeostasis is closely related to intervertebral disc degeneration.Acupotomy that releases posterior wall ligamentum flavum of the interforaminal orifice can improve the symptoms of patients with lumbar disc degeneration.Whether the mechanism of action is related to the regulation of cartilaginous endplate stromal homeostasis remains to be clarified.OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife relaxation of the internal orifice of the rabbit L7/S1 intervertebral foramina on the matrix homeostasis of the rabbit cartilage endplate.METHODS:A total of 24 male New Zealand rabbits were randomly divided into a control group(n=6)and a modeling group(n=18).Lumbar disc degeneration modeling was performed by intermittent standing after transection of the supraspinous interspinous ligament for 12 weeks.After modeling,the modeling group was randomly divided into model group,needle-knife group and fake needle knife group,with 6 rabbits in each group.In the needle-knife group,the ultrasound-guided needle-knife released the ligamentum flavum posterior wall of the right intervertebral foramina,while in the fake needle-knife group,the needle-knife only reached the surface of the posterior wall ligamentum flavum of the intervertebral foramina,with a total of four interventions,each time at an interval of 1 week.No intervention was performed in the control and model groups.Thirty days after the intervention,the disc degeneration was observed by MRI.The morphology of L7/S1 intervertebral disc cartilaginous endplate,nucleus pulposus and annulus fibrosus were observed with hematoxylin-eosin and safranin O-fast green staining and was then scored.The expressions of type II collagen,proteoglycan and matrix metalloproteinase-13 in nucleus pulposus and cartilage endplate of L7/S1 intervertebral disc were detected by immunohistochemistry.RESULTS AND CONCLUSION:MRI results showed that the relative gray value of L7/S1 nucleus pulposus was significantly lower in the model group than in the control group(P<0.01),and higher in the needle-knife group than in the model group and the fake needle-knife group(P<0.05).Hematoxylin-eosin and safranin O-fast green staining showed obvious degeneration of the nucleus pulposus and annulus fibrosus,thinning of the cartilaginous endplate,and obvious calcification at the junction with bone endplate in the model group.The morphology of the cartilaginous endplate and degeneration of the nucleus pulposus were improved in the needle-knife group compared with the model group.The morphological scores of the model group,needle-knife group and fake needle-knife group were significantly higher than those of control group(P<0.01).The morphological score of the needle-knife group was significantly lower than that of the model group and fake needle-knife group(P<0.01).Immunohistochemistry results showed that compared with the control group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate in the model group and fake needle-knife group were significantly decreased(P<0.01),while the expression of matrix metalloproteinase-13 was significantly increased(P<0.01).Compared with the model group and fake needle-knife group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate were increased in the needle-knife group(P<0.05),while the expression of matrix metalloproteinase-13 was decreased significantly(P<0.01).In conclusion,the relaxation of the interforaminal orifice by needle knife can regulate the matrix homeostasis of the rabbit cartilage endplate and improve the degeneration of the intervertebral disc.

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.

Background and purpose:Next generation sequencing-identified genetic alterations of diffuse large B cell lymphoma(DLBCL)and baseline SUVmax detected by 18F-FDG PET/CT were correlated with patients'prognosis.However,their relationship and the associations with R-CHOP response of DLBCL are still unclear.This study aimed to analyze the association bewteen genetic alterations and 18F-FDG PET/CT SUVmax and their correlations with clinicopathological characteristics and R-CHOP response of DLBCL.Methods:A total of 225 cases of primary DLBCL detected by next generation sequencing using 481 lymphoma gene panel and examined by 18F-FDG PET/CT before treatment between 2022 and 2023 were collected.This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethical No.:050432-4-2307E)and acquired the informed consent of the patients.The translocations of BCL2,BCL6 and MYC were identified by fluorescence in situ hybridization.The clinicopathological characteristics and the PET/CT scan after R-CHOP chemotherapy were collected.Results:Finally,191 patients were enrolled in this study.The frequency of MYD88 mutation,TP53 mutation,copy number variations of CDKN2A/2B,CD79B mutation in the 191 DLBCL patients were 24.6%,27.2%,32.5%and 16.8%,respectively.The range of baseline SUVmax was 5.10-63.10(24.44±10.70,median 22.80).The baseline SUVmax of MYD88L265P DLBCL was significantly higher than that of MYD88 wild type(P=0.039).There were no significant associations of SUVmax with other gene alterations including TP53 mutation,CDKN2A/B loss,CD79B mutation,KMT2D mutation,TNFAIP3 mutation,B2M mutation,EZH2 mutation,BTG1/2 mutation,CREBBP mutation,gene translocations of MYC,BCL2 and BCL6.The higher SUVmax before treatment was correlated with higher serum lactate dehydrogenase(LDH)level(P=0.012)and non-germinal center B-cell-like(non-GCB)DLBCL(P=0.040).However,there was no significant association of SUVmax with R-CHOP response(P=0.714).TP53 mutation was significantly associated with the poor response of R-CHOP(P=0.001)and was an independent predictor of non-complete metabolic response(non-CMR).TP53 mutation combined with Ann Arbor stage,International Prognostic Index(IPI)score and serum LDH level could better predict R-CHOP response than each factor alone.Conclusion:MYD88L265P DLBCL had higher baseline 18F-FDG PET/CT SUVmax.The baseline SUVmax was not associated with R-CHOP response.However,TP53 mutation was significantly correlated with poor response of R-CHOP in DLBCL patients.TP53 mutation combined with clinicopathological characteristics could better predict R-CHOP response.The associations of gene alterations and SUVmax with prognosis of DLBCL patients needed to be explored in the future.

BACKGROUND:Cartilaginous endplate stromal homeostasis is closely related to intervertebral disc degeneration.Acupotomy that releases posterior wall ligamentum flavum of the interforaminal orifice can improve the symptoms of patients with lumbar disc degeneration.Whether the mechanism of action is related to the regulation of cartilaginous endplate stromal homeostasis remains to be clarified.OBJECTIVE:To investigate the effect of ultrasound-guided needle-knife relaxation of the internal orifice of the rabbit L7/S1 intervertebral foramina on the matrix homeostasis of the rabbit cartilage endplate.METHODS:A total of 24 male New Zealand rabbits were randomly divided into a control group(n=6)and a modeling group(n=18).Lumbar disc degeneration modeling was performed by intermittent standing after transection of the supraspinous interspinous ligament for 12 weeks.After modeling,the modeling group was randomly divided into model group,needle-knife group and fake needle knife group,with 6 rabbits in each group.In the needle-knife group,the ultrasound-guided needle-knife released the ligamentum flavum posterior wall of the right intervertebral foramina,while in the fake needle-knife group,the needle-knife only reached the surface of the posterior wall ligamentum flavum of the intervertebral foramina,with a total of four interventions,each time at an interval of 1 week.No intervention was performed in the control and model groups.Thirty days after the intervention,the disc degeneration was observed by MRI.The morphology of L7/S1 intervertebral disc cartilaginous endplate,nucleus pulposus and annulus fibrosus were observed with hematoxylin-eosin and safranin O-fast green staining and was then scored.The expressions of type II collagen,proteoglycan and matrix metalloproteinase-13 in nucleus pulposus and cartilage endplate of L7/S1 intervertebral disc were detected by immunohistochemistry.RESULTS AND CONCLUSION:MRI results showed that the relative gray value of L7/S1 nucleus pulposus was significantly lower in the model group than in the control group(P<0.01),and higher in the needle-knife group than in the model group and the fake needle-knife group(P<0.05).Hematoxylin-eosin and safranin O-fast green staining showed obvious degeneration of the nucleus pulposus and annulus fibrosus,thinning of the cartilaginous endplate,and obvious calcification at the junction with bone endplate in the model group.The morphology of the cartilaginous endplate and degeneration of the nucleus pulposus were improved in the needle-knife group compared with the model group.The morphological scores of the model group,needle-knife group and fake needle-knife group were significantly higher than those of control group(P<0.01).The morphological score of the needle-knife group was significantly lower than that of the model group and fake needle-knife group(P<0.01).Immunohistochemistry results showed that compared with the control group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate in the model group and fake needle-knife group were significantly decreased(P<0.01),while the expression of matrix metalloproteinase-13 was significantly increased(P<0.01).Compared with the model group and fake needle-knife group,the expressions of type II collagen and Aggrecan in the nucleus pulposus and cartilage endplate were increased in the needle-knife group(P<0.05),while the expression of matrix metalloproteinase-13 was decreased significantly(P<0.01).In conclusion,the relaxation of the interforaminal orifice by needle knife can regulate the matrix homeostasis of the rabbit cartilage endplate and improve the degeneration of the intervertebral disc.

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.

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.