Objective To explore the similarities and differences in clinical efficacy and mRNA transcriptomics characteristics between acupuncture and shallow needling at non-acupoints and to provide a basis for determining whether shallow needling at non-acupoints is suitable as a sham acupuncture control in acupuncture clinical trials.Methods Eighty patients with chronic spontaneous urticaria(CSU)who visited the Dermatology Department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between July 8,2018 and to July 29,2019,were included.The patients were randomly divided into the acupuncture group(n=41)and the sham acupuncture group(n=39)using a computerized complete random design.Additionally,12 healthy individuals were included as the healthy control group.For patients in the acupuncture group,"Baihui(GV20),""Shenting(GV24),""Zhongwan(CV12),"and bilateral"Quchi(LI11),""Tianshu(ST25),""Xuehai(SP10),""Zusanli(ST36),"and"Sanyinjiao(SP6)"were selected for regular acupuncture.The sham acupuncture group received non-acupoint shallow needling at eight non-acupoints on the head,upper limbs,lower limbs,and abdomen.Both groups underwent daily treatment,with five consecutive days constituting one treatment course followed by a two-day interval.A total of two courses were administered.The urticaria activity score(UAS)was used to evaluate wheals and pruritus,whereas the visual analog scale(VAS)score was used to evaluate the degree of pruritus.Blinding effectiveness was also evaluated.Based on clinical evaluation and sample quality,serum samples from six patients in each treatment group before and after the intervention,along with those from six healthy individuals,were selected for RNA sequencing using the BGISEQ-500 sequencer.Differentially expressed mRNAs were identified using the"DEGseq"software package,and the similarities and differences in mRNA expression between the two groups were analyzed.Results UAS and VAS scores decreased in both groups at 1,2,3,and 4 weeks of treatment compared with before treatment(P＜0.01).The decrease in UAS and VAS scores in both groups was time-dependent(P＜0.01)but not related to the grouping or the interaction between grouping and time(P＞0.05).By the end of the second week of treatment,the number of patients in both groups who believed they had received true acupuncture was similar between the two groups,with no significant difference.mRNA transcriptomic sequencing revealed that,before and after treatment,the enrichment types and degrees of differentially expressed mRNA were similar between the acupuncture and sham acupuncture groups at the biological process,cellular component,and molecular function levels.In terms of biological processes,both groups were commonly enriched in coagulation,hematoma,oxygen transport,and gas transport.In terms of cellular components,both groups exhibited enrichment in hemoglobin complexes,platelet alpha granules,extracellular exosomes,extracellular organelles,and extracellular vesicles.At the molecular function level,both groups were commonly enriched in actin filament-binding substances,haptoglobin,peroxidase activity,and oxygen blood binding.In the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,both groups showed common enrichment in multiple entries such as cytokine-cytokine receptor interaction,ECM-receptor interaction,microRNAs in cancer,proteoglycans in cancer,bladder cancer,and malaria.Conclusion Acupuncture and sham acupuncture exhibited similar clinical treatment effects and mRNA transcriptomics profiles.In the design of acupuncture clinical trials,disease specificity should be carefully considered.Sham acupuncture control using non-acupoint shallow needling may not be suitable for skin diseases such as urticaria.

Objective To explore the similarities and differences in clinical efficacy and mRNA transcriptomics characteristics between acupuncture and shallow needling at non-acupoints and to provide a basis for determining whether shallow needling at non-acupoints is suitable as a sham acupuncture control in acupuncture clinical trials.Methods Eighty patients with chronic spontaneous urticaria(CSU)who visited the Dermatology Department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine between July 8,2018 and to July 29,2019,were included.The patients were randomly divided into the acupuncture group(n=41)and the sham acupuncture group(n=39)using a computerized complete random design.Additionally,12 healthy individuals were included as the healthy control group.For patients in the acupuncture group,"Baihui(GV20),""Shenting(GV24),""Zhongwan(CV12),"and bilateral"Quchi(LI11),""Tianshu(ST25),""Xuehai(SP10),""Zusanli(ST36),"and"Sanyinjiao(SP6)"were selected for regular acupuncture.The sham acupuncture group received non-acupoint shallow needling at eight non-acupoints on the head,upper limbs,lower limbs,and abdomen.Both groups underwent daily treatment,with five consecutive days constituting one treatment course followed by a two-day interval.A total of two courses were administered.The urticaria activity score(UAS)was used to evaluate wheals and pruritus,whereas the visual analog scale(VAS)score was used to evaluate the degree of pruritus.Blinding effectiveness was also evaluated.Based on clinical evaluation and sample quality,serum samples from six patients in each treatment group before and after the intervention,along with those from six healthy individuals,were selected for RNA sequencing using the BGISEQ-500 sequencer.Differentially expressed mRNAs were identified using the"DEGseq"software package,and the similarities and differences in mRNA expression between the two groups were analyzed.Results UAS and VAS scores decreased in both groups at 1,2,3,and 4 weeks of treatment compared with before treatment(P＜0.01).The decrease in UAS and VAS scores in both groups was time-dependent(P＜0.01)but not related to the grouping or the interaction between grouping and time(P＞0.05).By the end of the second week of treatment,the number of patients in both groups who believed they had received true acupuncture was similar between the two groups,with no significant difference.mRNA transcriptomic sequencing revealed that,before and after treatment,the enrichment types and degrees of differentially expressed mRNA were similar between the acupuncture and sham acupuncture groups at the biological process,cellular component,and molecular function levels.In terms of biological processes,both groups were commonly enriched in coagulation,hematoma,oxygen transport,and gas transport.In terms of cellular components,both groups exhibited enrichment in hemoglobin complexes,platelet alpha granules,extracellular exosomes,extracellular organelles,and extracellular vesicles.At the molecular function level,both groups were commonly enriched in actin filament-binding substances,haptoglobin,peroxidase activity,and oxygen blood binding.In the Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis,both groups showed common enrichment in multiple entries such as cytokine-cytokine receptor interaction,ECM-receptor interaction,microRNAs in cancer,proteoglycans in cancer,bladder cancer,and malaria.Conclusion Acupuncture and sham acupuncture exhibited similar clinical treatment effects and mRNA transcriptomics profiles.In the design of acupuncture clinical trials,disease specificity should be carefully considered.Sham acupuncture control using non-acupoint shallow needling may not be suitable for skin diseases such as urticaria.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

Objective To explore the molecular mechanisms of moxibustion in improving osteoporosis in rats using high-throughput micro-RNA(miRNA)sequencing analysis.Methods A total of 18 female Sprague-Dawley(SD)rats were randomly divided into an operation group(12 rats),which was subjected to ovariectomy to induce osteoporosis,and a sham operation control(SO)group(6 rats).The 12 osteoporosis model rats were randomly divided into a model(OVX)group and a moxibustion(MOX)group(6 rats per group),which were treated with once-daily moxibustion at the"Shenshu"(BL23)and"Guanyuan"(CV4)acupoints for 20 minutes each time,for 12 weeks.Micro-computed tomography(CT)scans of the rat femur were taken to analyze the trabecular bone thickness(Tb.Th),trabecular separation(Tb.Sp),and bone volume total volume(BV/TV)ratio of the trabecular bone.Hematoxylin and eosin staining was used for morphological observation of tibial tissues.Serum alkaline phosphatase(ALP)and osteocalcin(OCN)levels were measured using ELISA.Three randomly selected rats from each group were used for miRNA high-throughput sequencing to screen for differentially expressed miRNAs,which were subjected to functional enrichment analysis and target gene prediction.Results Micro-CT images showed that,compared with the OVX group,the MOX group had superior bone density,significant increases in the Tb.Th and BV/TV score,and a significant decrease in Tb.Sp(P＜0.05).ELISA indicated that,compared with the OVX group,the MOX group showed a significant decrease in serum ALP activity and a significant increase in serum OCN content(P＜0.05).The miRNA sequencing result showed that 34 miRNAs were commonly expressed between the OVX group and the intervention group,and 15 miRNAs were commonly expressed between the OVX group and the intervention group.KEGG pathway enrichment analysis showed that the differentially expressed genes were mainly enriched in signaling pathways involving MAPK,Ras,FoxO,TNF,and cancer-related microRNAs.For the top five most differentially expressed microRNAs,namely miR-153-5p,miR-201-5p,miR-449c-5p,miR-451-3p,and miR-153-3p,target gene predictions yielded 10 major targets:Ebf2,Rtn4,Fbxl3,Naa15,Vamp2,Daam1,Akap6,Camta1,Ptprz1,and Lamp1.Conclusions Acupuncture slowed the progression of osteoporosis,improved bone microstructure,and balanced bone metabolism in rats.This therapeutic effect may be achieved through regulation of the expression of microRNAs and their target genes;however,the underlying mechanism requires further exploration.

Objective:To explore the neurophysiological features of the prefrontal-limbic-striatal circuit in patients with early-stage bipolar disorder without manic or hypomanic episodes, and its role in identifying early-stage bipolar disorder.Methods:From 2009 to 2019, a total of 155 hospitalized patients with major depressive disorder (MDD) from Nanjing Brain Hospital were selected after at least 5 years of follow-up, 31 patients with depression transitioned to bipolar disorder(ctBD group) and 76 patients remained the diagnosis of MDD(MDD group) were recruited.Sixty-two healthy controls matched for age, gender, and education years were selected as control group(HC group). Resting-state magnetoencephalography (MEG) data in eyes-open state of all subjects were collected.Data were analyzed based on the fieldtrip toolkit on the MATLAB platform. The key brain area of the prefrontal-limbic-striatal circuit were selected. Inter-group statistical analysis were conducted on the spectral energy and power-correlated functional connectivity at the theta, alpha, beta, and gamma frequency bands in the brain area of interest. In addition, the prediction model was constructed to early recognize bipolar disorder.Results:(1)There were statistically significant differences in the spectral energy of theta and alpha frequency bands in the prefrontal-limbic-striatal circuit among the 3 groups (cluster- F=120.50, 112.39, both P<0.05). The spectral energy of theta and alpha frequency bands in interest brain regions of prefrontal-limbic-striatal circuit in MDD group was lower than that in HC group (cluster- t=89.52, P<0.05). The spectral energy of theta band in prefrontal-limbic-striatal circuit in ctBD group was lower than that in HC group(cluster- t=105.82, P<0.05), and the spectral energy of alpha band in inferior frontal gyrus, orbitofrontal gyrus and caudate nucleus was lower than that in HC group (cluster- t=75.78, P<0.05), while there was no significant difference between the MDD group and the ctBD group ( P>0.05).(2)After FDR correction, there were statistically significant differences in functional connectivity between the left orbitofrontal gyrus and the right ventral striatum among the three groups (0.26 (0.13, 0.34), 0.12 (0.09, 0.24), 0.27 (0.20, 0.37), H=13.51, P<0.05, FDR correction). The strength of functional connectivity between the left orbitofrontal gyrus and the right ventral striatum in the MDD group was weaker than that in the HC group and the ctBD group (all P<0.05).(3)Binary Logistic regression analysis showed that the functional connectivity of beta frequency band between the left orbitofrontal gyrus and the right ventral striatum ( B=1.50, OR=4.50, 95% CI=1.73-11.70), the functional connectivity between the right orbitofrontal gyrus and the right amygdala( B=0.98, OR=2.68, 95% CI=1.18-6.13), the total HAMD score ( B=0.80, OR=2.28, 95% CI=1.36-3.67), the body weight factor score ( B=-1.99, OR=0.14, 95% CI=0.04-0.45), the anxiety factor score ( B=-0.99, OR=0.37, 95% CI=0.19-0.71), and sleep factor score( B=-1.14, OR=0.32, 95% CI=0.16-0.65)were the influencing factors for depression transitioned to bipolar disorder. Conclusion:The decreased resting low-frequency energy in the prefrontal-limbic-striatal circuit may be the common neural basis for the onset of unipolar and bipolar depression, and enhanced functional connectivity may be a potential neural circuit mechanism for depression transitioned to bipolar disorder. Functional connectivity combined with clinical manifestations is helpful for early recognition of bipolar disorder.

Objective To explore the objective facial appearance characteristics of patients with coronary heart disease(CHD).Methods From April 7,2019 to December 1,2022,313 patients with CHD were recruited from Dongzhimen Hospital,Beijing University of Chinese Medicine,Dongfang Hospital,Beijing University of Chinese Medicine,and the First Affiliated Hospital of Hunan University of Chinese Medicine,together with 293 healthy controls.Standardized facial images were obtained using the tongue-face diagnostic instrument.The face was divided into six regions:the forehead,left cheek,right cheek,nose,lips,and chin.Nine color parameters were extracted from each region,including red(R),green(G),blue(B),hue(H),saturation(S),value(V),lightness(L),red-green axis(a),and yellow-blue axis(b).Comparisons between groups were performed.Results Compared with the healthy group,in the forehead region,values of R,S,V,a,and b were higher in the coronary heart disease group,whereas B was lower(P<0.05);in the left cheek,nose,and chin regions,R,G,B,V,and L decreased,whereas S,a,and b increased(P<0.05);in the right cheek region,R,G,B,H,V,and L decreased,while S,a,and b increased(P<0.05);in the lips region,R,G,B,H,V,L,and a decreased,whereas S and b increased(P<0.05).Conclusion Compared with healthy individuals,patients with CHD present with a darker,more saturated facial complexion with reduced brightness,overall manifesting as"dark red complexion"and"dense but not bright color,"suggesting the pathogenesis of qi and blood circulation stagnation and internal blood stasis retention.The objective expression of facial features may have greater application value in syndrome differentiation and auxiliary diagnosis in traditional Chinese medicine.

To further investigate the molecular genetic characteristics of enzomatic nasal tumor vi-rus of goats(ENTV-2)in Yunnan Province,this study measured and analyzed the entire genome of ENTV-2 in Yunnan Province.The results showed that the complete genome sequence of the EN-TV-2 YN2023 strain(GenBank accession number:PP682590.1)was successfully obtained.The YN2023 strain has a total length of 7 307 bp and a typical structure of 5'-M5-gag-pro-pol-env-M3-3'.Whole genome sequence homology analysis showed that the nucleotide homology between YN2023 strain and 41 reference strains ranges from 85.3％to 95.5％.The whole genome evolution-ary tree indicates that the YN2023 strain is closely related to the prevalent strains in China,with certain genetic diversity and geographical clustering.The analysis of the gag gene evolutionary tree shows that the gag gene cluster of YN2023 strain is on a branch of the ENTV-2 gag gene,and YN2023 is clustered on the same small branch as enENTV-FJ1 and GDQY2017 strains,with the closest genetic relationship.The env gene evolutionary tree shows that YN2023 is on the same branch as GDQY2017,GDZJ2022,ENTV-2CHN1-6,ENTV-FJ1,and ENTV-FJ3,and is also on the same branch as GDQY2017,indicating a close genetic relationship.Recombination analysis showed that the YN2023 strain underwent a potential recombination event between breakpoint positions 6378-7478 bp,with the Chinese Chongqing strain enENTV-CQ1(OR669623.1)as the primary parent and the Chinese Sichuan strain BH(MT254062.1)as the secondary parent.This study enriches the genomic information of the ENTV-2 strain in Yunnan Province and provides data sup-port for the genetic variation of ENTV-2 in Yunnan Province.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes （MDS） of different traditional Chinese medicine （TCM） patterns， so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected， including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations， the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group， and according to the results of the next-generation sequencing （NGS） test， they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed， the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared， and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group （119 cases with gene mutation） and 43 cases in the qi-yin deficiency group （23 cases with gene mutation）. No statistically significant differences were noted in effectiveness assessment， total effective rate， and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group （P＞0.05）. In the spleen-kidney deficiency group， the total effective rate of MDS with gene mutation was 65.55% （78/119）， which was lower than 80.28% （57/71） of MDS without gene mutation， with statistical significance （P = 0.033）， while no statistical differences in effectiveness assessment and total response rate were noted （P＞0.05）. In the qi-yin deficiency group， no statistical differences were observed in effectiveness assessment， total effective rate， and total response rate of the patients in with or without gene mutation （P＞0.05）. In the spleen-kidney deficiency group with gene mutation， the rate of complex karyotype （P = 0.031） and the mutation rate of CBL gene （P = 0.032） in the ineffective population were higher than those in the effective population， while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population （P = 0.033）. No statistically significant differences were found in other gene mutations， age， gender distribution， number of gene mutations， bone marrow hyperplasia degree， blast cell range， reticular fiber tissue proliferation or not， and prognosis of chromosomal abnormalities between the effective and ineffective populations （P＞0.05）. In the qi-yin deficiency group with gene mutation， no statistically significant differences were found in various items between populations with different outcomes （P＞0.05）. Multivariate Logistic regression analysis showed that complex karyotype， CBL mutation， and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation （P＜0.05）. DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group （OR＞1）， while complex karyotype and CBL mutation were independent risk factors （OR＜1）. ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation； and in MDS with spleen-kidney deficiency pattern without complex karyotypes， CBL mutation， and with DDX41 mutations. Furthermore， DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group， while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern， gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.