Rheumatoid arthritis （RA） is a chronic autoimmune disease with a complex pathogenesis. Immune dysfunction， synovial inflammation， and bone destruction are the key pathological links. The theory of "harmful hyperactivity and responding inhibition" is a high-level summary of the coordinated development of things in nature and the generation and restriction of the five elements and the six factors in nature. People and all things have the same origin， and the theory of "harmful hyperactivity and responding inhibition" represents the intrinsic regulation mechanism of the human body's homeostasis， reflecting the unity of opposites of "hyperactivity" and "inhibition" and emphasizing coordination and stabilization. In the pathogenesis of RA， the excessive immune response disrupts the normal body balance， which is closely related to the process of "hyperactivity becoming harmful". Synovial inflammation， tissue hyperplasia， and bone destruction are pathological results of the dysregulation of the body's immune self-stabilization function and can be regarded as the process of "failing to inhibition". Therefore， the theory of "hyperactivity harmful hyperactivity and responding inhibition" provides a unique perspective for understanding the modern pathological mechanisms of RA. Based on the theory of "harmful hyperactivity and responding inhibition" and the pathogenesis of RA， the author analyzed the modern medical basis of RA from the perspective of traditional Chinese medicine （TCM） and revealed the intrinsic connection between TCM pathogenesis such as insufficiency of vital energy and blood， strong defensive Qi and weak nutrient Qi， and intertwined phlegm and blood stasis and modern research on autoimmune disorders， synovial inflammation， and bone destruction. With the therapeutic criterion of "harm inhibition and responsible supporting"， the article summarized the mechanism of TCM in calming hyperactivity and supporting invincibility， which provided theoretical references for the clinical treatment of RA.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.

Objective:To investigate the molecular expression and pathological features of endothelial cell (EC) in a murine model of choroidal neovascularization (CNV) based on single-cell RNA sequencing (scRNA-seq).Methods:Six C57BL/6 mice aged 6-8 weeks were randomly divided into two groups, with 3 mice in each group.Bilateral eyeballs were enucleated.The choroidal tissues from the two groups were isolated by shearing the complex and scraping the choroid, respectively.Single-cell suspension was prepared by continuous digestion with trypsin/type Ⅰ collagenase at 37 ℃, and the cell viability and EC ratio were detected by flow cytometry to determine the preparation method of single-cell suspension.Another 6 mice were randomly assigned into the control group and the CNV group, with 3 mice in each group.The CNV model was induced by laser photocoagulation and single-cell suspensions were prepared 7 days after modeling.Gene expression library construction was performed using the Chromi-um (10x Genomics) instrument.High throughput sequencing was performed using the Illumina Novaseq6000 to obtain the expression matrix.The EC subpopulations were classified according to previous researches and the Cellmarker database.Pseudo-time analysis was performed in EC, revealing the gene expression matrix of different states.CNV-EC were further selected with preliminary analysis of the expression characteristics.Another 6 mice were selected to establish the CNV model and eyeball frozen sections were prepared 7 days after modeling.Expression and distribution as well as the area percentage of EC marker Pecam1, mitochondrial outer membrane proteins Tomm20 and mt-Co1, and capillary markers Kdr and Plvap were observed by immunofluorescence staining, and the vascular diameter was calculated.The use and care of animals followed the ARVO statement.This study protocol was approved by the Experimental Animal Welfare and Ethics Committee of Air Force Military Medical University (No.20200181).Results:The cell viability of the single-cell suspension prepared from choroidal-scleral fragments and choroidal scrapings was 99.4% and 99.1%, respectively, both of which met the sequencing requirements.The percentage of EC detected by flow cytometry was approximately 1.58%.The scRNA-seq result revealed that both the normal control and CNV groups contained 13 choroidal cell clusters.Compared with the normal control group, the proportions of rod/cone photoreceptor cells, EC and hematopoietic cells all increased, while the retinal pigment epithelium (RPE) and Schwan cells reduced in the CNV group.Among all clusters, EC constituted 18.4%.The pseudo-time analysis demonstrated that EC could be further divided into 4 states.The percentage of state 2 EC was 29.1% in the CNV group, which was significantly higher than 9.5% in the normal control group.Differentially expressed gene analysis showed that the expression of mitochondrion-related genes, including mt-Nd4 and mt-Atp6, were upregulated in state 2 EC, while capillary-related genes, including Kdr and Esm1, were downregulated.Immunofluorescent staining revealed that the area of Tomm20 and mt-Co1 in Pecam1-positive EC in the CNV area was (19.50±4.68)% and (4.64±2.82)%, respectively, which were both higher than (3.00±2.09)% and (0.18±0.34)% in normal area ( t=7.88, 3.84; both at P<0.01). The area of Kdr and Plvap in Pecam1-positive EC in the CNV area was (1.50±0.29)% and (0.79±0.97)%, respectively, which were both lower than (31.30±5.44)% and (10.43±2.28)% in the normal area ( t=13.40, 9.48; both at P<0.01). The vascular diameter in the CNV area was (5.52±1.85)μm, which was larger than (4.21±1.84)μm in the normal area ( t=9.57, P<0.001). Conclusions:When CNV occurs, the proportion of EC in choroid increases, and CNV-EC shows pathologic features of mitochondrial metabolic activation and loss of capillary properties, suggesting the mitochondrial activation of EC may play a role in the formation of CNV.

Objective:To study the impact of number and location of metastatic lymph nodes on prognosis of patients after radical resection for intrahepatic cholangiocarcinoma (ICC).Methods:A retrospective study was conducted on 105 patients who underwent radical resection and lymphadenectomy for ICC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2010 to December 2020. There were 49 males and 56 females, with age of (58±10) years old. These patients were divided into 2 groups using the TNM staging (8th edition) into the N0 stage group ( n=62) and N1 stage group ( n=43). Using the NMLN staging, those with 0, 1-2, and >3 number of metastatic lymph nodes (NMLN) were divided into 3 groups: the stage 0 group ( n=62), stage 1 group ( n=24), and stage 2 group ( n=19). Of the 43 patients with lymph node metastasis, they were divided into 2 groups according to whether the lymph node metastasis was limited to the first lymph node station: the first station metastasis group ( n=11) and the non-first station metastasis group ( n=32). The general data, extent of lymph node dissection, pathological examinations, and postoperative survival outcomes of these patients were collected. Determination of risk factors for prognosis of ICC after radical resection was carried out. Results:The median number of lymph node harvested, or the detection of N0 and N1 staging were 6 (3, 8) and 6 (3, 10), respectively. There were no significant differences between the two groups ( Z=-1.10, P>0.05). Overall survival of patients in the N0 stage group was better than the N1 stage group (32.0 vs. 9.0 months, χ 2=23.99, P<0.001). The median survival times of patients in the stage 0, stage 1 and stage 2 groups were 32.0, 14.0 and 6.0 months, respectively. There was a significant difference in overall survival among the 3 groups (χ 2=32.18, P<0.001). The time-dependent receiver operating characteristic curves showed that NMLN staging had better prognostic predictive ability than the N staging. The median survival times of the first station metastasis group and the non-first station metastasis group were 18.0 and 7.0 months, respectively. There was no significant difference between the two groups (χ 2=2.21, P>0.05). Multivariate analysis showed that tumor carbohydrate antigen 125>35.0 U/ml ( HR=4.297, 95% CI:2.418-7.634), hepatolithiasis ( HR=2.713, 95% CI:1.499-4.911), T4 staging ( HR=2.934, 95% CI:1.478-5.825), NMLN stage 1 ( HR=2.759, 95% CI:1.500-5.077) and NMLN stage 2 ( HR=7.376, 95% CI:3.553-15.312) were independent risk factors affecting prognosis of ICC after radical resection ( P<0.05). Conclusion:Lymph node metastasis was an important poor prognostic risk factor after radical resection of intrahepatic cholangiocarcinoma. The prognosis of ICC patients was related to the NMLN, but it was not related to the location of metastatic lymph nodes.

ObjectiveTo observe the effect of aqueous extract of Sophorae Tonkinensis Radix et Rhizoma （STRR） on rheumatoid arthritis （RA） and to explore the anti-bone destruction mechanism based on phosphatidylinositol 3-kinase （PI3K）/serine/threonine-protein kinase （Akt） pathway. MethodHigh-performance liquid chromatography （HPLC） was used to determine the content of main active components in aqueous extract of STRR， and type Ⅱ collagen to induce RA （CIA） in mice. The blank group， model group， methotrexate （MTX） group （0.5 mg·kg^-1）， and low-dose （100 mg·kg^-1） and high-dose （200 mg·kg^-1） STRR aqueous extract groups were designed. Joint swelling was observed and clinical scores of CIA mice were calculated. Pathological changes of mouse joints were observed based on hematoxylin and eosin （HE） staining， and Micro-CT was performed to monitor joint destruction. TRAP staining was used to observe osteoclast formation in mouse joint， and Western blot to detect the expression of key proteins in PI3K/Akt signaling pathway in mouse joint tissue. ResultThe model group demonstrated higher degree of joint swelling， clinical scores of CIA， and degrees of synovial hyperplasia， inflammatory cell infiltration （P<0.01）， and joint destruction， more osteoclasts， and higher levels of matrix metallopeptidase-9 （MMP-9）， cathepsin K （CTSK）， nuclear factor of activated T-cells cytoplasmic 1 （NFATc1）， PI3K， and phosphorylated-Akt （p-Akt） proteins than the blank group （P<0.01）. Compared with the model group， the low-dose and high-dose aqueous extract of STRR alleviated joint swelling， reduced the clinical scores of CIA mice （P<0.05， P<0.01）， relieved the pathological changes of joint tissue （P<0.01） and joint destruction， decreased osteoclasts （P<0.05， P<0.01）， and lowered the levels of PI3K/Akt signaling pathway-related proteins in joint tissue of mice （P<0.01）. ConclusionThe aqueous extract of STRR can significantly delay the inflammatory response of RA and especially inhibit bone destruction by down-regulating the PI3K/Akt signaling pathway.

ObjectiveTo investigate the therapeutic effect of Qingmei compound on acute gouty arthritis （AGA） in rats and preliminarily clarify its mechanism. MethodForty male SD rats were randomly divided into a blank group， a model group， a colchicine group （0.3 mg·kg^-1）， and low- and high-dose Qingmei compound groups （200 and 400 mg·kg^-1）， with eight rats in each group. The AGA model was induced by injecting 50 g·L^-1 monosodium urate （MSU） into the ankle joint of the rats except those in the blank group. The ankle swelling index was measured before and 6， 24， and 48 h after modeling. The pathological changes in the joint tissues of AGA rats were observed by hematoxylin-eosin （HE） staining. The expression of tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β） in the joint tissues of rats was detected by immunohistochemistry. The protein expression of NOD-like receptor protein 3 （NLRP3） pathway and key proteins in the joint tissues of rats was detected by Western blot. ResultCompared with the blank group， the model group showed increased ankle swelling index， synovial hyperplasia， and inflammatory infiltration， and up-regulated expression of IL-1β， TNF-α， and NLRP3 proteins in the ankle joint and the ratio of Caspase-1 shear body to Caspase-1 precursor protein （Caspase-1 p20/Caspase-1） （P<0.01）. Compared with the model group， the Qingmei compound groups showed reduced ankle swelling index of AGA rats， especially the low-dose Qingmei compound group （P<0.01）. Meanwhile， Qingmei compound inhibited synovial hyperplasia and inflammatory infiltration （P<0.01） and reduced the levels of IL-1β， TNF-α， and NLRP3 proteins and Caspase-1 p20/Caspase-1 in joint tissues （P<0.01）. ConclusionQingmei Compound can significantly alleviate the joint swelling and inflammatory infiltration of AGA， and its mechanism may be related to the inhibition of the NLRP3 signaling pathway.

Objective:To examine the correlation between perineural invasion and clinicopathological factors and the role of perineural invasion on the prognosis of patients with curatively resected gallbladder carcinoma.Methods:The clinicopathological and follow-up data of 548 patients with gallbladder carcinoma who underwent radical surgery from the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2020 were analyzed retrospectively. There were 173 males and 375 females,with age( M(IQR)) of 62(14)years(range:30 to 88 years). The correlations between perineural invasion and the clinicopathological features were analyzed. The relationship between prognosis and clinicopathological factors were further analyzed. The survival curve was drawn using the Kaplan-Meier method. The univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results:Radical resection was performed in 548 cases,including 59 cases(10.8%) with perineural invasion. The results of univariate analysis showed that perineural invasion was related to serum bilirubin level,serum carcinoembryonic antigen(CEA) level,CA19-9 level,T stage,lymph node metastasis,liver invasion,vessel invasion and tumor location(all P<0.05).The results of multivariate analysis showed that jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder were independent risk factors of perineural invasion in gallbladder carcinoma. Survival of 367 patients in T3-T4 stages were analyzed. The prognosis of gallbladder carcinoma patients with perineural invasion was significantly worse than that of patients without perineural invasion(median survival time:12.0 months vs. 34.7 months, P<0.01). Univariate analysis showed that perineural invasion,gallbladder stones,gallbladder polyps,CA125,CEA,CA19-9,serum bilirubin level,tumor location,N stage,liver invasion and pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). The results of Cox proportional hazard model showed that perineural invasion,N stage,liver invasion,gallbladder stones,pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). Conclusions:Jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder are independent risk factors for perineural invasion of gallbladder carcinoma. Perineural invasion is one of the independent risk factors affecting the prognosis of T3-T4 stage gallbladder carcinoma.

Objective:To examine the correlation between perineural invasion and clinicopathological factors and the role of perineural invasion on the prognosis of patients with curatively resected gallbladder carcinoma.Methods:The clinicopathological and follow-up data of 548 patients with gallbladder carcinoma who underwent radical surgery from the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2020 were analyzed retrospectively. There were 173 males and 375 females,with age( M(IQR)) of 62(14)years(range:30 to 88 years). The correlations between perineural invasion and the clinicopathological features were analyzed. The relationship between prognosis and clinicopathological factors were further analyzed. The survival curve was drawn using the Kaplan-Meier method. The univariate analysis and multivariate analysis were done using the Log-rank test and Cox proportional hazard model respectively. Results:Radical resection was performed in 548 cases,including 59 cases(10.8%) with perineural invasion. The results of univariate analysis showed that perineural invasion was related to serum bilirubin level,serum carcinoembryonic antigen(CEA) level,CA19-9 level,T stage,lymph node metastasis,liver invasion,vessel invasion and tumor location(all P<0.05).The results of multivariate analysis showed that jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder were independent risk factors of perineural invasion in gallbladder carcinoma. Survival of 367 patients in T3-T4 stages were analyzed. The prognosis of gallbladder carcinoma patients with perineural invasion was significantly worse than that of patients without perineural invasion(median survival time:12.0 months vs. 34.7 months, P<0.01). Univariate analysis showed that perineural invasion,gallbladder stones,gallbladder polyps,CA125,CEA,CA19-9,serum bilirubin level,tumor location,N stage,liver invasion and pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). The results of Cox proportional hazard model showed that perineural invasion,N stage,liver invasion,gallbladder stones,pathological differentiation were independent risk factors affecting prognosis of patients with gallbladder carcinoma(all P<0.05). Conclusions:Jaundice,high-level serum CA19-9,high-level serum CEA,T4 stage,vessel invasion and tumor located in the neck or cystic duct of the gallbladder are independent risk factors for perineural invasion of gallbladder carcinoma. Perineural invasion is one of the independent risk factors affecting the prognosis of T3-T4 stage gallbladder carcinoma.

To investigate the clinical manifestations and imaging characteristics of patients with different types of infectious sacroiliitis. Clinical data of 40 patients diagnosed with infectious sacroiliitis were retrospectively analyzed. Among the 40 patients, 16 patients were diagnosed as non-brucellar and non-tuberculous infectious sacroiliitis (ISI), 13 with tuberculous infectious sacroiliitis (TSI), and 11 with brucellar sacroiliitis (BSI). In the ISI and TSI group, female patients accounted for 11/16, 12/13, while the proportion of unilateral involvement was 15/16 and 12/13, respectively. Compared with ISI and TSI group, BSI patients were mainly male (8/11) and presented more bilateral involvement (6/11) ( P<0.05). Bone erosion was more common in ISI and TSI groups than in BSI group (6/15, 7/11 and 2/10), as well as abscess formation (3/15, 4/11 and 1/10, respectively). Symptoms in all patients relieved 1-2 weeks after administration of antibiotics or anti-tuberculosis treatment, but the resolution of the magnetic resonance imaging findings delayed about 6 (3-9) months. ISI and TSI patients with infectious sacroiliitis should be differentiated from spondyloarthritis, with a characteristic of more female patients, unilateral sacroiliitis, bone erosion, soft tissue involvement and abscess formation. However, BSI patients are mainly male, more bilateral involvement and less bone destruction and abscess formation. Antibiotic therapy demonstrates significant therapeutic effects, but resolution of the magnetic resonance imaging findings responses late.

Objective:To evaluate the related factors of gallstones related gallbladder intraepithelial neoplasia(GBIN) and establish the prediction models for gallstones related GBIN.Methods:The clinicopathological data of 750 patients who underwent cholecystectomy for gallstones at Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2018 and the postoperative pathological examination showed chronic cholecystitis or GBIN were analyzed retrospectively,including 150 cases of gallstones with GBIN and 600 cases of gallstones with chronic cholecystitis.There were 264 males and 486 females with age of (51.3±14.5) years (range: 18 to 90 years).The related factors for gallstones related GBIN were screened by χ 2 test and Logistic regression model,and the prediction models were established based on independent related factors and internal validation was conducted.The original data were randomly divided into a training cohort(526 cases) and a validation cohort(224 cases) at a ratio of 7∶3,and the nomogram and tree augmented na?ve Bayes were conducted to establish the prediction model for gallstones related GBIN.The consistency index(C-index),calibration chart,area under the receiver operating characteristic curve(AUC) and confusion matrix were used to evaluate the prediction performance of the two models. Results:Univariate analysis showed that age,gallstones history(years),gallbladder size,whether the gallbladder mucosa smooth or not,whether the gallbladder wall thickened or not,gallstones diameter,and number of gallstones were related factors for the occurrence of gallstones related GBIN (χ2=19.957,8.599,9.724,9.301,8.341,15.288,9.169,all P<0.05).Multivariate analysis showed that age ( OR=2.23,95% CI:1.50-3.31, P<0.01),gallbladder size ( OR=2.11,95% CI:1.17-3.80, P=0.013),whether the gallbladder mucosa smooth or not ( OR=1.80,95% CI:1.13-2.88, P=0.014),gallstones diameter( OR=2.98,95% CI:1.71-5.21, P<0.01),and number of gallstones ( OR=2.14,95% CI:1.34-3.42, P<0.01) were independent related factors for the occurrence of gallstones related GBIN; the C-index of the nomogram in training cohort and validation cohort were 0.708 and 0.696,respectively.The AUC of the two models in training cohort were 70.60% and 70.73%,and in validation cohort were 68.14% and 67.47%,respectively.The accuracy of the two models in training cohort were 69.96% and 70.72%,and in validation cohort were 66.96% and 67.41%,respectively. Conclusion:Age,gallbladder size,whether the gallbladder mucosa smooth or not,gallstones diameter and number of gallstones are independent related factors for the occurrence of gallstones related GBIN,and the nomogram and tree augmented na?ve Bayes prediction models based on the above factors can be used to predict the occurrence of GBIN.