Primary splenic lymphoma is a rare malignant neoplasm， with similar clinical manifestations to Sjogren’s syndrome and liver cirrhosis， which often leads to misdiagnosis. This article reports a case of primary splenic lymphoma misdiagnosed as Sjogren’s syndrome with liver cirrhosis， in order to improve the understanding of primary splenic lymphoma， Sjogren’s syndrome， and liver cirrhosis and avoid misdiagnosis and treatment delay.

Ruxolitinib， a small molecule inhibitor， selectively targets Janus kinase （JAK） by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain， thereby inhibiting JAK activation and signal transducer and activator of transcription （STAT） phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream， approved by the US FDA as the first non-segmental vitiligo home treatment drug， is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis， alopecia areata， and other conditions， indicating great application prospects.

Objective:To investigate the methylation status of SDC2, PPP2R5C and ADHFE1 genes in stool and their values in the screening of colorectal cancer and precancerous lesions.Methods:From August 2020 to March 2021, 64 patients with colorectal cancer, 72 patients with adenoma, 33 patients with hyperplastic polyps and 59 healthy people were recruited from Qingdao Central Hospital Affiliated to Qingdao University, and the morning stool samples were collected from the research subjects. The genomic DNA was extracted and modified with sulfite. The methylation status of SDC2, PPP2R5C and ADHFE1 genes were detected by methylation specific polymerase chain reaction (MSP), and the fecal occult blood test (FOBT) was performed. Taking the pathological results as the gold standard, receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to compare the effect of combined detection of methylation of three genes and FOBT in predicting colorectal cancer and precancerous lesions. R-Studio software was used to construct a nomogram for the prediction of colorectal cancer with combined detection of gene methylation in stool and other clinical features, and the calibration and validation were performed.Results:The positive rates of combined detection of methylation of SDC2, PPP2R5C and ADHFE1 genes in stool were higher than those of FOBT in colorectal cancer+adenoma [74.3% (101/136) vs. 47.1% (64/136), χ2 = 23.20, P = 0.001], colorectal cancer [90.6% (58/64) vs. 70.3% (45/64), χ2 = 8.91, P = 0.003] and adenoma [59.7% (43/72) vs. 26.4% (19/72), χ2 = 14.43, P = 0.002]. There was no significant difference in the positive rates in hyperplastic polyps [21.2% (7/33) vs. 6.1% (2/33), χ2 = 0.12, P = 0.125] and healthy controls [10.2% (6/59) vs. 8.5% (5/59), χ2 = 4.01, P = 1.000]. The combined detection of gene methylation was better than FOBT in the prediction of colorectal cancer + adenoma [AUC: 0.85 (95% CI 0.80-0.91) vs. 0.71 (95% CI 0.64-0.78), P < 0.05], especially in the prediction of adenoma [AUC: 0.82 (95% CI 0.74-0.89) vs 0.64 (95% CI 0.57-0.69), P < 0.001]. The sensitivity and specificity of ADHFE1 gene methylation status in predicting colorectal cancer were high (90.6% and 96.6%). In colorectal cancer patients over 50 years old, the positive rate of combined detection of gene methylation was higher than that of FOBT [90.2% (55/61) vs. 68.9% (42/61), P < 0.05]. The nomogram calibration curve for predicting colorectal cancer constructed based on the combined detection of gene methylation and each clinical feature showed a high degree of concordance between the predicted and observed diagnostic performance of colorectal cancer. Conclusions:The methylation levels of SDC2, PPP2R5C AND ADHFE1 genes in stool are increased in patients with colorectal cancer or adenoma. The combined detection of gene methylation is expected to be a non-invasive method for the screening of colorectal cancer and precancerous lesions.

Objective:To evaluate the role of nucleotide-binding oligomerization domain-2 (NOD2) in dorsal root ganglion in the development of neuropathic pain (NP) in rats.Methods:Thirty-two adult male SPF Sprague-Dawley rats, weighing 240-260 g, aged 2-3 months, were divided into 4 groups ( n=8 each) using a random number table method: control group (group C), NP group (group S), negative control siRAN group (group N), and NOD2-siRNA group (group R). In N and R groups, 1×10 8 IFU/ml negative control siRNA and NOD2-siRNA 10 μl were intrathecally injected, respectively, once a day for 3 consecutive days.Normal saline 10 μl was intrathecally injected once a day for 3 consecutive days in C and S groups.The model of NP was established using spared nerve injury (SNI) at 2 weeks after intrathecal injection.The mechanical paw withdrawal threshold (MWT) was measured at 1 day before surgery and 1, 3, 7, 10, 14 and 28 days after SNI.Animals were sacrificed after measuring pain threshold on day 28, and the dorsal root ganglions (DRGs) of the lumbar segment (L 4-6) were removed for determination of the expression of NOD2 (by Western blot) and expression of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), IL-6 and NOD2 mRNA (using quantitative real-time polymerase chain reaction). Results:Compared with group C, MWT was significantly decreased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was up-regulated in group NP ( P<0.01). Compared with group NP, MWT was significantly increased at each time point after SNI, and the expression of NOD2 protein and mRNA and TNF-α, IL-1β and IL-6 mRNA in DRGs was down-regulated in group R ( P<0.01), and no significant change was found in the parameters mentioned above in group N ( P>0.05). Conclusion:The mechanism underlying the development of NP may be related to the up-regulation of NOD2 expression in DRGs, thus further promoting the expression of pro-inflammatory factors in rats.

Objective:Based on the data of Global Burden of Disease 2019 data, to analyze the past, current, and future burden of disability-adjusted life years (DALYs) in China and compare with the international status.Methods:The total number of DALYs, age-standardized DALY rate, and the composition of different subgroups were extracted and described to analyze the time trend in 2000-2019 and the current situation in 2019 for Chinese female breast cancer. The burden of DALYs in 2050 was predicted by Joinpoint using average annual percent change (AAPC).Results:In 2000-2019, the ranking of DALYs caused by female breast cancer in China rose from the fourth to the second in all female cancers. The total DALYs increased by 48.4%, of which the years lived with disability increased from 4.8% to 8.8%. The age-standardized DALY rate only slightly decreased (AAPC=-0.3%; which increased during 2016-2019, AAPC=1.6%). In 2019, the age-standardized DALY rate for breast cancer in China was 278.0/100 000. The DALYs were 2.88 million (accounting for 14.2% of the global burden and 12.1% of all female cancers burden in China), 26.5% of which attributed known risk factors (overweight and obesity were the largest: 0.34 million DALYs, but some common breast cancer risk factors were not available on the platform, such as menstruation and fertility). In 2050, the prediction suggests that the total DALYs caused by female breast cancer in China will reach 3.80 million person-years-5.16 million person-years, increasing 32.1%-79.4% over 2019. From 2000 to 2019, the peak age of DALYs and DALY rate became older, and the DALYs among females aged 65 years and above increased faster than those younger than 65 years (AAPC were 4.8% and 1.3%, respectively). In 2019, females aged 45-74 (the starting age recommended by local guidelines for breast cancer screening) contributed 74.3% of the total DALYs.Conclusions:Over the past 20 years, the age-standardized DALY rate for breast cancer in female populations in China has not changed obviously. Without the continuous expansion of effective intervention and population aging, the burden of DALYs for female breast cancer in China will increase. DALYs for breast cancer attributed leading risk factors were still limited.

Objective:To evaluate the efficacy and safety profile of ixazomib/lenalidomide/dexamethasone (IRd) in Chinese patients with relapsed/refractory multiple myeloma (MM) .Methods:This study comprising 14 medical centers in China included patients with relapsed/refractory MM who received at least. Ixazomib at an initial oral dose of 4 mg was administered. Seven patients had dose adjustment to 3 mg at the time of first dose. The lenalidomide doses were adjusted according to creatinine clearance rate. The efficacy and safety were evaluated every cycle.Results:In the study cohort of 74 patients, the median age was 65 years and 11 (14.9% ) patients received over three lines of therapy. Overall response rate (ORR) was 54.1% (40/74) , and 7 (9.5% ) , 14 (18.9% ) , and 19 (25.7% ) patients achieved stringent complete response or complete response, very good partial response, and partial response, respectively. The median progression-free survival and overall survival were 9.9 and 20 months, respectively. The median time to response was 1 month. The efficacy and survival outcome were similar to those reported in the Tourmaline-MM1 China Continuous Study. The ORR of patients refractory to bortezomib, lenalidomide, and bortezomib plus lenalidomide were 52.0% (13/25) , 57.1% (4/7) , and 33.3% (6/18) , respectively. The rate of grade 3-4 adverse events was 36.5% (27/74) . Common hematological toxicities were anemia, thrombocytopenia, lymphopenia, and neutropenia. Common non-hematological toxicities were fatigue, gastrointestinal symptoms, and infections. Two cases of grade 3 peripheral neuropathy were reported. The patients eligible for the Tourmaline-MM1 China Continuous Study had a higher ORR than the ineligible patients [77.8% (14/18) vs 46.4% (26/56) , P=0.020]. There was no difference in the rate of grade 3-4 adverse events [33.3% (6/18) vs 37.5% (21/56) , P=0.749]. Conclusion:The IRd regimen had good efficacy and acceptable toxicity in Chinese patients with relapsed/refractory MM.

PURPOSE: Rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone administered every 3 weeks (R-CHOP-21) is the standard care for diffuse large B-cell lymphoma (DLBCL). It is unknown whether the dose-dense R-CHOP (R-CHOP-14) could improve the outcome of the disease in Asian population. MATERIALS AND METHODS: Newly diagnosed DLBCL patients were centrally, randomly assigned (1:1) to receive R-CHOP-14 or R-CHOP-21. R-CHOP-14 was administered every 2 weeks, and R-CHOP-21 was administered every 3 weeks. Primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), progression-free survival (PFS), response rate and toxicities. RESULTS: Seven hundred and two patients were randomly assigned to receive R-CHOP-14 (n=349) or R-CHOP-21 (n=353). With a median follow-up of 45.6 months, the two groups did not differ significantly in 3-year DFS (79.6% for R-CHOP-14 vs. 83.2% for R-CHOP-21, p=0.311), 3-year OS (77.5% for R-CHOP-14 vs. 77.6% for R-CHOP-21, p=0.903), or 3-year PFS (63.2% for R-CHOP-14 vs. 66.1% for R-CHOP-21, p=0.447). Patients with an International Prognostic Index (IPI) score ≥ 2 had a poorer prognosis compared to those with an IPI score < 2. Grade 3/4 hematologic and non-hematologic toxicities were manageable and similar between R-CHOP-14 and R-CHOP-21. CONCLUSION: R-CHOP-14 did not improve the outcome of DLBCL compared to R-CHOP-21 in Asian population. With manageable and similar toxicities, both of the two regimens were suitable for Asian DLBCL patients. For high-risk patients with IPI ≥ 2, new combination regimens based on R-CHOP deserve further investigation to improve efficacy.
Asian Continental Ancestry Group ; B-Lymphocytes ; Cyclophosphamide ; Disease-Free Survival ; Doxorubicin ; Follow-Up Studies ; Humans ; Lymphoma, B-Cell ; Prednisone ; Prognosis ; Rituximab ; Vincristine

AIM:To investigate the influence of matrine (MA) on the phenotype switching of mouse mono-cytes and alveolar macrophages induced by bleomycin ( BLM) .METHODS:All mice were randomly divided into normal saline (NS) group, BLM group, BLM+NS group and BLM +MA group.The mice were administered with BLM at 2.5 mg/kg via oropharyngeal instillation .The mice in BLM+MA group were treated with MA (15 mg· kg-1 · d-1 ) by oral gavage following BLM administration .The mice were sacrificed on days 3, 7, 14, and 21.The lungs were removed for pathological analysis .The circulating monocyte subsets and polarization state of bronchoalveolar lavage fluid ( BALF)-de-rived alveolar macrophages were analyzed by flow cytometry .RESULTS:The results of HE and Masson trichrome staining in BLM and BLM+NS groups exhibited classical pathological stages of lung fibrosis , including acute inflammation phase and later fibrosis phase .Compared with BLM +NS group, MA treatment alleviated the inflammatory response and the de-gree of fibrosis induced by BLM (P<0.05).There was a rapid change of circulating Ly6Chi monocytes and its magnitude was positively associated with the pulmonary inflammatory response .An expansion of M2-like alveolar macrophages was positively correlated with the magnitude of lung fibrosis .Moreover , MA treatment partially normalized the phenotype switc-hing of monocytes and alveolar macrophages .CONCLUSION:Matrine treatment attenuates BLM-induced pulmonary injury partially via modulating the phenotype switching of monocytes and alveolar mocrophages .

Objective: To observe the effect of electroacupuncture (EA) on the electrogastrogram and gastric antrum ghrelin in rats with diabetic gastroparesis (DGP). Methods: Fifty Sprague-Dawley (SD) rats were randomly divided into group A, group B, group C, group D and group E, 10 rats in each group. Group A was the blank control group without intervention. Group B, Group C, Group D and Group E were treated with single dose intraperitoneal injection of 2% streptozotocin (STZ), combined with 8-week high glucose and high fat diet to establish DGP rat models. Group B was the model group without treatment. Group C was the EA at acupoint group, was treated with EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6). Group D was the EA at non-acupoint group, was treated by EA at the control points of Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6). Rats in the metoclopramide control group received 1.7% metoclopramide solution [10 mL/(kg·bw)] by gavage. Rat's blood glucose level was measured by blood glucose meter; gastric emptying rate was detected using phenol red as a marker; the electrogastrogram was detected by BL-420F biological function system; the protein level of ghrelin was detected by enzyme-linked immunosorbent assay (ELISA); the expression of ghrelin mRNA was detected by real-time polymerase chain reaction (RT-PCR). Results: Compared with group A, the blood glucose of group B, C, D and E were significantly increased before and after the treatment (all P<0.01); after treatment, the gastric emptying rate of group B was significantly decreased (P<0.01), the migration rates of small intestine in group B, C, D and E were significantly lower (all P<0.01), and the protein content of ghrelin in group C was significantly decreased (P<0.01); the expressions of ghrelin mRNA were significantly increased in group B, C, D and E (all P<0.01), the mean amplitudes of electrogastrogram in group B and D were significantly decreased (both P<0.01). After treatment, compared with group B, the blood glucose of group C was significantly decreased (P<0.05), the gastric emptying rate and small intestine migration rate were significantly increased in group C and E (P<0.05, P<0.01), the small intestinal migration rate was significantly increased in group D (P<0.05), the expression of ghrelin in protein and mRNA in group C was significantly lower (P<0.01), the expression of ghrelin mRNA in group E was significantly lower (P<0.05), and the mean amplitude of electrogastrogram in group C was significantly increased (P<0.05). After treatment, compared with group D, the protein and mRNA expressions of ghrelin in group C were significantly decreased (P<0.01). After treatment, compared with group E, the protein expression of ghrelin in group C was significantly decreased (P<0.01). Conclusion: EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6) could regulate the blood glucose level of DGP model rats, enhance electrogastrogram activity, promote gastric emptying, and regulate ghrelin expression in protein and mRNA.

Objective: To observe the effect of electroacupuncture (EA) at Zusanli (ST 36) on the gastrointestinal motility and the ultrastructures of pacemaker cells [the interstitial cells of Cajal (ICC)] in diabetic gastroparesis (DGP) rats and explore the mechanism of EA for DGP.Methods: A total of 50 Sprague-Dawley (SD) rats were randomly divided into group A, group B, group C, group D and group E, with 10 rats in each group. Group A was the blank control; a single intraperitoneal injection of 2% streptozotocin (STZ) was performed in rats of group B, group C, group D and group E, with high glucose and high fat diet for 8 weeks to establish the DGP rat models. Group B was the model group and the rats did not receive any treatment; group C was EA at acupoint group and the rats received EA at Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6); group D was EA at non-acupoint group and the rats received EA at the control points of Zusanli (ST 36), Liangmen (ST 21) and Sanyinjiao (SP 6); group E was metoclopramide group and the rats were treated by intragastric administration of metoclopramide. Blood glucose was detected using ONE TOUCH blood glucose meter; gastric emptying rate and small intestine migration rate were measured using intragastric phenol red; ultrastructures of gastric antrum ICC were detected by transmission electron microscopy.Results: The differences of blood glucose between group B, group C, group D, group E versus that of group A were statistically significant after modeling (P<0.01); after treatment, the differences of blood glucose between group D, group E versus that of group C were statistically significant (P<0.05,P<0.01); the gastric emptying rate of rats in group B was statistically significant different from that in group A (P<0.01); the gastric emptying rate of rats in group C was statistically significant different from that in group B (P<0.01). The migration rates of rats' small intestines in group B, group C, group D and group E were all statistically significant different from that in group A (P<0.01); the migration rate of rats' small intestines in group C was statistically significant different from that in group B (P<0.01). The ultrastructure of rat's ICC in group B showed apoptosis compared with that in group A; rat's ICC in group C had complete basement membrane, more cytoplasm mitochondria, Golgi and rough endoplasmic reticulum, showing clear structure, occasional mitochondria swelling and gap junctions with adjacent smooth muscle cells; there were no significant differences between group D, group E versus group B.Conclusion: EA at Zusanli (ST 36) plus other acupoints can regulate the blood glucose and promote gastrointestinal motility in DGP rats, and the mechanism may be related to repairing the damaged ICC structure.