Objective To study the effect of compound matrine injection combined with chemotherapy on the immune function and life quality of elderly patients with colorectal cancer. Methods Seventy patients with colorectal cancer treated in Shanghai Jiao Tong University Affiliated Sixth People′s Hospital South Campus from January 2010 to December 2013 were involved in this survey. They were divided into the control group and the observation group randomly,each group had 35 cases,the control group was treated with chemotherapy only, the observation group was treated with compound matrine injection combine with chemotherapy. The curative effect,life quality and immune function in the two groups were compared. Results The number of complete remission patients in the observation group was 8 cases ( 22. 86%) ,the number of partial remission cases was 16 cases ( 45. 71%) , the effective rate was 68. 57%, while the control group had 4 cases of complete remission (11. 43%),11 cases of partial remission (31. 43%),the effective rate was 42. 86% (Z=-2. 259,P=0. 024) . In the observation group,life quality was significantly improved in 10 cases (28. 57%),improved in 19 cases ( 54. 29%) ,the effective rate was 82. 86%,while in the control group,life quality was significantly improved in 4 cases ( 11. 43%) ,and improved in 10 cases ( 28. 57%) ,the effective rate was only 40%. The improvement rate of the two groups was statistically significant ( Z=-3. 497,P=0. 000) . Before treatment,the immune function indexes of patients in the two groups were close ( P>0. 05) ,after treatment,the immune function in both groups were significantly improved,CD3+,CD4+,CD4+/CD8+ levels of patients in the observation group were higher than those in the control group,while the CD8+ level in the observation group was lower than that of the control group ( t=-3. 968,P=0. 000;t=-5. 351,P=0. 000;t=-5. 474,P=0. 000;t=6. 407,P=0. 000) . The follow?up time of the two groups was 36 months. After 36 months,the survival rates of the observation group and the control group were 85. 7% (30/35) and 80. 0% (28/35) respectively,and the difference was not statistically significant (χ2=0. 402,P=0. 526) . Conclusion Compound matrine injection combined with chemotherapy can significantly improve the clinical efficacy of elderly patients with colorectal cancer,improve the immune function and quality of life,it is worthy of clinical application.

Background and purpose: Hepatocellular carcinoma (HCC) is a hypervascular tumor associated with a poor prognosis and lack of effective treatments. Consequently, identifying novel therapeutic strategies are urgently needed. We have previously shown that the kringle 1 domain of human hepatocyte growth factor (HGFK1) is a more effective anti-angiogenesis molecule than angiostatin. In this study, we observed the effects and mechanisms of HGFK1 gene on the HCC. Methods: A recombinant adeno-associated vires carrying the HGFK1 gene (rAAV-HGFK1) was constructed.HCC of rat was induced by McA-RH7777. rAAV-HGFK1 was used to treat the rat, median survival time and metastasis rate were observed. Results: Ten days after tumor cell inoculation, surgery were performed to confirm the tumor formation, PBS, rAAV-EGFP or rAAV-HGFK1 was injected directly into the tumor nodule followed by portal vein injection. Results from our study demonstrated that rAAV-HGFK1 treatment significantly prolonged the median survival time of the HCC bearing rats from 30 days (PBS and rAAV-EGFP groups) to 49 days (rAAV-HGFK1 group). More importantly rAAV-HGFK1 inhibited tumor growth and completely prevented liver, lung and peritoneal metastasis. In the controlled PBS and AAV-EGFP group, liver and peritoneal metastasis rate were both 100%, and lung metastasis rate was 100% and 83%, respectively. While there was no metastasis found in treatment group, with only 33% of ascites happened. This was most possibly due to the primary tumor in liver but not due to the metastasis. Moreover, at a higher magnification (1000×), it was clear that the HGFK1 protein was expressed mainly in the cytoplasma of liver cells. In parallel, IHC staining of CD31 also demonstrated a significantly lower level of microvessel density (MVD) (6.21±1.6) in the liver tumor of the AAV-HGFK1 treatment group, as compared to the two control PBS and AAV-EGFP groups (25.1±2.1 and 26.8±2.5, respectively, P<0.01). HE staining showed that AAV-HGFK1 treatment induced large areas of necrosis in the tumor tissues, while minimal areas of necrosis were observed in the tumor tissue in the control groups. In addition, no toxicity appeared when high dosage (4.8× 1012 vg/rat) of rAAV-HGFK1 was administered in rats. Conclusion: Results from this study demonstrated that HGFK1 inhibited the growth and metastasis of HCC and prolonged the survival time of animals with HCC through anti-angiogenesis effects. No obvious toxicity was observed. It might be the novel promising treatment for HCC and other cancers.

Objective To investigate the effects of transient receptor potential cation channel 6 (TRPC6) on the expression of nephrin, desmin and caspase 9 and on the apoptosis of podocytes in a mouse model of podocyte injury induced by TGF-β1.Methods Conditionally immortalized mouse podocytes were cultured in vitro and divided into four groups: control, TGF-β1 treatment, TGF-β1+PGPU6/GFP/Neo-TRPC6-mus-581 (TRPC6 knockdown) and TGF-β1+PGPU6/GFP/Neo-NC (negative control).Real-time RT-PCR and Western blot analysis were performed to detect the expression of nephrin, desmin and caspase 9 at mRNA and protein levels, respectively.Flow cytometry was used to analyze the apoptotic rate of podocytes.DAPI fluorescent staining was used to observe the morphological changes of apoptotic podocytes.Results Green fluorescent protein (GFP)-expressing podocytes at 48 hours after transfection were significantly more than those at 24 hours after transfection.The level of TRPC6 in mouse podocytes transfected with PGPU6/GFP/Neo-TRPC6-mus-581 was significantly decreased as compared with that of the control group (P<0.05).No significant difference in the expression of TRPC6 was observed between the negative control group and the control group.Compared with the control group, the TGF-β1 treatment group showed increased expression of desmin and caspase 9 at both mRNA and protein levels (P<0.01), but decreased expression of nephrin at mRNA and protein levels at 48 hours after TGF-β1 intervention (P<0.05).The up-regulated desmin and caspase 9 and the down-regulated nephrin induced by TGF-β1 could be inhibited by the means of TRPC6 knockdown.The apoptosis rate of podocytes in TGF-β1 treatment group was (14.0±2.1)%, while that in TRPC6 knockdown was (10.90±0.56)% (P<0.05).The apoptosis rate of podocytes in negative control group was higher than that in TGF-β1 treatment group (P>0.05).More apoptotic cells with typical morphological features of apoptosis were observed after exposure to TGF-β1 for 48 hours.Conclusion TGF-β1 could induce the apoptosis of podocytes, inhibit the expression of nephrin and enhance the expression of caspase 9 and desmin, the possible mechanisms of which may be related to TRPC6 signal pathway.These changes in TGF-β1-treated podocytes could be alleviated by inhibiting the expression of TRPC6, which might have a protective effect on podocyte injury.

Objective:To study the signal enhancement of lung adenocarcinoma nude mice after injection of immunomagnetic bead solution (magnetic beads conjugated with monoclonal antibody NJ001) in micro-CT scan. Methods:The models of lung adenocarcino-ma nude mice were established by injecting SPC-A1-luc cells through the tail vein and were validated by bioluminescence imaging (BLI). The nude mice were divided into three groups: physiological saline group, bare magnetic bead group, and immunomagnetic bead group. Three groups of nude mice were injected with physiological saline, 750 nm bare magnetic bead solution, and immuno-magnetic bead solution via the tail vein every week, and micro-CT scan was taken before and 4 h after injection. Immunohistochemis-try (IHC) was used to detect the expression of antigen SP70 in tumor tissues. Results:The tumor was detected in the immunomagnetic bead group at the fourth week, whereas in the physiological saline and bare magnetic bead groups, the tumor was undetectable until the sixth week. The tumor intensities detected at the sixth week by micro-CT scan in the physiological saline, bare magnetic bead, and immunomagnetic bead groups were 59.05 ± 0.66, 60.69 ± 0.55, and 58.25 ± 0.32 before injection and 60.30 ± 1.83, 61.05 ± 0.68, and 67.41±3.82 after injection, respectively. Compared with the tumor intensities before injection, they significantly increased after injec-tion in the immunomagnetic bead group;the difference was statistically significant (P=0.0079). By contrast, no statistical significance was observed in the tumor intensities before and after injection in the physiological saline and bare magnetic bead groups (P=0.1867 and P=0.3839, respectively). Conclusion:The immunomagnetic beads had enhanced effect on micro-CT scan of lung adenocarcinoma nude mouse models.

The analysis of cerebrospinal fluid (CSF) facilitates the diagnosis and therapy of central nervous system (CNS) diseases. Compared to traditional methods, single-cell sequencing is conducive to analyze the cells composition and heterogeneity and discover scarce cells in CSF. Recent studies of single-cell sequencing in CSF has mainly focused on the neuroinfectious diseases, neurodegenerative and neuroinflammatory diseases, and leptomeningeal metastases (LM), reflecting the superiority and clinical value of single-cell sequencing in CNS diseases and providing new directions for the diagnosis and treatment of CNS diseases.

ObjectiveTo examine whether DNA extracted from free edge fingernails specimens from patient after hematopoietic stem cell transplantation (allo-HSCT) could be used for short tandem repeat (STR) genotyping and chimerism analyzing,and to observe the chimerism status in fingernails after allo-HSCT.MethodsPeripheral blood,bone marrow,oral mucosa and free edge fingernail specimens were collected from 25 patients which allo-HSCT were performed in Beijing Dao-pei Hospital during Jul.2009 to Sep.2011 and their donor.Genomic DNA was extracted and 15 STR loci genotyping and chimerism analysis were performed.For the first group which including 12 patients,pairs of fingernail and oral mucosa specimens were collected within one month after allo-HSCT and were comparative analyzed.For the second group which including 13 patients,chimerism status in fingernail samples were analyzed 3 months or longer after allo-HSCT,and 3 patients underwent repeated testing at different times.ResultsFor the first group,4 oral mucosa specimens showed donor chimerism with varying degrees,but no donor chimerism was detected.in all of 12 fingernail specimens.For the second group,6.7％ to 82.6％ donor chimerism was detected in fingernail specimens in 5 out of 13 patients.For the 3 patients underwent repeated testing,donor chimerism was continued negative in one cases,but continued positive in the other 2 cases.ConclusionsFree edge fingernail samples of patients within one month after allo-HSCT can be used for STR typing and chimerism analysis,and it is better than oral mucosa samples.There are cells in allo-HSCT donor graft can differentiate into skin cells,donor derived skin cells chimerism can be formed and persist in some patients.Med,2012,35:23-26)

Objective To explore the treatment strategies of pleuroparenchymal fibroelastosis (PPFE). Methods A 22-year-old male patient was complicated with PPFE after receiving chemotherapy in combination with stem cell transplantation for lymphoma. He underwent thoracoscopic left lung tongue wedge resection, bilateral pleurodesis followed by allogeneic left lung transplantation. Literature review was performed to analyze the etiology, pathogenesis, imaging features, pathological features and treatment of PPFE. Results The PPFE patient required the non-invasive ventilator for 24 h before lung transplantation. After lung transplantation, the shortness of breath and respiratory failure were cured and the quality of life was significantly improved. No eligible studies was found in the domestic database, and 26 literatures published in English were found in the international databases. Among them, 9 literatures (case reports) were finally included after screening. PPFE could be divided into the primary and secondary categories according to the etiology. The clinical manifestations of PPFE mainly included dry cough, dyspnea on exertion, chest pain, repeated pneumothorax and body weight loss. Chest CT scan demonstrated irregular thickening of the pleura in bilateral upper lungs. Pathological manifestations consisted of evident thickening of the visceral pleura, fibroelastosis and arrangement disorder in the pleura and the underlying pulmonary interstitium. PPFE could progress rapidly. Adrenocortical hormone and other immunosuppressive agents yielded low clinical efficacy and poor clinical prognosis. Lung transplantation was a necessary treatment for PPFE. Conclusions PPFE cannot be effectively treated by conservative therapy. It is recommended to deliver lung transplantation as early as possible.

Objective:In general, patients with seropositive rheumatoid arthritis (RA) are considered to show an aggressive disease course. However, the relationship between the two subgroups in disease severity is controversial. Our study is aimed to compare the clinical characteristics and prognosis of double-seropositive and seronegative RA in China through a real-world large scale study.Methods:RA patients who met the 1987 American College of Rheumatology (ACR) classification criteria or the 2010 ACR/European Anti-Rheumatism Alliance RA classification criteria, and who attended the 10 hospitals across the country from September 2015 to January 2020, were enrolled. According to the serological status, patients were divided into 4 subgroups [rheumatoid factor (RF)(-) anti-cyclic citrullinated peptide (CCP) antibody (-), RF(+), RF(+) anti-CCP antibody(+), anti-CCP antibody(+)] and compared the disease characteristics and treatment response. One-way analysis of variance was used for measurement data that conformed to normal distribution, Kruskal-Wallis H test was used for measurement data that did not conform to normal distribution; paired t test was used for comparison before and after treatment within the group if the data was normally distributed else paired rank sum test was used; χ2 test was used for count data. Results:① A total of 2 461 patients were included, including 1 813 RF(+) anti-CCP antibody(+) patients (73.67%), 129 RF(+) patients (5.24%), 245 RF(-) anti-CCP antibody(-) patients (9.96%), 74 anti-CCP antibody(+) patients (11.13%). ② Regardless of the CCP status, RF(+) patients had an early age of onset [RF(-) anti-CCP antibody(-) (51±14) years old, anti-CCP antibody(+) (50±15) years old, RF(+) anti-CCP antibody(+) (48±14) years old, RF(+)(48±13) years old, F=3.003, P=0.029], longer disease duration [RF(-) anti-CCP antibody(-) 50 (20, 126) months, anti-CCP antibody(+) 60(24, 150) months, RF(+) anti-CCP antibody(+) 89(35, 179) months, RF(+) 83(25, 160) months, H=22.001, P<0.01], more joint swelling counts (SJC) [RF(-) anti-CCP antibody(-) 2(0, 6), Anti-CCP antibody(+) 2(0, 5), RF(+) anti-CCP antibody(+) 2(0, 7), RF(+) 2(0, 6), H=8.939, P=0.03] and tender joint counts (TJC) [RF(-) anti-CCP antibody(-) 3(0, 8), anti-CCP antibody(+) 2(0, 6), RF(+) anti-CCP antibody(+) 3(1, 9), RF(+) 2(0, 8), H=11.341, P=0.01] and the morning stiff time was longer [RF(-) anti-CCP antibody(-) 30(0, 60) min, anti-CCP antibody(+) 20(0, 60) min, RF(+) anti-CCP antibody(+) 30(10, 60) min, RF(+) 30(10, 60) min, H=13.32, P<0.01]; ESR [RF(-) anti-CCP antibody(-) 17(9, 38) mm/1 h, anti-CCP antibody(+) 20(10, 35) mm/1 h, RF(+) anti-CCP antibody(+) 26(14, 45) mm/1 h, RF(+) 28(14, 50) mm/1 h, H=37.084, P<0.01] and CRP [RF(-) anti-CCP antibody(-) 2.3 (0.8, 15.9) mm/L, Anti-CCP antibody(+) 2.7(0.7, 12.1) mm/L, RF(+) anti-CCP antibody(+) 5.2(1.3, 17.2) mm/L, RF (+) 5.2(0.9, 16.2) mm/L, H=22.141, P<0.01] of the RF(+)patients were significantly higher than RF(-) patients, and RF(+) patients had higher disease severity(DAS28-ESR) [RF(-) anti-CCP antibody(-) (4.0±1.8), anti-CCP antibody(+) (3.8±1.6), RF(+) anti-CCP antibody(+) (4.3±1.8), RF(+) (4.1±1.7), F=7.269, P<0.01]. ③ The RF(+) anti-CCP antibody(+) patients were divided into 4 subgroups, and it was found that RF-H anti-CCP antibody-L patients had higher disease severity [RF-H anti-CCP antibody-H 4.3(2.9, 5.6), RF-L anti-CCP antibody-L 4.5(3.0, 5.7), RF-H anti-CCP antibody-L 4.9(3.1, 6.2), RF-L anti-CCP antibody-H 2.8(1.8, 3.9), H=20.374, P<0.01]. ④ After 3-month follow up, the clinical characteristics of the four groups were improved, but there was no significant difference in the improvement of the four groups, indicating that the RF and anti-CCP antibody status did not affect the remission within 3 months. Conclusion:Among RA patients, the disease activity of RA patients is closely related to RF and the RF(+) patients have more severe disease than RF(-) patients. Patients with higher RF titer also have more severe disease than that of patients with low RF titer. After 3 months of medication treatment, the antibody status does not affect the disease remission rate.

Objective:To explore the therapeutic characteristics of population with gout achieving treat-to-target (T2T) indicators through real-world research and evaluate their safety.Methods:A total of 3 287 patients diagnosed with gout by rheumatologists in 21 first-class tertiary hospitals in 10 provinces, municipalities, and autonomous regions in China from January 2015 to December 2021 were included in this polycentric cross-sectional study. The database included patients′ general information, disease characteristics, and clinical application of traditional Chinese and Western medicine treatment measures. SPSS and Excel software were used for data analysis. Frequency analysis, cluster analysis, and factor analysis were used to summarize the characteristics and rules of treatment measures for patients with gout who achieved the target after treatment. The occurrence of adverse events (AE) was recorded during treatment.Results:After treatment, 691 visits (7%) achieved the serum urate (SUA) target, and the most frequent use of urate-lowering therapy (ULT) was febuxostat, followed by benzbromarone. The most common treatment options were following: GroupⅠ: traditional Chinese medicine (TCM) decoction-TCM external treatment-physical exercise-proprietary Chinese medicine; GroupⅡ: ferulic acid-nonsteroidal anti-inflammatory drugs (NSAIDs); Group Ⅲ: allopurinol-sodium bicarbonate-benzbromarone; Group Ⅳ: glucocorticoid-colchicine; Group Ⅴ: febuxostat. A total of 5 898 visits (60%) chieved manifestations of joint pain VAS scores target, and the most frequently used drug to control joint symptoms was NSAIDs. The frequency of use of drugs to control joint symptoms were 2 118 times (usage rate reached 35.9%), while the frequency of ULT were 2 504 times (usage rate reached 42.5%), which was higher than the joint symptom control drug. The most common treatment options were following: Group Ⅰ: proprietary Chinese medicine-TCM decoction-TCM external treatment-physical exercise; Group Ⅱ: NSAIDs-colchicine hormones; Group Ⅲ: allopurinol, Group Ⅳ: benzbromarone; Group Ⅴ: febuxostat. A total of 59 adverse events occurred during treatment.Conclusion:The proportions of gout patients who reach target serum urate level & good control of joint symptoms are both very low, and ULT and anti-inflammatory prescription patterns are very different from international guidelines, so it is necessary to strengthen the standardized management of gout patients. At the same time, life intervention measures account for a certain proportion of the treatment plans for the T2T population, and further exploration is needed.