Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective To explore the predictive value of the expression of CD44v6 and EGFR on the efficacy of neoadjuvant chemotherapy (NACT) in stageⅡ-Ⅲ cervical cancer. Methods A total of 53 patients with stageⅡ-Ⅲ cervical cancer diagnosed by pathology were selected. All patients received two cycles of paclitaxel+platinum NACT. The pathological tissue samples of cervical tumors before NACT treatment were collected. The expression of CD44v6 and EGFR were detected by the immunohistochemical SP method, and we analyzed their predictive value of NACT in stageⅡ-Ⅲ cervical cancer. Results Among the 53 patients, 38 were in the NACT effective group (CR+PR), and 15 were in the NACT ineffective group (SD+PD). The expression of CD44v6 in the ineffective group was significantly higher than that in the effective group (P < 0.05). The expression of CD44v6 was significantly different in patients with CR, PR, and SD (P < 0.05). The AUC of CD44v6 to NACT effect on stage Ⅱ-Ⅲ cervical cancer was 0.74 (P < 0.05). The patients in the high expression group of CD44v6 had worse efficacy in NACT than those in the low expression group of CD44v6 (P < 0.05). Pearson test showed that CD44v6 and EGFR expression were correlated (R=0.34, P < 0.05). Conclusion High expression of CD44v6 may reduce the efficacy of NACT in stageⅡ-Ⅲ cervical cancer, suggesting that the expression of CD44v6 has a certain predictive value and clinical significance in the efficacy of paclitaxel+platinum NACT on cervical cancer. Moreover, CD44v6 is positively correlated with EGFR expression.

Objective: To investigate the effects of prostate cancer exosomes on the migration and invasion ability of stromal cells (WPMY-1), and to explore its mechanism. Methods: Exosomes in LNCaP-AI+F prostate cancer cell supernatant were isolated by ultracentrifugation and the typical structure of exosome was captured by electron microscope. The particle size distribution was analyzed by Zetaview, and Wb was used to identify the marker proteins and other proteins.After co-incubation of WPMY-1 cells and prostate cancer exosomes (40 µg/ml), laser confocal microscope was used to observe the uptake of PKH67-labeled exosomes by WPMY-1 cells; Transwell assay was used to detect the migration and invasion ability of WPMY-1 cells; qPCR was performed to detect the expression of three cancer-associated fibroblast (CAF)-related molecules (IL-8, PDGFB and MMP9) at mRNA level; and the phosphorylation of EGFR and ERK1/2 was analyzed by Wb. Results: Typical cup-shaped structure of exosomes was observed under electron microscope. The Zetaview results showed that the particle size distribution was concentrated at about 100 nm. The expression of exosome marker proteins CD63 andALIX further verified that the isolated particles were exosomes. Besides, EGFR, HER2 and SRC, which were related to the progression of prostate cancer, were also enriched in exosomes. After co-incubation, confocal microscope imaging showed a number of PKH67 labeled exosomes in recipient WPMY-1 cells. Transwell experiments showed that exosomes could significantly enhance the migration and invasion ability of WPMY-1 cells (all P<0.01). Compared with the control group, increased secretion of IL-8, PDGFB and MMP9 was observed after exosome treatment (40 µg/ml) (P<0.05 or P<0.01). Wb indicated that exosomes could promote the phosphorylation of EGFR and ERK1/2 of WPMY-1 cells (P<0.01). Conclusion: Prostate cancer cell exosomes could act on the stromal cell WPMY-1 to highly express multiple CAF-related molecules, promote the phosphorylation of EGFR and ERK1/2 and enhance the migration and invasion ability of WPMY-1 cells.

Objective To observe the correlation between zinc-a2-glycoprotein (ZAG) in human plasma and the degree of coronary atherosclerosis lesion.Methods A total of 242 research subjects were included.The clinical indexes were perfected and plasma ZAG level was detected.The coronary angiography was performed.The subjects were divided into the coronary atherosclerosis group (CAD group) and control group according to the examination results.The Gensini score was used to assess the degree of coronary artery lesion,different degree subgroups were divided according to the assessment results.The correlation between the ZAG level with the clinical indexes was analyzed by Spearman analysis.The ROC curve was used to evaluate the efficiency of ZAG in the diagnosis of coronary atherosclerosis and its sensitivity and specificity were analyzed.Results The plasma ZAG level in the CAD group was significantly lower than that in control group,the difference was statistically significant [(45.12±5.02)μg/mL vs.(53.93±2.96)μg/mL,P＜0.01].With the increase of Gensini score,plasma ZAG level showed the decreasing trend,the difference among the groups were statistically significant (P＜0.05).The Spearman correlation analysis showed that body mass index (BMI),waist circumference and waist to hip ratio(WHR) were negatively correlated with ZAG (P＜0.05),and positively correlated with high density lipoprotein cholesterol(HDL-C,P＜0.05).The sensitivity of plasma ZAG for evaluating coronary atherosclerosis was 89.8％ and its specificity was 91.2％.Conclusion Plasma ZAG is negatively correlated with the severity of coronary atherosclerosis lesion,and its level detection has a certain value in the screening of coronary atherosclerosis.

Objective: To investigate the anatomical characteristics of the parathyroid lymphatic system and the mechanism of the"negative development"of the carbon nanoparticles for parathyroid gland in thyroidectomy.Methods:This retrospective study used parathyroid tissue samples from patients that were obtained from archival records in the pathology department,including 45 cases of normal parathyroid gland tissues that were accidentally resected in thyroidectomy,10 cases of parathyroid adenomas,and 7 cases of parathyroid carcinoma.Ten cases of normal thyroid tissues were selected as positive control.Immunohistochemistry was performed using the antibodies specific for lymphatic endothelium,such as D2-40 and LYVE-1,and antibodies specific for vascular endothelial cell such as CD31 and CD34,to distinguish them from each other.Results:A total of 62 parathyroid glands samples were stained with vas-cular markers CD31,CD34 and lymphatic markers D2-40,LYVE-1 respectively(partial samples were stained unsuccessfully).Vascular vessels in the CD31 staining group were detected in 50 of 58 examined glands and the positive rate was 86.2%.In the CD34 staining group,positive rate was 100%(60/60).The positive cells were found in the central,periphery and vascular hilum of the glands.Howev-er,lymph vessels in the D2-40 staining group were detected from 17 out of 59 examined glands,with the positive rate of 28.8%;In the LYVE-1 staining group,positive rate was 39.6%(23/58).The positive cells were found in the membrane or vascular hilum,less frequent or undetectable in the central portion.Conclusions:Most of the parathyroid glands of adults might lack a lymphatic network.Only a few adult parathyroid glands had minority lymph vessels,and these lymphatics generally localized at the membrane area or in the vas-cular hilum, which could be one of the main and anatomical mechanisms resulting in drainage failure or obstruction of carbon nanoparticles and thus in parathyroid"negative development."

Objective To study the effect of temporary in vitro preservation of parathyroid on the activity of cells in the process of parathyroid auto-transplantation and function of postoperative in order to improve the survival rate of transplantation.Methods (1)Experimental rabbits for the study were randomly divided into three groups:group A,group B,group C,with 8 rabbits in each group.Then we remove the bilateral inferior parathyroid,in group A,the parathyroid glands were immediately formaldehyde-fixed;in group B and group C,the parathyroid glands were placed in normal saline in 4 ℃ and in room temperature (22-24 ℃) for 30 minutes respectively and then fixed;HE staining was performed on the left parathyroid glands to observe the morphology of the cells;Electron microscopic examination of the right parathyroid glands were performed to observe the ultrastructural changes of the cells.(2)Experimental rabbits were randomly divided into three groups:group D group E and group F,with 8 rabbits in each group,after total thyroidectomy,the double inferior parathyroid glands were took out,in group D,the parathyroid glands were immediately transplanted in bilateral anterior cervical muscles;in group E and group F,the parathyroid glands were placed in normal saline 4 ℃ and in room temperature (22-24 ℃) for 30 minutes respectively and then transplanted.All animals were monitored of serum calcium and PTH on preoperative 1 d and postoperative 1 d,3 d,5 d,7 d;the parathyroid was took out for HE staining to observed survival of parathyroid tissue and pathology damage when 7d after operation.Results (1) The normal parathyroid gland is mainly dominated by the chief cells,the nucleus of the chief cell was round and centered under electron microscope;there were no significant change in the morphology of parathyroid cells,and the mitoehondria of the cells were slightly swollen under 4 ℃;but the parathyroid gland cells were slightly swollen and partially vacuole degeneration,the morphology of the nucleus was irregular,and the mitochondria were extremely swollen and deformed,and the ridge was broken under room temperature.(2)three groups of rabbits after transplantation of parathyroid,serum calcium and PTH decreased significantly,and increased gradually,there was significant difference on the 7th day after the operaion between the two groups (P＜0.05);(3)in group D,the normal parathyroid cells densely distributed in the anterior cervical muscle tissue;in group E,A large number of parathyroid cells survived in muscle tissue,with some vacuolated;in group F,only part of healthy parathyroid ceils scattered in the muscle.Conclusion Parathyroid should be preserved in 4 ℃ normal saline during the operation,and the transplant should be completed in 30 minutes as far as possible.

Objective To study the effects of different type of parathyroid damage to the postoperative functional recovery of parathyroid,through establish an animal model by simulating total thyroidectomy and parathyroid damage during surgical operation.Methods Experimental rabbits for the study were randomly divided into A,B,C,D four groups (n =8),Group A (control group):simple exposure,exploration thyroid and parathyroid;group B (vascular injury group):total thyroidectomy and ligation bilateral parathyroid blood supply but keep the surrounding membrane;Group C (membrane damage group):total thyroidectomy and damage membrane but reservations blood supply.Group D (composite damage group):total thyroidectomy plus membrane and blood both damage;All animals were monitored of serum calcium and PTH,preoperative 1 days and postoperative 1 st day,3rd day,5th day,7t day;cut the parathyroid HE staining to observed survival of parathyroid tissue and pathology damage when 7th day after operation.Results (1) Animals in each group preoperative serum calcium and PTH were no significant difference (P ＞0.05);(2)Group A postoperative serum calcium decreased,but at 5th day returned to preoperative level (P ＞ 0.05);Group B and C postoperative 1st day,3rd day,5th day serum calcium decreased significantly(P ＜ 0.05)and to the lowest at 1 d and then gradually recovered,but group C faster recovered than group B (P ＜ 0.05);Group D postoperative 1 st day,3rd day serum calcium continued to decline significantly (P ＜ 0.05);(3) Group A postoperative serum PTH decreased,but at 7th days returned to preoperative level (P ＞ 0.05).Group B and C postoperative 1st day,3rd day,5th days serum PTH decreased significantly(P ＜0.05)and to the lowest at 1 d and then gradually recovered,but from postoperative 3rd day group C faster recovered than group B(P ＜ 0.05);Group D postoperative 1 st day,3rd day serum PTH continued to decline significantly (P ＜ O.05);(4) Pathology results:Group A parathyroid filled with chief cells and a small amount of vacuolar changes (5％ to 10％);Group B parathyroid hemorrhage,necrosis (40％ to 50％),part of the cell degeneration (30％ to 40％),center with fibrosis,seen granuloma and hyperplasia of parathyroid tissue in surrounding;Group C parathyroid bleeding (10％ to 20％),part of the cell degeneration (10％ to 20％);Group D parathyroid severe necrosis,almost no normal parathyroid tissue,significant fibrosis,less residual parathyroid tissue was scattered.Conclusions (l) The recover of Parathyroid function is influenced by the type of parathyroid in situ injury during thyroidectomy,composite damage of blood supply and membrane of parathyroid is the most serious,parathyroid ischemia necrosis,the function can not be restored,pure blood supply damaged,some can restore function,and the parathyroid gland with vascular pedicle can be recovered quickly.(2) Severe blood supply and membrane damaged,and even free parathyroid should be transplanted immediately during operation.

OBJECTIVECompare the characteristics of magnetic resonance imaging（MRI）liver T2*, cardiac T2* and serum ferritin on the assessment of iron overload.

METHODSA total of sixty-nine patients from November 2011 to June 2014 were enrolled in this study. Their cardiac and liver iron concentration levels were measured through MRI examination, with other clinical data were collected to perform statistical analysis.

RESULTSThe correlation between liver T2* and adjusted serum ferritin（ASF） was statistically significant（P=0.003）. However, no significant correlation was found between cardiac T2* and liver T2*, ASF, respectively. According to the statistical analysis of the 69 cases, it is found that the number of iron overload cases diagnosed by liver T2* was 62 and 20 cases were severe iron overload （32.26%）; the number of iron overload cases diagnosed by ASF was 47 and 14 cases were severe iron overload（29.79%）, while the number of iron overload cases diagnosed by cardiac T2* was only 25 and no severe iron overload cases.

CONCLUSIONSince SF was affected by other factors, it cannot reflect the level of iron overload in human body objectively. Now, liver T2* has become the gold standard for assessment of iron overload because of its good reliability and repeatability. However, cardiac T2* cannot correctly be used as assessment for iron overload, and it is only a method of evaluating the level of cardiac iron deposition.

Ferritins ; blood ; Hematologic Diseases ; diagnosis ; Humans ; Iron Overload ; diagnosis ; Liver ; Magnetic Resonance Imaging ; Myocardium ; Reproducibility of Results

Objective To evaluate the clinical effect of acupuncture in the treatment of depression after stroke. Methods 90 patients with cerebral apoplexy were randomly divided into 2 groups according to the random number table, with 45 cases in each group. Patients in both groups were given routine western medicine treatment, and guided to carry out suitable limb function rehabilitation training. In addition, the control group was given traditional acupuncture treatment, while the treatment group was given the brain acupuncture treatment with tiaodu in addition to the traditional acupuncture treatment. Hamilton depression scale (HAMD) was used to assess the degree of depression, Chinese stroke scale (CSS) was used to evaluate the degree of neurological deficit, and barthel index (BI) was used to evaluate the activity of daily living (ADL). Results After treatment, the treatment group has a lower CSS score than that of the control group (11.38 ± 3.94 vs. 15.16 ± 4.52, t=4.229), and a lower HAMD score than that of the control group (6.25 ± 3.76 vs. 9.32 ± 5.06, t=3.267). Meanwhile, the treatment group has a higher BI score than that of the control group (69.22 ± 7.05 vs. 55.67 ± 6.21; t=9.675, P<0.01). Furthermore, the treatment group has statistically significant higher cure rate than that of the control group (62.2% vs. 33.3%;χ2=6.413, P=0.011). Conclusions Tiaodu brain acupuncture treatment of depression after stroke has obvious clinical curative effect, and is superior to other traditional acupuncture method.