ObjectiveTo investigate the immunological characteristics of the patients with aplastic anemia （AA） and elevated hemogram parameters treated with Yiqi Yangxue prescription combined with Western medicine and the predictive effects of immunological indexes on elevated hemogram parameters， thus providing a reference for the prediction of the treatment efficacy and the adjustment of the treatment regimen. MethodA retrospective study was conducted， involving 77 AA patients treated with Yiqi Yangxue prescription combined with Western medicine for 6 months in 19 medical institutions including Xiyuan Hospital， China Academy of Chinese Medical Sciences from September 2018 to March 2021. The patients were assigned into two groups according to the elevations in hemogram parameters ［including hemoglobin （HGB）， white blood cell count （WBC）， platelet （PLT）， and absolute neutrophil count （ANC）］ after 6 months of treatment. One group had the elevation <50%， and the other group had the elevation ≥50% compared with the baseline. The clinical and immunological characteristics were compared between the two groups. Result① Compared with the group with HGB elevation<50%， the group with HGB elevation≥50% showed elevated level of CD3⁺ human leukocyte antigen-DR （HLA-DR）⁺ and increased proportion of patients with T-helper cell type 2 （Th2）<5%， CD8⁺≥50%， and CD3⁺HLA-DR⁺≥9% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD8⁺≥50% before treatment was the independent influencing factor for HGB elevation ≥50% ［odds ratio （OR）=12.000， 95% confidence interval （CI） 2.218， 64.928， P<0.01］. ② Compared with the group with WBC elevation<50%， the group with WBC elevation≥50% showed increased proportion of patients with CD3⁺HLA-DR⁺<6% and T-box transcription factor （T-bet）≥200% before treatment （P<0.05）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<6% （OR=2.998， 95%CI 1.036， 8.680， P<0.05） and T-bet≥200% （OR=3.634， 95%CI 1.076， 12.273， P<0.05） before treatment were independent influencing factors for WBC elevation≥50%. ③ Compared with the group with PLT elevation<50%， the group with PLT elevation≥50% presented lowered Th1 and CD3⁺HLA-DR⁺ levels and increased proportion of patients with Th1<12%， CD4⁺≥6%， and CD3⁺HLA-DR⁺<5% before treatment （P<0.05， P<0.01）. The multivariate Logistic regression analysis showed that CD3⁺HLA-DR⁺<5% before treatment was the independent influencing factor for PLT elevation≥50% （OR=16.190， 95%CI of 3.430 to 76.434， P<0.01）. ④ Compared with the group with ANC elevation<50%， the group with ANC elevation≥50% showed no significant changes in the hemogram parameters before treatment. ConclusionAs for the AA patients with rapid elevation in HGB， Yiqi Yangxue prescription combined with Western medicine demonstrate significant effects in the patients with Th2<5% and CD3⁺HLA-DR⁺≥9%， especially those with CD8⁺≥50%. As for the AA patients with rapid elevation in WBC， the therapy was particularly effective in the patients with CD3⁺HLA-DR⁺<6% and T-bet≥200%. As for the AA patients with rapid growth in PLT， the therapy was particularly effective in the patients with Th1<12% and CD4⁺≥6%， especially those with CD3⁺HLA-DR⁺<5%.

Objective:To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer.Methods:This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results:The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference ( P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion:Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

Objective:To explore the efficacy of immune checkpoint inhibitors combined with adjuvant chemotherapy in patients with phase III gastric cancer and esophagogastric junction cancer.Methods:This study used a retrospective cohort study method based on real-world data. Clinical data of 403 patients with stage III gastric/esophagogastric junction cancer who underwent gastrectomy followed by adjuvant therapy in the Department of Gastric Surgery at Sun Yat-sen University Cancer Center from January 2020 to December 2023 were retrospectively collected. The study cohort comprised 147 (36.5%) patients with stage IIIA, 130 (32.3%) with stage IIIB, and 126 (31.3%) with stage IIIC gastric/esophagogastric junction cancer. Of them, 15 (3.7%) were HER-2 positive, 25 (6.2%) dMMR, and 22 (5.5%) patients Epstein-Barr virus encoding RNA (EBER) positive. Based on treatment plans, the patients were divided into immune checkpoint inhibitor combined with chemotherapy group (immune therapy group, n=110, 71 males and 39 females, median age 59 years old) and chemotherapy alone group (chemotherapy group, n=293, 186 males and 107 females, median age 60 years old). All patients in the immunotherapy group received immune checkpoint inhibitors targeting the programmed cell death protein-1 (PD-1) and its ligand (PD-L1). Of them, 85 received pembrolizumab, 10 received sintilimab, 8 received tislelizumab, 4 received camrelizumab, 2 received toripalimab, and 1 received pabocizumab. The adjuvant chemotherapy regimens used among the chemotherapy alone group includes SOX regimen (132 cases), XELOX (102 cases), S-1 monotherapy (44 cases), and other regimens (15 cases). The 3-year DFS rate of the two groups was compared, and subgroup analysis was conducted based on different ages, molecular phenotypes, pTNM staging, extranodal infiltration, and tumor length. Results:The median follow-up was 20.5 months (range 3.1~46.3), with a 3-year overall DFS rate of 61.4% for the entire 403 patients. The 3-year DFS rate for the immunotherapy group was 82.7%, higher than the chemotherapy alone group (58.8%), with a statistically significant difference ( P=0.021). Multivariate analysis showed that postoperative immunotherapy was a protective factor for DFS (HR=0.352, 95%CI: 0.180~0.685). Subgroup analysis showed that stage IIIC (HR=0.416, 95%CI: 0.184~0.940), aged ≥60 years (HR=0.336, 95%CI: 0.121~0.934) and extranodal invasion (HR=0.378, 95%CI: 0.170~0.839) were associated with benefit from the combined immune adjuvant chemotherapy, while no association was observed for MMR, HER-2 or EBER status. Conclusion:Stage III gastric/esophagogastric junction cancer patients may benefite from postoperative immune checkpoint inhibitor combined with adjuvant chemotherapy in real-world settings.

ObjectiveTo explore the predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating aplastic anemia （AA） in non-elderly adults， so as to provide a reference for predicting the prognosis of this therapy. MethodA retrospective study was conducted with the clinical data of non-elderly adult AA patients who visited 19 hospitals including Xiyuan Hospital of the China Academy of Chinese Medical Sciences from September 2018 to March 2021 and were treated with Yiqi Yangxue Prescription combined with western medicine. According to the efficacy evaluation results at the 6^th month of treatment， the patients were assigned into effective and ineffective groups. The two groups were compared in terms of the gender， age， disease classification ［non-severe aplastic anemia （NSAA）/severe aplastic anemia （SAA）］， course of disease， family history， complications， history of drug allergy， baseline blood routine examination ［hemoglobin （HGB）， white blood cell （WBC）， neutrophil （ANC）， platelet （PLT）， and reticulocyte （Ret）］， T lymphocyte subsets， degree of proliferation of nucleated cells in bone marrow， and expression of T-bet and GATA-3. ResultA total of 101 non-elderly adult AA patients were enrolled in this study， including 81 in the effective group and 20 in the ineffective group. The effective group had a higher proportion of the patients without a history of drug allergy than the ineffective group （P<0.05）. The body height， body weight， gender， age， disease classification， course of disease， family history， and complications showed no significant differences between two groups. The effective group had higher levels of ANC and PLT before treatment （P<0.05） and higher proportion of patients with ANC≥1.6×10⁹/L and PLT≥25×10⁹/L （P<0.05， P<0.01） than the ineffective group. The baseline levels of WBC， HGB， and Ret showed no significant statistical differences between two groups. The levels of CD3⁺HLA-DR⁺T cells in the effective group before treatment was higher than that in the ineffective group （P<0.05）. The levels of CD3⁺CD19^-T cells， CD4⁺T cells， CD8⁺T cells， Th1 cells， Th2 cells， and CD3⁺CD25⁺T cells showed no significant statistical differences between two groups before treatment. The proportion of patients with active bone marrow nucleated cells proliferation in the effective group before treatment were significantly higher than that in the ineffective group, while the proportion of patients with reduced or extremely reduced proliferation were significantly lower than that in the ineffective group （P<0.05）. The expression levels of T-bet and GATA-3 genes had no significant differences between two groups before treatment. The multivariate binary logistic regression analysis showed that the ANC level before treatment and history of drug allergy were independent influencing factors for efficacy （P<0.05， P<0.01）， while other indicators were not influencing factors for efficacy. The receiver operating characteristic （ROC） curve was applied to analyze the predictive value of the ANC level before treatment in the treatment of AA in non-elderly adults with Yiqi Yangxue prescription combined with western medicine. The area under the curve was 0.679 （P<0.05）， with the critical value of 1.595×10⁹/L， the sensitivity of 0.42， and the specificity of 0.95. ConclusionThe history of drug allergy， pre-treatment ANC， PLT， CD3⁺HLA-DR⁺ T cell levels， and proliferation of nucleated cells in bone marrow before treatment are predictive factors for the efficacy of Yiqi Yangxue prescription combined with western medicine in treating AA in non-elderly adults. This therapy tends to be more effective for the patients with no history of drug allergy， higher ANC and PLT levels before treatment， especially those with ANC≥1.6×10⁹/L， PLT≥25×10⁹/L， and higher CD3⁺ HLA-DR⁺T cell levels and the more active proliferation of nucleated cells in bone marrow before treatment.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

OBJECTIVE To explore the effects of naringin on the proliferation and differentiation of osteoblasts in T cell - osteoblast co -culture system under simulated microgravity . METHODS This experiment was setting normal gravity control group ， normal gravity naringin group ，simulated microgravity control group and simulated microgravity naringin group .In the control group，T cells were co -cultured with osteoblasts under normal gravity or simulated microgravity conditions . In the naringin group ， 1×10－5 mol/L naringin solution was added additionally on the basis of control group .The morphology of osteoblasts was observed under the microscope . The proliferation rate of osteoblasts was detected by CCK -8 method. The alkaline phosphatase （ALP）activity was detected by ALP kit . mRNA relative expressions of Runt related transcription factor 2（Runx2）and interleukin -6（IL-6）were detected by real -time fluorescence quantitative polymerase chain reaction . The relative expression of Runx 2 and IL -6 protein were detected by Western blot . RESULTS Compared with normal gravity control group ，the density of osteoblasts in the simulated microgravity control group decreased ，only a small number of cells were aggregated ，and the cell morphology was mostly round ； compared with the simulated microgravity control group ，the osteoblasts in the simulated microgravity naringin group formed spindle or polygonal ，plump in shape ，and clustered in groups of fish . Compared with normal gravity control group ，the proliferation rate of osteoblasts ，ALP activity ，relative expressions of Runx 2 mRNA and protein in the normal gravity naringin group were significantly increased ，while the relative expressions of IL -6 mRNA and protein were significantly decreased （P＜ 0.05）；the proliferation rate of osteoblasts ，ALP activity ，relative expressions of Runx 2 mRNA and protein in the simulated microgravity control group were significantly decreased ，while relative expressions of IL -6 mRNA and protein were significantly increased（P＜0.05）. Compared with the simulated microgravity control group ，the proliferation rate of osteoblasts ，ALP activity ， relative expressions of Runx 2 mRNA and protein in the simulated microgravity naringin group were significantly increased ，while relative expressions of IL -6 mRNA and protein were significantly decreased （P＜0.05）. CONCLUSIONS In the T cell -osteoblast co-culture system ，simulated microgravity can inhibit the proliferation and differentiation of osteoblasts ；naringin can improve the proliferation and differentiation ability of osteoblasts under this condition， and its mechanism of action is related to the decrease of IL -6 level and the increase of Runx 2 level.

Objective:To assess whether air-charged urodynamic(ACC)can replace water-filled urodynamic(WFC)and the value of ACC for the diagnosis of benign prostatic hyperplasia(BPH)in these patients.Methods:In this prospective study, 27 male patients with BPH(aged 60-90 years)were randomly selected for WFC and ACC examinations during the same period to compare the values of urodynamic pressure parameters recorded for the two groups.Pressure values were compared using Bland-Altman plots and the paired sample t-test, and differences in abdominal pressure changes in the two groups were compared using the chi-square test. Results:Changes in WFC and ACC pressure values showed the same trends, but at the three points where data were recorded and compared, the mean abdominal pressure(Pabd), end of bladder filling pressure(Pves.fill)and maximum detrusor pressure(Pdet.void)were(25.3±8.5)cmH 2O(1 cmH 2O=0.098 kPa), (26.0±8.08.4)cmH 2O and(98.8±32.8)cmH 2O for WFC and(32.5, 5.5±5.3)cmH 2O, (32.6±5.0)cmH 2O and(95.3±36.3)cmH 2O for ACC, respectively, The pressure values of the two methods were significantly different( P<0.05). WFC pressure values were unstable, with 74.07%(20/27)showing a marked decrease during bladder filling, significantly different from those measured by ACC( P<0.001). Band-Altman plots illustrated high consistency between pressure values measured via WFC and ACC. Conclusions:The pressure measured by ACC does not represent that measured by WFC, suggesting a clinical need to establish standard reference data for ACC.The abdominal pressure instability measured by WFC may be one of the factors leading to different detrusor pressures from the two methods.The high consistency between pressure values from ACC and WFC indicates that the former can also be used to assess changes in bladder function in elderly BPH patients.

ObjectiveTo investigate the efficacy of Bushen Shengxue prescription and Yiqi Yangxue prescription in the treatment of chronic aplastic anemia and the effect on T cell subsets and the expression of T-box expressed in T cells （T-bet） and GATA binding protein 3 （GATA3）. MethodA total of 585 patients with chronic aplastic anemia who were treated in 19 hospitals in China from May 2018 to June 2021 were enrolled. With the prospective， double-blind and randomized control methods， the patients were randomized into three groups： kidney deficiency group， Qi and blood deficiency group， and control group. The three groups were respectively treated with Bushen Shengxue prescription granule， Yiqi Yangxue prescription granule， and Placebo （half the dose of Bushen Shengxue formula granules）. In addition， all of them were given oral cyclosporin and androgen. The treatment lasted 6 months， with 3 months as a course. The blood routine indexes， T cell subsets， and fusion genes T-bet and GATA3 before and after treatment were analyzed， and the safety indexes were monitored. ResultDuring the observation， a total of 75 cases dropped out and 18 were rejected. Finally， 161 cases in the kidney deficiency group， 164 in the Qi and blood deficiency group， and 167 in the control group were included. After 6 months of treatment， the total effective rate was 98.8% （159/161） in the kidney deficiency group， which was higher than the 79.9% （131/164） in the Qi and blood deficiency group （χ²=30.135， P<0.01） and the 61.7% （103/167） in the control group （χ²=70.126， P<0.01）. The total effective rate was higher in the Qi and blood deficiency group than in the control group （χ²=13.232， P<0.01）. After treatment， the hemoglobin （HGB） content increased significantly in three groups （P<0.05） as compared with that before treatment， particularly the kidney deficiency group （P<0.01）. After treatment， the white blood cell （WBC） count and platelet （PLT） count in the kidney deficiency group and the control group increased compared with those in the Qi and blood deficiency group （P<0.01）. There was no specific difference in neutrophils （ANC） after treatment among the three groups. At the same time point， the level of T helper type 1 （Th1） cells， Th1/Th2 ratio （P<0.05）， level of CD4⁺， and CD4⁺/CD8⁺ ratio （P<0.05） were significantly low in the kidney deficiency group among three groups. There was no significant difference in CD19^-， HLA/DR⁺， and CD25⁺ between the kidney deficiency group and the other two groups， but the T-bet of the kidney deficiency group and the control group was lower than that of the Qi and blood deficiency group （P<0.05）. ConclusionBushen Shengxue prescription exerts therapeutic effect on the aplastic anemia by improving the immunoregulatory mechanism， inhibiting the activity of immune system， modulating T cell subsets， suppressing Th1 and CD4⁺， and promoting bone marrow hematopoiesis. Moreover， it is safe with little side effects， which is worthy of further promotion.

Objective:To discuss the value of real-time three-dimensional speckle tracking imaging(RT3D-STI) in the evaluation of the left atrial (LA) volume and function in end-stage renal disease (ESRD) patients with different dialysis methods.Methods:Eighty-three ESRD patients who were treated in the Affiliated Hospital of Qingdao University from February to August 2019 were enrolled and divided into non-dialysis group ( n=25), hemodialysis group (HD group, n=31) and peritoneal dialysis group (PD group, n=27). And 30 healthy volunteers were enrolled as control group. Subsequently, the LA volume indexs including LA maximal volume index (LAVImax), LA minimal volume index (LAVImin) and LA presystolic volume index (LAVIpre), the LA function parameters including LA ejection fraction (LAEF), LA passive ejection fraction(LApEF) and LA active ejection fraction (LAaEF) and the LA global strain parameters including global longitudinal strain(GLS), global radial strain(GRS) and global circumferential strain(GCS) were obtained by RT3D-STI. The differences of the parameters among these groups were compared and the correlations between the myocardial strain parameters and dialysis time were analyzed. Results:①The LAVImax, LAVImin and LAVIpre of the non-dialysis group, PD group and HD group were higher than those in the control group, while the LAEF, LApEF, GLS, GRS and GCS were lower than those in the control group(all P<0.05); the LAVImin of the PD group as well as the LAVImin, LAVIpre and LAVImax of HD group were higher than those of non-dialysis group, while the LAEF, LApEF, GLS, GCS of the PD group and the LAEF, LApEF, GLS, GRS, GCS of HD group were lower than those of non-dialysis group (all P<0.05). The LAVImax, LAVImin, LAVIpre of HD group were higher than those of PD group, while the LAEF, LApEF, GLS, GRS and GCS of HD group were lower than those of PD group (all P<0.05). ②The GLS and GCS in PD group were negatively correlated with the dialysis time( r=-0.670, -0.596, all P<0.05), and the GLS, GCS and GRS in HD group were negatively correlated with the dialysis time( r=-0.624, -0.631, -0.551, all P<0.05). Conclusions:RT3D-STI can assess the LA volume and function of ESRD patients with different dialysis methods effectively and can further evaluate the prognosis of patients and guide timely clinical intervention.

Objective:To evaluate the diagnostic value of HPV detection in squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site.Methods:Clinical data of 6 patients who were initially diagnosed with squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site and eventually diagnosed with HPV-related oropharyngeal squamous cell carcinoma were collected, and the process of diagnosis was analyzed.Results:Upon the initial admission, all patients were diagnosed with squamous cell carcinoma of the cervical lymph node metastasis with positive p16 expression, positive HPV-16 subtype and negative EBER expression. No obvious primary lesion was found after comprehensive examination. Subsequently, four of them underwent ipsilateral tonsollar blind biopsy ( n=2) and ipsilateral tonsillectomy ( n=2). All these four patients were pathologically diagnosed with tonsillar squamous cell carcinoma. For the other two cases, MRI detected the thickening complicated with enhancement of ipsilateral wall of oropharynx and tongue root after follow-up for D149 and D545 , respectively. Biopsy confirmed the diagnosis of squamous cell carcinoma of the tonsil and tongue root, respectively. Conclusion:For patients with HPV-positive squamous cell carcinoma of the cervical lymph node metastasis from an unknown primary site, the possibility that the primary lesion originates from the oropharyngeal site, especially the tonsil and tongue root, should be highly suspected.