The excipient processing is an essential part of traditional Chinese medicine processing, and understanding its scientific connotations is a critical scientific issue that urgently needs resolution. Building upon a foundation where the composition of traditional Chinese medicine substances is fundamentally clear, this paper applies the techniques and methods of chemoinformatics to the study of the excipient processing mechanism. Relevant information on traditional Chinese medicines processed with four kinds of excipients (wine, vinegar, salt and honey) was collected, including properties, taste, meridian tropism, chemical components, etc. Molecular descritors and skeletons corresponding to each chemical component were calculated using chemoinformatics to characterize the properties and structural features of the components. Characteristic components associated with the four excipients (wine, vinegar, salt and honey) were explored through multivariate statistical analysis and Murcko skeleton analysis. Further analysis, taking honey-processed Astragali Radix as an example, the focus was on the impact of the processing excipient honey on the solubility and permeability of its characteristic pharmacologically active components (isoflavones). It was discovered that the excipient honey can increase their solubility and permeability, emphasizing that the impact of processing excipients on the pharmacological classification properties is a key breakthrough in elucidating the mechanism of excipient processing. In summary, this study analyzed the characteristic components associated with the processing excipients "wine, vinegar, salt and honey" based on their composition characteristics, providing data support for the research on the mechanism of excipient processing from a biopharmaceutical perspective.

Objective To investigate the oral health status of the first-grade primary school students in Shanghai and analyze its influencing factors.Methods In 2021,Huangpu,Xuhui,Jiading,and Jing'an districts were selected in Shanghai by random sampling method.The first-grade students of 8 primary schools in these 4 districts were enrolled by random cluster sampling.Oral clinical examinations and questionnaires were conducted according to the criteria of the Fourth National Oral Health Epidemiological Survey.EpiData 3.1 software was used to create the database.SPSS 26.0 software was applied for statistical analysis.Chi-square test was used to compare the caries prevalence between groups,and two independent samples non-parametric test was used to compare the decayed,missing and filled teeth(DMFT)between groups.Multifactorial logistic regression model was used to analyzse the influencing factors of caries.Results A total of 824 informed consent forms and questionnaires were collected,of which 764 were completed,with an effective rate of 92.7％.The total caries prevalence of the participating students was 65.6％(501/764),and the mean DMFT was 3.24±3.47.A total of 2 473 carious teeth were found in the participating students,and 671 teeth were filled,with a filling rate of 27.1％.There were 7.91±2.76 permanent teeth erupted per student,and 56.3％(430/764)of the students had all 4 first permanent molars erupted.Multivariate logistic regression showed that eating sweets＞3 times a day(P=0.030),eating regularly before bedtime(P=0.001),and parents'cognition of kids'poor oral health status(P=0.025)were the influencing factors for the detection of caries in children.Conclusion The first-grade primary school students in Shanghai have high prevalence of caries.Eating sweets＞3 times a day,eating regularly before bedtime,and parents'cognition of kids'poor oral health status(P＜0.05)are the influencing factors for the detection of caries in children.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Objective:To explore the clinical features and prognosis of patients with primary central nervous system lymphoma(PCNSL).Methods:A retrospective analysis was performed on the relationship between clinical features,treatment regimen and prognosis in 46 newly diagnosed patients with primary central nervous system lymphoma who were diagnosed and treated in The Second Hospital of Lanzhou University from January 2015 to September 2022.Fisher's exact probability method was used to analyze the differences in clinical data of different subgroups.Kaplan-Meier survival curve was used to analyze the overall survival rate and progression-free survival rate of patients with different treatments,and the factors influencing survival were analyzed.Results:Among 46 patients with PCNSL,which pathological type were diffuse large B-cell lymphoma(DLBCL).There were 26(56.5％)cases of male and 20(43.5％)of female,with a median age of 54(17-71)years.In Hans subtypes,14 cases(30.4％)of GCB subtype,32 cases(69.6％)of non-GCB subtype.32 cases(69.6％)of Ki-67 ≥80％.Among 36 patients who completed at least 2 cycles of treatment with follow-up data,the efficacy evaluation was as follows:overall response rate(ORR)was 63.9％,complete response(CR)rate was 47.2％,17 cases of CR,6 cases of PR.The 1-year progression-free survival rate and 1-year overall survival rate was 73.6％and 84.9％,respectively.The 2-year progression-free survival rate and 2-year overall survival rate was 52.2％and 68.9％,respectively.The ORR and CR rate of 17 patients treated with RMT regimen was 76.5％and 52.9％(9 cases CR and 4 cases PR),respectively.Univariate analysis of 3 groups of patients treated with RMT regimen,RM-BTKi regimen,and RM-TT regimen as first-line treament showed that deep brain infiltration was associated with adverse PFS(P=0.032),and treatment regimen was associated with adverse OS in PCNSL patients(P=0.025).Conclusion:Different treatment modalities were independent prognosis predictors for OS,the deep brain infiltration of PCNSL is a poor predictive factor for PFS.Patients with relapse/refractory(R/R)PCNSL have a longer overall survival time because to the novel medication BTKi.They have strong toleration and therapeutic potential as a first-line therapy for high-risk patients.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

One of the remarkable progresses regarding non-clear cell renal cell carcinoma in the 2024 ASCO-GU symposium was the survival update of KEYNOTE-B61 study, in which tyrosine kinase inhibitor plus immunotherapy (TKI-IO) combination maintained satisfactory efficacy and safety. The distinct response to immunotherapy between papillary versus chromophobe renal cell carcinoma was demonstrated closely correlated with tumor microenvironment. The fusion partner of TFE-rearranged renal cell carcinoma directly determined the tumor biological behavior and therapeutic response.

OBJECTIVE: To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation. METHODS: Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed. RESULTS: Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05). CONCLUSION Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.
Mice ; Animals ; Bone Marrow ; Reactive Oxygen Species ; Mice, Inbred C57BL ; Hematopoietic Stem Cells ; Whole-Body Irradiation ; Radiation, Ionizing ; Bone Marrow Cells

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.
Humans ; Aged ; Treatment Outcome ; Retrospective Studies ; Combined Modality Therapy ; Chemoradiotherapy/methods* ; Urinary Bladder Neoplasms/radiotherapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Neoplasm Staging

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing