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In recent years, the application of numerical simulation in the research and development(R&D) as well as the pharmaceutical processes of new drugs has expanded considerably. The discrete element method(DEM), an important approach among numerical simulation methods, offers an effective tool for the simulation of discontinuous media. Referring to the research progress of DEM and the formulation of solid traditional Chinese medicine(TCM) preparations in recent years, this paper summarizes and analyzes the application of DEM in the pharmaceutical processes of solid TCM preparations, and discusses the challenges of its application in these processes, in order to provide new methods and ideas for promoting the high-quality production of TCM preparations.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Chemistry, Pharmaceutical/methods , Drug Compounding/methodsABSTRACT
OBJECTIVE: To analyze the fluctuations of patient-reported outcomes (PROs) and their relationships with cytokines in the peripheral blood of patients undergoing chemotherapy for ovarian cancer (OC). METHODS: PROs burden was prospectively measured by the M.D. Anderson Symptom Inventory-Ovarian Cancer (MDASI-OC) at baseline before chemotherapy, on a daily basis during and post-chemotherapy days (PCD) 7, 14, and 20. Cytokines were collected at baseline, days prior to hospital discharge and PCD 20. Pearson correlation was used to explore the associations between PROs and cytokines levels in peripheral blood. RESULTS: The top 8 rated symptoms were compared between the neoadjuvant chemotherapy (NACT) group (n=20) and the postoperative adjuvant chemotherapy (PAC) group (n=7). Before chemotherapy, the mean scores of fatigue and lack of appetite in the NACT group were higher than those in the PAC group. After chemotherapy, pain, nausea, vomiting, disturbed sleep, lack of appetite, and constipation increased to peak during PCD 2-6; while, fatigue and numbness or tingling remained at high levels over PCD 2-13. By PCD 20, disturbed sleep and fatigue showed a significant increase in mean scores, particularly in the NACT group; while, other symptom scores decreased and returned to baseline levels. Additionally, the longitudinal fluctuations in pain, fatigue, and lack of appetite were positively associated with circulating levels of interleukin-6 and interferon gamma (p<0.05). CONCLUSION: MDASI-OC was feasible and adaptable for demonstrating the fluctuations of symptom burden throughout chemotherapy course. Moreover, symptoms changing along with cytokines levels could provide clues for exploring mechanism underlying biochemical etiology.
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This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1ß), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1ß, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1ß, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1ß, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.
Subject(s)
Acetaminophen , Chemical and Drug Induced Liver Injury , Cyclooxygenase 2 , Liver , NF-kappa B , Panax , Saponins , Signal Transduction , Animals , Acetaminophen/adverse effects , Acetaminophen/toxicity , Mice , Panax/chemistry , Male , Saponins/pharmacology , Saponins/administration & dosage , NF-kappa B/genetics , NF-kappa B/metabolism , Chemical and Drug Induced Liver Injury/drug therapy , Chemical and Drug Induced Liver Injury/metabolism , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Liver/drug effects , Liver/metabolism , Signal Transduction/drug effects , Humans , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/pharmacologyABSTRACT
OBJECTIVES: To identify an optimal magnetic resonance imaging (MRI)-based classification for the severity of adenomyosis and explore the factors associated with disease severity (dysmenorrhea or menorrhagia). DESIGN AND PARTICIPANTS: Several classifications based on MRI have been proposed, and their phenotypes are reported to be associated with the severity of adenomyosis. However, a consensus classification based on MRI findings has not yet been reached. Our study was designed to retrospectively analyze data from a cohort of patients in the Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to December 2021 before focused ultrasound ablation surgery (FUAS), to identify the optimal classification of adenomyosis severity from different classification criteria and explore factors associated with the presence of symptoms. METHODS: The proportions of disease severity among different classification groups were compared to obtain the one generating the most considerable chi-square value, which was identified as the optimal classification for informing disease severity. A logistic regression model was constructed to explore factors associated with disease severity. RESULTS: Classification of Kobayashi H (classification 4) concerning the affected areas and size (volumes of lesions) was recognized as the optimal one, which identified dysmenorrhea (χ2=18.550, p-value=0.002) and menorrhagia (χ2=15.060, p-value=0.010) secondary to adenomyosis. For volumes of uterine wall <2/3, the dysmenorrhea rate in subtype-4 was higher than that in subtype-1 (χ2=4.114, p-value=0.043), and the dysmenorrhea rate in subtype-5 was higher than that in subtype-2 (χ2=4.357, p-value=0.037). Age (OR=0.899, 95%CI=0.810ï½0.997, p-value=0.044) and external phenotype (OR=3.588, 95%CI=CI 1.018ï½12.643, p-value=0.047) were associated with dysmenorrhea. Concerning volumes of uterine wall ≥2/3, the menorrhagia rate in subtype-3 remarkably increased compared with that in subtype-6 (χ2=9.776, p-value=0.002), and internal phenotype was identified as an independent factor associated with menorrhagia (OR=1.706, 95%CI=1.131ï½2.573, p-value=0.011). LIMITATIONS: Patients in our study were all included before FUAS, which limited our result interpretation for the general patient population. CONCLUSIONS: MRI-based classification 4 is identified as an optimal classification for informing the severity of adenomyosis. The phenotype of classification is the main characteristic associated with disease severity.
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BACKGROUND: A referenced MRI-based classification associated with focused ultrasound ablation surgery (FUAS) outcomes is lacking in adenomyosis. PURPOSE: To identify an MRI-based classification system for informing the FUAS outcomes. STUDY TYPE: Retrospective. POPULATION: Patients with FUAS for adenomyosis, were divided into a training set (N = 643; 355 with post-FUAS gonadotropin-releasing hormone/levonorgestrel, 288 without post-FUAS therapy) and an external validation set (N = 135; all without post-FUAS therapy). FIELD STRENGTH/SEQUENCE: 1.5 T, turbo spin-echo T2-weighted imaging and single-shot echo-planar diffusion-weighted imaging sequences. ASSESSMENT: Five MRI-based adenomyosis classifications: classification 1 (C1) (diffuse, focal, and mild), C2 (intrinsic, extrinsic, intramural, and indeterminate), C3 (internal, adenomyomas, and external), C4 (six subtypes on areas [internal or external] and volumes [<1/3 or ≥2/3]), and C5 (internal [asymmetric or symmetric], external, intramural, full thickness [asymmetric or symmetric]) for FUAS outcomes (symptom relief and recurrence). STATISTICAL TESTS: The optimal classification was significantly associated with the most subtypes of FUAS outcomes. Relating to the timing of recurrence was measured using Cox regression analysis and median recurrence time was estimated by a Kaplan-Meier curve. A P value <0.05 was considered statistically significant. RESULTS: Dysmenorrhea relief and recurrence were only associated with C2 in training patients undergoing FUAS alone. Compared with other subtypes, the extrinsic subtype of C2 was significantly associated with dysmenorrhea recurrence in the FUAS group. Besides, the median dysmenorrhea recurrence time of extrinsic subtype was significantly shorter than that of other subtypes (42.0 months vs. 50.3 months). In the validation cohort, C2 was confirmed as the optimal system and its extrinsic subtype was confirmed to have a significantly shorter dysmenorrhea recurrence time than other subtypes. DATA CONCLUSION: Classification 2 can inform dysmenorrhea relief and recurrence in patients with adenomyosis undergoing FAUS only. Itsextrinsic subtype was associated with an earlier onset of dysmenorrhea recurrence after treatment. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 5.
Subject(s)
Adenomyosis , High-Intensity Focused Ultrasound Ablation , Female , Humans , Adenomyosis/diagnostic imaging , Adenomyosis/surgery , Dysmenorrhea/diagnostic imaging , Dysmenorrhea/complications , Dysmenorrhea/surgery , Treatment Outcome , Retrospective Studies , High-Intensity Focused Ultrasound Ablation/methods , Magnetic Resonance Imaging/methods , Ultrasonography, Interventional/methodsABSTRACT
OBJECTIVE: To estimate the rate and risk factors of re-intervention for patients with uterine fibroids (UFs) undergoing high-intensity focused ultrasound (HIFU) at different age distributions. METHOD: A retrospective cohort study was conducted in Nanchong Central Hospital, recruiting a total of 672 patients with UFs undergoing HIFU from June 2017 to December 2019. Using univariate and multivariate logistic regression, risk factors for re-intervention were assessed. RESULTS: Among 401 patients with UFs who completed the follow-up visits (median 47 months, range 34-61), 50 (12.46%) patients underwent re-intervention (such as high-intensity focused ultrasound, uterine artery embolization, myomectomy and hysterectomy). In the different age distributions, the re-intervention rate was 17.5% (34/194) in patients aged <45 years and 7.7% (16/207) in those aged ≥45 years. Regarding the younger patient group (aged <45 years), hypo- or iso-intensive fibroids in T2-weighted magnetic resonance imaging (T2WI) intensity may elevate the risk of re-intervention for UFs (odds ratio [OR] 2.96, 95% confidence interval [CI] 1.37-6.62; P = 0.007). Among the older patient group (aged ≥45 years), preoperative anemic patients had an increased risk of re-intervention compared with those without anemia (OR 3.30, 95% CI 1.01-10.37; P = 0.041). CONCLUSION: The re-intervention rate of HIFU decreased with increasing age. Among those aged <45 years, T2WI intensity was the independent risk factor for re-intervention, and among those aged ≥45 years, preoperative anemic status may be related to re-intervention outcome.
Subject(s)
High-Intensity Focused Ultrasound Ablation , Leiomyoma , Uterine Myomectomy , Uterine Neoplasms , Female , Humans , Uterine Neoplasms/surgery , Retrospective Studies , High-Intensity Focused Ultrasound Ablation/methods , Leiomyoma/surgery , Uterine Myomectomy/adverse effects , Treatment Outcome , Magnetic Resonance Imaging/methodsABSTRACT
In recent years, the use of active substances as excipients or as substitutes for other excipients in the design of modern drug delivery systems has received widespread attention, which has promoted the development of the theory of unification of medicines and excipients in the design of traditional Chinese medicine(TCM) preparations. Adopting the theory of unification of medicines and excipients to design drug delivery systems can reduce the use of excipients and thus the cost of preparations, reduce drug toxicity, increase drug solubility and biocompatibility, enhance synergistic effect, and realize targeted delivery and simultaneous delivery of multiple components. However, the research on the application of this theory in the modern drug delivery system of TCM preparations is still insufficient, with few relevant articles. In addition, the TCM active substances that can be used as the excipients remain to be catalogued. In this paper, we review the types and applications of the drug delivery systems with TCM active substances as excipients and describe their common construction methods and mechanisms, aiming to provide references for the in-depth research on the modern drug delivery systems for TCM preparations.
Subject(s)
Drugs, Chinese Herbal , Medicine, Chinese Traditional , Excipients , Nanomedicine , Pharmaceutical PreparationsABSTRACT
OBJECTIVE: To explore the association between CA125 and dysmenorrhea in adenomyosis, and the factors affecting CA125 in adenomyosis. METHODS: Patients were grouped a the presence of dysmenorrhea. The receiver operating characteristic (ROC) curve was applied to assess the utility of CA125 for dysmenorrhea. Binary logistic regression was employed to identify the factors associating dysmenorrhea and CA125 level. RESULTS: Patients in the dysmenorrhea group had higher CA125 levels than those in the non-dysmenorrhea group. For those with dysmenorrhea, CA125 levels of diffuse subtype group were higher than those of the focal subtype group. The CA125 level of 35 U/mL was validated as the optimal cut-point for dysmenorrhea in ROC curves. Compared with patients whose CA125 was 35 U/mL or less, those with CA125 levels greater than 35 U/mL were more likely to have dysmenorrhea. Thereafter, the multiple regression analysis showed that adenomyotic lesion volume was positively correlated with CA125 level in the total cohort and subtype groups, while age was negatively correlated with CA125 level in the total cohort and diffuse subtype. CONCLUSIONS: The pathogenesis of adenomyosis is not clear. CA125 was associated with dysmenorrhea in adenomyosis, and, furthermore, CA125 level is positively correlated with the severity of the disease.
Subject(s)
Adenomyosis , Female , Humans , Adenomyosis/complications , Adenomyosis/pathology , Dysmenorrhea/etiology , CA-125 Antigen , Logistic ModelsABSTRACT
Objective: To compare the return to work (RTW) time between single-port laparoscopic surgery (SPLS) and multiport laparoscopic surgery (MPLS) for benign ovarian tumors. Methods: A cross-sectional cohort study was conducted, which consisted of 335 women of reproductive age with benign ovarian tumors and who were keen on returning to work as early as possible. Surgical outcomes, postoperative pain score, postoperative satisfaction with the cosmesis score (CS), and the RTW time of the SPLS group were compared with those of the MPLS group. Besides, the RTW time and CS were calculated from the questionnaire survey by a single specialized gynecologist. Results: Women who met the inclusion criteria were included in the SPLS (n = 106) and MPLS groups (n = 229). The RTW time in the SPLS group (22.13 ± 27. 06 days) was significantly shorter than that in the MPLS group (46.08 ± 57.86 days) (P < 0.001). The multivariate Cox analysis results showed that age (HR = 0.984, 95% CI, 0.971-0.997, P = 0.020), SPLS (HR = 3.491, 95% CI, 2.422-5. 032, P < 0.001), and return to normal activity time (HR = 0.980, 95% CI, 0.961-0.998, P = 0.029) were independent factors of the RTW time. Conclusions: SPLS may be advantageous in terms of shortening the RTW time for women with benign ovarian tumors.
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OBJECTIVES: To investigate the relationship between preoperative CA125 and symptom recurrence in adenomyosis after ultrasound-guided high-intensity focused ultrasound ablation surgery (FUAS). METHODS: A total of 502 adenomyosis patients after FUAS in Affiliated Nanchong Central Hospital of North Sichuan Medical College from June 2017 to March 2021 were reviewed. Factors associated with symptom recurrence of adenomyosis were analyzed by binary logistic regression model. ROC was used to determine the optimal cutpoint. Magnitude of preoperative CA125 relating to timing of symptom recurrence was measured by cox regression and Kaplan-Meier (K-M) curves. Besides, multiple liner regression model was used to identify the impacting factors for preoperative CA125. RESULTS: Multiple binary logistic analysis showed preoperative CA125 was related to symptom recurrence (OR = 1.002, 95%: 1.000ï½1.004, p = 0.043). The ROC of preoperative CA125 for recurrence validated 35 U/ml had a high sensitivity (82.5%). Preoperative CA125 was related to timing of symptom recurrence (HR = 2.255, 95%: 1.387-3.667, p = 0.001). K-M curves showed medium recurrence time in preoperative CA125 level >35 U/ml group (38.5 months) was shorter than that in CA125 level ≤35 U/ml group (44.5 months) (p = 0.001). Multiple liner regression analyses showed uterus volume and adenomyotic lesions volume positively correlated to preoperative CA125 level, while age negatively correlated to preoperative CA125 level. CONCLUSION: The higher level of preoperative CA125 was related to an earlier onset of symptom recurrence after FUAS.
Subject(s)
Adenomyosis , High-Intensity Focused Ultrasound Ablation , Adenomyosis/diagnostic imaging , Adenomyosis/pathology , Adenomyosis/surgery , CA-125 Antigen , Female , Humans , Retrospective Studies , Risk Factors , Treatment Outcome , Ultrasonography, InterventionalABSTRACT
Objectives: This study was to analyze the relationships between lymphocyte-to-monocyte ratio (LMR) alone or combined with serum CA125 (COLC) and advanced stage of ovarian cancer (OC). Methods: The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC staging OC were constructed by a retrospective study. Furthermore, a binary logistic regression model was used to assay the independent risk factors for OC staging. Results: Two hundred and twenty-five patients with OC were identified in this cohort. Eighty-five OC patients were diagnosed at an early stage, and 140 OC patients were diagnosed at an advanced stage. The median of LMR in the early stage was higher than that in advanced stage (4.4 vs. 2.8), and the median of serum CA125 was lower than that in advanced stage (80 U/mL vs. 251.3 U/mL). Multivariate logistic regression LMR≤3.7 (OR=0.299, 95% CI: 0.093-0.962, P=0.043) and CA125>95.7 U/mL (OR=4.317, 95% CI: 1.436-12.977, P=0.009) were risk factors for stage of advanced OC whether presence or absence of malignant ascites. Furthermore, the area under the curve of COLC was higher than that of LMR (0.782 vs. 0.732) or serum CA125 (0.782 vs. 0.708) in staging OC. The specificity of COLC was higher than that of LMR (87.1% vs. 70.6%) or serum CA125 (87.1% vs. 61.2%) in staging OC. Conclusion: LMR alone or in combination with serum CA125 might be associated with OC staging. Besides, as a predictive factor, COLC may have a high specificity in staging OC.
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Objectives: To investigate the role of inflammation-related factors, lymphocyte-to-monocyte ratio (LMR) alone and combined detection with cancer antigen 125 (CA125), in the prognostic assessment of ovarian cancer (OC). Methods: A retrospective clinicopathologic review was performed. The receiver-operating characteristic (ROC) curves of LMR, CA125, and COLC predicting mortality in OC patients were constructed. Besides, Kaplan-Meier and Cox logistic regression models were used to plot the survival curves and determine the independent prognostic factors. Results: A total of 214 OC patients were identified in this cohort. The mean duration of follow-up was 64 months (minimum 8 months, maximum 116 months). In this cohort, 135 cases died (63.1%), and the median progression-free survival (PFS) and overall survival (OS) were 20 and 39.5 months, respectively. Results of the multivariate Cox regression model showed that LMR≤3.8 (HR = 0.494, 95% CI: 0.329-0.742, P = 0.001) and CA125>34 U/ml (HR = 1.641, 95% CI: 1.057-2.550, P = 0.027) were significantly associated with poor PFS; and LMR≤3.8 (HR = 0.459, 95% CI: 0.306-0.688, P = <0.001) and CA125>34 U/ml (HR = 1.946, 95% CI: 1.256-3.015, P = 0.003) were significantly associated with OS. Furthermore, the area under the curve of COLC was higher (0.713) than that of LMR (0.709) or CA125 (0.583), the specificity of COLC was higher (75.9%) than that of LMR (62%) or CA125 (40.5%) in predicting mortality in OC patients. Conclusions: LMR alone and combined with CA125 might be used as predictive markers in OC. Furthermore, as a prognostic factor, COLC might have a higher specificity to predict the outcome.
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OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of motherwort injection (MI, Yi mu cao) in preventing post-abortion hemorrhage and promoting uterine retraction after induced abortion surgery. METHODS: In this multi-center randomized controlled trial undertaken between September 2014 and August 2016, 408 child-bearing age women who underwent induced abortion surgery and randomly assigned to two groups: MI group who received intramuscular MI treatment (nâ¯=â¯207) and no-treatment group (nâ¯=â¯201). The volume of vaginal bleeding and its duration were used as primary end points; and uterine size and dimension were measured as secondary end points. Blood coagulation indices, routine blood and adverse events were recorded to evaluate the safety. RESULTS: The efficacy analysis was based on 366 patients. No significant difference were found in baseline characteristics between the two groups (P > 0.05). The amount of vaginal bleeding and duration of bleeding were significantly reduced in MI group compared with on-treatment group in Full Analysis Set (FAS) and Per Protocol Set (PPS) populations (P < 0.001). The volume and perimeter of the uterine dimensions in MI group were smaller than no-treatment group (P < 0.001). No significant abnormal vital signs were observed. Only 1 case of mild, transient erythema was found in MI group. CONCLUSIONS: MI could reduce post-abortion hemorrhage and improve uterine retraction in women undergoing surgical induced abortion, without serious adverse events. It was a safe and effective treatment in preventing post-abortion hemorrhage after induced abortion.