Hongjin Xiaojie Capsule, a Chinese patent medicine, for treating moderate to severe cyclical breast pain: A single-blind randomized controlled trial.

BACKGROUND: Moderate to severe breast pain has major effects on the quality of life for patients. Patent Chinese medicines are widely used in the treatment of breast pain due to their stable dosage form and good efficacy. OBJECTIVE: To evaluate the beneficial effects and safety of Hongjin Xiaojie Capsule (HJXJC), a Chinese patent medicine, for the treatment of cyclical breast pain. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This is a multicenter, single-blind randomized controlled trial conducted in 3 medical centers in China from 2019 to 2021. Patients with moderate to severe cyclic breast pain were randomly divided into the intervention group (who took HJXJC, four capsules per dose, three times a day for 12 weeks) and the control group (waiting for the treatment) in a 1:1 ratio. MAIN OUTCOME MEASURES: The primary outcome was pain duration, and the patients recorded measurements at baseline and at the end of weeks 4, 8, 12 and 16 on a patient log card. RESULTS: The full analysis set (FAS) population included 298 participants (intervention group, n = 150; control group, n = 148), while the per-protocol analysis set (PPS) included 274 participants. After 12 weeks, the duration of breast pain was significantly shorter in the intervention group (FAS: mean difference, -6.69; 95% CI, -7.58 to -5.80; P < 0.01, vs control. PPS: mean difference, -7.09; 95% CI, -8.01 to -6.16; P < 0.01, vs control). The Short-form McGill Pain Questionnaire (SF-MPQ) scores were significantly lower in the intervention group (FAS: mean difference, -12.55; 95% CI, -13.90 to -11.21; P < 0.01, vs control. PPS: mean difference, -13.07; 95% CI, -14.48 to -11.66; P < 0.01, vs control). The above indicators continued to be significantly different through week 16. Moreover, in the intervention group, breast lumps shrank after 12 weeks and the size of breast lumps was statistically smaller than that in the control group (P < 0.05), whereas the sizes of breast nodules and uterine fibroid showed no statistically significant difference compared with the control group (P > 0.05). At weeks 8 and 12, the dysmenorrhea scores in the intervention group were lower than those in the control group (P < 0.05). No obvious adverse reactions were observed in any group. CONCLUSION: HJXJC can significantly shorten the duration of breast pain, reduce breast pain, reduce the size of breast lumps, and relieve dysmenorrhea. However, it has no significant effect on the size of breast nodules or uterine fibroid. TRIAL REGISTRATION: This trial has been registered at the ISRCTN Registry. Number: ISRCTN44184398. PLEASE CITE THIS ARTICLE AS: Zhang Q, Fan YY, Wu XQ, Huo YD, Wang CH, Liang SB, Wang T, Zhong R, Wang X, Lai BY, Pei XH, Liu JP. Hongjin Xiaojie Capsule, a Chinese patent medicine, for treating moderate to severe cyclical breast pain: A single-blind randomized controlled trial. J Integr Med. 2024; Epub ahead of print.

PRSS50-mediated inhibition of MKP3/ERK signaling is crucial for meiotic progression and sperm quality.

Serine protease 50 (PRSS50/TSP50) is highly expressed in spermatocytes. Our study investigated its role in testicular development and spermatogenesis. Initially, PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes. To further explore this, we generated PRSS50 knockout ( Prss50 -/- ) mice ( Mus musculus), which exhibited abnormal spermatid nuclear compression and reduced male fertility. Furthermore, dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50 -/- mice, accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells. Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and elevated levels of MAP kinase phosphatase 3 (MKP3), a specific ERK antagonist, potentially accounting for testicular dysplasia in adolescent Prss50 -/- mice. Taken together, these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis, with the MKP3/ERK signaling pathway playing a significant role in this process.

A feasibility study of tumor motion monitoring for SBRT of lung cancer based on 3D point cloud detection and stacking ensemble learning.

PURPOSE: To construct a tumor motion monitoring model for stereotactic body radiation therapy (SBRT) of lung cancer from a feasibility perspective. METHODS: A total of 32 treatment plans for 22 patients were collected, whose planning CT and the centroid position of the planning target volume (PTV) were used as the reference. Images of different respiratory phases in 4DCT were acquired to redefine the targets and obtain the floating PTV centroid positions. In accordance with the planning CT and CBCT registration parameters, data augmentation was accomplished, yielding 2130 experimental recordings for analysis. We employed a stacking multi-learning ensemble approach to fit the 3D point cloud variations of body surface and the change of target position to construct the tumor motion monitoring model, and the prediction accuracy was assess using root mean squared error (RMSE) and R-Square (R2). RESULTS: The prediction displacement of the stacking ensemble model shows a high degree of agreement with the reference value in each direction. In the first layer of model, the X direction (RMSE =0.019 ∼ 0.145mm, R2 =0.9793∼0.9996) and the Z direction (RMSE = 0.051 ∼ 0.168 mm, R2 = 0.9736∼0.9976) show the best results, while the Y direction ranked behind (RMSE = 0.088 ∼ 0.224 mm, R2 = 0.9553∼ 0.9933). The second layer model summarizes the advantages of unit models of first layer, and RMSE of 0.015 mm, 0.083 mm, 0.041 mm, and R2 of 0.9998, 0.9931, 0.9984 respectively for X, Y, Z were obtained. CONCLUSIONS: The tumor motion monitoring method for SBRT of lung cancer has potential application of non-ionization, non-invasive, markerless, and real-time.

A feasibility study of dosimetry for breast cancer radiotherapy based on body surface changes.

BACKGROUND: The requirement for precise and effective delivery of the actual dose to the patient grows along with the complexity of breast cancer radiotherapy. Dosimetry during treatment has become a crucial component of guaranteeing the efficacy and security. PURPOSE: To propose a dosimetry method during breast cancer radiotherapy based on body surface changes. METHODS: A total of 29 left breast cancer radiotherapy cases were retroactively retrieved from an earlier database for analysis. Non-rigid image registration and dose recalculation of the planning computed tomography (CT) referring to the Cone-beam computed tomography were performed to obtain dose changes. The study used 3D point cloud feature extraction to characterize body surface changes. Based on the correlation proof, a mapping model is developed between body surface changes and dose changes using neural network framework. The MSE metrics, the Euclidean distances of feature points and the 3D gamma pass rate metric were used to assess the prediction accuracy. RESULTS: A strong correlation exist between body surface changes and dose changes (first canonical correlation coefficient = 0.950). For the dose deformation field and dose amplitude difference in the test set, the MSE of the predicted and actual values were 0.136 pixels and 0.229 cGy, respectively. After deforming the planning dose into a deformed one, the feature points' Euclidean distance between it and the recalculated dose changes from 9.267 ± 1.879 mm to 0.456 ± 0.374 mm. The 3D gamma pass rate of 90% or higher for the 2 mm/2% criteria were achieved by 80.8% of all cases, with a minimum pass rate of 75.9% and a maximum pass rate of 99.6%. Pass rate for the 3 mm/2% criteria ranged from 87.8% to 99.8%, with 92.3% of the cases having a pass rate of 90% or higher. CONCLUSIONS: This study provides a dosimetry method that is non-invasive, real-time, and requires no additional dose for breast cancer radiotherapy.

The clinical features and prognostic factors of miliary tuberculosis in a high tuberculosis burden area.

BACKGROUND: Miliary Tuberculosis (TB) remains an important infectious disease that threatens human health. The clinical characteristics and prognostic factors of miliary TB are summarized in this study. METHODS: The clinical information of miliary TB patients between 2010 and 2022 was retrospectively analyzed. Patients with miliary TB were characterized and compared to adverse outcomes cases. Factors independently associated with adverse outcomes were determined via multivariate logistic regression analysis. RESULTS: A total of 288 patients were analyzed, including 181 with adverse outcomes. The clinical manifestations are atypical. 88.54% Of them experienced systemic symptoms, whilst 69.79% manifested respiratory symptoms. 40.97% Presented with neurologic symptoms, while 35.07% reported gastrointestinal symptoms. The major comorbidities were pharmacological immunosuppression (21.53%), pneumoconiosis (15.28%), diabetes (10.76%), and pregnancy or postpartum (7.29%). Regarding microbiology, most patients were diagnosed via sputum or Bronchoalveolar Lavage Fluid (BALF), pleural effusion, ascites, cerebrospinal fluid, urine TB-DNA, and tuberculosis culture. Meanwhile, 2.43% of patients were diagnosed via cerebrospinal fluid NGS. Independent risk factors predictive of adverse outcomes were current smoking, leukocytosis, elevated alanine aminotransferase (ALT) levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis. The accuracy of the model was validated by an area under the ROC curve of 0.753 (95% IC 0.697-0.810). CONCLUSIONS: The clinical manifestations of miliary TB are atypical, and early diagnosis is challenging. The major comorbidities in miliary TB patients were pharmacological immunosuppression, pneumoconiosis, diabetes, pregnancy, and postpartum. Regarding etiological detection, multi-site and multi-type specimens should be collected for a timely diagnosis. Cerebrospinal fluid mNGS test may be a viable choice in some cases. Finally, current smoking, leukocytosis, elevated ALT levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis were identified as independent risk factors for adverse outcomes.

The clinical manifestations of miliary TB are atypical, and early diagnosis is challenging. The major comorbidities in miliary TB patients were pharmacological immunosuppression, pneumoconiosis, diabetes, pregnancy, and postpartum. Current smoking, leukocytosis, elevated ALT levels, and the combination of lymphopenia with bone marrow tuberculosis or tuberculous lymphadenitis were identified as independent risk factors for adverse outcomes.

Simultaneous integrated boost intensity-modulated radiotherapy post breast-conserving surgery: clinical efficacy, adverse effects, and cosmetic outcomes in breast cancer patients.

BACKGROUND: Simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) is an innovative technique delivering a higher dose to the tumor bed while irradiating the entire breast. This study aims to assess the clinical outcomes, adverse effects, and cosmetic results of SIB-IMRT following breast-conserving surgery in breast cancer patients. METHODS: We conducted a retrospective analysis of 308 patients with stage 0-III breast cancer who underwent breast-conserving surgery and SIB-IMRT from January 2016 to December 2020. The prescribed doses included 1.85 Gy/27 fractions to the whole breast and 2.22 Gy/27 fractions or 2.20 Gy/27 fractions to the tumor bed. Primary endpoints included overall survival (OS), local-regional control (LRC), distant metastasis-free survival (DMFS), acute and late toxicities, and cosmetic outcomes. RESULTS: The median follow-up time was 36 months. The 3-year OS, LRC, and DMFS rates were 100%, 99.6%, and 99.2%, respectively. Five patients (1.8%) experienced local recurrence or distant metastasis, and one patient succumbed to distant metastasis. The most common acute toxicity was grade 1-2 skin reactions (91.6%). The most common late toxicity was grade 0-1 skin and subcutaneous tissue reactions (96.7%). Five patients (1.8%) developed grade 1-2 upper limb lymphedema, and three patients (1.1%) had grade 1 radiation pneumonitis. Among the 262 patients evaluated for cosmetic outcomes at least 2 years post-radiotherapy, 96.9% achieved excellent or good results, while 3.1% had fair or poor outcomes. CONCLUSIONS: SIB-IMRT after breast-conserving surgery in breast cancer patients demonstrated excellent clinical efficacy, mild acute and late toxicities, and satisfactory cosmetic outcomes in our study. SIB-IMRT appears to be a feasible and effective option for breast cancer patients suitable for breast-conserving surgery.

Yiqigubiao pill treatment regulates Sirtuin 5 expression and mitochondrial function in chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous group of pathophysiological bases of airway inflammation and its anti-inflammatory response. Aberrant mitochondrial signaling and mitochondrial dysfunction underlie the pathomechanisms leading to COPD. This study aims to investigate the effects of the Yiqigubiao (YQGB) pill, a traditional Chinese medicine (TCM), on Sirtuin 5 (SIRT5) and mitochondrial function in patients with COPD. Methods: Thirty-four patients with COPD were randomized into oral YQGB or placebo groups concurrent with a 24-week routine treatment. The pulmonary function was assessed by examining the levels of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), FEV1, and FVC. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect SIRT5 expression in mitochondria isolated from peripheral blood. Flow cytometry was used to detect changes in mitochondrial membrane potential and reactive oxygen species (ROS) in peripheral blood lymphocytes. Human bronchial epithelial (HBE) cells stimulated by cigarette smoke extract (CSE) were treated with YQGB. After SIRT5 was knocked down in cells, the changes in mitochondrial membrane potential, levels of adenosine triphosphate (ATP), and ROS were detected. Results: YQGB treatment significantly improved lung function in patients with COPD. The expression of SIRT5 and the mitochondrial membrane potential significantly increased and ROS decreased in patients with COPD after YQGB treatment. The CSE decreased cell proliferation and SIRT5 expression, which was alleviated after YQGB treatment. Furthermore, SIRT5 was knocked down in CSE-stimulated HBE cells, and its expression was elevated upon YQGB treatment. The knockdown of SIRT5 significantly altered the CSE-stimulation-induced dysregulation of mitochondrial membrane potential, ATP levels, and ROS. This was also restored after YQGB treatment. Conclusions: YQGB treatment can elevate SIRT5 expression, restore mitochondrial function in COPD, and exert protective effects.

d-type peptides based fluorescent probes for "turn on" sensing of heparin.

Developing "turn on" fluorescent probes was desirable for the detection of the effective anticoagulant agent heparin in clinical applications. Through combining the aggregation induced emission (AIE) fluorogen tetraphenylethene (TPE) and heparin specific binding peptide AG73, the promising "turn on" fluorescent probe TPE-1 has been developed. Nevertheless, although TPE-1 could achieve the sensitive and selective detection of heparin, the low proteolytic stability and undesirable poor solubility may limit its widespread applications. In this study, seven TPE-1 derived fluorescent probes were rationally designed, efficiently synthesized and evaluated. The stability and water solubility were systematically estimated. Especially, to achieve real-time monitoring of proteolytic stability, the novel Abz/Dnp-based "turn on" probes that employ the internally quenched fluorescent (IQF) mechanism were designed and synthesized. Moreover, the detection ability of synthetic fluorescent probes for heparin were systematically evaluated. Importantly, the performance of d-type peptide fluorescent probe XH-6 indicated that d-type amino acid substitutions could significantly improve the proteolytic stability without compromising its ability of heparin sensing, and attaching solubilizing tag 2-(2-aminoethoxy) ethoxy) acid (AEEA) could greatly enhance the solubility. Collectively, this study not only established practical strategies to improve both the water solubility and proteolytic stability of "turn on" fluorescent probes for heparin sensing, but also provided valuable references for the subsequent development of enzymatic hydrolysis-resistant d-type peptides based fluorescent probes.

Six versus four or five cycles of first-line etoposide and platinum-based chemotherapy combined with thoracic radiotherapy in patients with limited-stage small-cell lung cancer: A propensity score-matched analysis of a prospective randomized trial.

OBJECTIVES: The recommended treatment for limited-stage small-cell lung cancer (LS-SCLC) is a combination of thoracic radiotherapy (TRT) and etoposide plus cisplatin (EP) chemotherapy, typically administered over 4-6 cycles. Nonetheless, the optimal duration of chemotherapy is still not determined. This study aimed to compare the outcomes of patients with LS-SCLC who received either 6 cycles or 4-5 cycles of EP chemotherapy combined with TRT. MATERIALS AND METHODS: In this retrospective analysis, we utilized data from our prior prospective trial to analyze the outcomes of 265 LS-SCLC patients who received 4-6 courses of EP combined with concurrent accelerated hyperfractionated TRT between 2002 and 2017. Patients were categorized into two groups depending on their number of chemotherapy cycles: 6 or 4-5 cycles. To assess overall survival (OS) and progression-free survival (PFS), we employed the Kaplan-Meier method after conducting propensity score matching (PSM). RESULTS: Among the 265 LS-SCLC patients, 60 (22.6%) received 6 cycles of EP chemotherapy, while 205 (77.4%) underwent 4-5 cycles. Following PSM (53 patients for each group), the patients in the 6 cycles group exhibited a significant improvement in OS and PFS in comparison to those in the 4-5 cycles group [median OS: 29.8 months (95% confidence interval [CI], 23.6-53.1 months) vs. 22.7 months (95% CI, 20.8-29.1 months), respectively, p = 0.019; median PFS: 17.9 months (95% CI, 13.7-30.5 months) vs. 12.0 months (95% CI, 9.8-14.2 months), respectively, p = 0.006]. The two-year and five-year OS rates were 60.38% and 29.87% in the 6 cycles group, whereas 47.17% and 15.72% in the 4-5 cycles group, respectively. CONCLUSION: Patients diagnosed with LS-SCLC who were treated with EP regimen chemotherapy combined with TRT exhibited notably enhanced survival when administered 6 cycles of chemotherapy, as compared to those who underwent only 4-5 cycles.