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; 22(5): 552-560.

Transcription repression of estrogen receptor alpha by ghrelin/Gq/11/YAP signaling in granulosa cells promotes polycystic ovary syndrome.

Polycystic ovarian syndrome (PCOS) is a prevalent endocrinological disorder affected by ghrelin. This study aimed to investigate the molecular mechanisms underlying the effects of ghrelin on PCOS manifestations in mice and to assess the therapeutic potential of ghrelin. Female C57BL/6 mice were subcutaneously injected with 6 mg/100 g dehydroepiandrosterone (DHEA) for 20 days to induce PCOS. Alterations in reproductive cycles, ovarian morphology, serum sex hormone levels, and related signaling markers were examined. Furthermore, ghrelin-induced effects on granulosa cells and the role of ghrelin/Gq/11/ Yes-associated protein (YAP) signaling were studied by silencing Gαq/11 or YAP using si-RNAs. Finally, we evaluated the therapeutic potential of anti-ghrelin antibodies in DHEA-induced PCOS mice. DHEA administration led to significant PCOS-associated changes including weight gain, disrupted estrous cycles, ovarian morphological alterations, and hormonal imbalances in mice, with elevated Gαq/11 and acylated ghrelin expression, which was also noted in PCOS patients. However, treatment with anti-ghrelin antibodies effectively managed DHEA-induced damage in PCOS mice. In vitro, ghrelin exposure resulted in granulosa cell injury and modulated estrogen receptors alpha (ERα) and YAP protein levels, whereas silencing YAP and Gαq/11 reversed ghrelin-induced detrimental effects and up-regulated ERα expression. This study revealed that DHEA-induced PCOS traits in mice could be improved by anti-ghrelin antibodies, with the ghrelin/Gq/11/YAP signaling pathway identified as a crucial mediator in granulosa cells, affecting ERα transcription to regulate PCOS. These findings suggest a potential therapeutic strategy for the treatment of PCOS.

A New Method for Scoliosis Screening Incorporating Deep Learning With Back Images.

STUDY DESIGN: Retrospective observational study. OBJECTIVES: Scoliosis is commonly observed in adolescents, with a world0wide prevalence of 0.5%. It is prone to be overlooked by parents during its early stages, as it often lacks overt characteristics. As a result, many individuals are not aware that they may have scoliosis until the symptoms become quite severe, significantly affecting the physical and mental well-being of patients. Traditional screening methods for scoliosis demand significant physician effort and require unnecessary radiography exposure; thus, implementing large-scale screening is challenging. The application of deep learning algorithms has the potential to reduce unnecessary radiation risks as well as the costs of scoliosis screening. METHODS: The data of 247 scoliosis patients observed between 2008 and 2021 were used for training. The dataset included frontal, lateral, and back upright images as well as X-ray images obtained during the same period. We proposed and validated deep learning algorithms for automated scoliosis screening using upright back images. The overall process involved the localization of the back region of interest (ROI), spinal region segmentation, and Cobb angle measurements. RESULTS: The results indicated that the accuracy of the Cobb angle measurement was superior to that of the traditional human visual recognition method, providing a concise and convenient scoliosis screening capability without causing any harm to the human body. CONCLUSIONS: The method was automated, accurate, concise, and convenient. It is potentially applicable to a wide range of screening methods for the detection of early scoliosis.

Prevalence and disparities in sexual and reproductive health of women of reproductive age (20-49 years) in China: A national cross-sectional study.

Background: Ensuring women's sexual and reproductive health (SRH) is a fundamental human right and key to 2030 agenda of the UN Sustainable Development Goals (SDGs), yet limited evidence exists on SRH in China, including national estimates and disparities of women's SRH experiences, gynaecological diseases, and sexually transmitted diseases (STDs). Methods: A national cross-sectional survey based on a multistage stratified sampling from 15 provinces of China was performed from May 2019 to April 2021. A total of 12 815 reproductive-aged (20-49 years) women were involved. The SRH experiences (including age at menarche, age at first sexual activity, history of abortion, miscarriage, recurrent miscarriage, stillbirth, age at first delivery, types of delivery), the history of gynaecological diseases and STDs, as well as the environmental factors of participants were investigated. Human development index (HDI) was utilised to categorise and describe the socioeconomic status of the regions. The prevalence rates of diseases were compared among different HDI regions. Results: We observed a decrease in the mean age at menarche, an increase in the proportion of women who became sexually active before 20, and a modest rise in mean age at first childbirth across generations. Age-standardised prevalence estimates of miscarriage, recurrent miscarriage, artificial abortion, ectopic pregnancy, and stillbirth were 9.3, 1.4, 55.7, 3.3, and 2.1%, respectively. Approximately 50% of participants reported a history of gynaecological diseases, with vulvovaginitis, cervicitis, and pelvic infection diseases being the most prevalent. The overall prevalence of STDs was estimated at 22.2‰, with mycoplasma genitalium infection having the highest reported prevalence. Disease prevalence varies across HDI regions. Conclusions: Women's SRH behaviours and experiences have evolved, along with shifts in the spectrums of gynaecological diseases and STDs in China. Urgent recalibration of health care policies and disease control strategies is necessary, aligning them with women's changing SRH needs, ultimately ensuring their reproductive health and rights.

Blocking of SIRT7/FOXO3a axis by miR-152-3p enhances cisplatin sensitivity in breast cancer.

BACKGROUND: Cisplatin-based chemoresistance is major obstacle for breast cancer (BC) including Triple-negative breast cancer (TNBC). SIRT7 is reportedly involved in the progression of BC, the underlining mechanism in Cisplatin-based chemoresistance in BC remains unclear. This work is to elucidate effects of SIRT7 on cisplatin resistance in breast cancer regulated by miR-152-3p. METHODS: The RNA expression of SIRT7 and miRNAs in breast cancer were available from TCGA database. SIRT7-targeted miRNAs were predicted by TargetScan, miRanda, miRDB databases. The association of SIRT7 expression with predicted miRNA was validated by Luciferase assay. Cell apoptosis was determined by Flow cytometry. Cell viability was detected by CCK8 assay. The mRNA expression was measured by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Protein expression was determined by Western blotting assay. RESULTS: SIRT7 mRNA levels were dramatically enhanced in BC tissues compared to para-carcinoma tissues, also increased in BC patients with Cisplatin-based chemotherapy containing TNBC compared with those without. The increase of SIRT7 expression was obviously relevant to shorter survive time of them. Importantly, SIRT7 inhibition facilitated Cisplatin-induced cell apoptosis of TNBC (MDA-MB-231 and MDA-MB-468) and non- TNBC (MCF-7). Notably, miR-152-3p was predicted as a negative regulator of SIRT7 by overlapping downregulated miRNAs in BC patients treated with Cisplatin-based chemotherapy and miRNAs to target SIRT7. Mechanically, miR-152-3p blocked SIRT7 to stimulate an activation of FOXO3a, cleaved PARP1 and Caspase-3, sensitizing Cisplatin-induced apoptosis of BC cells. CONCLUSIONS: Inhibition of SIRT7 by miR-152-3p may be a promising strategy against the resistance to cisplatin-based chemotherapy in BC containing TNBC.

Evaluation of the clinical efficacy of Ru'ai Shuhou recipe for the prevention of lung metastases from breast cancer: a retrospective study based on propensity score matching.

Background: Breast cancer lung metastasis occurs at a high rate and at an early stage, and is the leading cause of death in breast cancer patients. The aim of this study was to investigate the effect of Ru'ai Shuhou Recipe (RSR) intervention on the occurrence of recurrent metastases, especially lung metastases, in postoperative patients with breast cancer. Materials and Methods: A retrospective cohort study was implemented at Shuguang Hospital of Shanghai University of Traditional Chinese Medicine in China between January 2014 to January 2019. Female patients were included according to the propensity score matching (PSM) method and balanced on the basis of general and clinical information such as age, body mass index, neo-adjuvant therapy, and surgical approach. Patients with pathological diagnosis of breast cancer were included in this study. Breast cancer patients were divided into exposed and non-exposed groups according to whether they took RSR-based botanical drugs after surgery. Kaplan-Meier survival analysis and Cox survival analysis to explore the relationship between RSR and 5-year disease-free survival and incidence of lung metastases in breast cancer patients after surgery. Results: 360 female patients were assessed and 190 patients were included in the study after PSM (95 in each of the exposed and non-exposed groups). Of the 190 patients after PSM, 55.79% were over 50 years of age. The mean follow-up time was 60.55 ± 14.82 months in the exposed group and 57.12 ± 16.37 months in the non-exposed group. There was no significant baseline characteristics difference between two groups. Kaplan-Meier analysis showed that the 5-year incidence of lung metastases was significantly lower in the exposed group, and the disease-free survival of patients was significantly longer. Cox univariate and multivariate analysis showed that neoadjuvant chemotherapy and lymph node metastasis were independent risk factors for the development of breast cancer lung metastasis, with risk ratios of 17.188 and 5.812, while RSR treatment was an independent protective factor against the development of breast cancer lung metastasis, with a risk ratio of 0.290. Conclusion: Standard biomedical treatment combined with RSR intervention can better prevent breast cancer recurrence and metastasis, reduce the incidence of lung metastasis in patients, and improve long-term prognosis.

Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae.

AIMS: To investigate the molecular events associated with acquiring macrolide resistance genes [mefE/mel (Mega) or ermB] in Streptococcus pneumoniae (Spn) during nasopharyngeal colonization. METHODS AND RESULTS: Genomic analysis of 128 macrolide-resistant Spn isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn916-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn916-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (>23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose. CONCLUSIONS: Pneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.

Ventral posteromedial nucleus of the thalamus gates the spread of trigeminal neuropathic pain.

BACKGROUND: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. METHODS: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. RESULTS: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. CONCLUSION: These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Opposite Effects of Planting on Antibiotic Resistomes in Rhizosphere Soil with Different Sulfamethoxazole Levels.

Achieving consensus about the rhizosphere effect on soil antibiotic resistomes is challenging due to the variability in antibiotic concentrations, sources, and the elusory underlying mechanisms. Here, we characterized the antibiotic resistomes in both the rhizosphere and bulk soils of soybean plants grown in environments with varying levels of antibiotic contamination, using sulfamethoxazole (SMX) as a model compound. We also investigated the factors influencing resistome profiles. Soybean cultivation altered the structure of antibiotic-resistant genes (ARGs) and increased their absolute abundance. However, the rhizosphere effect on the relative abundance of ARGs was dependent on SMX concentrations. At low SMX levels, the rhizosphere effect was characterized by the inhibition of antibiotic-resistant bacteria (ARBs) and the promotion of sensitive bacteria. In contrast, at high SMX levels, the rhizosphere promoted the growth of ARBs and facilitated horizontal gene transfer of ARGs. This novel mechanism provides new insights into accurately assessing the rhizosphere effect on soil antibiotic resistomes.

Classic congenital adrenal hyperplasia with unilateral functional adrenal cortical adenoma: case report.

Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders related to adrenal steroid biosynthesis, and mainly caused by mutations in the CYP21A2 gene encoding 21-hydroxylase. Adrenal tumors are common in CAH, but functional adrenal tumors are rare. Here, we report a 17-year-old female with virilized external genitalia and primary amenorrhea, accompanied by a right adrenal tumor. Her 17-OHP level was normal, cortisol and androgen levels were significantly elevated, and the tumor pathology showed adrenal cortical adenoma. Gene testing for CYP21A2 showed c.518T > A in exon 4 and c.29313C > G in intron 2. The possibility of untreated classic CAH with 21-OH deficiency causing functional adrenal cortical adenoma should be considered. When clinical diagnosis highly considers CAH and cannot rule out the influence of functional adrenal tumors' secretion function on 17-OHP, gene mutation analysis should be performed.