Baroreflex afferent function is a part of insights of Leptin-mediated blood pressure reduction and Leptin-resistance hypertension.

The aim of this study is to verify the impact of Leptin in blood pressure (BP) regulation and Leptin-resistance in metabolic/neurogenic hypertension through baroreflex afferents and dysregulation. Artery BP/heart rate (HR) were measured while nodose (NG) microinjection of Leptin, membrane depolarization/inward current were obtained by whole-cell patch from NG neurons isolated from adult female rats. Baroreflex sensitivity (BRS) tested with PE/SNP, distribution/expression of Leptin/receptors in the NG/nucleus tractus solitary (NTS) examined using immumostaining and qRT-PCR, and serum concentrations of Leptin/NE measured by ELISA were observed in control and high fructose-drinking induced hypertension (HTN-HFD) rats. The results showed that BP was significantly/dose-dependently reduced by Leptin NG microinjection likely through direct excitation of female-specific subpopulation of Ah-type neurons showing a potent membrane depolarization/inward currents. Sex-specific distribution/expression of OB-Ra/OB-Rb in the NG were detected with estrogen-dependent manner, similar observations were also confirmed in the NTS. As expected, BRS was dramatically decreased in the presence of PE/SNP in both male and female rats except for the female with PE at given concentrations. Additionally, serum concentration of Leptin was elevated in HFD-HTN model rats of either sex with more obvious in females. Under hypertensive condition, the mean fluorescent density of OB-R and mRNA expression for OB-Ra/OB-Rb in the NG/NTS were significantly down-regulated. These results have demonstrated that Leptin play a role in dominant parasympathetic drive via baroreflex afferent activation to buffer Leptin-mediated sympathetic activation systemically and Leptin-resistance is an innegligible mechanism for metabolic/neurogenic hypertension through baroreflex afferent dysregulation.

Hypoxia-activated ADCC-enhanced humanized anti-CD147 antibody for liver cancer imaging and targeted therapy with improved selectivity.

Therapeutic antibodies (Abs) improve the clinical outcome of cancer patients. However, on-target off-tumor toxicity limits Ab-based therapeutics. Cluster of differentiation 147 (CD147) is a tumor-associated membrane antigen overexpressed in cancer cells. Ab-based drugs targeting CD147 have achieved inadequate clinical benefits for liver cancer due to side effects. Here, by using glycoengineering and hypoxia-activation strategies, we developed a conditional Ab-dependent cellular cytotoxicity (ADCC)-enhanced humanized anti-CD147 Ab, HcHAb18-azo-PEG5000 (HAP18). Afucosylated ADCC-enhanced HcHAb18 Ab was produced by a fed-batch cell culture system. Azobenzene (Azo)-linked PEG5000 conjugation endowed HAP18 Ab with features of hypoxia-responsive delivery and selective targeting. HAP18 Ab potently inhibits the migration, invasion, and matrix metalloproteinase secretion, triggers the cytotoxicity and apoptosis of cancer cells, and induces ADCC, complement-dependent cytotoxicity, and Ab-dependent cellular phagocytosis under hypoxia. In xenograft mouse models, HAP18 Ab selectively targets hypoxic liver cancer tissues but not normal organs or tissues, and has potent tumor-inhibiting effects. HAP18 Ab caused negligible side effects and exhibited superior pharmacokinetics compared to those of parent HcHAb18 Ab. The hypoxia-activated ADCC-enhanced humanized HAP18 Ab safely confers therapeutic efficacy against liver cancer with improved selectivity. This study highlights that hypoxia activation is a promising strategy for improving the tumor targeting potential of anti-CD147 Ab drugs.

Plasma-derived from human umbilical cord blood restores ovarian function and improves serum reproductive hormones levels in mice with premature ovarian insufficiency (POI) through cytokines and growth factors.

Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model. Initially, hUCB was utilized to obtain CBP (CBP), which was subsequently analyzed for cytokine and growth factor profiles in comparison to adult blood plasma (ABP) by use of flow cytometry. Subsequently, POI mouse models were established through the induction of 4-vinylcyclohexene diepoxide, followed by the injection of CBP into the tail. At 7, 14, and 21 days posttreatment, mouse ovaries and blood were collected, and their estrus cycle, body weight, and ovarian weights were evaluated using precise electronic balance. Finally, ovarian morphology and follicle number were assessed through HE staining, while serum levels of anti-Müllerian hormone (AMH), estradiol (E2) and follicle-stimulating hormone (FSH) were determined by ELISA. Our study revealed that individuals with CBP exhibited significantly lower concentrations of proinflammatory cytokines, including IL-ß (p < 0.01) and IL-2 (p < 0.05), while displaying elevated levels of anti-inflammatory cytokines and chemokines, such as IL-2, IL-4, IL-6, IL-8, IL-12P70, IL-17A, IP-10, interferon-γ, and tumor necrosis factor-α (p < 0.01). Furthermore, CBP demonstrated remarkably higher levels of growth factors, including transforming growth factor-ß1, vascular endothelial growth factor, and insulin-like growth factor-1 (p < 0.01) than ABP. Notably, our investigation also revealed that CBP restored the content of serum reproductive hormones, such as AMH, E2, and FSH (p < 0.05), and increased the number of primordial and primary follicles (p < 0.01) and decreased the number of luteal and atretic follicles (p < 0.01) in vivo. Our findings suggested that CBP-secreted cytokines and growth factors could be restored POI ovarian function, enhanced serum reproductive hormones and rescued follicular development in vivo. These findings further support the potential of CBP as a promising strategy in clinical applications for POI related infertility.

Rheumatoid Arthritis Patient With Neurofibromatosis Type 1: Case Report and Review of the Literature.

A 66-year-old neurofibromatosis type 1 (NF1) patient with polyarticular pain for nine years, aggravated for two days, was transferred from the Emergency Intensive Care Unit (EICU) to our rheumatology department. She was diagnosed with NF1 nine years ago by a gene mutation detection and coronary heart disease (CHD) three months ago. The patient was diagnosed with rheumatoid arthritis (RA) this time. After 24 days of treatment with appropriate medication, the patient was discharged with relieved joint pain. However, about four months later, the patient died of circulatory failure caused by myocardial infarction. We analyzed the possible reasons for her outcome and made a review of the literature. There are few clinical reports of NF1 complicated with RA. We found five cases reported in the literature up to date during our search and included them in our communication to compare with our case. NF1 combined with RA mainly affects adult women and usually starts with NF1 and is followed by RA after at least six years of NF1 symptom onset. Although the summarized characteristics of clinical and potential pathogenesis of NF1 combined with RA were limited with these six cases, we hope that this will help clinicians to increase their understanding of this rare complication, thus helping to guide clinical medication.

[Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity].

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 µm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 µL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 µmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Nasopharyngeal carcinoma with synchronous breast metastasis: A case report.

BACKGROUND: Recent reports have described cases of metachronous breast metastasis in patients with nasopharyngeal carcinoma. However, no similar cases of synchronous breast metastasis have been reported, and evidence that can be used to support the clinical diagnosis of stage IV nasopharyngeal carcinoma in patients with concurrent breast metastasis remains lacking. Therefore, additional evidence is required to elucidate the clinical characteristics of this condition and aid in the development of optimal management strategies. CASE SUMMARY: We report the case of a 46-year-old woman who visited our hospital with a right breast mass as the first symptom. The first pathological biopsy report suggested triple-negative breast invasive carcinoma. Subsequent imaging revealed a nasopharyngeal mass. Further puncture biopsy of the nasopharyngeal mass, molecular pathological Epstein-Barr virus in situ hybridization, and immunohistochemistry confirmed the diagnosis of nasopharyngeal carcinoma with breast metastasis. The patient did not undergo a mastectomy and achieved complete remission after chemotherapy and radiotherapy. She continued to receive oral chemotherapy as maintenance therapy and experienced no recurrence or metastasis during the 6-month follow-up period. CONCLUSION: This case report suggests that breast specialists should carefully rule out secondary breast cancers when diagnosing and treating breast masses. Furthermore, clinicians should aim to identify the pathological type of the tumor to obtain the most accurate diagnosis and prevent excessive diagnosis and treatment.

[Simultaneous determination of five indole/indazole amide-based synthetic cannabinoids in electronic cigarette oil by ultra performance liquid chromatography].

Synthetic cannabinoids (SCs), which are considered some of the most widely abused new psychoactive substances available today, are much more potent than natural cannabis and display greater efficacy. New SCs can be developed by adding substituents such as halogen, alkyl, or alkoxy groups to one of the aromatic ring systems, or by changing the length of the alkyl chain. Following the emergence of the so-called first-generation SCs, further developments have led to eighth-generation indole/indazole amide-based SCs. Given that all SCs were listed as controlled substances on July 1, 2021, the technologies used to detect these substances must be quickly improved. Due to the sheer number of SCs, the chemical diversity and the fast update speed, it is challenging to determine and identify the new SCs. In recent years, several types of indole/indazole amide-based SCs have been seized, but systematic research on these compounds remains limited. Therefore, developing rapid, sensitive, and accurate quantitative methods to determine new SCs are of great importance. Compared with high performance liquid chromatography (HPLC), ultra performance liquid chromatography (UPLC) shows higher resolution, better separation efficiency, and faster analysis speeds; thus, it can meet the demand for the quantitative analysis of indole/indazole amide-based SCs in seized materials. In this study, a UPLC method was developed for the simultaneous determination of five indole/indazole amide-based SCs, including N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-butyl-1H-indazole-3-carboxamide (ADB-BUTINACA), methyl 2-(1-(4-fluorobutyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate (4F-MDMB-BUTICA), N-(1-methoxy-3,3-dimethyl-1-oxobutan-2-yl)-1-(5-fluoropentyl)-1H-indole-3-carboxamide (5F-MDMB-PICA), methyl 3,3-dimethyl-2-(1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido)butanoate (MDMB-4en-PINACA), and N-(adamantan-1-yl)-1-(4-fluorobutyl)-1H-indazole-3-carboxamide (4F-ABUTINACA) in electronic cigarette oil; these SCs have been detected with increasing frequency in seized materials in recent years. The main factors influencing the separation and detection performance of the proposed method, including the mobile phase, elution gradient, column temperature, and detection wavelength, were optimized. The proposed method successfully quantified the five SCs in electronic cigarette oil via the external standard method. The samples were extracted using methanol, and the target analytes were separated on a Waters ACQUITY UPLC CSH C18 column (100 mm×2.1 mm, 1.7 µm) at column temperature of 35 ℃ and flow rate of 0.3 mL/min. The injection volume was 1 µL. The mobile phase consisted of acetonitrile and ultrapure water, and gradient elution was employed. The detection wavelengths were 290 and 302 nm. The five SCs were completely separated within 10 min under optimized conditions and showed good linear relationships between 1-100 mg/L, with correlation coefficients (r2) of up to 0.9999. The limits of detection (LOD) and quantification (LOQ) were 0.2 and 0.6 mg/L, respectively. Precision was determined using standard solutions of the five SCs at mass concentrations of 1, 10, and 100 mg/L. The intra-day precision (n=6) was <1.5%, and the inter-day precision (n=6) was <2.2%. Accuracy was determined by spiking electronic cigarette oil with low (2 mg/L), moderate (10 mg/L), and high (50 mg/L) levels of the five SCs, with six replicates per determination. The recoveries of the five SCs were 95.5%-101.9%, and their relative standard deviations (RSDs, n=6) were 0.2%-1.5%, with accuracies ranging from -4.5% to 1.9%. The proposed method showed good performance when applied to the analysis of real samples. It is accurate, rapid, sensitive, and effective for the determination of five indole/indazole amide-based SCs in electronic cigarette oil. Thus, it satisfies the requirements for practical determination and provides a reference for the determination of SCs with similar structures by UPLC.

The Active Fraction of Polyrhachis vicina Roger (AFPR) activates ERK to cause necroptosis in colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Polyrhachis vicina Roger (P. vicina), a traditional Chinese medicinal animal, has been used to treat rheumatoid arthritis, hepatitis, cancer, and other conditions. Due to its anti-inflammatory properties, our previous pharmacological investigations have demonstrated that it is effective against cancer, depression, and hyperuricemia. Nevertheless, the key active components and targets of P. vicina in cancers are still unexplored. AIM OF THE STUDY: The study aimed to evaluate the pharmacological treatment mechanism of the active fraction of P. vicina (AFPR) in treating colorectal cancer (CRC) and to further reveal its active ingredients and key targets. METHODS: To examine the inhibitory impact of AFPR on CRC growth, tumorigenesis assays, cck-8 assays, colony formation assays, and MMP detection were utilized. The primary components of AFPR were identified by GC-MS analysis. The network pharmacology, molecular docking, qRT-PCR, western blotting, CCK-8 assays, colony formation assay, Hoechst staining, Annexin V-FITC/PI double staining, and MMP detection were performed to pick out the active ingredients and potential key targets of AFPR. The function of Elaidic acid on necroptosis was investigated through siRNA interference and the utilization of inhibitors. Elaidic acid's effectiveness to suppress CRC growth in vivo was assessed using a tumorigenesis experiment. RESULTS: Studies confirmed that AFPR prevented CRC from growing and evoked cell death. Elaidic acid was the main bioactive ingredient in AFPR that targeted ERK. Elaidic acid greatly affected the ability of SW116 cells to form colonies, produce MMP, and undergo necroptosis. Additionally, Elaidic acid promoted necroptosis predominantly by activating ERK/RIPK1/RIPK3/MLKL. CONCLUSION: According to our findings, Elaidic acid is the main active component of AFPR, which induced necroptosis in CRC through the activation of ERK. It represents a promising alternative therapeutic option for CRC. This work provided experimental support for the therapeutic application of P. vicina Roger in the treatment of CRC.

Effects of sericin on oxidative stress and PI3K/AKT/mTOR signal pathway in cryopreserved mice ovarian tissue.

Ovarian tissue cryopreservation is an effective fertility protective strategy for preadolescent female cancer patients, whose tumor treatment cannot be delayed. In the present study, the effects of sericin, as an antioxidant, on mice ovarian tissue freezing and thawing were investigated. Mice ovarian tissues were cryopreserved and thawed in medium containing 0.5% or 1%sericin (w/v), and 0.1 mM melatonin. Then, the follicular morphology was observed. The levels of antioxidant enzymes were determined, including glutathione (GSH), glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), total antioxidant capacity (T-AOC) and catalase (CAT). Moreover, the levels of nitric oxide (NO), malondialdehyde (MDA) and lactate dehydrogenase (LDH) were also tested. Besides, apoptosis-related proteins Bcl-2 and Bax were determined. Our results showed that 1% sericin maintained follicular morphology, inhibited apoptosis, decreased MDA and NO levels, and boosted endogenous antioxidant enzyme levels, while had no significant effect on LDH levels. Furthermore, these effects may be related with the activation of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of Rapamycin (mTOR) signaling pathway, as demonstrated by increased PI3K, p-AKT and mTOR levels. These findings demonstrate that 1% sericin may reduce oxidative stress and protect ovarian tissues during freezing and thawing via PI3K/AKT/mTOR signaling pathway.

One Case of Pituitary Stalk Interruption Syndrome Associated with Liver Cirrhosis.

INTRODUCTION: Pituitary stalk interruption syndrome (PSIS) is featured by hypopituitarism and a classic triad of absence or slender pituitary stalk, absence or ectopic posterior lobe, and hypoplasia of the anterior lobe. Hypopituitarism, which induces hormone deficiencies, is associated with non-alcoholic fatty liver disease (NAFLD) and liver cirrhosis. CASE PRESENTATION: A 29-year-old male patient was presented with intermittent nosebleeds and underdeveloped secondary sexual characteristics. Laboratory examination revealed low gonadal hormone, thyroxine, and cortisol levels. Magnetic resonance imaging revealed an interrupted pituitary stalk, ectopic posterior pituitary, and hypoplastic anterior pituitary. PSIS was confirmed. Liver cirrhosis was supported by bilirubin metabolism disorder, abnormal coagulation, the varicose vein of the esophagus and fundus of the stomach, hypersplenism, and signs on a computer tomography scan. He received glucocorticoid, levothyroxine, androgen, and human chorionic gonadotropin supplements, and growth hormone was not given because of poverty. Five months later, the patient developed Cushing-like symptoms and further deterioration of liver function. CONCLUSION: PSIS can cause liver impairment and even cirrhosis, which may be associated with multiple hormone deficiencies. A case of PSIS with cirrhosis as the initial symptom and progression of cirrhosis in the absence of growth hormone (GH) therapy suggests that GH therapy may be important in PSIS-related cirrhosis.

[Expression of SCD1 in TFE3-rRCC and its effect on proliferation and migration].

OBJECTIVE: To investigate the expression of SCD1 in TFE3-rRCC and its effect on the proliferation and migration of TFE3-rRCC cells. METHODS: GEPIA database was used to analyze the expression level of SCD1 in different tumors and its effect on the prognosis of patients. The expression levels of SCD1 in TFE3-rRCC patients and cell lines UOK109 and UOK120 were detected by QPCR and Western blot. Liposomal shRNA was used to knock down SCD1 expression in cell lines. The changes of cell proliferation and migration ability before and after SCD1 knockdown were detected by CCK-8 and Transwell experiments. RESULTS: SCD1 expression levels were higher in all three common renal cancers, and patients with high SCD1 expression had shorter survival and worse prognosis (Logrank P<0.001). The mRNA and protein levels of SCD1 were also significantly increased in renal cancer tissues of patients with high expression of TFE3 and in TFE3-rRCC cell lines UOK109 and UOK120. After SCD1 knockdown, the proliferation and migration ability of UOK109 and UOK120 cells decreased significantly. CONCLUSION: SCD1 is highly expressed in TFE3-rRCC and can promote the proliferation and migration of TFE3-rRCC cell lines, which may be a key molecule in promoting the development of TFE3-rRCC.

Network Pharmacology-Based Identification of Key Mechanisms of Xihuang Pill in the Treatment of Triple-Negative Breast Cancer Stem Cells.

Xihuang pill, an approved Chinese medicine formula (state medical permit number. Z11020073), is a commonly used adjuvant drug for cancer patients in China. Xihuang pill has a satisfactory effect in treating breast cancer in clinics, especially triple-negative breast cancer (TNBC), which is the most aggressive type of breast cancer, and finite effective therapies. However, the mechanism of Xihuang pill in treating TNBC remains unclear. The present study aims to explore the pharmacological mechanism of Xihuang pill in treating advanced TNBC. We identified the main chemical components of Xihuang pill by using HPLC-Q-TOF-MS/MS. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis shows that serum containing Xihuang pill (XS) had no obvious killing effect on any subtype of breast cancer cells, but it inhibited mammosphere colony formation of two TNBC cell lines (4T1 and HCC1806 cells) and could enhance the inhibitory effect of paclitaxel (PTX) on the proliferation of 4T1 and HCC1806 cells when combined with PTX. Seventy-six active compounds in Xihuang pill, their 300 protein targets, and 16667 TNBC stem cell-related genes were identified. The drug-herb-active compound-target gene-disease network and enrichment analyses were constructed with 190 overlapping candidate targets. Through text mining and molecular docking, the target gene NR3C2 and its active compound naringenin were selected for further validation. According to the TCGA database, we observed that a high expression of NR3C2 promoted a higher survival probability regarding overall survival (OS). In vitro experiments indicated that naringenin presented an identical effect to XS, possibly by regulating the NR3C2 expression. Overall, this study explored the effect of Xihuang pill in treating advanced TNBC cells and showed that naringenin, which is the key active compound of Xihuang pill, could lessen the stemness of TNBC cells to produce a synergistic effect on PTX by regulating the NR3C2 gene.

1,10/1,11-Cyclization catalyzed by diverged plant sesquiterpene synthases is dependent on a single residue.

The exquisite chemodiversity of terpenoids is the product of the large diverse terpene synthase (TPS) superfamily. Here, by using structural and phylogenetic analyses and site-directed mutagenesis, we identified a residue (Cys440 in Nicotiana tabacum 5-epi-aristolochene synthase) proximal to an ion-binding motif common to all TPSs and named the preNSE/DTE residue, which determines the product specificity of sesquiterpene synthases from different plant species. In sesquiterpene synthases catalyzing 1,10-cyclization (1,10-cyclases) of farnesyl diphosphate, mutation of the residue in both specific and promiscuous 1,10-cyclases from different lineages leads to the accumulation of monocyclic germacrene A-11-ol, which is "short-circuited" from complex cyclization cascades, suggesting a key role of this residue in generating the first common intermediate of 1,10-cyclization. Altering this residue in a specific 1,11-cyclase results in alternative 1,10-cyclization products. Moreover, the preNSE/DTE residue can be harnessed to engineer highly specific sesquiterpene synthases for an improved proportion of high-value terpenoids, such as patchoulol, a main constituent of several traditional Chinese medicines that could treat SARS-CoV-2.

Clinical and pathological features and risk factors for primary breast cancer patients.

BACKGROUND: Breast cancer is the most common malignancy in women all around the world. According to the latest statistics in 2018, there were more than 2.08 million new breast cancer cases all around the world and more than 620000 deaths; the proportion of breast cancer deaths in women with cancer is 15%. By studying age, clinicopathological characteristics and molecular classification, age at menarche, age at birth, number of births, number of miscarriages, lactation time, surgical history of benign breast lesions, history of gynecological diseases, and other factors, we retrospectively summarized and compared the disease history of patients with primary breast cancer and patients with benign thyroid tumors admitted to our hospital in the past 10 years to explore the clinicopathological characteristics and risk factors for primary breast cancer. AIM: To investigate the clinical and pathological features and risk factors for primary breast cancer treated at our center in order to provide a reference for the prevention and treatment of breast cancer in the Zhuhai-Macao region. METHODS: Through a retrospective case-control study, 149 patients with primary breast cancer diagnosed and treated at Zhuhai Hospital of Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2013 to March 2020 were included as a case group, and 165 patients with benign breast tumors diagnosed and treated from January 2019 to March 2020 were included as a control group. The data collected included age, age at menarche, age at first birth, number of births, number of miscarriages, lactation time, history of surgery for benign breast lesions, history of familial malignant tumors, history of gynecological diseases, history of thyroid diseases, and the tumor characteristics of the patients in the case group including pathological diagnosis, pathological type, tumor size, lymph node metastasis, distant metastasis, stage, and molecular classification, among others. In the case group, the chi-square test was used to analyze the clinical and pathological features of patients in three age groups (< 40, 40-59, and ≥ 60 years). A multifactor logistic regression analysis was used to analyze correlations between the two groups. RESULTS: Among 149 patients with primary breast cancer, the average age was 48.20 ± 12.06 years, and the proportion of patients at 40-59 years old was the highest, accounting for 61.8% of cases. The molecular type was mainly luminal B type, accounting for 69.2% of cases, and at the time of diagnosis, the tumor stage was mainly stage I/II, accounting for 62.4% of cases. There were no statistically significant differences in the distributions of tumor location, pathological type, tumor size, lymph node metastasis, stage, or molecular classification among the three age groups (< 40, 40-59, and ≥ 60 years) (P ≥ 0.05). The differences in the distribution of distant metastasis among the three age groups (< 40, 40-59, and ≥ 60 years) were statistically significant (P < 0.01). The differences in lactation time, history of familial malignant tumors, history of gynecological diseases, and history of thyroid diseases between the two groups were not statistically significant (P ≥ 0.05). The differences in age at disease diagnosis, age at menarche, and history of surgery for benign breast lesions were statistically significant (P < 0.01). The difference in age at first birth was also statistically significant (P < 0.05). CONCLUSION: The highest incidence of breast cancer in the Zhuhai-Macao region is present among women aged 40-59 years. There is a larger proportion of stage I/II patients, and the luminal B type is the most common molecular subtype. Distant metastasis occurs mainly in the ≥ 60-year-old group at the first diagnosis; increased age, late age at menarche, and late age at first birth may be risk factors for primary breast cancer, and a history of surgery for benign breast lesions may be a protective factor for primary breast cancer.

Three new diterpenoids from Euphorbia peplus.

Three new diterpenoids (1-3) (two abietane type diterpenoids and a paralianone type diterpenoid), together with four known compounds (4-7) were isolated from the whole plants of Euphorbia peplus. Their structures were elucidated through spectroscopic analysis and physicochemical characteristics. The cytotoxic activities of compounds 1-7 against five human tumour cell lines were evaluated, however, they were inactive at the concentration of 40 µM. The compound 3 enhanced lysosomal biogenesis with Lyso Tracker staining intensity of 132.6%.

Comparison of Hasner valvulotomy outcomes in pediatric and adult patients: does age matter?

BACKGROUND: Hasner valve incision has been recently introduced as a new treatment for ophthalmic patients with epiphora symptoms. The aim of this study was to examine whether surgical outcomes of Hasner valve incision for inferior nasolacrimal duct obstruction were different between pediatric and adult patients. METHODS: A total of 53 eyes of 52 patients who underwent Hasner valve incision in the Beijing Tongren Hospital from October 2016 to November 2019 were retrospectively observed. Patients were divided into two groups, including pediatric group (23 eyes of 22 patients, <18 years old) and adult group (30 eyes of 30 patients, ≥18 years old). Success rate of surgery was determined by both subjective measure (complete resolution of epiphora) and objective measure (lacrimal passage irrigation and tear meniscus height). Fisher exact test was conducted. RESULTS: By conducting Fisher exact test and comparing complete resolution of epiphora (P = 0.627), lacrimal passage irrigation (P = 0.663), measurement of Tear Meniscus Height (P = 0.561), and appearance of complication (P = 0.339), there was no statistically significant difference of surgical outcomes between pediatric and adult patients (P > 0.05). CONCLUSION: Hasner valve incision was effective for both adult and children with inferior nasolacrimal duct obstruction, with no difference in surgical outcomes between the two groups.

Hypoxia-Induced miR-137 Inhibition Increased Glioblastoma Multiforme Growth and Chemoresistance Through LRP6.

PURPOSE: Glioblastoma multiforme (GBM) is one of the deadliest tumors, which is involved in numerous dysregulated microRNAs including miR-137. However, the mechanism of how miR-137 suppression associated with cancer progression and chemoresistance still remains to be elucidated. METHODS: Quantitative reverse transcriptase-PCR (qRT-PCR), DNA methylation analysis, cell proliferation assay, flow cytometric analysis, invasion assay, in situ tumor formation experiment were performed to test the expression levels and functions of miR-137 in GBM. Bioinformatics analysis, luciferase reporter assay, qRT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry assay were used to identify and verify the target of miR-137. RESULTS: We found that miR-137 was downregulated in primary and recurrent GBM compared with normal brain tissues. Overexpression of miR-137 inhibited cell invasion and enhanced cell chemosensitivity to temozolomide (TMZ) by directly targeting low-density lipoprotein receptor-related protein 6 (LRP6) in GBM. Forced expression of LRP6 cDNA without its 3'-UTR region partly restored the effects of miR-137 in vitro and in vivo. Hypoxia-induced miR-137 methylation was responsible for the miR-137 suppression, leading to the cell chemoresistance and poor prognosis of GBM. CONCLUSIONS: These findings demonstrated the detailed molecular mechanism of miR-137 in regulating GBM growth and chemoresistance in hypoxia microenvironment, suggesting the potentiality of miR-137 as a therapeutic target for GBM.

Active fraction of Polyrhachis vicina Rogers (AFPR) suppressed breast cancer growth and progression via regulating EGR1/lncRNA-NKILA/NF-κB axis.

Breast cancer (BC) is a major contributor of cancer-associated mortality in women. It is essential to find new therapeutic targets and drugs. Polyrhachis vicina Rogers is one of the Traditional Chinese Medicine (TCM). Our previous studies have shown an active fraction of Polyrhachis vicina Rogers (AFPR) has significant anti-inflammatory activity, suggesting its anti-cancer effect. Here, we aimed to explore the inhibitory effects of AFPR on BC and reveal its mechanism. The effects of AFPR on BC were examined by cell proliferation assay, wound healing assay, invasion assay and xenograft assay. Microarray sequencing, qRT-PCR, Western blot, chromatin immunoprecipitation assay and luciferase reporter assay were performed to investigate the regulation of AFPR on related genes and underlying mechanisms. As a result, AFPR suppressed BC cell growth, migration and invasion and inhibited tumor growth. LncRNA NKILA was most prominently upregulated in AFPR-treated MCF7 cells. AFPR inactivated NF-κB signaling pathway via regulating NKILA. Furthermore, AFPR regulated the expression of NKILA by inhibiting its transcript suppressor EGR1. This study firstly indicated that AFPR was a potential inhibitor of BC development via regulating EGR1/NKILA/NF-κB axis.

Malignant syphilis accompanied with neurosyphilis in a malnourished patient: A case report.

BACKGROUND: Syphilis is a common sexually transmitted disease caused by the Treponema pallidum (T. pallidum). Malignant syphilis is a rare presentation of secondary syphilis. Here, we present a case diagnosed with malignant syphilis accompanied with neurosyphilis. CASE SUMMARY: A 56-year-old man present with a 2-mo history of spreading ulcerous and necrotic papules and nodules covered with thick crusts over the face, trunk, extremities, and genitalia. The patient was diagnosed with malignant syphilis accompanied by neurosyphilis based on the characteristic morphology of the lesions, positive serological and cerebrospinal fluid tests for syphilis, brain magnetic resonance imaging, and histopathology, along with resolution of the lesions following the institution of penicillin therapy. The lesions and neurological condition successfully resolved after a course of treatment with penicillin. CONCLUSION: We suggest that neurosyphilis should be considered whenever people have psychiatric symptoms without cutaneous lesions or human immunodeficiency virus.

Self-Expanded Metallic Stent Insertion for Hilar Cholangiocarcinoma: Comparison of Unilateral and Bilateral Stenting.

Purpose: This study aims to ascertain the relative outcomes in patients with hilar cholangiocarcinoma (HCCA) undergoing either unilateral or bilateral self-expanded metallic stent (SEMS) insertion. Materials and Methods: In this retrospective single-center study, 93 patients with HCCA were treated through percutaneous insertion of either unilateral or bilateral SEMS during January 2012 to December 2018. We compared technical success, clinical success, and long-term outcomes of the treatment method. Results: Overall, 51 and 42 patients were treated through unilateral and bilateral SEMS insertion, respectively, with technical success rates of 92.2% (47/51) and 95.3% (40/42), respectively, (P = .859). No patients experienced any procedure-related complications, with unilateral and bilateral clinical success rates of 95.7% (45/47) and 97.4% (38/39), respectively, (P = 1.000) and with comparable adverse event rates between these groups (3/47 vs. 5/40; P = .541). Moreover, 8 and 3 patients treated with unilateral and bilateral stents exhibited stent dysfunction, respectively, (P = .183). In unilateral and bilateral groups, median patency rates were189 and 198 days, respectively, (P = .887). During the follow-up period, all patients died, with respective mean overall survival rates of 222 and 202 days for those treated using unilateral and bilateral stents (P = .755). Both Bismuth type III HCCA (P = .025) and a lack of chemotherapy (P = .000) correlated with reduced survival in univariate and multivariate regression analyses. Conclusion: Insertion of unilateral and bilateral SEMS exhibits similar clinical efficacy and long-term outcomes in patients with HCCA.