Bibliometric and visual analysis of hypoxic pulmonary hypertension from 2013 to 2022.

Hypoxic pulmonary hypertension (HPH) is caused by chronic persistent hypoxia, which leads to the continuous increase of pulmonary artery pressure and pulmonary vascular resistance. In recent years, there has been a substantial increase in research on HPH. To study the trends of HPH research over the last decade, we used WOSCC to search for relevant research on this topic, and dealt with the relevant information using VOSviewer, CiteSpace, and R-tool. Our results show that the number of publications on HPH has generally increased in the last decade, albeit not significantly, while the average number of citations has been declining year by year. Researchers from the USA top the list with 5498 publications, who widely cooperate with researchers from other countries, followed by those from China. Kurt R. Stenmark has an authoritative position in this field, ranking first with 635 citations. American Journal of Physiology Lung Cellular and Molecular Physiology and Pulmonary Circulation have published 151 articles on HPH in the last 10 years, but the former has higher impact factor and article quality. Circulation proved its leadership in this field with 8812 citations. Our findings reveal the trends in HPH research and should provide researchers with plenty of useful information.

Enteral lorlatinib after immune hyperprogression as a treatment option for anaplastic lymphoma kinase­positive non­small cell lung cancer: A case report.

Fusion of the anaplastic lymphoma kinase (ALK) gene is a rare driver in non-small cell lung cancer (NSCLC). Lorlatinib is a third-generation ALK inhibitor approved for the treatment of locally advanced or metastatic ALK+ NSCLC. The traditional administration method of lorlatinib is whole tablet ingestion, while the efficacy effect of gastric tube injection after water dissolution remains unclear. In the present report, a marked response to lorlatinib in a 49-year-old patient with ALK+ NSCLC who was administered lorlatinib through a gastric tube, was described. The patient had received chemotherapy combined with immune checkpoint inhibitors prior to targeted drug therapy and developed hyperprogression, which was mainly manifested as rapid enlargement of the primary lesion with multiple new systemic metastases, accompanied by poor performance status score, esophageal compression and difficulty eating. The patient was injected with pre-dissolved lorlatinib through the nasogastric tube. After 6 days, related symptoms, such as dyspnea and dysphagia, were relieved. After 18 days, the esophageal stenosis was significantly alleviated, and the gastric tube was removed. In conclusion, gastric tube injection be used as a means of lorlatinib administration in patients with ALK+ NSCLC with dysphagia, regardless of previous immunotherapy-associated hyperprogression.

LncRNA XIST Promotes Migration and Invasion of Papillary Thyroid Cancer Cell by Modulating MiR-101-3p/CLDN1 Axis.

Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy in the worlds. Long non-coding RNA X-inactive specific transcript (XIST) was found to upregulate in PTC tissues and cell lines. However, the molecular mechanism underlying PTC metastasis and whether XIST plays regulatory role in PTC are still largely unknown. qRT-PCR was performed to detect the expression of lncRNA XIST and mRNAs. Western blotting was carried out to detect CLDN1, MMP2, and MMP9. Transwell assay was used to detect migration and invasion. Starbase bioinformatics prediction and luciferase assay were used to validate the relationship of miR-101-3p and XIST or CLDN1. LncRNA XIST was upregulated in PTC tissues and cells. XIST knockdown suppressed migration and invasion of PTC cells. XIST could directly bind with miR-101-3p. Overexpression of miR-101-3p suppressed migration and invasion of PTC cells. CLDN1 was the target of miR-101-3p, and overexpression of CLDN1 can reverse the inhibition of cell migration and invasion by miR-101-3p, What's more, miR-101-3p inhibition and CLDN1 overexpression can reverse the affection of sh-XIST on migration and invasion of PTC cells inhibition. XIST promotes migration and invasion of papillary thyroid cancer cell via directly regulating miR-101-3p/CLDN1 axis, which is a novel mechanistic of XIST in the regulation of PTC.

LINC00689 participates in proliferation, chemoresistance and metastasis via miR-31-5p/YAP/ß-catenin axis in colorectal cancer.

As a kind of high-incidence malignant tumors in the digestive tract, colorectal cancer (CRC) has extremely morbidity and mortality in the population. LncRNAs have been proved to regulate the proliferation, chemoresistance and metastasis of tumors including CRC. LINC00689 and miR-31-5p in CRC were found misregulated in CRC by TCGA analysis. However, the mechanism of LINC00689 and miR-31-5p in regulating CRC remains unknown. The expression levels of LINC00689, miR-31-5p and LATS2 in CRC tissues and cell lines were examined by qRT-PCR assay. Cell proliferation, metastasis (including invasion and migration) were quantified by MTT assay, colony formation and Transwell assay, respectively. Western blotting assay was then performed to verify the levels of YAP/ß-catenin and metastasis-related proteins. Dual-luciferase reporter assay and RIP assay were performed to evaluate the interaction between LINC00689 (LATS2) and miR-31-5p. Moreover, the function of LINC00689 and miR-31-5p were confirmed by CRC xenograft in nude mice. LINC00689 was decreased while miR-31-5p was increased in CRC. The overexpression of LINC00689 or the knockdown of miR-31-5p inhibited cell proliferation, chemoresistance and metastasis of CRC cells. Meanwhile, the up-regulated LATS2 suppressed the activity of YAP/ß-catenin pathway to repress CRC occurrence. Silencing LATS2 reversed the inhibition effects of overexpression of LINC00689 or knockdown of miR-31-5p on proliferation, chemoresistance and metastasis of CRC cells. LINC00689 indeed acted as a miR-31-5p sponge to inhibit CRC proliferation, chemoresistance and metastasis through up-regulating LATS2 and repressing YAP/ß-catenin signaling pathway.

Downregulation of RKIP promotes radioresistance of nasopharyngeal carcinoma by activating NRF2/NQO1 axis via downregulating miR-450b-5p.

Dysregulation of RKIP and NRF2 has been widely involved in the therapy resistance of multiple malignances, however, their relation and the corresponding mechanisms, especially in radiation response, have not been elucidated. In this study, we revealed that RKIP could negatively regulate the expression of NRF2 in nasopharyngeal carcinoma (NPC) cells. Depletion or ectopic expression of NRF2 countered the pro- or anti- radioresistant effects of RKIP knockdown or overexpression on NPC cells, respectively, both in vitro and in vivo. Furthermore, our results indicated that NQO1 was positively regulated by NRF2 and served as the downstream effector of RKIP/NRF2 axis in regulation of NPC radioresistance. Mechanistically, miR-450b-5p, being positively regulated by RKIP in NPC cells, could sensitize NPC cells to irradiation by directly targeting and suppressing the level of NRF2. Besides, we analyzed the level of aforementioned molecules in NPC tissues. The results indicated that RKIP was significantly downregulated, NRF2 and NQO1 were notably upregulated in NPC tissues compared with in normal nasopharyngeal mucosa (NNM) tissues. Furthermore, RKIP and miR-450b-5p were remarkably lower, yet NRF2 and NQO1 were notably higher, in radioresistant NPC tissues relative to in radiosensitive NPC tissues. Consistent with the pattern in NPC cells, the RKIP/miR-450b-5p/NRF2/NQO1 axis was significantly correlated in NPC tissues. Downregulation of RKIP and miR-450b-5p, and upregulation of NRF2 and NQO1, positively correlated to malignant pathological parameters such as primary T stage, Lymph node (N) metastasis, and TNM stage. Finally, RKIP and miR-450b-5p served as favorable prognostic indicators, and NRF2 and NQO1 acted as unfavorable prognostic biomarkers in patients with NPC. Collectively, our outcomes reveal that RKIP downregulation promotes radioresistance of NPC by downregulating miR-450b-5p and subsequently upregulating and activating NRF2 and NQO1, highlighting RKIP/miR-450b-5p/NRF2/NQO1 axis as a potential therapeutic target for improving the radiosensitivity of NPC.

miR-181a Upregulation Promotes Radioresistance of Nasopharyngeal Carcinoma by Targeting RKIP.

BACKGROUND: Radioresistance is the leading cause of treatment failure for nasopharyngeal carcinoma (NPC). Therefore, screening the critical regulators in radioresistance and revealing the underlying mechanisms is imperative for improvement of therapeutical efficacy in NPC. MATERIALS AND METHODS: Our previous study has proved that miR-181a may serve as a pro-radioresistant miRNA. In this study, we explored the expression of miR-181a in NPC, especially in radioresistant NPC samples, by qPCR. Moreover, the clinical significance of miR-181a level was also analyzed. Furthermore, the functions of miR-181a, both in vitro and in vivo, were detected via a serial of assays such as CCK-8, plate clone survival, apoptosis, and xenograft tumor model. The downstream target of miR-181a was also validated by dual luciferase reporter assay and the roles of miR-181a's target in the regulation of NPC radioresistance were investigated. RESULTS: The results revealed that miR-181a was significantly upregulated in NPC, especially in radioresistant NPC. MiR-181a level is positively correlated to lymph node metastasis and advanced TNM stages and negatively associated with overall survival rate in NPC. Ectopic expression of miR-181a in radiosensitive NPC cells, or overexpression of miR-181a inhibitor in radioresistant NPC cells, could enhance or impair the radioresistance of NPC cells supported by the results from both in vitro and in vivo, respectively. Mechanistically, dual luciferase report assay indicated that miR-181a could directly target RKIP. Moreover, both in vitro and in vivo experimental outcomes indicated that RKIP restoration and knockdown could antagonize the effects of miR-181a and miR-181a inhibitor in the regulation of NPC radioresistance. CONCLUSION: Collectively, the findings of this study proved that miR-181a is upregulated and promotes radioresistance by targeting RKIP in NPC. Targeting miR-181a/RKIP axis may be a valid path for reinforcing radiosensitivity and eventually improving the outcomes of clinical treatment in NPC.

Boron neutron capture therapy for malignant melanoma: first clinical case report in China.

A phase I/II clinical trial for treating malignant melanoma by boron neutron capture therapy (BNCT) was designed to evaluate whether the world's first in-hospital neutron irradiator (IHNI) was qualified for BNCT. In this clinical trial planning to enroll 30 patients, the first case was treated on August 19, 2014. We present the protocol of this clinical trial, the treating procedure, and the clinical outcome of this first case. Only grade 2 acute radiation injury was observed during the first four weeks after BNCT and the injury healed after treatment. No late radiation injury was found during the 24-month follow-up. Based on positron emission tomography-computed tomography (PET/CT) scan, pathological analysis and gross examination, the patient showed a complete response to BNCT, indicating that BNCT is a potent therapy against malignant melanoma and IHNI has the potential to enable the delivery of BNCT in hospitals.

Changes in regional cerebral blood flow with Chaihu-Shugan-San in the treatment of major depression.

BACKGROUND: Chaihu-Shugan-San (CHSGS) is a well-known Chinese traditional prescription used for depression. OBJECTIVE: To observe the regional cerebral blood flow (rCBF) changes in patients with major depression and to investigate rCBF and clinical response to CHSGS. MATERIALS AND METHODS: A total of 33 unmedicated patients with major depression and 12 healthy comparison subjects underwent single photon emission computed tomography (SPECT) imaging. A total of 33 unmedicated patients with major depression all met the diagnostic criteria of stagnation of liver qi of traditional Chinese medicine and were divided into two groups: CHSGS group (n = 20) and fluoxetine group (n = 13). SPECT imaging was restudied in posttreatment. RESULTS: SPECT detected abnormalities in all (100.0%) patients both in CHSGS group and fluoxetine group. All healthy subjects were normal results. The depressed patients showed rCBF decreased in the multiple regions. The semiquantitative values of bilateral frontal and left temporal lobes both in CHSGS group and fluoxetine group were lower than that in healthy group (P < 0.05). Reexamined SPECT after 8 weeks treatment with CHSGS showed the consistency between the increase in perfusion defects and the improvement of clinical cerebral symptoms. The semiquantitative values increased in posttreatment, when compared with pretreatment (P < 0.05). CONCLUSION: SPECT represents a sensitive tool to detect the major depressive disorder, which show the rCBF decreased. rCBF perfusion defects can be reversed and clinical symptoms can be improved by CHSGS treatment. CHSGS treatment is effective, well-tolerated, and safe for depression. By semiquantitative analysis, SPECT can objectively detect rCBF changes that is useful for guiding treatment.

The effect of Chaihu-Shugan-San and its components on the expression of ERK5 in the hippocampus of depressed rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Chaihu-Shugan-San (CSS) is a well-known, Chinese traditional medicine used to treat depression. Little is known about the antidepressant mechanism of CSS. The main aims of the this study were to evaluate the antidepressant-like effects of CSS and its components and further explore the CSS׳s effect upon signal transduction of extracellular signal-regulated kinase 5 (ERK5) expressions in the hippocampus of rats with depression induced by chronic unpredicted mild stress. MATERIALS AND METHODS: SD rats were randomly divided into six groups: Normal; Model; CSS; Component I; Component II; and Fluoxetine. Antidepressant-like effects of CSS and two of its constituents, Components I and II in aqueous extract, were assessed using rats exposed to chronic unpredictable mild stress (CUMS) by measuring weight change, observing the open-field test and measuring sucrose water consumption. Antidepressant mechanism were examined by measuring the effect of CSS, and two of its constituents, on extracellular signal-regulated kinase 5 (ERK5) expression, phosphorylation-ERK5 (p-ERK5), and ERK5 mRNA in the hippocampus by using western blotting and Real-time Polymerase Chain Reaction (PCR). Three preparations were prepared: (1) an aqueous extract of CSS (5.9 g/kg·d); (2) Component I (3.3 g/kg·d); and (3) Component II (2.6 g/kg·d). During the 28-day CUMS, the three preparations were intragastrically administered all three preparations. Simultaneously a parallel positive fluoxetine control group was given fluoxetine hydrochloride (1.8mg/kg·d). Normal and Model groups were intragastrically administered with a isovolumic distilled water (4.5 ml/kg·d). RESULTS: Depressed rats had decreased weight gain; decreased locomotor activity as measured by the open field test; and reduced sucrose consumption. The rats׳ hippocampus ERK5 activation was significantly suppressed. CSS reduced the incidence of depressive-like behaviors and increased ERK5 activation in depressed rats at the same rate as fluoxetine. Component I, and II, each had only a partial effect on the depression indicators measured. CONCLUSIONS: CSS aqueous extract has antidepressant-like effects on CUMS-induced depression model rats. The antidepressant effect of CSS is greater than that of either the two separate components measured. CSS׳s antidepressant mechanism may be mediated by reversing the stress-induced disruption of ERK5 activity.

Design, synthesis, and biological evaluation of 4-(5-dimethylamino-naphthalene-1-sulfon-amido)-3-(4-iodophenyl)butanoic acid as a novel molecular probe for apoptosis imaging.

Apoptosis (programmed cell death) plays a crucial role in the pathogenesis of many disorders, thus the detection of apoptotic cells can provide the physician with important information to further therapeutic strategies and would substantially advance patient care. A small molecule, 4-(5-dimethylamino-naphthalene-1-sulfonamido)-3-(4-iodo-phenyl)butanoic acid (DNSBA), was designed as a novel probe for imaging apoptosis and synthesized with good yield. The biological characterization demonstrated that DNSBA can be used to specifically and selectively detect apoptotic cancer cells at all stages. DNSBA is also designed as a potential SPECT and PET probe when labeled with radioiodine (I-123, -124, and -131).