Optimizing nicardipine dosage for effective control of pituitrin-induced hypertension in laparoscopic myomectomy undergoing total intravenous anesthesia.

BACKGROUND: This study aimed to determine the median effective dose (ED50) and 95% effective dose (ED95) of nicardipine for treating pituitrin-induced hypertension during laparoscopic myomectomy, providing guidance for the management of intraoperative blood pressure in such patients. METHODS: Among the initial 40 participants assessed, 24 underwent elective laparoscopic myomectomy. A sequential up-and-down method was employed to ascertain the ED50 of nicardipine based on its antihypertensive efficacy. Nicardipine was initially administered at 6 µg/kg following the diagnosis of pituitrin-induced hypertension in the first patient. Dosing adjustments were made to achieve the desired antihypertensive effect, restoring systolic blood pressure and heart rate to within ± 20% of baseline within 120 s. The dosing increment or reduction was set at 0.5 µg/kg for effective or ineffective responses, respectively. The ED50 and ED95 of nicardipine were calculated using Probit regression by Maximum Likelihood Estimation (MLE) to establish dose-response curves and confidence intervals. RESULTS: 24 patients were included for analysis finally. The ED50 and ED95 of nicardipine for blood pressure control after pituitrin injection were determined. The study found that the ED50 of nicardipine for treating pituitrin-induced hypertension was 4.839 µg/kg (95% CI: 4.569-5.099 µg/kg), and the ED95 was estimated at 5.308 µg/kg (95% CI: 5.065-6.496 µg/kg). Nicardipine effectively mitigated the hypertensive response caused by pituitrin without inducing significant tachycardia or hypotension. CONCLUSIONS: Nicardipine effectively controlled blood pressure after pituitrin injection during laparoscopic myomectomy, with ED50 and ED95 values established. This research highlights the potential utility of nicardipine in addressing hypertensive responses induced by pituitrin, particularly in clinical settings where pituitrin is routinely administered.

Benzosceptrin C induces lysosomal degradation of PD-L1 and promotes antitumor immunity by targeting DHHC3.

Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) blockade has become a mainstay of cancer immunotherapy. Targeting the PD-1/PD-L1 axis with small molecules is an attractive approach to enhance antitumor immunity. Here, we identified a natural marine product, benzosceptrin C (BC), that enhances the cytotoxicity of T cells to cancer cells by reducing the abundance of PD-L1. Furthermore, BC exerts its antitumor effect in mice bearing MC38 tumors by activating tumor-infiltrating T cell immunity. Mechanistic studies suggest that BC can prevent palmitoylation of PD-L1 by inhibiting DHHC3 enzymatic activity. Subsequently, PD-L1 is transferred from the membrane to the cytoplasm and cannot return to the membrane via recycling endosomes, triggering lysosome-mediated degradation of PD-L1. Moreover, the combination of BC and anti-CTLA4 effectively enhances antitumor T cell immunity. Our findings reveal a previously unrecognized antitumor mechanism of BC and represent an alternative immune checkpoint blockade (ICB) therapeutic strategy to enhance the efficacy of cancer immunotherapy.

Predictive value of the Oxford Acute Severity of Illness Score in acute stroke patients with stroke-associated pneumonia.

Background: Stroke-associated pneumonia (SAP) is associated with a poor prognosis and a high mortality rate in stroke patients. However, the accuracy of early prediction of SAP is insufficient, and there is a lack of effective prognostic evaluation methods. Therefore, in this study, we investigated the predictive value of the Oxford Acute Severity of Illness Score (OASIS) in SAP to provide a potential reference index for the incidence and prognosis of SAP. Methods: We recruited a total of 280 patients with acute ischemic stroke who had been diagnosed and treated in the Zhumadian Central Hospital between January 2021 and January 2023. These patients were divided into an SAP group (86 cases) and a non-SAP group (194 cases) according to SAP diagnostic criteria by expert consensus on the diagnosis and treatment of SAP. We collated general and clinical data from all patients, including the survival of SAP patients during the follow-up period. Multivariate logistic regression was used to analyze the risk factors for SAP. Kaplan-Meier and multivariate COX regression analyses were used to investigate the relationship between OASIS and the prognosis of SAP, and a receiver operating characteristic (ROC) curve was drawn to analyze the predictive value of OASIS for SAP. Results: Our analyses identified body temperature, C-reactive protein, procalcitonin, OASIS, and a prolonged length of intensive care unit (ICU) stay as the main risk factors for SAP (all Ps < 0.05). Advanced age and an elevated OASIS were identified as the main risk factors for death in SAP patients (all Ps < 0.05). The risk of death in patients with OASIS of 31-42 points was significantly higher than that in patients with OASIS of 12-20 points (HR = 5.588, 95% CI = 1.531-20.401, P = 0.009). ROC curve analysis further showed that OASIS had a high predictive value for morbidity and the incidence of death in SAP patients. Conclusion: OASIS can effectively predict the onset and death of SAP patients and provides a potential reference index for early diagnosis and the prediction of prognosis in patients with SAP. Our findings should be considered in clinical practice.

Increased risk of postpartum depression in women with lactational mastitis: a cross-sectional study.

Background: A high incidence of lactational mastitis mainly occurs during the first month of breastfeeding. It may cause severe pain, frustration, fatigue, stress, and breastfeeding concerns. However, few studies investigated the effects of lactational mastitis on postpartum depression. This study investigated the potential association between lactational mastitis and postpartum depression. Methods: We examined the associations of lactational mastitis with postpartum depression in 1,551 Chinese women. Lactational mastitis was diagnosed by breast specialists. The presence of depression symptoms was evaluated by the Edinburgh Postnatal Depression Scale (EPDS) and Patient Health Questionnaire 9 (PHQ9) at 6 weeks after delivery. Multiple linear regression analysis and multivariable log-binomial regression analysis were performed to estimate the association between lactational mastitis and postpartum depression. Results: Among the 1,551 mothers, 147 (9.5%) experienced lactational mastitis diagnosed by breast specialists during the postpartum period. Compared with women without lactational mastitis, the proportion of women with depression symptoms was significantly higher (38.1% vs. 27.4%, p = 0.008), and the risk of postpartum depression increased by 68% (RR = 1.68, 95% CI, 1.18, 2.40) in women who had experienced lactational mastitis. In addition, the risk of self-harm or suicidal ideation increased by 89% (RR = 1.89, 95% CI, 1.08, 3.29) in women who experienced lactational mastitis. In stratified analysis, the associations of lactational mastitis with postpartum depression appeared stronger among women aged ≥35 years, with maternal comorbidities, and who delivered a female neonate. Conclusion: The study results suggest that lactational mastitis is a risk factor for depression during the postpartum period. The impact of lactational mastitis on maternal mental health requires further attention. Clinical trial registration: chictr.org.cn, ChiCTR2000041519.

The Discovery and Anti-Colorectal Cancer Activities of Cembranolides from the South China Sea Soft Coral Sinularia pendunculata.

A new cembranolide, namely, sinupendunculide A (1), along with eight known related compounds (2-9), was isolated from the South China Sea Soft coral Sinularia pendunculata. The structure of sinupendunculide A (1) was established by extensive spectroscopic analysis and X-ray diffraction experiments. In a bioassay, anti-colorectal cancer (CRC) activity was performed, and the results showed that several compounds exhibited cytotoxicity against RKO cells, and a preliminary structure-activity relationship was analysed. Meanwhile, the most effective compound 7 was proven to increase reactive oxygen species levels, which promoted cell apoptosis and inhibited cell proliferation.

Virtual reality training improves accommodative facility and accommodative range.

AIM: To evaluate the effects of virtual reality (VR) training on different parameters of vision. METHODS: Sixty individuals ranged 18-60 years old with asthenopia were randomly divided into short-term (n=40) and long-term (n=20) treatment groups. They were given a specially designed VR training device only once for 15min or 3-4 times a day for 15min each time for 1mo. The visual acuity, spherical equivalent, accommodative range, accommodative facility, pupil size, and visual fatigue were evaluated before (control) and after VR training. RESULTS: The visual acuity, accommodative range, and accommodative facility increased in subjects of the short-term treatment group, whereas their pupil size contracted significantly. No significant changes in spherical equivalent and visual fatigue were observed. The changes in distant vision and corrected visual acuity were positively correlated with those in pupil size, but not with spherical equivalent. The accommodative range and accommodative facility improved significantly in subjects of the long-term treatment group. No significant changes in visual acuity, spherical equivalent, pupil size, and visual fatigue were noted. CONCLUSION: VR training can improve the accommodative range and accommodative facility of human eyes. Although short-term VR training can transiently improve vision, which probably due to bright light adaptation, there is no evidence that it can improve myopia.

FL-DTD: an integrated pipeline to predict the drug interacting targets by feedback loop-based network analysis.

Drug target discovery is an essential step to reveal the mechanism of action (MoA) underlying drug therapeutic effects and/or side effects. Most of the approaches are usually labor-intensive while unable to identify the tissue-specific interacting targets, especially the targets with weaker drug binding affinity. In this work, we proposed an integrated pipeline, FL-DTD, to predict the drug interacting targets of novel compounds in a tissue-specific manner. This method was built based on a hypothesis that cells under a status of homeostasis would take responses to drug perturbation by activating feedback loops. Therefore, the drug interacting targets can be predicted by analyzing the network responses after drug perturbation. We evaluated this method using the expression data of estrogen stimulation, gene manipulation and drug perturbation and validated its good performance to identify the annotated drug targets. Using STAT3 as a target protein, we applied this method to drug perturbation data of 500 natural compounds and predicted five compounds with STAT3 interacting activities. Experimental assay validated the STAT3-interacting activities of four compounds. Overall, our evaluation suggests that FL-DTD predicts the drug interacting targets with good accuracy and can be used for drug target discovery.

Application of berberine-loaded albumin nanoparticles in infections of traumatic wounds.

In recent years, the morbidity of infections in traumatic wounds has been on the increase. There are not many kinds of drugs for clinical treatment of infections, and their efficacy and safety are limited. Plant antimicrobial drugs are increasingly popular in mainstream medicine due to the challenges of traditional antibiotics abuse. Berberine has a scavenging effect on infections, however, berberine was restricted from using as a drug preparation with poor stability and bioavailability. Due to the low toxicity of nanoparticles, the green-synthetic, size-controlled approach of nanoparticles has been paid more attention. Therefore, based on the intermolecular disulfide bond network platform built earlier, we designed and developed a strategy to assemble molecular bovine serum albumin into large-sized nanostructures through the reconstructed intermolecular disulfide bond and hydrophobic interaction, and berberine with poor water solubility was encapsulated in it. Nanoassembly with bovine serum albumin increased biostability of berberine and significantly improved its activity against Staphylococcus Aureus (S.aureus) activity, which gives some new insights into the preparation and development of anti-infectives for Chinese medicine.

Retinal Transcriptomics Analysis Reveals the Underlying Mechanism of Disturbed Emmetropization Induced by Wavelength Defocus.

PURPOSE: Wavelength signals play a vital role in refractive development. This study aimed to explore the retinal transcriptome signature in these processes. METHODS: Guinea pigs were randomly divided into three groups exposed to white, blue, or green environmental light for eight weeks. Refraction and axial length were evaluated every 4 weeks, and the retinal transcriptome was profiled at 8 weeks. RESULTS: Compared with the white group, ocular refraction significantly decreased and ocular axial length significantly extended in the green group whereas these parameters showed opposite trends in the blue group. RNA-sequencing showed that, compared with the white group, 184 and 171 differentially expressed genes (DEGs) were found in the blue and green groups, respectively. Among these DEGs, only 31 overlapped. These two sets of DEGs were enriched in distinct biological processes and pathways. There were 268 DEGs between the blue and green groups, which were primarily enriched in the extracellular matrix, and metabolism, receptor activity, and ion binding processes. In addition, nine human genes, including ECEL1, CHRND, SHBG, PRSS56, OVOL1, RDH5, WNT7B, PEBP4, CA12, were identified to be related to myopia development and wavelength response, indicating the potential role of these genes in human wavelength-induced myopia. CONCLUSIONS: In this study, we identified retinal targets and pathways involved in the response to wavelength signals in emmetropization.

A new perspective on the inhibition of plant photosynthesis by uranium: decrease of root activity and stomatal closure.

Uranium (U) is difficult to be transported from roots to leaves, but it has been reported to inhabit photosynthesis in leaves, so how does this work? In the present study, the effects of U (0-25 µM) on the development and photosynthesis in V. faba seedlings were studied under hydroponics. The results showed that U significantly inhibited the growth and development of V. faba plants, including decreased biomass, water content, lateral root number and root activity. U also led to a large accumulation of reactive oxygen species (ROS) in the leaves which affects leaf structural traits (e.g., decreased leaf area and chlorophyll a content). When U concentration was 25 µM, the net photosynthetic rate (Pn) and transpiration rate (Tr) were inhibited, which were only 66.53% and 41.89% of the control, respectively. Further analysis showed that the stomatal density of leaves increased with the increase of U concentration, while the stomatal aperture and stomatal conductance (Gs) were on the contrary. The results of chlorophyll fluorescence showed that the non-photochemical quenching coefficient (NPQ) increased and the electron transfer rate (ETR) decreased after U exposure, but fortunately, photosystem II (PSII) suffered little damage overall. In conclusion, the accumulation of U in the roots inhibited the root activity, resulting in water shortage in the plants. To prevent water loss, leaves have to regulated stomatal closure at the cost of weakening photosynthesis. These results provide a new insight into the mechanism by which U affects plant photosynthesis.

Biological activities of the extracts and compounds from the bark of Pterocarya hupehensis skan.

This study was undertaken in order to investigate the antioxidant, anti-inflammatory and antimicrobial activities of various fractions and compounds obtained from the bark of P. hupehensis. The ethyl acetate fraction exhibited strong antioxidant, anti-inflammatory and antimicrobial effects. Six compounds were isolated from this fraction, three of which showed antioxidant activity and anti-inflammatory activity. The biological activities and the active compounds of P. hupehensis were reported for the first time.

Comparison of anterior chamber angle changes following phakic intraocular lens with and without a central hole implantation for moderate to high myopic eyes.

The aim of this study was to compare the anterior chamber angle changes after implantation of phakic intraocular lens with and without a central hole for moderate to high myopic eyes in Chinese people.This study enrolled 106 eyes of 54 people with intraocular lens V4 implantation and 105 eyes of 53 people with intraocular lens V4c implantation. Postoperative vault, intraocular pressure, and anterior chamber angle changes were assessed using noncontract tonometer and ultrasound biomicroscope, respectively, at 1, 3, 6, and 12months after the surgery.There were no significant differences (all P > .05) between the 2 groups in the depth of the central vault, intraocular pressure, or the width of anterior chamber angle at any time point post-surgery. The anterior chamber angle width in degree had a baseline of 54.40 ±â€Š10.51 in V4c group, and decreased to 27.80 ±â€Š5.62, 26.95 ±â€Š5.56, 27.32 ±â€Š5.66, 27.04 ±â€Š5.47 at 1, 3, 6, and 12 months post-surgery, respectively. Mean preoperative value of 50.62 ±â€Š11.77 decreased to 27.28 ±â€Š6.53, 26.82 ±â€Š6.03, 26.61 ±â€Š5.80, 26.83 ±â€Š5.76 at 1, 3, 6, 12 months, respectively, in V4 group. It had sufficient evidence (P < .001) that anterior chamber angle will narrow done after surgery, but there were no statistically significant differences within groups at any time point after surgery.The anterior chamber angle changes of the V4c group was essentially equivalent to that of conventional V4 group, although implantation of both models will lead to the decrease in anterior chamber angle width.

Investigation of dry eye symptoms of medical staffs working in hospital during 2019 novel coronavirus outbreak.

The aim of this study was to survey the prevalence of dry eye symptoms (DES) among doctors and nurses in the period of 2019, novel coronavirus (COVID-19) outbreak.To evaluate the DES of doctors and nurses worked at front-line hospitals with protective glasses for a mean time of 4 to 6 hours, a questionnaire developed by the researchers with the Ocular Surface Disease Index (OSDI) was used. These data were evaluated using descriptive statistics and correlation test with SPSS 22.0.The study included 13 doctors and 40 nurses, among which 16 were male and 37 were female, and the mean age of the participants was 32.43 ±â€Š5.15 years old. According to the OSDI scores, 64.15, 24.52, 7.54, and 3.77% of the participants experienced occasional, mild, moderate, and severe DES, respectively. The factors significantly correlated with OSDI scores were age and duration of wearing protective glasses, while the duration of wearing protective glasses may be a protective factor of dry eye symptoms.Our study showed that most of the doctors and nurses worked at the front-line of combating COVID-19 did not experience DES, while the symptoms of those who experienced DES might be improved by wearing protective glasses.

Relapsing viral keratoconjunctivitis in COVID-19: a case report.

BACKGROUND: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, many studies have reported the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the conjunctival sac of patients infected with this virus, with several patients displaying symptoms of viral conjunctivitis. However, to our best knowledge, there is no in-depth report on the course of patients with COVID-19 complicated by relapsing viral conjunctivitis or keratoconjunctivitis. CASE PRESENTATION: A 53-year-old man confirmed with COVID-19 developed symptoms of viral conjunctivitis in the left eye approximately 10 days after the onset of COVID-19. The results of a nucleic acid test were positive for SARS-CoV-2 in the conjunctival sac of the left eye. The symptoms were relieved 6 days after treatment. However, the patient was subsequently diagnosed with viral keratoconjunctivitis in both eyes 5 days after the symptoms in the left eye were satisfactorily relieved. The disease progressed rapidly, with spot staining observed at the periphery of the corneal epithelium. Although SARS-CoV-2 could not be detected in conjunctival secretions, the levels of inflammatory factors, such as interleukin-6, were increased in both eyes. Both eyes were treated with glucocorticoids, and symptoms were controlled within 5 days. There was no recurrence. CONCLUSIONS: In this case report, the pathogenesis, clinical manifestations, treatment, and outcome of a case with COVID-19 complicated by relapsing viral keratoconjunctivitis is described, and the involvement of topical cytokine surge in the pathogenesis of COVID-19 as it relates to viral keratoconjunctivitis is reported.

Evaluation of ocular symptoms and tropism of SARS-CoV-2 in patients confirmed with COVID-19.

PURPOSE: The SARS-CoV-2 RNA has been detected in tears and conjunctival samples from infected individuals. Conjunctivitis is also reported in a small number of cases. We evaluated ocular symptoms and ocular tropism of SARS-CoV-2 in a group of patients with COVID-19. METHOD: Fifty-six patients infected with SARS-CoV-2 were recruited as subjects. Relevant medical histories were obtained from the electronic medical record system. Ocular history and ocular symptoms data were obtained by communicating directly with the subjects. The Ocular Surface Disease Index (OSDI) and Salisbury Eye Evaluation Questionnaire (SEEQ) were used to assess the anterior ocular surface condition before and after the onset of disease. RESULTS: Patients classified as severe COVID-19 cases were more likely to have hypertension compared to mild cases (p = 0.035). Of the 56 subjects, thirteen patients (23%) were infected in Wuhan, 32 patients (57%) were community-infected, 10 patients (18%) were unknown origin, 1 (2%) was a physician likely infected by a confirmed patient. Three patients wore face mask with precaution when contacting the confirmed patients. Fifteen (27%) had aggravated ocular symptoms, of which 6 (11%) had prodromal ocular symptoms before disease onset. The differences in mean scores of OSDI questionnaire and SEEQ between before and after onset of COVID-19 were all significant (p < 0.05 for both). CONCLUSIONS: Ocular symptoms are relatively common in COVID-19 disease and may appear just before the onset of respiratory symptoms. Our data provided the anecdotal evidences of transmission of SARS-CoV-2 via ocular surface.

Evaluation of coronavirus in tears and conjunctival secretions of patients with SARS-CoV-2 infection.

OBJECTIVE: This study aimed to assess the presence of novel coronavirus in tears and conjunctival secretions of SARS-CoV-2-infected patients. METHODS: A prospective interventional case series study was performed, and 30 confirmed novel coronavirus pneumonia (NCP) patients were selected at the First Affiliated Hospital of Zhejiang University from 26 January 2020 to 9 February 2020. At an interval of 2 to 3 days, tear and conjunctival secretions were collected twice with disposable sampling swabs for reverse-transcription polymerase chain reaction (RT-PCR) assay. RESULTS: Twenty-one common-type and nine severe-type NCP patients were enrolled. Two samples of tear and conjunctival secretions were obtained from the only one patient with conjunctivitis yielded positive RT-PCR results. Fifty-eight samples from other patents were all negative. CONCLUSION: We speculate that SARS-CoV-2 may be detected in the tears and conjunctival secretions in NCP patients with conjunctivitis.

Neuropathic pain releasing calcitonin gene related peptide protects against stroke in rats.

Neuropathic pain (NPP) is deemed as a potential risk of stroke; however, recent pieces of evidence showed that calcitonin gene-related peptide is involving in pain progression as well as organ protection. The mechanisms underlying the neuroprotection of calcitonin gene-related peptide are yet poorly described with respect to stroke. The present study showed that the elevated level of calcitonin gene-related peptide-induced by NPP exerts a protective effect against stroke in rats, which was further confirmed in vivo and vitro via mitigation of inflammatory response, inhibition of neuronal cell apoptosis, and increase in regional cerebral blood flow. Repetitive transcranial magnetic stimulation at trigeminal ganglion was performed to simulate to facilitate the release of calcitonin gene-related peptide for a similar neuroprotective effect. Together, these findings posit that the release of calcitonin gene-related peptide-induced by NPP or repetitive transcranial magnetic stimulation protects against stroke in rats. Thus, repetitive transcranial magnetic stimulation could have high application prospects for the prevention and treatment of stroke.

Anti-inflammatory and antitumour activity of various extracts and compounds from the fruits of Piper longum L.

OBJECTIVES: To explore effective extraction method and to find active constituents, we investigated the biological activity of three extracts and isolated active compounds from the fruits of Piper longum L. METHODS: Three extracts from the fruits were obtained by reflux, ultrasonic and supercritical fluid extraction, respectively. Active compounds were isolated by the bioassay-guided method. The anti-inflammatory activity, antiproliferation activity and cytotoxicity were evaluated. The apoptosis was detected by Hoechst 33258 staining assay. The relevant proteins were investigated by Western blot assay. KEY FINDINGS: The anti-inflammatory activity and cytotoxicity of supercritical fluid extract (SE) were stronger than those of the other two extracts. Among all isolated compounds, the anti-inflammatory activity of eight compounds was stronger than that of indomethacin, and compounds 8, 9, 11, 14 and 15 were found to possess anti-inflammatory effect for the first time. Compounds 1, 2, 3 and 14 exhibited significant cytotoxicity against cancer cells. SE and piperine were found to reduce colony formation, inhibit cell migration and promote apoptosis through increasing cleaved PARP and the ratio of Bax/Bcl-2. CONCLUSIONS: The anti-inflammatory and antitumour effects of SE were better than those of the other two extracts. The compounds responsible for the activity were elucidated. SE and piperine inhibit cell growth through apoptosis.

Botulinum toxin A in the treatment of trigeminal neuralgia.

AIMS: The aims of this study were to investigate the clinical effects and safety of botulinum toxin A (BTX-A) in treating trigeminal neuralgia and its influences on accompanied depression, anxiety, sleep disorders, and quality of life. METHODS AND MATERIAL: Eighty-seven patients with one-branch classical trigeminal neuralgia were injected with BTX-A in the pain area. The visual analogic scale score, sleep interference score, Hamilton Anxiety Scale score, Hamilton Depression Scale score, and side effects were assessed at 1 week prior to and 8 weeks after treatment, respectively. RESULTS: The effective rates after 1, 2, 4, and 8 weeks of treatment were 48.28%, 66.67%, 78.16%, and 80.46%, respectively. The effective rates of anxiety and depression were 90.32% and 96.77%, respectively. When compared to that before treatment, the quality of life was significantly better in terms of role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health (all P < 0.01), while physical function was not significantly improved (P = 0.317). CONCLUSION: BTX-A treatment can significantly relieve the pain in trigeminal neuralgia patients; improve anxiety, depression, and sleep; and increase the quality of life. BTX-A treatment is a safe and effective method to treat classical trigeminal neuralgia.