Sishen Wan enhances intestinal barrier function via regulating endoplasmic reticulum stress to improve mice with diarrheal irritable bowel syndrome.

BACKGROUND: Diarrheal irritable bowel syndrome (IBS-D), characterized primarily by the presence of diarrhea and abdominal pain, is a clinical manifestation resulting from a multitude of causative factors. Furthermore, Sishen Wan (SSW) has demonstrated efficacy in treating IBS-D. Nevertheless, its mechanism of action remains unclear. METHODS: A model of IBS-D was induced by a diet containing 45 % lactose and chronic unpredictable mild stress. Additionally, the impact of SSW was assessed by measuring body weight, visceral sensitivity, defecation parameters, intestinal transport velocity, intestinal neurotransmitter levels, immunohistochemistry, and transmission electron microscopy analysis. Immunofluorescent staining was used to detect the expression of Mucin 2 (MUC2) and Occludin in the colon. Western blotting was used to detect changes in proteins related to tight junction (TJ), autophagy, and endoplasmic reticulum (ER) stress in the colon. Finally, 16S rRNA amplicon sequencing was used to monitor the alteration of gut microbiota after SSW treatment. RESULTS: Our study revealed that SSW administration resulted in reduced visceral sensitivity, improved defecation parameters, decreased intestinal transport velocity, and reduced intestinal permeability in IBS-D mice. Furthermore, SSW promotes the secretion of colonic mucus by enhancing autophagy and inhibiting ER stress. SSW treatment caused remodeling of the gut microbiome by increasing the abundance of Blautia, Muribaculum and Ruminococcus torques group. CONCLUSION: SSW can improve intestinal barrier function by promoting autophagy and inhibiting ER stress, thus exerting a therapeutic effect on IBS-D.

Establishment and application of a screening method for α-glucosidase inhibitors based on dual sensing and affinity chromatography.

α-Glucosidase plays a direct role in the metabolic pathways of starch and glycogen, any dysfunction in its activity could result in metabolic disease. Concurrently, this enzyme serves as a target for diverse drugs and inhibitors, contributing to the regulation of glucose metabolism in the human body. Here, an integrated analytical method was established to screen inhibitors of α-glucosidase. This step-by-step screening model was accomplished through the biosensing and affinity chromatography techniques. The newly proposed sensing program had a good linear relationship within the enzyme activity range of 0.25 U mL-1 to 1.25 U mL-1, which can quickly identify active ingredients in complex samples. Then the potential active ingredients can be captured, separated, and identified by an affinity chromatography model. The combination of the two parts was achieved by an immobilized enzyme technology and a microdevice for reaction, and the combination not only ensured efficiency and accuracy for inhibitor screening but also eliminated the occurrence of false positive results in the past. The emodin, with a notable inhibitory effect on α-glucosidase, was successfully screened from five traditional Chinese medicines using this method. The molecular docking results also demonstrated that emodin was well embedded into the active pocket of α-glucosidase. In summary, the strategy provided an efficient method for developing new enzyme inhibitors from natural products.

Sinapine targeting PLCß3 EF hands disrupts Gαq-PLCß3 interaction and ameliorates cardiovascular diseases.

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) over-activation is highly involved in cardiovascular diseases (CVDs), with the Gαq-PLCß3 axis acting as a core node of RAAS. PLCß3 is a potential target of CVDs, and the lack of inhibitors has limited its drug development. PURPOSE: Sinapine (SP) is a potential leading compound for treating CVDs. Thus, we aimed to elucidate the regulation of SP towards the Gαq-PLCß3 axis and its molecular mechanism. STUDY DESIGN: Aldosteronism and hypertension animal models were employed to investigate SP's inhibitory effect on the abnormal activation of the RAAS through the Gαq-PLCß3 axis. We used chemical biology methods to identify potential targets and elucidate the underlying molecular mechanisms. METHODS: The effects of SP on aldosteronism and hypertension were evaluated using an established animal model in our laboratory. Target identification and underlying molecular mechanism research were performed using activity-based protein profiling with a bio-orthogonal click chemistry reaction and other biochemical methods. RESULTS: SP alleviated aldosteronism and hypertension in animal models by targeting PLCß3. The underlying mechanism for blocking the Gαq-PLCß3 interaction involves targeting the EF hands through the Asn-260 amino acid residue. SP regulated the Gαq-PLCß3 axis more precisely than the Gαq-GEFT or Gαq-PKCζ axis in the cardiovascular system. CONCLUSION: SP alleviated RAAS over-activation via Gαq-PLCß3 interaction blockade by targeting the PLCß3 EF hands domain, which provided a novel PLC inhibitor for treating CVDs. Unlike selective Gαq inhibitors, SP reduced the risk of side effects compared to Gαq inhibitors in treating CVDs.

Local Multiple-site Injections of a Plasmid Encoding Human MnSOD Mitigate Radiation-induced Skin Injury by Inhibiting Ferroptosis.

BACKGROUND: Most patients who undergo radiotherapy develop radiation skin injury, for which effective treatment is urgently needed. MnSOD defends against reactive oxygen species (ROS) damage and may be valuable for treating radiation-induced injury. Here, we (i) investigated the therapeutic and preventive effects of local multiple-site injections of a plasmid, encoding human MnSOD, on radiation-induced skin injury in rats and (ii) explored the mechanism underlying the protective effects of pMnSOD. METHODS: The recombinant plasmid (pMnSOD) was constructed with human cytomegalovirus (CMV) promoter and pUC-ori. The protective effects of pMnSOD against 20-Gy X-ray irradiation were evaluated in human keratinocytes (HaCaT cells) by determining cell viability, ROS levels, and ferroptosisrelated gene expression. In therapeutic treatment, rats received local multiple-site injections of pMnSOD on days 12, 19, and 21 after 40-Gy γ-ray irradiation. In preventive treatment, rats received pMnSOD injections on day -3 pre-irradiation and on day 4 post-irradiation. The skin injuries were evaluated based on the injury score and pathological examination, and ferroptosis-related gene expression was determined. RESULTS: In irradiated HaCaT cells, pMnSOD transfection resulted in an increased SOD2 expression, reduced intracellular ROS levels, and increased cell viability. Moreover, GPX4 and SLC7A11 expression was significantly upregulated, and erastin-induced ferroptosis was inhibited in HaCaT cells. In the therapeutic and prevention treatment experiments, pMnSOD administration produced local SOD protein expression and evidently promoted the healing of radiation-induced skin injury. In the therapeutic treatment experiments, the injury score in the high-dose pMnSOD group was significantly lower than in the PBS group on day 33 post-irradiation (1.50 vs. 2.80, P < 0.05). In the prevention treatment experiments, the skin injury scores were much lower in the pMnSOD administration groups than in the PBS group from day 21 to day 34. GPX4, SLC7A11, and Bcl-2 were upregulated in irradiated skin tissues after pMnSOD treatment, while ACSL4 was downregulated. CONCLUSION: The present study provides evidence that the protective effects of MnSOD in irradiated HaCaT cells may be related to the inhibition of ferroptosis. The multi-site injections of pMnSOD had clear therapeutic and preventive effects on radiation-induced skin injury in rats. pMnSOD may have therapeutic value for the treatment of radiation-induced skin injury.

Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction.

CONTEXT: Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear. OBJECTIVE: We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles. MATERIALS AND METHODS: Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days' administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed. RESULTS: 0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%). DISCUSSION AND CONCLUSION: The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.

Exploring the mechanism of Astragali radix for promoting osteogenic differentiation based on network pharmacology, molecular docking, and experimental validation.

The present study used network pharmacology and molecular docking to predict the active ingredients and mechanisms of action of Astragalus radix (AR) to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs), and cell experiments were conducted for verification. First, network pharmacology was used to predict the effective components, targets, and mechanisms of action of AR to promote osteogenic differentiation. The effective components and corresponding target proteins of AR, and the target proteins of osteogenic differentiation were collected through the database. The intersection targets of the two were used for the construction and analysis of a protein-protein interaction (PPI) network. Gene Oncology (GO) and Kyoto Encyclopedia of Genes, and Genomes (KEGG) enrichment analyses were conducted. Next, molecular docking technology was carried out to verify the interaction between the active ingredient and the target protein, and to select the appropriate effective active ingredient. Finally, the results of network pharmacology analysis were verified by in vitro experiments. A total of 95 potential targets were retrieved by searching the intersection of AR and osteogenic differentiation targets. PPI network analysis indicated that RAC-α-serine-threonine-protein kinase (Akt1) was considered to be the most reliable target for AR to regulate osteogenic differentiation. GO enrichment analysis included 21 biological processes, 21 cellular components and 100 molecular functions. KEGG enrichment analysis indicated that the class I phosphatidylinositol-3 kinase (PI3K)-serine-threonine kinase (Akt) signaling pathway may play an important role in promoting osteogenic differentiation. The results of molecular docking showed that quercetin's performance was improved compared with that of kaempferol. In vitro experiments showed that quercetin promoted the expression of osteogenic marker proteins (including collagen I, Runt-related transcription factor 2 and osteopontin) in BMSCs and activated the PI3K/Akt signaling pathway. AR acted on Akt1 targets through its main active component quercetin, and promoted the osteogenic differentiation of BM-MSCs by activating the PI3K/Akt signaling pathway.

Targeted co-delivery of curcumin and erlotinib by MoS2 nanosheets for the combination of synergetic chemotherapy and photothermal therapy of lung cancer.

BACKGROUND: Curcumin (Cur), a bioactive component of Chinese traditional medicine, has demonstrated inhibitory properties against cancer cell proliferation while synergistically enhancing the anticancer efficacy of erlotinib (Er). However, the individual limitations of both drugs, including poor aqueous solubility, lack of targeting ability, short half-life, etc., and their distinct pharmacokinetic profiles mitigate or eliminate their combined antitumor potential. RESULTS: In this study, we developed a molybdenum disulfide (MoS2)-based delivery system, functionalized with polyethylene glycol (PEG) and biotin, and co-loaded with Cur and Er, to achieve efficient cancer therapy. The MoS2-PEG-Biotin-Cur/Er system effectively converted near-infrared (NIR) light into heat, thereby inducing direct photothermal ablation of cancer cells and promoting controlled release of Cur and Er. Biotin-mediated tumor targeting facilitated the selective accumulation of MoS2-PEG-Biotin-Cur/Er at the tumor site, thus enhancing the synergistic antitumor effects of Cur and Er. Remarkably, MoS2-PEG-Biotin-Cur/Er achieved the combination of synergistic chemotherapy and photothermal therapy (PTT) upon NIR irradiation, effectively suppressing lung cancer cell proliferation and inhabiting tumor growth in vivo. CONCLUSIONS: The as-synthesized MoS2-PEG-Biotin-Cur/Er, featuring high targeting ability, NIR light-responsive drug release, and the integration of synergistic chemotherapy and PTT, may provide a promising strategy for the treatment of lung cancer in clinical practice.

Efficacy Comparison Between Toric Posterior Chamber Phakic IOL and Posterior Chamber Phakic IOL Plus Modified Steep Meridian Corneal Relaxing Incision for Moderate to High Astigmatism Corrections.

PURPOSE: To compare posterior chamber phakic intraocular lens (Implantable Collamer Lens [STAAR Surgical]) (ICL) plus modified steep meridian corneal relaxing incision (MS-CRI) to toric posterior chamber phakic intraocular lens (Toric Implantable Collamer Lens [STAAR Surgical]) (TICL) implantation for the correction of moderate to high astigmatism. METHODS: In this prospective, randomized clinical trial, patients with myopia who had moderate to high astigmatism (200 eyes) were enrolled and divided into TICL (n = 100) and MSCRI (n = 100) groups. All patients underwent examinations for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and subjective refraction before surgery and at the 1- and 6-month follow-up visits. Vector astigmatism analysis was evaluated using the Alpins method. RESULTS: The mean UDVA and CDVA demonstrated significant improvement after surgery in both groups. During the 6-month follow-up, the MS-CRI group showed a slight regression tendency (P < .001) and the TICL group was stable for the astigmatism correction (P = .510). At 6 months postoperatively, the mean magnitudes of the surgically induced astigmatism were 1.46 ± 0.53 and 1.10 ± 0.48 diopters (P < .001). The correction index of the TICL group was closer to 1 compared to that of the MS-CRI group (0.95 vs 0.76). Approximately 99% of eyes in the TICL group had angle of error within ±15°, whereas 89% eyes in the MS-CRI group were within that range. A significant relationship between the magnitudes of target induced astigmatism and correction index was noted in the MS-CRI group (P < .001), but not in the TICL group (P = .592). CONCLUSIONS: TICL implantation could achieve better visual outcomes for correcting moderate to high astigmatism compared to ICL implantation plus MS-CRI. [J Refract Surg. 2023;39(8):539-545.].

Spoken language processing activates the primary visual cortex.

Primary visual cortex (V1) is generally thought of as a low-level sensory area that primarily processes basic visual features. Although there is evidence for multisensory effects on its activity, these are typically found for the processing of simple sounds and their properties, for example spatially or temporally-congruent simple sounds. However, in congenitally blind individuals, V1 is involved in language processing, with no evidence of major changes in anatomical connectivity that could explain this seemingly drastic functional change. This is at odds with current accounts of neural plasticity, which emphasize the role of connectivity and conserved function in determining a neural tissue's role even after atypical early experiences. To reconcile what appears to be unprecedented functional reorganization with known accounts of plasticity limitations, we tested whether V1's multisensory roles include responses to spoken language in sighted individuals. Using fMRI, we found that V1 in normally sighted individuals was indeed activated by comprehensible spoken sentences as compared to an incomprehensible reversed speech control condition, and more strongly so in the left compared to the right hemisphere. Activation in V1 for language was also significant and comparable for abstract and concrete words, suggesting it was not driven by visual imagery. Last, this activation did not stem from increased attention to the auditory onset of words, nor was it correlated with attentional arousal ratings, making general attention accounts an unlikely explanation. Together these findings suggest that V1 responds to spoken language even in sighted individuals, reflecting the binding of multisensory high-level signals, potentially to predict visual input. This capability might be the basis for the strong V1 language activation observed in people born blind, re-affirming the notion that plasticity is guided by pre-existing connectivity and abilities in the typically developed brain.

[Characterization and identification of chemical components in traditional Chinese medicine Psoraleae Fructus based on UHPLC-Q-TOF-MS].

This study was designed to comprehensively characterize and identify the chemical components in traditional Chinese medicine Psoraleae Fructus by establishing an ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry(UHPLC-Q-TOF-MS) method in combination with in-house library. The chromatographic separation conditions(stationary phase, column temperature, mobile phase, and elution gradient) and key MS monitoring parameters(capillary voltage, nozzle voltage, and fragmentor) were sequentially optimized via single-factor experiments. A BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) was finally adopted, with the mobile phase consisting of 0.1% formic acid in water(A) and acetonitrile(B) at the flow rate of 0.4 mL·min~(-1) and column temperature of 30 ℃. Auto MS/MS was utilized for data acquisition in both positive and negative ion modes. By comparison with reference compounds, analysis of the MS~2 fragments, in-house library retrieval and literature research, 83 compounds were identified or tentatively characterized from Psoraleae Fructus, including 58 flavonoids, 11 coumarins, 4 terpenoid phenols, and 10 others. Sixteen of them were identified by comparison with reference compounds, and ten compounds may have not been reported from Psoraleae Fructus. This study achieved a rapid qualitative analysis on the chemical components in Psoraleae Fructus, which provided useful reference for elucidating its material basis and promoting the quality control.

Fuziline Ameliorates Glucose and Lipid Metabolism by Activating Beta Adrenergic Receptors to Stimulate Thermogenesis.

Radix aconiti carmichaeli is a widely used traditional Chinese medicine that has been found to be effective in treating cardiovascular diseases and metabolic disorders. Patients with these diseases often experience a heat generation disorder, which is characterized by chilliness and can worsen the progression of the disease. This study established an in vitro screening model combining the examination of cellular mitochondrial membrane potential and mitochondrial temperature to screen drugs with thermogenic activity. After differentiation and determination of the content of characteristic metabolites of the drug-containing serum blood components, it was found that Fuziline (FZL) is the key thermogenic property in Radix aconiti carmichaeli, responsible for its thermogenic effects with a high relative importance of 33%. Experiments were conducted to evaluate the thermogenic activity of Radix aconiti carmichaeli and FZL in vivo by assessing temperature changes in various organs, including the rectum, liver, and brown adipose tissue. Moreover, the effects of intracellular ß3-adrenergic receptor (ß3-AR) agonistic effects were evaluated using transient ß3-AR transfection and dual-luciferase assay systems. The molecular mechanism by which FZL promotes thermogenesis and improves mitochondrial function was investigated by verifying the ß-adrenergic receptors (ß-AR) downstream signaling pathway. The results suggest that FZL activates ß-AR nonselectively, which in turn activates the downstream cAMP-PKA signaling pathway and leads to an increase in liver glycogenolysis and triglyceride hydrolysis, accompanied by enhancing mitochondrial energy metabolism. Consequently, the liver and brown adipose tissue receive energy to generate heat. In summary, these findings provide insight into the therapeutic application of Radix aconiti carmichaeli for metabolic disorders associated with heat generation disorders.

Efficacy of acupuncture for tension-type headache prophylaxis: systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Acupuncture has been shown to reduce tension-type headache (TTH) frequency in previous studies. Nevertheless, repeated significance testing might inflate type I error. We aimed to verify the effectiveness and safety of acupuncture in reducing TTH frequency by meta-analysis and trial sequential analysis (TSA). METHODS: Ovid Medline, Embase, and Cochrane Library were searched until September 29, 2022. Randomized controlled trials comparing acupuncture with sham acupuncture, no acupuncture, or other active therapies in adults with TTH were included. The primary outcome was TTH frequency. The secondary outcomes were responder rate and adverse event. RESULTS: Fourteen studies involving 2795 participants were included. Acupuncture had more reduction than sham acupuncture in TTH frequency, both after treatment (standardized mean difference [SMD] - 0.80, 95% CI - 1.36 to - 0.24, P = 0.005) and at the follow-up period (SMD - 1.33, 95% CI - 2.18 to - 0.49, P = 0.002), while TSA showed the included sample size did not exceed required information size (RIS). Acupuncture was superior over no acupuncture after treatment (SMD - 0.52, 95% CI - 0.63 to - 0.41, P < 0.001), and cumulative sample size reached RIS. In terms of responder rate, acupuncture had a higher responder rate compared with sham acupuncture both after treatment (relative ratio [RR] 1.28, 95% CI 1.12 to 1.46, P = 0.0003) and the follow-up period (RR 1.37, 95% CI 1.19 to 1.58, P < 0.0001), but the sample size is inadequate. CONCLUSION: Acupuncture is an efficacious and safe treatment for TTH prevention, but this conclusion might be limited by the generally very low to low quality evidence. TSA suggested that high-quality trials are needed to verify the efficacy and safety of acupuncture compared to sham acupuncture.

CIB2 and CIB3 Regulate Stereocilia Maintenance and Mechanoelectrical Transduction in Mouse Vestibular Hair Cells.

The mechanoelectrical transduction (MET) protein complex in the inner-ear hair cells is essential for hearing and balance perception. Calcium and integrin-binding protein 2 (CIB2) has been reported to be a component of MET complex, and loss of CIB2 completely abolishes MET currents in auditory hair cells, causing profound congenital hearing loss. However, loss of CIB2 does not affect MET currents in vestibular hair cells (VHCs) as well as general balance function. Here, we show that CIB2 and CIB3 act redundantly to regulate MET in VHCs, as MET currents are completely abolished in the VHCs of Cib2/Cib3 double knock-out mice of either sex. Furthermore, we show that Cib2 and Cib3 transcripts have complementary expression patterns in the vestibular maculae, and that they play different roles in stereocilia maintenance in VHCs. Cib2 transcripts are highly expressed in the striolar region, and knock-out of Cib2 affects stereocilia maintenance in striolar VHCs. In contrast, Cib3 transcripts are highly expressed in the extrastriolar region, and knock-out of Cib3 mainly affects stereocilia maintenance in extrastriolar VHCs. Simultaneous knock-out of Cib2 and Cib3 affects stereocilia maintenance in all VHCs and leads to severe balance deficits. Taken together, our present work reveals that CIB2 and CIB3 are important for stereocilia maintenance as well as MET in mouse VHCs.SIGNIFICANCE STATEMENT Calcium and integrin-binding protein 2 (CIB2) is an important component of mechanoelectrical transduction (MET) complex, and loss of CIB2 completely abolishes MET in auditory hair cells. However, MET is unaffected in Cib2 knock-out vestibular hair cells (VHCs). In the present work, we show that CIB3 could compensate for the loss of CIB2 in VHCs, and Cib2/Cib3 double knock-out completely abolishes MET in VHCs. Interestingly, CIB2 and CIB3 could also regulate VHC stereocilia maintenance in a nonredundant way. Cib2 and Cib3 transcripts are highly expressed in the striolar and extrastriolar regions, respectively. Stereocilia maintenance and balance function are differently affected in Cib2 or Cib3 knock-out mice. In conclusion, our data suggest that CIB2 and CIB3 are important for stereocilia maintenance and MET in mouse VHCs.

Comparison study of Beninese and Chinese herbal medicines in treating COVID-19.

ETHNOPHARMACOLOGICAL RELEVANCE: The worldwide use of natural remedies is an alternative therapeutic solution to strengthen immunity, fight, and prevent this disease. The rapid spread of the coronavirus disease worldwide has promoted the search for therapeutic solutions following different approaches. China and Benin have seen the use of natural remedies such as Chinese herbal medicine and local endemic plants as alternative solutions in treating COVID-19. AIM OF THE STUDY: The present study was designed to identify the prevalence of medicinal plant use in four municipalities of Benin most affected by COVID-19 and compare them with traditional Chinese medicine and finally verify the efficacy of the main components of the six plants most frequently used, via in vitro experiments. MATERIALS AND METHODS: This study targeting market herbalists and traditional healers was conducted in the form of an ethnomedicinal survey in four representative communities (Cotonou, Abomey-Calavi, Zè, and Ouidah) of southern Benin. The chemical compositions of the six most commonly used herbs were investigated using network pharmacology. Network-based global prediction of disease genes and drug, target, function, and pathway enrichment analysis of the top six herbs was conducted using databases including IPA and visualised using Cytoscape software. The natural botanical drugs involved three medicines and three formulas used in the treatment of COVID-19 in China from the published literature were compared with the top six botanical drugs used in Benin to identify similarities between them and guide the clinical medication in both countries. Finally, the efficacy of the common ingredients in six plants was verified by measuring the viability of BEAS-2B cells and the release of inflammatory factors after administration of different ingredients. Binding abilities of six components to COVID-19 related targets were verified by molecular docking. RESULTS: According to the medication survey investigation, the six most used herbs were Citrus aurantiifolia (13.18%), Momordica charantia (7.75%), Ocimum gratissimum (7.36%), Crateva adansonii (6.59%), Azadirachta indica (5.81%), and Zanthoxylum zanthoxyloides (5.42%). The most represented botanical families were Rutaceae, Lamiaceae, Cucurbitaceae, Meliaceae, and Capparaceae. The network pharmacology of these six herbal plants showed that the flavonoids quercetin, kaempferol, and ß-sitosterol were the main active ingredients of the Benin herbal medicine. Chinese and Beninese herbal medicine are similar in that they have the same targets and pathways in inflammation and oxidative stress relief. Mild COVID-19-related targets come from C. aurantiifolia and M. charantia, and severe COVID-19-related targets come from A. indica A. Juss. Cell viability and enzyme-linked immunosorbent assay results confirmed that six major compounds could protect BEAS-2B cells against injury by inhibiting the expression of inflammatory factors, among which quercetin and isoimperatorin were more effective. Docking verified that the six compounds have good binding potential with COVID-19 related targets. CONCLUSIONS: These results suggest that Benin herbal medicine and Chinese herbal medicine overlap in compounds, targets, and pathways to a certain extent. Among the commonly used plants in Benin, C. aurantiifolia and M. charantia may have a good curative effect on the treatment of mild COVID-19, while for severe COVID-19, A. indica can be added on this basis.

Understanding the mechanism of twenty-five ingredient decoction for setting a fracture in the treatment of fractures based on network pharmacology.

To study the mechanism of 25 ingredient decoction for setting a fracture (TDSF) in fracture treatment using network pharmacology. The TCMSP, BATMAN-TCM, HERB, and Uniprot protein databases were used to identify the active ingredients and targets of TDSF. Fracture-related targets were collected from the gene cards and the online mendelian inheritance in man databases. The acquisition of common genes of active compounds of TDSF and disease fractures was carried out using the Venny software. The Cytoscape 3.7.1 software and String database were used to construct a network diagram of drug-active ingredient-target-disease and the main core targets were obtained by protein interaction analysis. The Metascape platform was used to perform gene oncology functional and Kyoto encyclopedia of genes and genomes pathway enrichment analyses for common drug-disease targets. A total of 311 active ingredients and 348 targets were associated with TDSF, with 5197 targets related to fractures and 224 common targets between the 2 keywords. Key targets included serine/threonine protein kinase 1, tumor necrosis factor, interleukin 6, tumor protein 53, and vascular endothelial growth factor. Important roles of the following pathway were identified: cancer, lipid, and atherosclerosis; AGE-RAGE signaling pathway in diabetic complications; chemical carcinogenesis - receptor activation; PI3K -Akt signaling pathway; platinum drug resistance; cAMP signaling pathway; transcriptional mis regulation in cancer; serotonergic synapse; and malaria. TDSF mainly treats fractures by acting on multiple targets, such as serine/threonine protein kinase 1, tumor necrosis factor, interleukin 6, tumor protein 53, and vascular endothelial growth factor, and regulating the PI3K/AKT and cAMP signaling pathways.

The Efficacy of Scouting Technology in Pedicle Screw Placement in the Patients With Degenerative Scoliosis.

Objective: To investigate the curative effect of ball tip technology in pedicle screw placement in the patients with degenerative scoliosis (DS), as compared to traditional freehand technique. Methods: A total of 90 patients with degenerative scoliosis who were admitted to Affiliated Hospital of Hebei Engineering University from October 2019 to October 2021 were selected as the objects in this prospective study. They were randomly divided into an experimental group and a control group with 45 cases in each. The clinical indications, the accuracy of pedicle screw placement, the occurrence of surgical complications, the measurement of spinal and pelvic parameters, the recovery of spinal function and pain degree were recorded and compared within the two groups. Results: After treatment, the operation time, intraoperative blood loss, total number of screws, and time of screwing were compared between the two groups, and the difference was not significant (P > .05). However, the bedding time and the hospital stay were shorter in the experimental group than the control group with difference (P < .05). There was no significant difference in clinical standards and poor implantation in the Gertzbein-Robbins A-E classification between the two groups (P > .05). While the number of perfect placement of screws in the experimental group was higher (P < .05). Before treatment, the Cobbs angle and pelvic incidence-lumbar lordosis (PI-LL) levels of the two groups were comparable (P > .05); after treatment, the Cobbs angle and PI-LL levels of the two groups were lower than those before treatment, and the difference was significant (P < .05). There was no significant difference in Cobbs angle and PI-LL levels between groups (P > .05). Before treatment, the JOA and DOI scores of the two groups were comparable (P > .05); after treatment, the JOA and DOI scores of the two groups were improved (P < .05); the improvement of JOA and DOI scores of the experimental group were better than those in the control group (P < .05). Before treatment, there was no significant difference in the pain degree between the two groups (P > .05); after treatment, the pain of the two groups was improved compared with that before treatment, and the pain degree of the experimental group was lower than that of the control group (P < .05). The incidence of postoperative complications in the experimental group was lower than that in the control group, but there was no significant difference in the total incidence of postoperative complications between the two groups (P > .05). Conclusion: The scouting technique-assisted screw placement can effectively improve the spinal function of patients with degenerative scoliosis, with obvious curative effect and high safety.

Effect of Highly Active Antiretroviral Therapy on Fundus Images and Retinal Microvessel Diameter in HIV/AIDS Patients.

Introduction: We aimed to investigate whether there were changes in fundus picture and retinal microvascularity of patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) who were treated with highly active antiretroviral therapy (HAART). Methods: From July 2015 to November 2016, 130 HIV/AIDS patients were collected by the Yunnan Institute of Traditional Chinese Medicine, including 63 treatment-naïve patients and 67 that received HAART for 12 months. Fundus picture lesions, retinal microvascular diameters, CD4+ T lymphocyte count and HIV-1 plasma viral loads were compared between the two groups. The recruited patients were mainly young and middle-aged, with more males than females. There were no significant differences in smoking history, comorbidities and opportunistic infections between the two groups. Results: According to the analysis results from SPSS 20.0 software, the number of CD4+ T lymphocytes in the treated patients (563.34±2.56 cells/µL) increased significantly (P=0.009) as compared with untreated patients (451.37±2.10 cells/µL), and the HIV-1 plasma viral load reduced considerably (4794 vs 0 copy/mL, P=0.000). No significant differences were observed from the fundus picture of patients after effective HAART therapy, including the retinal artery diameter, venous diameter and arteriovenous diameter ratio.

Network pharmacology and computer-aided drug design to explored potential targets of Lianhua Qingwen and Qingfei Paidu decoction for COVID-19.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2, has spread globally, affecting people's lives worldwide and hindering global development. Traditional Chinese Medicine (TCM) plays a unique role in preventing and treating COVID-19. Representative prescriptions for the COVID-19 treatment, Lianhua Qingwen (LHQW) and Qingfei Paidu Decoction (QFPD), effectively alleviate COVID-19 symptoms, delaying its progression and preventing its occurrence. Despite the extensive similarity in their therapeutic effects, the mechanisms and advantages of LHQW and QFPD in in treating mild-to-moderate COVID-19 remain elusive. To characterize the mechanisms of LHQW and QFPD in treating COVID-19, we used integrated network pharmacology and system biology to compare the LHQW and QFPD components, active compounds and their targets in Homo sapiens. LHQW and QFPD comprise 196 and 310 active compounds, some of which have identical targets. These targets are enriched in pathways associated with inflammation, immunity, apoptosis, oxidative stress, etc. However, the two TCM formulas also have specific active compounds and targets. In LHQW, arctiin, corymbosin, and aloe-emodin target neurological disease-related genes (GRM1 and GRM5), whereas in QFPD, isofucosterol, baicalein, nobiletin, oroxylin A, epiberberine, and piperlonguminine target immunity- and inflammation-related genes (mTOR and PLA2G4A). Our findings indicate that LHQW may be suitable for treating mild-to-moderate COVID-19 with nervous system symptoms. Moreover, QFPD may effectively regulate oxidative stress damage and inflammatory symptoms induced by SARS-CoV-2. These findings may provide references for the clinical application of LHQW and QFPD.

The Protective Effect of Artesunate on LPS-Induced Acute Respiratory Distress Syndrome through Inhibiting NLRP3 Inflammasome Signaling.

Background: Artesunate (AS) is a derivative of artemisinin that can exert anti-inflammatory effects. This study aims to explore the effect of AS on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS). Methods: The newborn mice were used for experimental ARDS model establishment by intraperitoneal injection of LPS (10 mg/kg) into mice with or without AS (20 mg/kg) pretreatment. After that, the pathological morphology of mouse lung tissue was observed by H&E staining. The content of inflammatory factors in serum was measured by ELISA and mRNA expression and lung tissue was determined by qRT-PCR. The expression of NLRP3 inflammasome and related proteins in lung tissue was confirmed by immunohistochemistry and Western blot. Results: AS treatment effectively alleviated the LPS-induced lung injury and pulmonary edema, and reduced the expression of IL-1ß, IL-18, IL-6, IL-8, MCP-1, and TNF-α in serum and lung tissues of experimental ARDS mice. In addition, AS treatment reduced the expression of NLRP3, ASC, and caspase-1 in lung tissues of experimental ARDS mice. Conclusion: AS alleviated LPS-induced lung injury in ARDS mice by inhibiting the activation of NLRP3 inflammasome.

CuS NP-based nanocomposite with photothermal and augmented-photodynamic activity for magnetic resonance imaging-guided tumor synergistic therapy.

Although many treatments have been developed for oncotherapy, the lack of effective imaging guidance in the therapeutic process is still an urgent problem to be solved. In this study, magnetic resonance contrast agent (Gd) chelated on CuS nanoparticles and glucose oxidase (GOx) were coloaded into mesoporous silica nanoparticles (MSNs) to form GOx-Gd-CuS@MSNs, in which the Gd provided magnetic resonance imaging (MRI) for therapeutic process monitor while GOx could catalyze the generation of H2O2 to enhance the photodynamic therapy (PDT). The in vitro results show that under near-infrared (NIR) laser irradiation (2 W·cm-2, 5 min), temperature rapidly increased by approximately 30 °C for the accumulation of heat. At the same time, GOx on GOx-Gd-CuS@MSNs effectively consumed glucose to produce a large amount of H2O2, which was used to augment PDT through producing highly toxic hydroxyl radicals (·OH) and singlet oxygen (1O2). The photothermal and augmented-photodynamic could induce apoptosis and death of tumor cells. More importantly, the study found that GOx-Gd-CuS@MSNs had MRI performance, which provided imaging guidance during the treatment process, and it can monitor the diffusion of water molecules in the tumor tissue during the treatment and microcirculation perfusion of capillary network. These results indicate that the nanomaterial produced significant synergistic therapeutic effects through photothermal and photodynamic forces, meanwhile showed excellent spatial resolution and deep tissue penetration in imaging.