Chattonella marina blooms in a trophic gradient system: Interaction with environmental drivers.

For coastal eutrophication, lots of studies focused on the influence from environmental factors, especially nitrogen and phosphorus, on algae blooms. The interaction between algae and environmental factors has been often ignored. Using Chattonella marina, a dominant species in marine algal blooms, we established a trophic gradient system that simulated C. marina blooms at three trophic levels: eutrophic, mesotrophic, and oligotrophic, and examined the life history patterns of C. marina and the interactions with environmental factors. Increased trophic levels influenced the growth potential of C. marina, while its unique cyst reproduction allowed it to thrive in nutrient-limited environments. Adequate nutrients caused changes in dissolved oxygen (DO) and pH led by C. marina, with the carbonate system playing a crucial role in regulating pH under nutrient-limited conditions. Limiting the growth of C. marina in areas with low nutrient by manipulating reactive silicate (SiO32-) availability may prove effective. Nitrate (NO3-) was the preferred nutrient for C. marina when its concentration exceeded that of ammonium (NH4+). Phosphorus played a crucial role in the growth and proliferation of C. marina, especially when other nutrients were scarce. The findings of this study may provide valuable insights into the effective management and prevention of algae blooms.

[Construction and application of virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients].

PURPOSE: To construct a virtual simulation teaching platform for in-hospital emergency nursing of craniofacial injury patients by virtual simulation technology, and to evaluate its application effect. METHODS: Through virtual reality, animation, human-computer interaction and other technologies, a 3D experiment scene based on high simulation virtual human was constructed to reproduce the virtual rescue scenes of craniofacial injury patients, such as emergency reception, first-aid cooperation, massive hemorrhage rescue cooperation, and tracheotomy cooperation in emergency rescue of sudden airway obstruction, and exercise modules and assessment modules were set. In the virtual simulation platform, the students used the holistic nursing theory and the PDCA cycle method to observe, evaluate and care for craniofacial injury patients. Preliminary evaluation of the platform was carried out in the training of 62 dental nurses. RESULTS: The virtual simulation platform could improve students' comprehensive first-aid ability for craniofacial injury patients. The item with the highest satisfaction rate for the virtual simulation platform was the consistency between the content of the virtual simulation platform and the theoretical course (the satisfaction rate was 91.9%), and the lowest satisfaction rate was the convenience of the virtual simulation platform operation and the page setting (the satisfaction rate was 80.6%). The evaluation module of the virtual simulation platform showed that the highest score of the comprehensive evaluation was 97, the lowest score was 56, and the average score was 80.2. CONCLUSIONS: The virtual simulation teaching platform for in-hospital first aid of craniofacial injury patients can create an immersive learning mode, provide an intuitive rescue experience to the students, and improve their comprehensive first-aid ability.

Soil legacy nutrients contribute to the decreasing stoichiometric ratio of N and P loading from the Mississippi River Basin.

Human-induced nitrogen-phosphorus (N, P) imbalance in terrestrial ecosystems can lead to disproportionate N and P loading to aquatic ecosystems, subsequently shifting the elemental ratio in estuaries and coastal oceans and impacting both the structure and functioning of aquatic ecosystems. The N:P ratio of nutrient loading to the Gulf of Mexico from the Mississippi River Basin increased before the late 1980s driven by the enhanced usage of N fertilizer over P fertilizer, whereafter the N:P loading ratio started to decrease although the N:P ratio of fertilizer application did not exhibit a similar trend. Here, we hypothesize that different release rates of soil legacy nutrients might contribute to the decreasing N:P loading ratio. Our study used a data-model integration framework to evaluate N and P dynamics and the potential for long-term accumulation or release of internal soil nutrient legacy stores to alter the ratio of N and P transported down the rivers. We show that the longer residence time of P in terrestrial ecosystems results in a much slower release of P to coastal oceans than N. If contemporary nutrient sources were reduced or suspended, P loading sustained by soil legacy P would decrease much slower than that of N, causing a decrease in the N and P loading ratio. The longer residence time of P in terrestrial ecosystems and the increasingly important role of soil legacy nutrients as a loading source may explain the decreasing N:P loading ratio in the Mississippi River Basin. Our study underscores a promising prospect for N loading control and the urgency to integrate soil P legacy into sustainable nutrient management strategies for aquatic ecosystem health and water security.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Cancer-associated thrombosis by cancer sites and inherited factors in a prospective population-based cohort.

Cancer-associated thrombosis (CAT) is common and associated with mortality. We estimated CAT rate by cancer sites and inherited factors among cancer patients from the UK Biobank (N =70,406). The 12-month CAT rate after cancer diagnosis was 2.37% overall but varied considerably among cancer sites. Among the 10 cancer sites classified as 'high-risk' of CAT by the National Comprehensive Cancer Network guidelines, 6 had CAT rate <5%. In contrast, 5 cancer sites classified as 'average-risk' by the guidelines had CAT rate >5%. For inherited risk factors, both known mutation carriers in two genes (F5/F2) and polygenic score for venous thromboembolism (VTE) (PGSVTE) were independently associated with increased CAT risk. While F5/F2 identified 6% patients with high genetic-risk for CAT, adding PGSVTE identified 13 % patients at equivalent/higher genetic-risk to CAT than that of F5/F2 mutations. Findings from this large prospective study, if confirmed, provide critical data to update guidelines for CAT risk assessment.

Chinese Ecliptae herba (Eclipta prostrata (L.) L.) extract and its component wedelolactone enhances osteoblastogenesis of bone marrow mesenchymal stem cells via targeting METTL3-mediated m6A RNA methylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese Ecliptae herba (Eclipta prostrata (L.) L.) is an ethnomedicinal herb, which is used mainly to nourish kidney and thus strengthen bones according to traditional Chinese medicine theory. Pharmacological studies have supported the ethnomedicine use, showing that Ecliptae herba extract has an anti-osteoporotic effect in vivo and promoted osteoblast proliferation and activity in vitro. However, the molecular mechanism of Ecliptae herba on osteoblast differentiation from bone marrow mesenchymal stem cells (BMSC), the progenitors of osteoblasts, is still unclear. AIM OF THE STUDY: N6-methyladenosine (m6A) mRNA epigenetic modification may play a key role in promoting osteoblastic differentiation, and thus treating osteoporosis. This study sought to assess the mechanism through which Eclipate herba and its component wedelolactone influence m6A modification during the process of osteoblastogenesis from BMSC. MATERIAL AND METHODS: The alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were applied to determine osteoblastogenesis from BMSC. Western blot and quantitative real-time PCR were performed. RNA sequencing analysis was used to determine the characteristics of m6A methylation. Stable knocking down of METTL3 using lentiviral-based shRNA was performed. RESULTS: Upon 9 d treatment of BMSC with ethyl acetate extract of Ecliptae herba (MHL), ALP activity and ossification level increased in comparison with osteogenic medium (OS)-treated control. The expression of methyltransferase METTL3 and METTL14 was significantly increased, but WTAP expression had no change in response to MHL treatment. Knocking down of METTL3 resulted in a decrease in MHL-induced ALP activity, ossification level as well as mRNA expression of Osterix and Osteocalcin, two bone formation-related markers. The level of m6A increased when BMSC was treated with MHL for 9 d. RNA sequencing analysis indicated that MHL treatment altered mRNA m6A modification of genes associated with osteoblastogenesis. By kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, HIF-1α, PI3K/Akt, and Hippo signaling pathways were enriched and associated with m6A modification. The expression of m6A-modified genes including HIF-1α, VEGF-A, and RASSF1, was upregulated by MHL, but the upregulation was reversed after METTL3 knockdown. Additionally, the enhanced expression of METTL3 was also observed after treatment with wedelolactone, a component from MHL. CONCLUSIONS: These results suggested a previously uncharacterized mechanism of MHL and wedelolactone on osteoblastogenesis, by which METTL3-mediated m6A methylation is involved and thus contributes to the enhancement of osteoblastogenesis.

Acupuncture ameliorates Mobile Phone Addiction with sleep disorders and restores salivary metabolites rhythm.

Objectives: Mobile Phone Addiction (MPA) is a novel behavioral addiction resulting in circadian rhythm disorders that severely affect mental and physical health. The purpose of this study is to detect rhythmic salivary metabolites in MPA with sleep disorder (MPASD) subjects and investigate the effects of acupuncture. Methods: Six MPASD patients and six healthy controls among the volunteers were enrolled by MPA Tendency Scale (MPATS) and Pittsburgh Sleep Quality Index (PSQI), then the salivary samples of MPASD and healthy controls were collected every 4-h for three consecutive days. Acupuncture was administered for 7 days to MPASD subjects, then saliva samples were collected again. Salivary metabolomes were analyzed with the method of LC-MS. Result: According to our investigation, 70 (57.85%) MPA patients and 56 (46.28%) MPASD patients were identified among 121 volunteers. The symptoms of the 6 MPASD subjects were significantly alleviated after acupuncture intervention. The number of rhythmic saliva metabolites dropped sharply in MPASD subjects and restored after acupuncture. Representative rhythmic saliva metabolites including melatonin, 2'-deoxyuridine, thymidine, thymidine 3',5'-cyclic monophosphate lost rhythm and restored after acupuncture, which may attribute to promising MPASD treatment and diagnosis biomarkers. The rhythmic saliva metabolites of healthy controls were mainly enriched in neuroactive ligand-receptor interaction, whereas polyketide sugar unit biosynthesis was mainly enriched in MPASD patients. Conclusion: This study revealed circadian rhythm characteristics of salivary metabolites in MPASD and that acupuncture could ameliorate MPASD by restoring part of the dysrhythmia salivary metabolites.

Proteomic Identification of Plasma Components in Tachypleus tridentatus and Their Effects on the Longitudinal Bone Growth Rate in Rats.

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10-30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10-30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10-30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent.

Integrating metabolomics and lipidomics revealed a decrease in plasma fatty acids but an increase in triglycerides in children with drug-refractory epilepsy.

OBJECTIVE: The drug-refractory epilepsy (DRE) in children is commonly observed but the underlying mechanisms remain elusive. We examined whether fatty acids (FAs) and lipids are potentially associated with the pharmacoresistance to valproic acid (VPA) therapy. METHODS: This single-center, retrospective cohort study was conducted using data from pediatric patients collected between May 2019 and December 2019 at the Children's Hospital of Nanjing Medical University. Ninety plasma samples from 53 responders with VPA monotherapy (RE group) and 37 non-responders with VPA polytherapy (NR group) were collected. Non-targeted metabolomics and lipidomics analysis for those plasma samples were performed to compare the potential differences of small metabolites and lipids between the two groups. Plasma metabolites and lipids passing the threshold of variable importance in projection value >1, fold change >1.2 or <0.8, and p-value <0.05 were regarded as statistically different substances. RESULTS: A total of 204 small metabolites and 433 lipids comprising 16 different lipid subclasses were identified. The well-established partial least squares-discriminant analysis (PLS-DA) revealed a good separation of the RE from the NR group. The FAs and glycerophospholipids status were significantly decreased in the NR group, but their triglycerides (TG) levels were significantly increased. The trend of TG levels in routine laboratory tests was in line with the lipidomics analysis. Meanwhile, cases from the NR group were characterized by a decreased level of citric acid and L-thyroxine, but with an increased level of glucose and 2-oxoglutarate. The top two enriched metabolic pathways involved in the DRE condition were biosynthesis of unsaturated FAs and linoleic acid metabolism. SIGNIFICANCE: The results of this study suggested an association between metabolism of FAs and the medically intractable epilepsy. Such novel findings might propose a potential mechanism linked to the energy metabolism. Ketogenic acid and FAs supplementation might therefore be high-priority strategies for DRE management.

Maternal Betaine Supplementation Mitigates Maternal High Fat Diet-Induced NAFLD in Offspring Mice through Gut Microbiota.

Maternal betaine supplementation has been proven to alleviate non-alcoholic fatty liver disease (NAFLD) in offspring caused by maternal high-fat diet (MHFD). The gut-liver axis plays an important role in NAFLD pathogenesis. However, whether maternal betaine supplementation can alleviate NAFLD in offspring by the gut-liver axis is unknown. C57BL/6J mice were fed with high-fat diet for 4 weeks before mating, and supplemented with 1% betaine during pregnancy and lactation. After weaning, offspring mice were fed with standard diet to 10 weeks. Maternal betaine supplementation reduced hepatic triglyceride content and alleviated hepatic steatosis in offspring mice exposed to MHFD. Furthermore, the mRNA expression of PPARα, CPT1α and FATP2 was increased and TNFα was reduced by maternal betaine supplementation. Maternal betaine intake decreased the relative abundances of Proteobateria, Desulfovibrio and Ruminococcus, but increased the relative abundances of Bacteroides and Parabacteroides. Moreover, maternal betaine intake increased the concentrations of short-chain fatty acids (SCFAs), including acetic acid, butyric acid and valeric acid, in the feces. Gut microbiota and SCFAs were significantly correlated with hepatic triglyceride content and expression of the above genes. Maternal betaine intake had no effect on other gut microbiota-related metabolites (bile acid and trimethylamine-n-oxide). Altogether, maternal betaine supplementation ameliorated MHFD-induced NAFLD possibly through regulating gut microbiota and SCFAs in offspring mice.

Optimization of a compact on-site stormwater runoff treatment system: Process performance and reactor design.

Stormwater runoff has become a major anthropogenic urban pollution source that threatens water quality. In this study, coagulation-sedimentation, and ammonium ion exchange and regeneration (AIR) modules were coupled as a CAIR system to efficiently treat stormwater runoff. In the coagulation module, 99.3%, 91.7%, and 97.0% of turbidity, total phosphorus, and chemical oxygen demand could be removed at an optimized poly-aluminum ferric chloride dosage of 30 mg/L, and the continuous experiment confirmed that the full load mode was more suitable for its rapid start-up. In the AIR module, dynamic ammonium removal indicated that the breakthrough time decreased with the rising initial concentration and superficial velocity. The Modified Dose Response (MDR) model described the ammonium exchange behavior better than the Thomas and the Bohart-Adams models. Then, a design flow of the ion exchange reactor was constructed by correlating constants in the MDR model with engineering parameters, and the ion exchange reactor was designed for continuous operation of the CAIR system. The average concentrations of chemical oxygen demand, total phosphorus, ammonium nitrogen, and total nitrogen in the effluent of the CAIR system were 7.22 ± 2.26, 0.17 ± 0.05, 1.49 ± 0.01, and 1.62 ± 0.02 mg/L, respectively. The almost unchanged exchange capacity and physicochemical properties after the multicycle operation confirmed the durability of zeolite for ion exchange. Techno-economic analysis suggested that the CAIR system is practically promising for stormwater management with efficient pollutants removal, small footprint, and acceptable operating cost.

Yunvjian Improves Glucose and Insulin Function in Diabetic Rats by Regulating Gastric Emptying Function.

Background: Diet acts on the human body through digestion in the stomach and absorption in the intestines. Thus, the emptying of the stomach should be the focus of the research mechanism of the combined medicine and food treatment of diabetes. The emptying function of the stomach and the secretion of related hormones may be the key points of traditional Chinese medicine. In the clinic, Yunvjian is a famous traditional Chinese formula for preventing and curing diabetes. However, the pharmacological action and mechanism of Yunvjian are also need to be probe. Objective: To assess the effect of Yunvjian on glucose, insulin level and gastric emptying function and related hormones on high-fat diet combined with STZ-induced diabetic rats. Methods: High-fat diet combined with STZ was used to construct type 2 diabetes mellitus (T2DM) rats model and received a 4-week Yunvjian administration. The animals were divided into 6 groups, respectively, as the Control group, the DM group, the DM + Acarbose group, the DM + YNH group, and the DM + YNL group. Radionuclide single-photon emission computed tomography (SPECT) technology was used to observe the gastric emptying rate and half-empty time; blood was took to test fasting insulin, and then the insulin resistance index (HOMA-IR) was calculated; HE staining was performed to detect islets and gastric antrum, immunohistochemical staining was performed to detect the number and morphology of pancreatic ß cells and gastric antrum Cajal cells, and the average optical density was calculated; the expression of ghrelin hormone in gastric antrum and serum was detected by ELISA and immunofluorescence; the expression of GHRS mRNA in gastric antrum was detected by RT-PCR method. Results: Yunvjian could significantly improve the glucose level and insulin function of rats. Compared with the DM group, Yunvjian was beneficial to low fasting blood glucose (FBG) (P < 0.01), increased glucose tolerance, and improved islet function at the same time (P < 0.05). At the same time, compared with the DM group (25.02 ± 0.05, 44 ± 12.33), the emptying rate of the DM + YNH group was significantly faster (64.98 ± 0.12), and the half row time was shortened (26 ± 8.29, P < 0.05). The gastric ghrelin levels in each group of Yunvjian increased with different degrees compared with the DM group (616.2 ± 26.23), especially in the DM + YNH group (863.51 ± 23.76, P < 0.01). Correspondingly, the expression of gastric GHSR mRNA in the DM + YNH and DM + YNL groups increased significantly compared with the DM group (P < 0.01). Conclusions: Yunvjian can effectively control glucose and improve islet function, which may be closely related to its influence on gastric emptying function and related hormone secretion regulation.

[Effect of transurethral thuliumlaser vapoenucleation of the prostate with low-power conventional pulse mode on sexual function in patients with benign prostatic hyperplasia].

OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.

[Analysis of absorbed constituents and network pharmacology research of Xiaoer Fupi Granules].

Xiaoer Fupi Granules, a refined version of the classical prescription Shenling Baizhu Powder, has the effect of invigora-ting spleen, replenishing Qi, harmonizing stomach and resolving accumulation and is commonly used to treat Qi deficiency in spleen and stomach, disordered transportation and transformation, and indigestion of children. However, its medicinal constituents and mechanism remain unclear. We studied the main active constituents and action mechanism of Xiaoer Fupi Granules by integrating network pharmacology and prototype constituent analysis in vivo. This study will help to increase the reliability of database analysis results and lay a foundation for precise medication and mining of quality control markers. On the basis of Bioinformatics Analysis Tool for Molecular mechanism of Traditional Chinese Medicine(BATMAN-TCM), the "key chemical constituents-target" network was constructed. Ultra-performance liquid chromatography coupled with linear ion trap-orbitrap mass spectrometry(UPLC-LTQ-Orbitrap-MS) was employed to analyze the absorbed constituents in rat urine and plasma, so as to validate the network. Further, we used BATMAN-TCM to construct the "absorbed constituents-target-pathway" network and explore the functioning mechanism of Xiaoer Fupi Granules. A total of 86 chemical constituents of Xiaoer Fupi Granules were predicted via BATMAN-TCM, among which only 18.6% were detected in rat plasma and urine. Accor-ding to the "absorbed constituents-target-pathway" network, 8 chemical constituents such as stearic acid and caprylic acid capable of regulating gastric acid and insulin secretion may be the critical constituents of Xiaoer Fupi Granules in invigorating spleen and harmonizing stomach. This study identified the critical active constituents and predicted the action mechanism of Xiaoer Fupi Granules, providing the reference for the research on the material basis of Xiaoer Fupi Granules.

Diterpene promptly executes a non-canonical autophagic cell death in doxorubicin-resistant lung cancer.

16-hydroxycleroda-3,13-dien-15,16-olide (HCD) has antitumor activity reported in numerous types of cancers. However, the efficacy of HCD treatment in non-small-cell lung cancer (NSCLC) cells and doxorubicin-resistant (Dox-R)-NSCLC cells remains to be unraveled. The underlying anti-cancer mechanism of HCD on Dox-R and Dox-sensitive (Dox-S) of A549 cells was also investigated. Cytotoxicity of HCD against two cell lines (Dox-S and Dox-R) were determined via MTT assay, flow cytometry, and Western blot. A further examination of its anti-cancer efficacy was performed in A549-bearing xenograft mice via orthotopic intratrachea (IT) inoculation, which showed that HCD could arrest both Dox-S and Dox-R cells at G2/M phase without altering the sub-G1 cycle along with increasing of cleaved-PARP. HCD downregulated the mTOR/Akt/PI3K-p85 and PI3K-ClassIII/Beclin-1 signals and upregulated p62/LC3-I/II expressions to further confirm that the cell autophagy of NSCLC cells after being HCD-induced. Morphological observations of mouse lung sections illustrated that fewer cancer cells accumulated close to the trachea while less neoplastic activities were found in HCD orthotopic treated mice without liver, kidney, and spleen toxicity. Lastly, Dox, HCD, and target therapy medicines of EGFR and ALK were nicely docked with EGFR, ALK, and mTOR. Conclusively, HCD was demonstrated the chemotherapeutic potential regardless of Dox-R and Dox-S cells, suggesting natural autophagic inducer HCD provides a promising lead compound for new drug discovery and development of lung cancer therapies.

Ji-Chuan decoction ameliorates slow transit constipation via regulation of intestinal glial cell apoptosis.

BACKGROUND: Slow transit constipation (STC) is a common intestinal disease with increasing incidence. STC results from various factors, such as the enteric nervous system and metabolic changes. As a classical formula of traditional Chinese medicine, Ji-Chuan decoction (JCD) has been extensively and effectively used in STC treatment, yet its pharmacological mechanism remains unclear. AIM: To explore the integrated regulatory pattern of JCD against STC through hyphenated techniques from metabolism, network pharmacology and molecular methods. METHODS: STC model mice were generated by intragastric administration of compound diphenoxylate (10 mg/kg/d) for 14 d. The STC mice in the low dose of JCD (3.04 g/kg), middle dose of JCD (6.08 g/kg) and high dose of JCD (12.16 g/kg) groups were orally administered JCD solution once a day for 2 wk. The acetylcholine (ACH) level was examined by enzyme-linked immunosorbent assay. The pathological features of colon tissue were observed by hematoxylin and eosin staining. The differentially expressed metabolites and metabolic pathways were tested by nontargeted metabolomics. The main targets and core ingredients of JCD were identified by network pharmacology, and the expression of AKT was confirmed by immunohistochemistry. Finally, the pathways involved in JCD treatment were predicted using a combination of differentially expressed metabolites and targets, and intestinal glial cell apoptosis was demonstrated by immunofluorescence. RESULTS: JCD significantly promoted intestinal motility, increased the levels of the excitatory neurotransmitter ACH and reduced intestinal inflammation in STC mice. Untargeted metabolomics results showed that JCD significantly restored metabolic dysfunction and significantly affected taurine and hypotaurine metabolism. Network pharmacology and molecular experiments showed that JCD regulates AKT protein expression, and the core component is quercetin. Combined analysis demonstrated that apoptosis may be an important mechanism by which JCD relieves constipation. Further experiments showed that JCD reduced enteric glial cell (EGC) apoptosis. CONCLUSION: This work demonstrated that reducing EGC apoptosis may be the critical mechanism by which JCD treats STC. These findings call for further molecular research to facilitate the clinical application of JCD.

Clinical data analysis of 22 cases with hypoparathyroidism misdiagnosed as epilepsy.

OBJECTIVE: Patients with hypoparathyroidism always present with recurrent tetany caused by hypocalcemia. These patients are usually misdiagnosed with epilepsy and incorrectly treated with anti-epileptic drugs. This research analyzed clinical data about 22 patients with hypoparathyroidism misdiagnosed as epilepsy and summarized the clinical experience for reducing misdiagnosis and incorrect therapy about hypoparathyroidism. METHOD: Totally 160 patients with hypoparathyroidism, administrated to the First Medical Center of Chinese PLA General Hospital from January 1st, 2008, to July 1st, 2021, were enrolled in this report. Clinical data about 22 patients initially misdiagnosed with epilepsy were analyzed. RESULTS: Of the 160 cases with hypoparathyroidism, 22 patients (12 males and 10 females) were misdiagnosed with epilepsy in local hospitals. The misdiagnosis rate was 13.75% and the median duration of misdiagnosis was 8.0 (2.0, 14.8) years. The clinical manifestations of the 22 patients misdiagnosed as epilepsy included tetany 81.8% (18/22), disturbance of consciousness 27.3% (6/22), limb numbness 13.6% (3/22), limb weakness 27.3% (6/22), mental and behavioral abnormality 9.1% (2/22), and memory impairment 13.6% (3/22), etc. Electroencephalogram (EEG) was performed in 9 cases, which presented as slow wave and spike-slow complex wave in 3 cases, slowing down of Î¸ and δ band background in 2 cases and normal EEG in 4 cases. Out of the 15 cases that underwent head computed tomography (CT) scan, in which 13 cases had intracranial calcification. Anti-epileptic drugs were used to treat 22 patients, of which 17 patients were treated with two kinds of drugs. With calcium and calcitriol supplement in all these 22 patients, the anti-epileptic drugs were gradually reduced and withdrawn in 17 cases. In the other 5 cases with secondary epilepsy, the type of anti-epileptic drugs was reduced to one and the clinical condition improved obviously. CONCLUSION: The clinical manifestations of hypoparathyroidism are complex and usually be misdiagnosed as primary epilepsy. Detection of serum calcium, phosphorus and parathyroid hormone is very important to avoid misdiagnosis and incorrect therapy about hypoparathyroidism.

Prediction of clinical efficacy of subcutaneous immunotherapy for Artemisia sieversiana pollen allergic rhinitis by serum metabolomics.

BACKGROUND/PURPOSE: Specific immunotherapy is the only effective etiological treatment for allergic rhinitis, but subcutaneous immunotherapy has a slow onset and poor compliance. Predicting the clinical efficacy of subcutaneous immunotherapy in advance can reduce unnecessary medical costs and resource waste. This study aimed to identify metabolites that could predict the efficacy of subcutaneous immunotherapy on seasonal allergic rhinitis by serum metabolomics. METHODS: Patients (n = 43) with Artemisia sieversiana pollen allergic rhinitis were enrolled and treated with subcutaneous immunotherapy for one year. Patients were divided into the ineffective group (n = 10) and effective group (n = 33) according to the therapeutic index. Serum samples were collected before treatment. Metabolomics was determined by liquid chromatography-mass spectrometry combined with gas chromatography-mass spectrometry and analyzed differential compounds and related metabolic pathways. RESULTS: A total of 129 differential metabolites (P < 0.05) were identified and 4 metabolic pathways, namely taurine and hypotaurine metabolism, pentose and glucuronate interconversions, pentose phosphate pathway, and alanine, aspartate, and glutamate metabolism, were involved. CONCLUSION: Some metabolites, such as hypotaurine, taurine, and l-alanine, have the potential to become predictive biomarkers for effective subcutaneous immunotherapy.

Moxibustion plus Acupuncture for the Treatment of Poststroke Shoulder Pain: A Randomized Controlled Pilot Study.

BACKGROUND: In China, 45% of stroke patients suffer from poststroke shoulder pain, which brings about many obstacles to further rehabilitation. To date, there have been a few studies evaluating the effects of acupuncture or massage in treating poststroke shoulder pain, and good effects have been shown. However, better clinical treatments are still needed. OBJECTIVE: To explore a more effective treatment for poststroke shoulder pain, the clinical effects of moxibustion plus acupuncture were assessed. METHODS: Sixty patients were randomly divided into the control and intervention groups. The control group received a standard stroke treatment protocol including acupuncture, and the intervention group was given moxibustion combined with acupuncture. The visual analogue scale (VAS), National Institutes of Health Stroke Scale (NIHSS), Fugl-Meyer motor assessment, Barthel Index, and 17-item Hamilton Rating Scale for Depression (HAMD-17) were applied, and differences were analyzed. RESULTS: After 4 weeks of treatment, compared with the control group, the intervention group demonstrated significant improvement in Fugl-Meyer motor assessment and HAMD-17 (both p < 0.01) as well as in the VAS, NIHSS, and Barthel Index (all p < 0.05). CONCLUSION: Moxibustion plus acupuncture treatment can alleviate poststroke shoulder pain, improve upper limb motor function and the ability to perform activities of daily living, and relieve patients' depression.

Clinical practice guideline for transurethral plasmakinetic resection of prostate for benign prostatic hyperplasia (2021 Edition).

Benign prostatic hyperplasia (BPH) is highly prevalent among older men, impacting on their quality of life, sexual function, and genitourinary health, and has become an important global burden of disease. Transurethral plasmakinetic resection of prostate (TUPKP) is one of the foremost surgical procedures for the treatment of BPH. It has become well established in clinical practice with good efficacy and safety. In 2018, we issued the guideline "2018 Standard Edition". However much new direct evidence has now emerged and this may change some of previous recommendations. The time is ripe to develop new evidence-based guidelines, so we formed a working group of clinical experts and methodologists. The steering group members posed 31 questions relevant to the management of TUPKP for BPH covering the following areas: questions relevant to the perioperative period (preoperative, intraoperative, and postoperative) of TUPKP in the treatment of BPH, postoperative complications and the level of surgeons' surgical skill. We searched the literature for direct evidence on the management of TUPKP for BPH, and assessed its certainty generated recommendations using the grade criteria by the European Association of Urology. Recommendations were either strong or weak, or in the form of an ungraded consensus-based statement. Finally, we issued 36 statements. Among them, 23 carried strong recommendations, and 13 carried weak recommendations for the stated procedure. They covered questions relevant to the aforementioned three areas. The preoperative period for TUPKP in the treatment of BPH included indications and contraindications for TUPKP, precautions for preoperative preparation in patients with renal impairment and urinary tract infection due to urinary retention, and preoperative prophylactic use of antibiotics. Questions relevant to the intraoperative period incorporated surgical operation techniques and prevention and management of bladder explosion. The application to different populations incorporating the efficacy and safety of TUPKP in the treatment of normal volume (< 80 ml) and large-volume (≥ 80 ml) BPH compared with transurethral urethral resection prostate, transurethral plasmakinetic enucleation of prostate and open prostatectomy; the efficacy and safety of TUPKP in high-risk populations and among people taking anticoagulant (antithrombotic) drugs. Questions relevant to the postoperative period incorporated the time and speed of flushing, the time indwelling catheters are needed, principles of postoperative therapeutic use of antibiotics, follow-up time and follow-up content. Questions related to complications incorporated types of complications and their incidence, postoperative leukocyturia, the treatment measures for the perforation and extravasation of the capsule, transurethral resection syndrome, postoperative bleeding, urinary catheter blockage, bladder spasm, overactive bladder, urinary incontinence, urethral stricture, rectal injury during surgery, postoperative erectile dysfunction and retrograde ejaculation. Final questions were related to surgeons' skills when performing TUPKP for the treatment of BPH. We hope these recommendations can help support healthcare workers caring for patients having TUPKP for the treatment of BPH.