Massage ameliorates lumbar disc herniation-related radicular pain in rats by suppressing TLR4/NLRP3 inflammasome signaling transduction.

BACKGROUND: Lumbar disc herniation (LDH) is a common spinal disease that can cause severe radicular pain. Massage, also known as Tuina in Chinese, has been indicated to exert an analgesic effect in patients with LDH. Nonetheless, the mechanism underlying this effect of massage on LDH remains unclarified. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups. A rat LDH model was established by autologous nucleus pulpous (NP) implantation, followed by treatment with or without massage. A toll-like receptor 4 (TLR4) antagonist TAK-242 was administrated to rats for blocking TLR4. Behavioral tests were conducted to examine rat mechanical and thermal sensitivities. Western blotting was employed for determining TLR4 and NLRP3 inflammasome-associated protein levels in the spinal dorsal horn (SDH). Immunofluorescence staining was implemented for estimating the microglial marker Iba-1 expression in rat SDH tissue. RESULTS: NP implantation induced mechanical allodynia and thermal hyperalgesia in rat ipsilateral hindpaws and activated TLR4/NLRP3 inflammasome signaling transduction in the ipsilateral SDH. Massage therapy or TAK-242 administration relieved NP implantation-triggered pain behaviors in rats. Massage or TAK-242 hindered microglia activation and blocked TLR4/NLRP3 inflammasome activation in ipsilateral SDH of LDH rats. CONCLUSION: Massage ameliorates LDH-related radicular pain in rats by suppressing microglia activation and TLR4/NLRP3 inflammasome signaling transduction.

Risk factors of recurrent secondary hyperparathyroidism after adequate primary surgical treatment.

Background: Secondary hyperparathyroidism (SHPT) is a common condition in patients with end-stage renal disease (ESRD) who are on dialysis. Parathyroidectomy is a treatment for patients when medical therapy has failed. Recurrence may occur and is indicated for further surgery in the era of improved quality of care for ESRD patients. Methods: We identified, 1060 patients undergoing parathyroidectomy from January, 2011 to June, 2020. After excluding patients without regular check-up at our institute, primary hyperparathyroidism, or malignancy, 504 patients were enrolled. Sixty-two patients (12.3%, 62/504) were then excluded due to persistent SHPT even after the first parathyroidectomy. We aimed to identify risk factors for recurrent SHPT after the first surgery. Results: During the study period, 20% of patients who underwent parathyroidectomy at our institute (in, 2019) was due to recurrence after a previous parathyroidectomy. There were 442 patients eligible for analysis of recurrence after excluding patients with the persistent disease (n = 62). While 44 patients (9.95%) had recurrence, 398 patients did not. Significant risk factors for recurrent SHPT within 5 years after the first parathyroidectomy, including dialysis start time to first operation time < 3 years (p = 0.046), postoperative PTH >106.5 pg/mL (p < 0.001), and postoperative phosphorus> 5.9 mg/dL (p = 0.016), were identified by multivariate analysis. Conclusions: The starting time of dialysis to first operation time < 3 years in the patients with dialysis, postoperative PTH> 106.5 pg/mL, and postoperative phosphorus> 5.9 mg/dL tended to have a higher risk for recurrent SHPT within 5 years after primary treatment.

Improving calcium citrate food functions through spherulitic growth in reactive crystallization and a mechanism study.

Calcium citrate, a high-end daily calcium supplement, whose irregular particle morphology leads to poor powder properties, limited food functions, and paste-like suspension problems. This study prepared the spherical calcium citrate by investigating four aspects of this reactive process: side reaction, crystallization, agglomeration, and fragmentation. Consequently, a concentration-dependent spherulitic growth operating space was established, in which reactive crystallization followed the second-category spherulitic growth mechanism depending on supersaturation. Besides, the temperature, stirring rate, and residence time were critical parameters for regulating the spherulite shape and size. These spherulites exhibited improved flowability and tabletability as calcium fortification ingredient, it also had a smoother and more pleasant texture. Furthermore, the micronized spherical powder showed high suspension stability as a calcium supplement during brewing. These spherical particles did not form paste-like suspension. Finally, the success of the scale-up experiments in semi-batch mode raised the possibility of industrialization of spherical calcium citrate.

Phenethoxy Derivatives with Anti-inflammatory Activities from the Betelnut Endophytic Trichoderma asperellum G10.

Eight new phenethoxy derivatives, trichoasperellins A-H (1-8), were isolated from the endophytic fungus Trichoderma asperellum G10 isolated from the medicinal plant Areca catechu L. The structures of these compounds were elucidated from spectroscopic data, J-based configurational analysis, and Mosher's methods. Compounds 1-4 and 6-8 bear one or two multioxidized C7 moieties with the same carbon skeleton. The carbon skeletons of compounds 6-8 are new, all containing three moieties connected via two acetal carbons similar to those of disaccharide glycosides. Compound 4 inhibited nitric oxide production with an IC50 value of 48.3 µM, comparable to that of the positive control indomethacin (IC50, 42.3 µM).

Optimal Perioperative Nutrition Therapy for Patients Undergoing Pancreaticoduodenectomy: A Systematic Review with a Component Network Meta-Analysis.

Numerous strategies for perioperative nutrition therapy for patients undergoing pancreaticoduodenectomy (PD) have been proposed. This systematic review aimed to summarize the current relevant published randomized controlled trials (RCTs) evaluating different nutritional interventions via a traditional network meta-analysis (NMA) and component network meta-analysis (cNMA). EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched to identify the RCTs. The evaluated nutritional interventions comprised standard postoperative enteral nutrition by feeding tube (Postop-SEN), preoperative enteral feeding (Preop-EN), postoperative immunonutrients (Postop-IM), preoperative oral immunonutrient supplement (Preop-IM), and postoperative total parenteral nutrition (TPN). The primary outcomes were general, infectious, and noninfectious complications; postoperative pancreatic fistula (POPF); and delayed gastric emptying (DGE). The secondary outcomes were mortality and length of hospital stay (LOS). The NMA and cNMA were conducted with a frequentist approach. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Two primary outcomes, infectious complications and POPF, were positively influenced by nutritional interventions. Preop-EN plus Postop-SEN (OR 0.11; 95% CI 0.02~0.72), Preop-IM (OR 0.22; 95% CI 0.08~0.62), and Preop-IM plus Postop-IM (OR 0.11; 95% CI 0.03~0.37) were all demonstrated to be associated with a decrease in infectious complications. Postop-TPN (OR 0.37; 95% CI 0.19~0.71) and Preop-IM plus Postop-IM (OR 0.21; 95% CI 0.06~0.77) were clinically beneficial for the prevention of POPF. While enteral feeding and TPN may decrease infectious complications and POPF, respectively, Preop-IM plus Postop-IM may provide the best clinical benefit for patients undergoing PD, as this approach decreases the incidence of both the aforementioned adverse effects.

Metabolism of Proteins and Amino Acids in Critical Illness: From Physiological Alterations to Relevant Clinical Practice.

The clinical impact of nutrition therapy in critically ill patients has been known for years, and relevant guidelines regarding nutrition therapy have emphasized the importance of proteins. During critical illness, such as sepsis or the state following major surgery, major trauma, or major burn injury, patients suffer from a high degree of stress/inflammation, and during this time, metabolism deviates from homeostasis. The increased degradation of endogenous proteins in response to stress hormones is among the most important events in the acute phase of critical illness. Currently published evidence suggests that adequate protein supplementation might improve the clinical outcomes of critically ill patients. The role of sufficient protein supplementation may even surpass that of caloric supplementation. In this review, we focus on relevant physiological alterations in critical illness, the effects of critical illness on protein metabolism, nutrition therapy in clinical practice, and the function of specific amino acids.

Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement.

BACKGROUND & AIM: Several studies explored the association of vitamin B6 intake with the risk of cancers. However, it is unclear whether different doses of vitamin B6 have distinct effects on the prognosis of nasopharyngeal carcinoma (NPC) patients. This study investigated the relationship between different doses of B6 intake and the prognosis of NPC patients. METHODS: This retrospective cohort analysis included 792 newly diagnosed NPC patients with a median follow-up of 62.05 months. Restricted cubic spline and maximally selected rank statistics were performed to determine the cut-off value of vitamin B6 during treatment (VB6DT). Kaplan-Meier method and log-rank tests were performed to analyze survival outcomes. A multivariable Cox proportional hazard model was performed to determine the independent prognostic factors. RESULTS: NPC patients were divided into three groups according to the cut-off value of VB6DT: non-users (0 mg/d), VB6DT > 8.6 mg/d, and VB6DT ≤ 8.6 mg/d. Patients with VB6DT > 8.6 mg/d had significantly lower 5-year overall survival (OS) (83.5% vs. 90.8%, p = 0.006), distant metastasis-free survival (DMFS) (83.5% vs. 91.0%, p = 0.004), and progression-free survival (PFS) (73.7% vs. 81.7%, p = 0.011) and slightly but not significantly lower 5-year local recurrence-free survival (LRFS) (87.7% vs. 90.7%, p = 0.214) than the non-users. Patients with VB6DT ≤ 8.6 mg/d had slightly but not significantly better 5-year OS (93.3% vs. 90.8%, p = 0.283) than the non-users, while all other primary endpoints were similar (p > 0.50). Multivariable analyses confirmed that VB6DT > 8.6 mg/d was an independent negative prognostic factor of OS (p = 0.010), DMFS (p = 0.017), and PFS (p = 0.030) but not of LRFS (p = 0.428). CONCLUSIONS: Excessive VB6DT higher than the cut-off value is an independent negative prognostic factor for NPC patients. Additionally, low dose intake improved OS only slightly but not significantly.

Rationally designed dual-plasmonic gold nanorod@cuprous selenide hybrid heterostructures by regioselective overgrowth for in vivo photothermal tumor ablation in the second near-infrared biowindow.

NIR-II plasmonic materials offer multiple functionalities for in vivo biomedical applications, such as photothermal tumor ablation, surface-enhanced Raman scattering biosensing, photoacoustic imaging, and drug carriers. However, integration of noble metals and plasmonic semiconductors is greatly challenging because of the large lattice-mismatch. This study reports the regioselective overgrowth of Cu2-xSe on gold nanorods (GNRs) for preparation of dual-plasmonic GNR@Cu2-xSe hybrid heterostructures with tunable NIR-II plasmon resonance absorption for in vivo photothermal tumor ablation. Methods: The regioselective deposition of amorphous Se and its subsequent conversion into Cu2-xSe on the GNRs are performed by altering capping agents to produce the GNR@Cu2-xSe heterostructures of various morphologies. Their photothermal performances for NIR-II photothermal tumor ablation are evaluated both in vitro and in vivo. Results: We find that the lateral one- and two-side deposition, conformal core-shell coating and island growth of Cu2-xSe on the GNRs can be achieved using different capping agents. The Cu2-xSe domain size in these hybrids can be effectively adjusted by the SeO2 concentration, thereby tuning the NIR-II plasmon bands. A photothermal conversion efficiency up to 58-85% and superior photostability of these dual-plasmonic hybrids can be achieved under the NIR-II laser. Results also show that the photothermal conversion efficiency is dependent on the proportion of optical absorption converted into heat; however, the temperature rise is tightly related to the concentration of their constituents. The excellent NIR-II photothermal effect is further verified in the following in vitro and in vivo experiments. Conclusions: This study achieves one-side or two-side deposition, conformal core-shell coating, and island deposition of Cu2-xSe on GNRs for GNR@Cu2-xSe heterostructures with NIR-II plasmonic absorption, and further demonstrates their excellent NIR-II photothermal tumor ablation in vivo. This study provides a promising strategy for the rational design of NIR-II dual-plasmonic heterostructures and highlights their therapeutic in vivo potential.

Up-regulation of hepatic fatty acid transporters and inhibition/down-regulation of hepatic OCTN2 contribute to olanzapine-induced liver steatosis.

Olanzapine, a representative of antipsychotics, is a first-line drug for treatment of schizophrenia. However, olanzapine-induced liver steatosis limits its clinical utilization. This study is to explore the mechanism of liver steatosis induced by olanzapine based on the regulation of transporters involved in uptake and oxidation of fatty acids. Our results revealed that 12-week oral administration of olanzapine increased hepatic triglyceride(TG), caused liver steatosis. Our further studies showed that the expression of fatty acid transporter 2(FATP2) and fatty acid binding protein 1(FABP1) were up-regulated in liver of female mice after 12-week olanzapine exposure, as well as in primary mouse hepatocytes treated with olanzapine. Olanzapine treatment also reduced hepatic ß-hydroxybutyrate level (indicator of fatty acid ß-oxidation), meanwhile, the L-carnitine (L-Car) concentration in liver of olanzapine group was significantly lower than that in control group. Further study demonstrated that both mRNA and protein expression of hepatic OCTN2 (carnitine/organic cation transporter 2) were obviously down-regulated in male mice after 12-week olanzapine treatment. Also, olanzapine markedly inhibited L-Car uptake in MDCK-hOCTN2 cells (1.06 µM of IC50), HepG2 cells and primary mouse hepatocytes. Supplementation of L-Car attenuated hepatic TG rise and improved simple steatosis in olanzapine treatment mice. Taken together, up-regulation of FATP2/FABP1 and down-regulation/inhibition of hepatic OCTN2 probably contribute to olanzapine-induced liver steatosis. Supplementation of L-Car is a promising strategy to attenuate olanzapine-induced simple steatosis.

Identification of Plastrum Testudinis used in traditional medicine with DNA mini-barcodes

ABSTRACT The carapace of the tortoise Chinemys reevesii is an ingredient of "Guijia", a traditional Chinese medicine. However, C. reevesii is difficult to raise in aquaculture and is rare in the wild. Counterfeit tablets are made from carapaces of other species. In addition to C. reevesii, other species including Mauremys sinensis, Indotestudo elongate and Trachemys scripta have been used in Plastrum Testudinis as well. After processing, these carapaces are difficult to identify on the basis of morphological characteristics, which impedes law enforcement. Our study used DNA barcoding technology to identify C. reevesii and its substitutes. We extracted concentrated genomic DNA for PCR amplification. Based on the analysis of 61 full-length COI sequences, we designed four pairs of mini-barcode primers: Tu-A, Tu-B, Tu-C and Tu-D. The Tu-B primers sequenced genomic DNA with a success rate of 76.47%, and the Tu-D primers sequenced genomic DNA with a success rate of 88.24%. The identification efficiency of these two mini-barcodes was 70.59% and 64.71%, and the overall identification efficiency was approximately 76.47%. Similarly, a set of mini barcode systems was generated, which may provide an effective and low-cost method for the identification of authentic tortoise shells.

[Resource situation investigation and analysis about endangered Chinese herbal medicine Daphnes Cortex].

In order to figure out the status and distribution of the wild and cultivated resources of traditional Chinese medicine Daphnes Cortex, its suitable habitat and endangering factors were analyzed to provide the basis for its rational use, protection and cultivation.Our research group tooka resources survey in Shanxi, Gansu, Sichuan and Qinghai provinces, which include 23 counties. Investigation and sampling investigation combined with interview were carried out. The total reserve of resources was estimated through route-quadrat method in combination with the vegetation and soil-type map area method. The results indicated that there was no obvious change between the present distribution ranges of the wild Daphnes Cortex and its historical records, but the density of the population has undergone major changes. The wild reserves resources has declined seriously, even on the verge of exhaustion in some regions. According to the survey results, the current total reserve of the wild Daphnes Cortex in the four provinces was no more than 600 tons. Simultaneously, we only found the cultivated resource in a mountain at an altitude of about 2 800 m in Kang county of Gansu province, which cropping scope was about 33 000 m². The cultivated resource can't provide medicinal products at present, because their growing period is too short to have curative effect. Destructive excavation and the longer growth cycle result in a sharp decline of the wild resources reserves, even to the point of extinction. Artificial cultivation of product will become the main source of medicinal resources in the future. Therefore, we must protect its suitable habitat, formulate rational harvesting policy, strengthen the supervision of government departments, collect and establish the germplasm nursery and seed bank. On the basis, we must carry out studies into seed-selecting and breeding as well as rapid propagation and growth technology at once.

[Effect of electroacupuncture stimulation of "Guanyuan" (CV 4), bilateral "Housanli" (ST 36), etc. on anti-fatigue ability and liver mitochondrial respiratory function in ageing rats with Yang-deficiency].

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Guanyuan" (CV 4) and bilateral "Housanli" (ST 36) plus acupuncture stimulation of "Baihui" (GV 20) [an acupoint recipe for "Shuanggu Yitong" (strengthening both congenital foundation and the acquired constitution and regulating the yang-qi of the body] on the anti-fatigue ability and liver mitochondrial respiratory function in yang-deficiency ageing rats. METHODS: A total of 48 male SD rats were equally and randomly divided into normal control, model, EA and EA control groups. The aged yang-deficiency model was established by subcutaneous injection of D-galactose (125 mg/kg, once daily for 40 days) and sequential muscular injection of hydrocortisone (1.5 mg/100 g, once daily for 7 days). For rats of the normal control group, subcutaneous injection of same dose of normal saline was gi-ven. EA stimulation (2 Hz, 1 mA) of "Guanyuan" (CV 4) and bilateral "Housanli"(ST 36) and manual acupuncture stimulation of "Baihui" (GV 20) were given to rats of the EA group. For rats of the EA control group, EA of "Zhongji"(CV 3) and bilateral "Yinlinquan"(SP 9), and manual acupuncture stimulation of "Yintang" (EX-HN 3) were given. The treatment was conducted once daily, 6 time a week and continuously for 4 weeks. Rats of the normal control and model groups were grabbed and fixed in the same way. The anti-fatigue ability was evaluated by using the time of exhausted swimming task and liver mitochondrial respiratory function was detected by Clark oxygen electrode. RESULTS: In comparison with the normal control group, the exhausted swimming time was significantly shortened in the model group (P < 0.01). Compared with the model group, the exhausted swimming time was evidently prolonged in the EA group (P < 0.01) not in the EA control group (P > 0.05). As for the liver mitochondrial respi-ratory function, the oxygen consumption rate IV was obviously higher in the model group than in the normal control group (P < 0.01), and significantly lower in the EA group than in the model group (P < 0.01). Both liver mitochondrial respiratory control rate (RCR) and ratio of phosphorus/oxgen (P/O) were significantly lower in the model group than in the normal control group (P < 0.01), and considerably higher in the EA group than in the model group (P < 0.01, P < 0.05). Comparison between the EA and EA control groups showed that the effects of the former group were evidently superior to those of the latter group in prolonging the exhausted swimming time, lowering oxygen consumption rate IV and upregulating RCR and P/O (P < 0.05). CONCLUSION: Electroacupuncture of CV 4 and ST 36 plus manual acupuncture stimulation of GV 20 can improve the anti-fatigue capability in aging rats with yang-deficiency, which may be related to its effects in reducing liver mitochondrial oxygen consumption and increasing liver mitochondrial RCR and ratio of P/O.

Genome-based expression profiles as a single standardized microarray platform for the diagnosis of bladder pain syndrome/interstitial cystitis: an array of 139 genes model.

INTRODUCTION AND HYPOTHESIS: The aim of the study was to investigate the molecular signatures underlying bladder pain syndrome/interstitial cystitis (BPS/IC) using cDNA microarray. METHODS: Microarray gene expression profiles were [corrected] studied in a matched case-control study [corrected] by using a system of conditional regression modeling. RESULTS: The main [corrected] findings are summarized as follows: Firstly, a "139-gene" model was discovered to contain high expressions of bladder epithelium, which feature in BPS/IC. Secondly, complex metabolic reactions, including carbohydrate, lipid, cofactors, vitamins, xenobiotics, nucleotide, and amino acid metabolisms, were [corrected] found to have a strong relationship with bladder smooth muscle contraction through IC status. Thirdly, we [corrected] found the transcriptional regulations of IC-induced bladder smooth muscle contraction status, including the level of contractile force, tissue homeostasis, energy homeostasis, and the development of the [corrected] nervous system. In addition, our study suggested the mast-cell activation mediated by the high-affinity receptor of Fc epsilon [corrected] RI triggering allergic inflammation through IC status. Such genetic changes, jointly termed "bladder remodeling," [corrected] can constitute an important long-term consequence of BPS/IC. [corrected]. CONCLUSIONS: The success of this innovation has supported the use of microarray-based expression profiling as a single standardized platform for diagnosis of PBS/IC and offers [corrected] drug discovery.