[Intervention effect of Erchen Decoction on methionine and choline deficient diet-induced non-alcoholic steatohepatitis in mice].

This study investigated the effect of Erchen Decoction(ECD) on the prevention of non-alcoholic steatohepatitis(NASH) in mice and explored its possible mechanism, so as to provide scientific data for the clinical application of ECD in the prevention of NASH. C57BL/6 male mice were randomly divided into normal group(methionine and choline supplement, MCS), model group(methionine and choline deficient, MCD), low-dose ECD group(ECD＿L, 6 g·kg~(-1)), medium-dose ECD group(ECD＿M, 12 g·kg~(-1)), and high-dose ECD group(ECD＿H, 24 g·kg~(-1)), with eight mice in each group. The MCS group was fed with an MCS diet, and the other groups were fed with an MCD diet. The mice in each group were given corresponding diets, but the drug intervention group was given low-, medium-, and high-dose ECD(10 mL·kg~(-1)·d~(-1)) by intragastric administration for six weeks on the basis of MCD diet feeding, and the mice could eat and drink freely during the whole experiment. At the end of the experiment, mice were fasted overnight(12 h) and were anesthetized with 20% urethane. Thereafter, the blood and liver tissue were collected. The serum was used to detect the levels of alanine aminotransferase(ALT), aspartate aminotransaminase(AST), interleukin-1ß(IL-1ß), interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α). Liver tissue was processed by hematoxylin-eosin(HE) staining and used for hepatic histological analysis and detection of the expression levels of genes and proteins related to nuclear factor erythroid 2-related factor 2/glutathione peroxidase 4(Nrf2/GPX4) pathway by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR) and Western blot analysis, respectively. The results showed that compared with the MCS group, the MCD group showed higher serum ALT and AST levels; the HE staining exhibited fat vacuoles and obvious inflammatory cell infiltration in liver tissue; serum IL-1ß, IL-6, and TNF-α levels were significantly increased, and the serum IL-10 level was significantly decreased. The mRNA expressions of fatty acid synthase(FASN), monocyte chemoattractant protein-1(MCP-1), and IL-1ß in liver tissue were significantly up-regulated, while those of GPX4, Nrf2, and NAD(P)H:quinine oxidoreductase(NQO1) were significantly down-regulated. Compared with the MCD group, the serum ALT and AST levels of ECD＿M and ECD＿H groups were significantly decreased, and the AST level in the ECD＿L group was significantly decreased. The number of fat vacuoles and the degree of inflammatory cell infiltration in liver tissue were improved; serum IL-1ß, IL-6, and TNF-α levels were significantly decreased, but the serum IL-10 level was significantly increased only in the ECD＿H group. The mRNA expressions of FASN, MCP-1, and IL-1ß in liver tissue were significantly down-regulated, and those of GPX4 and NQO1 were significantly up-regulated. The mRNA expressions of Nrf2 in ECD＿M and ECD＿H groups were significantly up-regulated. Western blot results showed that compared with the MCD group, the protein expression levels of Nrf2 and GPX4 in each group were significantly increased after ECD administration, and the protein expression level of FASN was significantly decreased; the protein expression of NQO1 was increased in ECD＿M and ECD＿H groups. In summary, ECD can reduce hepatic lipid accumulation, oxidative stress, liver inflammation, and liver injury in NASH mice, which may be related to the activation of the Nrf2/GPX4 pathway.

Effects of allicin on growth performance, antioxidant profile, and microbiota compared to monensin of growing goats.

Allicin is a sulfur-containing compound extracted from raw garlic (Allium sativum L.). We compared the effect of allicin addition on growth performance, serum biochemical parameters, and rumen microbiota of goats compared to monensin. Twenty-four Anhui white goats were assigned randomly to one of three dietary treatments: 1) a basal diet (CON); 2) the basal diet with allicin addition at 750 mg per head per day (AC); 3) the basal diet with monensin addition at 30 mg per kg of diet (MS). Animals were fed for 8 weeks. Results showed the average daily gain, and feed efficiency was increased with allicin and monensin addition. Serum levels of IgG, total superoxide dismutase, and glutathione peroxidase were higher in the AC group than those in the CON and MS groups. The microbiota analysis revealed that monensin addition mainly affected genera related to carbohydrate and protein metabolism, and allicin mainly affected genera related to energy metabolism and intestinal health. In conclusion, allicin could improve growth performance and have advantages over monensin in improving the antioxidant capacity and immune function of goats. Allicin may be a potential alternative to monensin.

Targeting BDNF with acupuncture: A novel integrated strategy for diabetes and depression comorbidity.

Diabetes and depression are common comorbid conditions that impose a substantial health burden. Acupuncture may effectively improve symptoms in patients with diabetes and depression, but the underlying mechanism remains unclear. Brain-derived neurotrophic factor (BDNF) may play a vital role in the effects of acupuncture on diabetes and depression comorbidity. This review summarizes the potential role of BDNF in acupuncture for diabetes and depression comorbidity. BDNF appears to exert its effects via the BDNF-TrkB-ERK-CREB signaling pathway. BDNF levels are reduced in diabetes and depression, and acupuncture may increase BDNF expression, improving symptoms and glycemic control. High-quality research is needed to validate the efficacy of acupuncture for diabetes and depression comorbidity. Randomized controlled trials and mechanistic studies should investigate the BDNF pathway and other potential mechanisms. Improved understanding of the links between diabetes, depression and acupuncture may enable targeted and individualized patient care. Earlier diagnosis and management of diabetes and depression comorbidity should also be a priority.

Therapeutic effect of a self-made herbal formula on a multi-drug resistant Eimeria tenella isolate infection in broiler chickens.

In-feed prophylactic chemotherapy is widely considered the mainstay of avian coccidiosis control, while serious drug resistance strictly restricts its application. Confronted with the urgent need for an alternative strategy, a traditional Chinese medicine formula (TCMF) was developed. Meanwhile, its potential to iron out complicated clinical coccidiosis was scrutinized in vivo with a field-isolated multi-drug resistant Eimeria tenella (E. tenella) isolate. Birds were inoculated with 5 × 104 sporulated oocysts and administrated with TCMF supplementation in water from 72 h post-infection to the end of the experiment, diclazuril (DIC) was set as a positive control. As a result, TCMF intervention reduced oocyst shedding, cecal lesion and mortality, and enhanced body weight gain. According to the above, anticoccidial index (ACI) was calculated and TCMF exerted a moderate anticoccidial activity. Besides, macroscopic, histopathological, and ultrastructural observations revealed the safeguarding effects of TCMF on E. tenella-induced cecal injury. Following, TCMF treatment presented an obvious inhibition effect on E. tenella caused oxidative stress and inflammatory response. Moreover, TCMF supplementation restored the cecal flora abundance and diversity, reduced the colonization of harmful bacteria, and increased the probiotics abundance. In conclusion, TCMF exhibited a moderate anticoccidial effect along with alleviating E. tenella-induced cecal injury, redox imbalance, and inflammatory response which may be associated with the microflora modulatory effect.

Methylmalonic acid, vitamin B12, and mortality risk in patients with preexisting coronary heart disease: a prospective cohort study.

BACKGROUND: The inconsistent relationship between Vitamin B12 (B12), methylmalonic acid (MMA, marker of B12 deficiency) and mortality was poorly understood, especially in patients with coronary heart disease (CHD). This study aims to investigate the association of serum MMA, and B12-related biomarkers (serum level, dietary intake, supplement use, and sensibility to B12) with all-cause and cardiovascular mortality in adults with CHD. METHODS: The data of this study were from a subcohort within the US National Health and Nutrition Examination Survey (NHANES). We included adults with preexisting CHD with serum MMA and B12, and dietary B12 intake measurements at recruitment. All participants were followed up until 31 December 2019. Weighted Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CI of mortality risk. RESULTS: Overall, 1755 individuals (weighted mean [SE] age, 65.2 [0.5] years; 1047 men [weighted 58.5%]) with CHD were included, with geometric mean levels of serum MMA 182.4 nmol/L, serum B12 494.5 pg/ml, and dietary B12 intake 4.42 mg/day, and percentage of B12 supplements use 39.1%. During a median follow-up of 7.92 years, 980 patients died. Serum B12 concentration, dietary B12 intake and supplements use were not significantly associated with mortality risk (each p ≥ 0.388). In contrast, individuals in the top tertile of MMA had multivariable-adjusted HRs (95% CIs) of 1.70 (1.31-2.20) for all-cause mortality, and 2.00 (1.39-2.89) for cardiovascular mortality (both p trend < 0.001) compared to those in the bottom tertile of MMA. MMA-related mortality risk was particularly higher among participants with sufficient serum B12 (p < 0.001). CHD patients with increased levels of both MMA and B12 had a doubled mortality risk compared to those with lower MMA and B12 (p < 0.001). CONCLUSION: MMA accumulation but not serum or dietary vitamin B12 was associated with increased cardiovascular mortality risk among patients with CHD. This paradox may be related to decreased response to vitamin B12.

Veronica persica ameliorates acetaminophen-induced murine hepatotoxicity via attenuating oxidative stress and inflammation.

Excess acetaminophen (APAP) commonly causes severe acute liver injury (ALI), characterized by oxidative stress, pro-inflammatory responses, and hepatocyte damage. Veronica persica (VP) is a traditional medicine with antioxidant and anti-inflammatory properties. There is a paucity of information on its medicinal value, especially its potential mechanisms for alleviating ALI. This study aimed to clarify the ameliorative effects and intracellular mechanisms of VP on APAP-induced ALI via attenuating oxidative stress and inflammation. Mice were given VP for 7 days before exposure to APAP (300 mg/kg). The HPLC and radical scavenging assay found that VP contains 12 phenolic acids and 6 flavonoids, as well as show robust antioxidant capacity. In the APAP-induced ALI model, pre-treatment with VP significantly reduces APAP-induced hepatotoxicity by observing improved hepatocyte pathological injury and further confirmed by serum biochemical indicator. Also, the reduction of TUNEL-positive regions and the regulation of Bcl-2-associated X protein indicated that VP attenuates hepatocytotoxicity. Moreover, VP pre-intervention inhibits the formation of liver pro-inflammatory cytokines, the expression of inflammatory response genes, and increases in myeloperoxidase (MPO) in APAP-exposed mice. The elevated reduced glutathione (GSH) levels and decreased oxidative stress markers indicate that VP reduces APAP-promoted oxidative stress. Further study revealed that VP inhibited the phosphorylation of NF-κB/STAT3 cascade, blocked ERK and JNK phosphorylation, and activated AMP-activated protein kinase (AMPK). To sum up, this study demonstrated that VP exists hepatoprotective abilities on APAP-induced ALI, primarily by suppressing the phosphorylation of NF-κB/STAT3 cascade and ERK-JNK and inducing AMPK activation to alleviate oxidative stress and inflammation.

Identification of quality markers for Cyanotis arachnoidea and analysis of its physiological mechanism based on chemical pattern recognition, network pharmacology, and experimental validation.

Cyanotis arachnoidea C. B. Clarke is a traditional Chinese medicinal herb that has a limited clinical use in the treatment of diabetes mellitus (DM) in minority areas of Guizhou in China. However, few prior reports are available on the quality control of Cyanotis arachnoidea, and its quality markers and hypoglycemic mechanism are still unclear. The purpose of this study is to explore the quality markers (Q-markers) of Cyanotis arachnoidea and predict its hypoglycemic mechanism. In this study, ultra-high-performance liquid chromatography (UHPLC) fingerprint combined with chemical pattern recognition were performed, and four differential components were screened out as quality markers, including 20-Hydroxyecdysone, 3-O-acetyl-20-hydroxyecdysone, Ajugasterone C, and 2-O-acetyl-20-hydroxyecdysone. Network pharmacology analysis revealed 107 therapeutic target genes of Cyanotis arachnoidea in DM treatment, and the key targets were Akt1, TNF, IL-6, MAPK3, and JUN. The hypoglycemic mode of action of Cyanotis arachnoidea may be mediated by tumor necrosis factor (TNF) signaling, cancer, insulin resistance, and JAK-STAT pathways. Molecular docking analysis disclosed that the foregoing quality markers effectively bound their key target genes. An in vitro experiment conducted on pancreatic islet ß-cells indicated that the forenamed active components of Cyanotis arachnoidea had hypoglycemic efficacy by promoting PI3K/Akt and inhibiting MAPK signaling. UHPLC also accurately quantified the quality markers. The identification and analysis of quality markers for Cyanotis arachnoidea is expected to provide references for the establishment of a quality control evaluation system and clarify the material basis and hypoglycemic mechanisms of this traditional Chinese medicine (TCM).

American ginseng with different processing methods ameliorate immunosuppression induced by cyclophosphamide in mice via the MAPK signaling pathways.

This study aimed to clarify the effects of two processed forms of American ginseng (Panax quinquefolius L.) on immunosuppression caused by cyclophosphamide (CTX) in mice. In the CTX-induced immunosuppressive model, mice were given either steamed American ginseng (American ginseng red, AGR) or raw American ginseng (American ginseng soft branch, AGS) by intragastric administration. Serum and spleen tissues were collected, and the pathological changes in mice spleens were observed by conventional HE staining. The expression levels of cytokines were detected by ELISA, and the apoptosis of splenic cells was determined by western blotting. The results showed that AGR and AGS could relieve CTX-induced immunosuppression through the enhanced immune organ index, improved cell-mediated immune response, increased serum levels of cytokines (TNF-α, IFN-γ, and IL-2) and immunoglobulins (IgG, IgA, and IgM), as well as macrophage activities including carbon clearance and phagocytic index. AGR and AGS downregulated the expression of BAX and elevated the expression of Bcl-2, p-P38, p-JNK, and p-ERK in the spleens of CTX-injected animals. Compared to AGS, AGR significantly improved the number of CD4+CD8-T lymphocytes, the spleen index, and serum levels of IgA, IgG, TNF-α, and IFN-γ. The expression of the ERK/MAPK pathway was markedly increased. These findings support the hypothesis that AGR and AGS are effective immunomodulatory agents capable of preventing immune system hypofunction. Future research may investigate the exact mechanism to rule out any unforeseen effects of AGR and AGS.

[Analysis of WRKY transcription factor family based on full-length transcriptome sequencing in Polygonatum cyrtonema].

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.

[Research progress on application of multi-enzyme-catalyzed cascade reactions in enzymatic synthesis of natural products].

As a biocatalyst, enzyme has the advantages of high catalytic efficiency, strong reaction selectivity, specific target products, mild reaction conditions, and environmental friendliness, and serves as an important tool for the synthesis of complex organic molecules. With the continuous development of gene sequencing technology, molecular biology, genetic manipulation, and other technologies, the diversity of enzymes increases steadily and the reactions that can be catalyzed are also gradually diversified. In the process of enzyme-catalyzed synthesis, the majority of common enzymatic reactions can be achieved by single enzyme catalysis, while many complex reactions often require the participation of two or more enzymes. Therefore, the combination of multiple enzymes together to construct the multi-enzyme cascade reactions has become a research hotspot in the field of biochemistry. Nowadays, the biosynthetic pathways of more natural products with complex structures have been clarified, and secondary metabolic enzymes with novel catalytic activities have been identified, discovered, and combined in enzymatic synthesis of natural/unnatural molecules with diverse structures. This study summarized a series of examples of multi-enzyme-catalyzed cascades and highlighted the application of cascade catalysis methods in the synthesis of carbohydrates, nucleosides, flavonoids, terpenes, alkaloids, and chiral molecules. Furthermore, the existing problems and solutions of multi-enzyme-catalyzed cascade method were discussed, and the future development direction was prospected.

Lacticaseibacillus casei CNRZ1874 supplementation promotes M1 alveolar macrophage activation and attenuates Mycoplasma pneumoniae pneumonia.

AIMS: To evaluate the protective effect of intestinal supplementation with Lacticaseibacillus casei CNRZ1874 on the inflammatory response induced by Mycoplasma pneumoniae in C57BL/6 J mice, and provide a potential strategy for alleviating M. pneumoniae pneumonia. METHODS AND RESULTS: C57BL/6 J mice were gavaged with L. casei CNRZ1874 or PBS for 7 consecutive days, and then infected with M. pneumoniae on day 8. Treatment with L. casei CNRZ1874 significantly reduced M. pneumoniae loads in the lungs and alleviated the lung inflammation on day 3 and 10 after pathogen infection. Importantly, oral administration with L. casei CNRZ1874 promoted M1 alveolar macrophages activation as evidenced by increased expression of iNOS, TNF-α, and CXCL1, while inhibited M2 alveolar macrophages activation as the expression of Arg1 and Chi3l3 were significantly decreased. In consistent with the M1 alveolar macrophages activation and enhanced mycoplasma clearance, the level of TNF-α was increased while the level of IL-4 was decreased in lung tissue from the L. casei CNRZ1874 group compared with the control group. However, oral administration with L. casei CNRZ1874 may not influence adaptive immunity induced by M. pneumoniae as evaluated by M. pneumoniae specific antibodies and T cells responses in spleen. CONCLUSIONS: Intestinal supplementation with L. casei CNRZ1874 can promote M1 alveolar macrophages activation, which contributes to the clearance of M. pneumoniae and attenuation of M.pneumoniae pneumonia.

Bone metabolism characteristics and gender differences in patients with COPD: a cross-sectional study.

BACKGROUND: Gender differences in bone metabolism of people with chronic obstructive pulmonary disease (COPD) remain unclear. We aim to explore the characteristics of bone metabolism and its clinical significance for patients with COPD. METHODS: A total of 564 cases (282 COPD cases and 282 controls) were preselected. Clinical and analytical characteristics of these cases were assessed. After excluding patients with other conditions known to disturb calcium metabolism, 333 patients (152 COPD cases and 181 controls) were identified. The medical records, indexes of bone turnover markers, serum calcium and phosphorus of the 333 patients were collected and their correlation was analyzed. RESULTS: The 152 cases with COPD were 82.61 ± 7.745 years, 78.3% males, and the 181 age- and sex-matched control cases were 79.73 ± 11.742 years, 72.4% males. Levels of total procollagen type I amino-terminal propeptide (tPINP), osteocalcin (OC), serum calcium and phosphate were significantly lower (P < 0.001) while the level of parathormone (PTH) was significantly higher (P = 0.004) in COPD than in controls. The 25-hydroxycholecalciferol (25(OH)D3) was below the lower limit of normal value (LLN) in both groups, which was significantly lower in COPD males than in control males (P = 0.026). In COPD group, PTH level was significantly higher in females (P = 0.006), and serum P was lower in males (P = 0.006). The adjusted linear regression analysis showed that the levels of tPINP, OC and serum Ca were decreasing greatly in COPD group [ß (95%CI) - 8.958 (- 15.255 to - 2.662), P = 0.005; - 4.584 (- 6.627 to - 2.542), P < 0.001; - 0.065 (- 0.100 to - 0.031), P < 0.001]. Besides, smoke exposure, gender (male) were also related to hypocalcemia [ß (95%CI) - 0.025 (- 0.045 to - 0.005), P = 0.017; - 0.041 (- 0.083 to - 0.001), P = 0.047], and 25(OH)D3 was correlated with serum calcium, phosphorus, and PTH [ß (95%CI) 15.392(7.032-23.753), P < 0.001; - 7.287 (- 13.450 to - 1.124), P = 0.021; - 0.103(- 0.145 to - 0.061), P < 0.001], and female was more likely to have secondary hyperparathyroidism [ß (95%CI) 12.141 (4.047-20.235), P = 0.002]. CONCLUSION: COPD patients have remarkably low bone turnover (indicated by OC) and impaired bone formation (low tPINP), and they are also more prone to low calcium. Smoking and male may play roles in the formation of hypocalcemia, and the secondary hyperparathyroidism is more significant in COPD women. There may be gender differences in bone metabolism abnormalities and their mechanisms of COPD. The conclusion above still need further research and demonstration.

Agricultural land use regulates the fate of soil phosphorus fractions following the reclamation of wetlands.

Over half of the Earth's wetlands have been reclaimed for agriculture, leading to significant soil P destabilization and leaching risks. To evaluate the effects of agricultural land use on soil P stability, we used sequential P extraction to investigate the long-term effects of wetland cultivation for rice and soybean on soil P fractions, including labile and moderately labile inorganic/organic P (LPi, LPo, MPi, and MPo), and stable P in Northeast China. The results showed that soybean cultivation decreased the total P by 35.9 %, whereas rice cultivation did not influence the total P content (p < 0.05). Both the soybean and rice cultivations significantly increased LPi (p < 0.05). Soybean cultivation significantly decreased the LPo and MPo compared to rice cultivation, and the latter increased MPi by 309.28 % compared with the reference wetlands (p < 0.05). Redundancy analysis indicated that pH, poorly crystalline Fe (Feca), crystalline Fe (Fec), and total organic carbon (TOC) explained similar variations in P fractions during soybean and rice cultivation (54.9 % and 49.7 %, respectively). Similarly, during soybean or rice cultivation, pH negatively influenced LPo and MPo, while Feca positively influenced MPi and LPi. Furthermore, TOC showed a positive role in LPo, and MPo, but a negative effect on LPi and MPi during rice cultivation. Hence, we concluded that the cultivation of soybean or rice create contrasting modifications to wetland soil P fractionation by altering TOC, Feca, Fec, and pH. Our study indicates that agricultural land use can regulate the fate of wetland soil P fractionation, with potential benefits to both i) P risk management in cultivated wetlands and ii) potential approaches for future wetland restoration.

Hybrid Au-star@Prussian blue for high-performance towards bimodal imaging and photothermal treatment.

In recent years, branched or star-shaped Au nanostructures composed of core and protruding arms have attracted much attention due to their unique optical properties and morphology. As the clinically adapted nanoagent, prussian blue (PB) has recently gained widespread attention in cancer theranostics with potential applications in magnetic resonance (MR) imaging. In this article, we propose a hybrid star gold nanostructure（Au-star@PB）as a novel theranostic agent for T1-weighted magnetic resonance imaging (MRI)/ photoacoustic imaging（PAI） and photothermal therapy (PTT) of tumors. Importantly, the Au-star@PB nanoparticles function as effective MRI/PA contrast agents in vivo by increasing T1-weighted MR/PAI signal intensity and as effective PTT agents in vivo by decreasing the tumor volume in MCF-7 tumor bearing BALB / c mouse model as well as in vitro by lessening tumor cells growth rate. Interestingly, we found the main photothermal effect of Au-star@PB is derived from Au-star, but not PB. In summary, the hybrid structure of Au-star@PB NPs with good biological safety, significant photostability, dual imaging capability, and high therapeutic efficiency, might offer a novel avenue for the future diagnosis and treatment of cancer.

[Effect of manual acupuncture at "Sanyinjiao" (SP6) on spermatogenic cells of mice with oligoasthenospermia induced by microwave radiation].

OBJECTIVE: To observe the effect of acupuncture at "Sanyinjiao" (SP6) on sperm motility, testicular B cell lymphoma/leukelia-2 (Bcl-2), Bcl-2 associated X protein (Bax), and Caspase-3 in mice with oligoasthenospermia induced by microwave radiation, so as to explore its underlying mechanisms in improving oligoasthenospermia. METHODS: Male BALB/C mice were randomly divided into control, model and acupuncture groups(n=6 in each group). The oligoasthenospermia model was established by continuous microwave irradiation with frequency of 2 450 MHz and power density of 40 mW/cm2, 1 h daily for 18 days. At the same time, manual acupuncture was applied to the acupuncture group on bilateral "Sanyinjiao" (SP6) for 30 s, once daily for 18 days. Sperm motility including the percentages of progressive motility (PR), non-progressive motility (NP), and PR + NP sperms was detected by computer-assisted sperm analysis, H.E. staining was used to observe the testicular morphology and Johnson score was calculated, the expression levels of Bcl-2, Bax and Caspase-3 in testis were detected by immunofluorescence. RESULTS: Compared with the control group, the percentages of PR sperms, NP sperms, PR+NP sperms, Johnson score, and expression level of Bcl-2 were significantly decreased (P<0.05), while the expression levels of Bax and Caspase-3 were increased (P<0.05) in the model group. Compared with the model group, the percentages of PR sperms, PR+NP sperms, Johnson score, and expression level of Bcl-2 were significantly increased (P<0.05), while the expression levels of Bax and Caspase-3 were decreased (P<0.05) in the acupuncture group. Outcomes of H.E. staining showed that the seminiferous tubules became thinner, spermatogenic cells and sperm decreased or even disappeared, and the supporting cells were partially missing in the model group, which was relatively milder in the acupuncture group. CONCLUSION: Manual acupuncture at SP6 can improve sperm motility in oligoasthenospermia mice induced by microwave radiation, which may be related to its effects in down-regulating the expressions of Bax and Caspase-3, increasing expression of Bcl-2 in the testis.

[Comparative study of the protective effect of Xuebijing injection and Sivelestat sodium on acute lung injury/acute respiratory distress syndrome rats].

OBJECTIVE: To compare the protective effect of Xuebijing injection versus Sivelestat sodium on acute lung injury/acute respiratory distress syndrome (ALI/ARDS) rats. METHODS: A total of 71 male Sprague-Dawley (SD) rats were randomly divided into the blank control group (n = 8), ALI/ARDS model group (n = 21), Xuebijing injection group (n = 21) and Sivelestat sodium group (n = 21). Rats in the blank control group were injected with normal saline while the other three groups were intravenously injected 25 mg/kg lipopolysaccharide (LPS) via the tail vein to establish ALI/ARDS model. After induction of ALI/ARDS model, the blank control group and ALI/ARDS model group were given intraperitoneal injection of an equal volume of normal saline twice a day. Rats in the Xuebijing injection group were given tail vein injection of 8 mL/kg Xuebijing injection twice a day, and those in the Sivelestat sodium group were given intraperitoneal injection of 100 mg/kg Sivelestat sodium three times a day. All rats were administered continuously for five days. During the experiment, the general status of rats was observed, and the weight and survival were recorded. At the end of the experiment, bronchoalveolar lavage fluid (BALF) of rats was collected for the detection of inflammatory cells and inflammatory factors. Histopathological changes of rats lung tissue were observed. RESULTS: Compared with the ALI/ARDS model group, the Xuebijing injection group and Sivelestat sodium group had significantly decreased white blood cell (WBC) count and percent of neutrophil (NEU%) [WBC (×109/L): 55.86±6.68, 49.96±6.76 vs. 73.13±7.35, NEU%: 0.459±0.077, 0.315±0.047 vs. 0.709±0.067, all P < 0.05], significantly increased percent of lymphocytes (LYM%: 0.412±0.067, 0.517±0.051 vs. 0.232±0.057, both P < 0.05), and reduced interleukin-6 (IL-6) level (ng/L: 295.2±39.7, 281.9±33.1 vs. 469.6±77.0) in BALF. However, there were no significant differences in these parameters between the Xuebijing injection group and Sivelestat sodium injection group (all P > 0.05). Survival rate at the end of experiment was higher in the Xuebijing group than that in the Sivelestat sodium injection group and ALI/ARDS model group [52.4% (11/21) vs. 28.6% (6/21), 14.3% (3/21)], and survival rate at the end of experiment was higher in the Sivelestat sodium injection group than that in the ALI/ARDS model group, but the differences were not statistically significant (P > 0.05). In addition, weight and weight growth rate in the Xuebijing injection group were higher than the Sivelestat sodium group at the end of the experiment [weight (g): 217.1±6.4 vs. 207.1±7.0, weight growth rate: (-0.9±2.8)% vs. (-4.3±3.5)%], there were no significant difference between the two groups (both P > 0.05). Lung histopathology in the ALI/ARDS model group revealed high level of inflammatory exudate and inflammatory cells infiltrated in the alveoli of rats, along with damage of local alveolar epithelial cell and alveolar structure. However, these histological changes were improved in the Xuebijing injection group and in the Sivelestat sodium group. CONCLUSIONS: Xuebijing injection can alleviate ALI/ARDS-induced lung injury and systemic damage and improve the survival of rats by inhibiting inflammation. The protective effect of Xuebijing injection is essentially consistent with that of Sivelestat sodium.

Case Report: Torsade de Pointes Induced by the Third-Generation Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitor Osimertinib Combined With Litsea Cubeba.

Torsades de Pointes (TdP) occurred in a 68-year-old female with epidermal growth factor receptor (EGFR) mutant lung cancer administered osimertinib, the third-generation EGFR tyrosine kinase inhibitor (TKI). Electrocardiogram (ECG) recorded at Tdp showed QT prolongation (QTc = 515 ms), to which a Traditional Chinese Medicine (TCM) named "Litsea Cubeba" may have contributed. After discontinuation of osimertinib and Litsea Cubeba, magnesium supplementation, potassium supplementation, lidocaine infusion, and the pacemaker frequency adjustment, Tdp terminated. However, QT prolongation sustained at discharge (QTc = 528 ms), partly because of the emergency use of amiodarone. Osimertinib may prolong the QT interval leading to TdP, especially when multiple risk factors to lengthen QT interval are incidentally overlapped. Thus, regular monitoring of ECG and appropriate management of concomitant drugs are highly recommended.

[Observation on the efficacy of post-stroke dysphagia treated with He's santong acupuncture therapy through surface electromyography: a randomized controlled trial].

OBJECTIVE: To observe the clinical therapeutic effect on post-stroke dysphagia treated with He's santong (triple promotion) acupuncture therapy through surface electromyography (sEMG). METHODS: A total of 60 patients with post-stroke dysphagia were divided into a routine treatment group and a He's santong acupuncture therapy group, using blocked randomization, 30 cases in each one. In the routine treatment group, the secondary prevention and swallowing rehabilitation training were adopted. In the He's santong acupuncture therapy group, on the base of the treatment as the routine treatment group, weitong (mild promotion, routine acupuncture at bilateral Fengchi ï¼»GB20ï¼½, Fengfu ï¼»GV16ï¼½, Yifeng ï¼»TE17ï¼½, Lianquan ï¼»CV23ï¼½, Jia-lianquan ï¼»Extraï¼½, Fenglong ï¼»ST40ï¼½ and Tongli ï¼»HT5ï¼½, needle retaining for 30 min, 5 treatments a week), wentong (warm promotion, pricking with fire needle at bilateral GB20 and CV23, twice a week) and qiangtong (strong promotion, blood-letting with three-edge needle at Jinjin ï¼»EX-HN12ï¼½, Yuye ï¼»EX-HN13ï¼½ and Yanhoubi ï¼»Extraï¼½, twice a week) treatment was added. The therapy was given consecutively for 4 weeks in each group. The score of fiberoptic endoscopic examination of swallowing (FEES) and Rosenbek-penetration-aspiration scale (PAS), the score of swallowing grading scale, the score of the modified Mann assessment of swallowing ability (MMASA) and the peak amplitude of sEMG were recorded before and after treatment in patients. RESULTS: Compared with before treatment, the score of FEES and PAS after treatment was decreased (P<0.05), the scores of swallowing grading scale and MMASA after treatment were increased in both routine treatment group and He's santong acupuncture therapy group (P<0.05), the peak amplitude of sEMG was increased (P<0.05) in the He's santong acupuncture therapy group and decreased (P<0.05) in the routine treatment group. Compared with the routine treatment group, the score of FEES and PAS was decreased (P<0.05), the scores of swallowing grading scale and peak amplitude of sEMG were increased in the He's santong acupuncture therapy group (P<0.05). CONCLUSION: He's santong acupuncture therapy is obviously effective on post-stroke dysphagia, which may be related to its effects in increasing the contraction of swallowing-related muscles and improving the peak amplitude of hyoid muscle group.

Preparation and evaluation of bilayer-core osmotic pump tablets contained topiramate.

Topiramate (TPM) was an antiepileptic agent commonly used in clinical. Studies showed that an oral preparation of TPM with extended-release manner could bring some benefits for epileptics. In this paper, controlled release push-pull osmotic pump (PPOP) tablets of sparingly water-soluble TPM were successfully prepared. This bi-layer tablet core mainly consisted of sodium chloride as osmotic promoting agent and polyethylene oxide as suspending and pushing agents. The influences of osmotic agents, pushing agents and the compositions of coating membrane on TPM release profiles were evaluated. An optimal formulation of TPM-PPOP was obtained through single-factor experiments. In vitro release tests showed that the optimum formulation could release TPM at an approximate zero-order rate up to 8 h. Pharmacokinetic behaviors of TPM-PPOP tablets were evaluated and compared with the immediate release capsules after an oral single dose in beagle dogs. Pharmacokinetics results demonstrated that the TPM-PPOP tablet was able to provide a prolonged release of TPM with longer tmax and mean residence time. Lower fluctuations of drug plasma levels could also be achieved with TPM-PPOP tablets. These results suggested that sparely water-soluble drugs as TPM can be designed to PPOP for efficacy and safety use.

[Effect of acupuncture on migraine without aura: a resting-state functional magnetic resonance study].

OBJECTIVE: To observe therapeutic effect of acupuncture on migraine without aura and the changes of brain functional connectivity (FC) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Thirty-four patients with migraine without aura were included into an observation group and treated with acupuncture at Baihui (GV 20), Xuanlu (GB 5), Shuaigu (GB 8), Taiyang (EX-HN 5), etc. Using G6805-Ⅱ electric acupuncture apparatus, the ipsilateral Fengchi (GB 20) and Shuaigu (GB 8) were connected and stimulated with continuous wave, 2 Hz in frequency and 0.1 mA to 1.0 mA in current intensity, depending on patient's tolerance. Acupuncture stimulation lasted 20 min each time, twice weekly (at the interval>2 days). A total of 6 weeks of treatment (12 times) was required. Matching the gender and age as those of the observation group, 16 healthy subjects were recruited into a control group and no any intervention was provided. The headache days, the score of visual analogue scale (VAS) for headache severity, the total score of headache symptoms, the score of migraine-specific quality of life questionnaire (MSQ), the score of self-rating anxiety scale (SAS), and the score of self-rating depression scale (SDS) were compared before and after acupuncture, and the clinical efficacy was assessed in the observation group. The data of the resting-state functional magnetic resonance were collected in the observation group before and after treatment as well as the control group at baseline. The periaqueductal gray (PAG) was taken as the seed to analyze the effect of acupuncture on the brain FC and the correlation between FC and VAS scores, headache days in the patients of migraine without aura. RESULTS: After treatment, the headache days, VAS score, the total score of headache symptoms, SAS score and SDS score were all reduced (P<0.01); and the scores of the restrictive, preventive, and emotional functional domains of the MSQ were increased (P<0.01) in the observation group compared with those before treatment. The total effective rate was 94.1% (32/34). Compared with the control group, FC between PAG and the right cerebellum Ⅷ was decreased in the observation group before treatment (P<0.05). FC of PAG with the bilateral cerebellum Ⅷ and the left precuneus was increased in the observation group after treatment compared with those before treatment (P<0.05). In the observation group, the FC intensity of PAG and the right cerebellum Ⅷ was negatively correlated with VAS score (r =-0.41, P<0.05) before treatment, while the FC intensity of PAG and the left precuneus was positively correlated with the improvement in headache days (r =0.40, P<0.05) after treatment. CONCLUSION: Acupuncture is effective on migraine without aura. The brain functional connectivity is abnormal in the patients. The effect onset of acupuncture is obtained probably by regulating the abnormal brain regions and activating brain regions relevant with pain and emotions.