Gehua Jiejiu Dizhi decoction ameliorates alcoholic fatty liver in mice by regulating lipid and bile acid metabolism and with exertion of antioxidant stress based on 4DLabel-free quantitative proteomic study.

OBJECTIVE: To analyze the effect and molecular mechanism of Gehua Jiejiu Dizhi decoction (, GJDD) on alcoholic fatty live disease (AFLD) by using proteomic methods. METHODS: The male C57BL/6J mouse were randomly divided into four groups: control group, model group, GJDD group and resveratrol group. After the AFLD model was successfully prepared by intragastric administration of alcohol once on the basis of the Lieber-DeCarli classical method, the GJDD group and resveratrol group were intragastrically administered with GJDD (4900 mg/kg) and resveratrol (400 mg/kg) respectively, once a day for 9 d. The fat deposition of liver tissue was observed and evaluated by oil red O (ORO) staining. 4DLabel-free quantitative proteome method was used to determine and quantify the protein expression in liver tissue of each experimental group. The differentially expressed proteins were screened according to protein expression differential multiples, and then analyzed by Gene ontology classification and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. Finally, expression validation of the differentially co-expressed proteins from control group, model group and GJDD group were verified by targeted proteomics quantification techniques. RESULTS: In semiquantitative analyses of ORO, all kinds of steatosis (ToS, MaS, and MiS) were evaluated higher in AFLD mice compared to those in GJDD or resveratrol-treated mice. 4DLabel-free proteomics analysis results showed that a total of 4513 proteins were identified, of which 3763 proteins were quantified and 946 differentially expressed proteins were screened. Compared with the control group, 145 proteins were up-regulated and 148 proteins were down-regulated in the liver tissue of model group. In addition, compared with the model group, 92 proteins were up-regulated and 135 proteins were down-regulated in the liver tissue of the GJDD group. 15 differentially co-expressed proteins were found between every two groups (model group vs control group, GJDD group vs model group and GJDD group vs control group), which were involved in many biological processes. Among them, 11 differentially co-expressed key proteins (Aox3, H1-5, Fabp5, Ces3a, Nudt7, Serpinb1a, Fkbp11, Rpl22l1, Keg1, Acss2 and Slco1a1) were further identified by targeted proteomic quantitative technology and their expression patterns were consistent with the results of 4D label-free proteomic analysis. CONCLUSIONS: Our study provided proteomics-based evidence that GJDD alleviated AFLD by modulating liver protein expression, likely through the modulation of lipid metabolism, bile acid metabolism and with exertion of antioxidant stress.

Association between Elevated Magnesium Intake and Reduced Risk of Recurrent Falls and Frailty in Osteoarthritis: Data from the Osteoarthritis Initiative.

OBJECTIVES: The objective of this 8-year follow-up study was to investigate the relationship between magnesium intake and frailty, as well as recurrent falls, in individuals diagnosed with Osteoarthritis (OA) or those at a heightened risk for developing the condition. METHODS: This study utilized data from the Osteoarthritis Initiative (OAI) database and conducted a prospective cohort study with a 8-year follow-up period. Total magnesium intake from both food sources and supplements was assessed using a food frequency questionnaire (FFQ), while frailty and recurrent falls were evaluated through established criteria and self-report, respectively. To account for potential confounding factors, various covariates were considered, and statistical analyses, including generalized additive mixed models (GAMMs), were employed to examine the associations. RESULTS: Among the 4,667 participants with OA, those with lower total magnesium intake were characterized by younger age, a higher proportion of African American individuals, higher body mass index (BMI), and lower dietary fiber intake (P<0.001). Notably, this group exhibited higher odds of experiencing recurrent falls and frailty (P = 0.034 and 0.006, respectively). Controlling for various factors, the GAMMs consistently revealed negative correlations between magnesium intake and the likelihood of frailty and recurrent falls, with each 1 mg/1000 kcal increase in magnesium intake associated with a 0.5% reduced frailty risk (p < 0.001) and a 0.2% decreased risk of recurrent falls (p = 0.001). Subgroup analyses suggested that increased total magnesium intake from both food sources and supplements may exert a more pronounced preventive effect on recurrent falls and frailty in men, older adults, individuals with normal BMI, and those with higher dietary fiber intake. CONCLUSIONS: Elevated total magnesium intake from both food sources and supplements was found to be associated with a decreased risk of recurrent falls and frailty in individuals diagnosed with OA or those at risk of developing the condition. These findings imply that increased total magnesium intake might be beneficial in managing the risk of these outcomes, particularly within specific subgroups, including men, older adults, those with a normal BMI, and those with higher dietary fiber intake.

[Analysis on the iron status and associated factors during the first trimester of pregnancy].

OBJECTIVE: To investigate the impact of dietary and underlying factors on the iron status of women in early pregnancy and to provide evidence for preventing iron deficiency and iron deficiency anemia, thereby reducing the incidence of associated adverse outcomes. METHODS: From November to December 2018, women in the first trimester of pregnancy (< 12 weeks gestation) who established prenatal records at the Shunyi District Maternal and Child Health Hospital, Beijing, were enrolled in this study, in which 388 participants were accessed for data including demographic characteristics, anthropometric measurements, parity, biomarkers reflecting iron status, and food-frequency questionnaire. SPSS 26.0 were used for statistical analysis. Dietary patterns were extracted using principal component analysis, and factor scores of each dietary pattern were calculated. Two-sided Fisher exact probability test and one-way ANOVA were conducted to access differences in iron status among the groups, and the differences were significant if P < 0.05. Iron deficiency was defined as serum ferritin(SF) < 30 µg/L. To analyze the potential role of dietary factors on iron deficiency during the first trimester, the collected data listed above were adopted as independent factors for the cross-sectional Logistic regression. We used Logistic regression to analyze the potential effects of baseline characteristics and dietary factors on iron status. RESULTS: Among the 388 participants included in the analysis, 121 (32.2%) were iron deficient, in which 107 (27.6%) were iron depletion (ID), 8 (2.1%) were iron deficiency erythropoiesis (IDA), 6(1.5%) were iron deficiency anemia. The mean SF concentration was (50.4±35.3) µg/L. Multiparity(OR=3.9, 95%CI: 1.81-8.42, P=0.001)was a risk factor for iron deficiency during early pregnancy. No significant iron status differences were found among the participants with different educational levels and anthropometric measurements. In contrast, age (OR =0.96, 95%CI: 0.94-0.97, P < 0.001) was a protective factor. For multiparas, taking iron-containing supplements might have a protective effect for iron deficiency (OR=0.27, 95%CI: 0.09-0.83, P=0.022). The balance-diet pattern (OR=0.81, 95%CI: 0.66-1.00, P=0.054) only showed a marginally significant effect. CONCLUSION: Increasing attention should be paid to the iron status of pregnant multiparas and young pregnant women. For those women of reproductive age with the risk factors listed above, especially for multiparas, iron-containing supplements should be recommended to prevent gestational iron deficiency. The effect of the "balance" dietary pattern on iron status in the first trimester and following requires further research and discussion.

[Advances in the diagnosis and treatment strategy of polymyxin resistant Klebsiella pneumoniae].

In recent years, the detection rate of multidrug-resistant and pandrug-resistant Klebsiella pneumoniae has increased year on year, so polymyxin has received increasing attention as an antibiotic that is still sensitive to most of the multidrug-resistant strains. However, widespread use of polymyxin is likely to lead to the emergence of polymyxin-resistant Klebsiella pneumoniae. At the same time, the polymyxin hetero-resistance has made clinical prevention and treatment difficult. In addition to relying on the combination of polymyxins with other antibiotics, the search for new antibacterial drugs has also become a research hotspot. Research into early detection methods for polymyxin resistance can also help to optimize and improve the diagnosis and treatment strategies. This article reviewed the epidemic status, mechanism, detection methods and prevention measures of polymyxin-resistant Klebsiella pneumoniae.

[Explore the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab in patients with ulcerative colitis].

Objectives: To analyze the influence of vitamin D supplementation on clinical efficacy and drug retention rate of vedolizumab (VDZ) in patients with ulcerative colitis (UC). Methods: Retrospective study. By retrieving the clinical database of the Second Affiliated Hospital of Wenzhou Medical University, the patients with moderately to severely active UC were collected, who underwent VDZ treatment from January 2020 to June 2022. The modified Mayo score and Mayo endoscopic score (MES) were employed to evaluate disease activity and intestinal inflammation in UC patients, respectively. According to whether vitamin D was supplemented during VDZ treatment, the patients were divided into supplementary group and non-supplementary group. According to baseline serum 25(OH) D level, UC patients were divided into vitamin D deficiency group and non-deficiency group. According to whether vitamin D was supplemented, the patients of each group were divided into supplementary subgroup and non-supplementary subgroup, respectively. The clinical response rate, clinical remission rate and mucosal healing rate at week 30 after receiving VDZ treatment and the retention rate of VDZ at the 72nd week were observed. The effect of baseline serum 25 (OH) D level on the efficacy of vitamin D supplementation was analyzed by chi-square test. The effects of vitamin D supplementation on the clinical efficacy and drug retention of VDZ in UC were analyzed by chi-square test and Kaplan-Meier curve, respectively. Results: A total of 80 patients with moderately to severely active UC, who were aged (39.4±13.0) years(18-75 years), 37 male and 43 female, were included. There were 43 cases in supplementary group and 37 cases in non-supplementary group. There were 59 cases in the deficiency group, including 32 cases in the supplementary subgroup and 27 cases in the non-supplementary subgroup. There were 21 cases in the non-deficiency group, including 11 cases in the supplementary subgroup and 10 cases in the non-supplementary subgroup. At week 30, the average level of serum 25(OH) D was shown to be higher in supplementary group than that at week 0 [(24.5±5.4) vs (17.7±6.7) µg/L, P<0.001]. At week 30, in contrast with non-supplementary group, erythrocyte sedimentation rate(ESR)[75.0% (24.3%, 86.7%) vs 32.7% (-2.6%, 59.3%), P=0.005] and modified Mayo score [(4.7±2.8) vs (2.3±2.7) points, P<0.001] and MES score [(1.2±1.1) vs (0.4±0.9) points, P=0.001] were significantly reduced, clinical response rate [79.1%(34/43) vs 56.8%(21/37), P=0.032], clinical remission rate [67.4%(29/43) vs 29.7%(11/37), P=0.001] and mucosal healing rate [72.1%(31/43) vs 37.8%(14/37), P=0.002] were higher. At week 72, drug retention rate of VDZ was shown to be higher in supplementary group than in non-supplementary group [55.8%(24/43) vs 27.0%(10/37), P=0.004]. The further analysis showed that vitamin D supplementation could only improve clinical response rate[71.9%(23/32) vs 44.4%(12/27), P=0.033], clinical remission rate[62.5%(20/32) vs 14.8%(4/27), P<0.001], mucosal healing rate[68.8%(22/32) vs 22.2%(6/27), P<0.001] and drug retention rate [53.1%(17/32) vs 13.8%(4/27), P=0.001] in the patients with vitamin D deficiency. Conclusion: Vitamin D supplementation contributes to improving clinical response rate, clinical remission rate, mucosal healing rate and drug retention rate of VDZ in UC patients.

Effects of dietary niacinamide and CP concentrations on the nitrogen excretion, growth performance, and meat quality of pigs.

Reducing the dietary CP concentration in the formulation of low-protein diets without adverse effects on animal growth performance and meat quality remains challenging. In this study, we investigated the effects of nicotinamide (NAM) on the nitrogen excretion, growth performance, and meat quality of growing-finishing pigs fed low-protein diets. To measure the nitrogen balance, we conducted two trials: in nitrogen balance trial 1, four crossbred (Duroc × Landrace × Large White) barrows (40 ± 0.5 kg BW) were used in a 4 × 4 Latin square design with four diets and periods. The diets consisted of a basal diet + 30 mg/kg NAM (a control dose), basal diet + 90 mg/kg NAM, basal diet + 210 mg/kg NAM, and basal diet + 360 mg/kg NAM. In nitrogen balance trial 2, another four barrows (40 ± 0.5 kg BW) were used in a 4 × 4 Latin square design. The diets consisted of a basal diet + including 30 mg/kg NAM (control), basal diet + 360 mg/kg NAM, low-protein diet + 30 mg/kg NAM, and low-protein diet + 360 mg/kg NAM. To measure growth performance, two trials were conducted. In growth performance trial 1, 40 barrows (37.0 ± 1.0 kg) were randomly allocated to one of four dietary treatments (n = 10 per group), whereas in growth performance trial 2, 300 barrows (41.4 ± 2.0 kg) were randomly allocated to one of four dietary treatments, with each dietary treatment conducted in five repetitions with 15 pigs each. The four diets in the two growth performance trials were similar to those in nitrogen balance trial 2. Supplementing the diet with 210 or 360 mg/kg NAM reduced urinary nitrogen excretion and total nitrogen excretion and increased nitrogen retention comparted with the control diet (P < 0.05). Compared with the control diet, the low-protein diet with 360 mg/kg NAM reduced faecal, urinary, and total nitrogen excretion (P < 0.05) without affecting nitrogen retention and average daily gain (P > 0.05). Pigs fed the low-protein diet with 360 mg/kg NAM showed a decreased intramuscular fat content in the longissimus thoracis muscle when compared with pigs fed the control diet (P > 0.05). Our results suggest NAM as a suitable dietary additive to reduce dietary CP concentration, maximise nitrogen retention and growth performance, and decrease fat deposition in pigs.

[Recent progress and future prospects of treatment for peritoneal metastasis in gastric cancer].

Peritoneal metastasis is one of the most frequent patterns of metastasis in gastric cancer, and remains a major unmet clinical problem. Thus, systemic chemotherapy remains the mainstay of treatment for gastric cancer with peritoneal metastasis. In well-selected patients, the reasonable combination of cytoreductive surgery, hyperthermic intraperitoneal chemotherapy (HIPEC), and neoadjuvant intraperitoneal chemotherapy with systemic chemotherapy will bring significant survival benefits to patients with gastric cancer peritoneal metastasis. In patients with high-risk factors, prophylactic therapy may reduce the risk of peritoneal recurrence, and improves survival after radical gastrectomy. However, high-quality randomized controlled trials will be needed to determine which modality is better. The safety and efficacy of intraoperative extensive intraperitoneal lavage as a preventive measure has not been proven. The safety of HIPEC also requires further evaluation. HIPEC and neoadjuvant intraperitoneal and systemic chemotherapy have achieved good results in conversion therapy, and it is necessary to find more efficient and low-toxicity therapeutic modalities and screen out the potential benefit population. The efficacy of CRS combined with HIPEC on peritoneal metastasis in gastric cancer has been preliminarily validated, and with the completion of clinical studies such as PERISCOPE II, more evidence will be available.

[Effects of three medical nutrition therapies for weight loss on metabolic parameters and androgen level in overweight/obese patients with polycystic ovary syndrome].

Objective: To investigate the effects of calorie-restricted diet (CRD), high protein diet (HPD), high protein, and high dietary fiber diet (HPD+HDF) on metabolic parameters and androgen level in overweight/obese patients with polycystic ovary syndrome(PCOS). Methods: Ninety overweight/obese patients with PCOS from Peking University First Hospital from October 2018 to February 2020 were given medical nutrition weight loss therapy for 8 weeks and were randomly divided into CRD group, HPD group, and HPD+HDF group, with 30 patients in each group. Body composition, insulin resistance, and androgen level were detected before and after weight loss, and the efficacy of three weight loss therapies was compared through variance analysis and Kruskal-Wallis H test. Results: Eight patients in CRD group quit because they could not strictly complete the follow-up, therefore at the end of weight loss, 22, 30, and 30 patients in CRD group, HPD group and HPD+HDF group, respectively, were included in the final analysis. The baseline ages of the three groups were (31±2) years, (32±5) years and (31±5) years, respectively (P=0.952). After weight loss, the relevant indicators in HPD group and HPD+HDF group decreased more than those in CRD group. The body weight of CRD group, HPD group and HPD+HDF group decreased by 4.20 (11.92, 1.80), 5.00 (5.10, 3.32) and 6.10 (8.10, 3.07) kg, respectively (P=0.038); BMI of the three groups decreased by 0.80 (1.70, 0.40), 0.90 (1.23, 0.50) and 2.20 (3.30, 1.12) kg/m2, respectively (P=0.002); homeostatic model assessment-insulin resistance(HOMA-IR) index decreased by 0.48(1.93, 0.05), 1.21(2.91, 0.18) and 1.22(1.75, 0.89), respectively (P=0.196); and free androgen index(FAI) decreased by 0.23(0.67, -0.04), 0.41(0.64, 0.30) and 0.44(0.63, 0.24), respectively (P=0.357). Conclusions: The three medical nutrition therapies can effectively reduce the weight of overweight/obese patients with PCOS, and improve insulin resistance and hyperandrogenism. Compared with CRD group, HPD group, and HPD+HDF group have better fat-reducing effect, and can better preserve muscle and basal metabolic rate while losing weight.

Guanidinoacetic acid supplementation improves intestinal morphology, mucosal barrier function of broilers subjected to chronic heat stress.

The current study is designed to investigate dietary guanidinoacetic acid (GAA) supplementation on the growth performance, intestinal histomorphology, and jejunum mucosal barrier function of broilers that are subjected to chronic heat stress (HS). A total of 192 male broilers (28-d old) were randomly allocated to four groups. A chronic HS model (at a temperature of 32 °C and 50%-60% relative humidity for 24 h daily) was applied in the experiment. Normal control (NC, ad libitum feeding, 22 °C), HS group (HS, ad libitum feeding, 32 °C), pair-fed group (PF, received food equivalent to that consumed by the HS group on the previous day, 22 °C), guanidinoacetic acid group (HG, ad libitum feeding, supplementing the basal diet with 0.6 g/kg GAA, 32 °C). The experiment lasted from 28 to 35 and 28 to 42 d of age of broilers. Our results showed that broilers subjected to HS had lower average daily feed intake and average daily gain (P < 0.05), higher feed-to-gain ratio and relative length of the small intestine (P < 0.05), as well as lower relative weight and weight per unit length of the small intestine (P < 0.05). HS damaged the small intestinal histomorphology by decreasing the small intestinal VH and the VH/CD (P < 0.05). Compared with the HS group, supplementation with 0.6 g/kg GAA increased jejunal VH and VH/CD (P < 0.05), but decreased relative weight and relative length of the small intestine (P < 0.05). Moreover, in comparison with NC, HS elevated intestinal permeability (D-Lactic acid concentration and diamine oxidase activity) and mRNA expression levels of interleukin-1ß, interleukin-6, and tumor necrosis factor-α (P < 0.05), reduced jejunal mucus thickness, number of goblet cells, IgA + cell density, and mucin2 mRNA expression level of broilers (P < 0.05). Compared with the HS group, dietary GAA elevated jejunal mucus thickness, goblet cell number and IgA+ cell density (P < 0.05), and up-regulated jejunal mRNA expression of interleukin-1ß and tumor necrosis factor-α (P < 0.05). In conclusion, HS impaired growth performance, and the intestinal mucosal barrier function of broilers. Dietary supplementation with 0.6 g/kg GAA alleviated HS-induced histomorphology changes of small intestine and jejunal mucosal barrier dysfunction.

With the global warming getting worse, heat stress (HS) has been a serious problem faced by poultry industry. As one of the main target organs, the intestine is easily affected by HS. Broilers are particularly sensitive to hot temperatures, and HS occurs when temperatures rise above the optimum (16­26 °C). Moreover, ambient humidity below 40% and above 80% also affects broilers adversely. HS can impair intestinal morphology and function of the intestinal barrier. The intestinal mucosal barrier not only plays key roles in nutrient digestion and absorption but also serves as the innate defense barrier fending off noxious substances within the intestinal luminal environment. Therefore, protecting intestinal mucosal barrier from HS is important to animal health. Nutrient regulation is an economical and effective method to alleviate HS of intensively-farmed broiler chickens. The results of current study demonstrated that chronic HS impaired the growth performance and intestinal mucosal barrier function of broilers, while dietary supplementation with 0.6 g/kg guanidinoacetic acid improved intestinal histomorphology and alleviated intestinal barrier dysfunction of broilers subjected to chronic HS, which is beneficial for improving health of broilers.

[Evaluation of vestibular-evoked myogenic potential for functional integrity of the brain stem in Kennedy's disease].

Objective: To investigate whether vestibular-evoked myogenic potentials(VEMPs) can be used to assess brainstem involvement in patients with Kennedy's disease (KD). Method: This was a case-control study.Twenty consecutive patients with genetically confirmed KD and 20 age-and sex-matched healthy subjects were enrolled from November 2018 to September 2020.All subjects were tested for three types of VEMPs, including cervical VEMP (c-VEMP) recorded by the sternocleidomastoid muscle (parameter:p13, n23), masseter VEMP (m-VEMP) recorded by the masseter muscle(parameter: p11), and ocular VEMP (o-VEMP) recorded by the inferior oblique muscle (parameter n10, p15).The latency of each wave, interside peak latency and interpeak latency of c-VEMP, the corrected amplitude and amplitude asymmetry ratio were recorded. Bilateral sternocleidomastoid muscle (SCMM) electromyography (EMG) was performed. The spinal cord and bulbous muscular atrophy functional rating scale (SBMAFRS) was used for assessment. Results: The mean p13 latency of c-VEMP was (15.5±1.4)ms, which was longer than that of the control group[(13.3±0.9)ms](P<0.05); the mean n23 latency was(25.5±1.4)ms, which was also longer than that of the control group[(22.5±1.0)ms] (P<0.05); the difference of bilateral p13[(2.3±0.6)ms] was significantly higher than that of the control group(P<0.05). The abnormal rates of c-, m-, o-VEMP in KD patients were 75%(15/20), 30%(6/20) and 20%(4/20), respectively. There was a significant positive correlation between c-VEMP latency and course of disease in KD patients(left: r=0.715, 0.695, right: r= 0.708, 0.715, both P<0.05). However, c-VEMP latency was negatively correlated with SBMAFRS score (left: r=-0.701, -0.694, right: r=-0.644, -0.685, both P<0.05). Abnormal rates of SCMM EMG in KD group were as follows: 15%(3/20)of patients showed spontaneous potential in resting state and 45% (9/20) of patients exhibited simple recruitment. Conclusions: The c-VEMP latency is a sensitive tool for detecting lower brainstem involvement in patients with KD, and the degree of damage increases with prolongation of disease course. The o-and m-VEMP abnormalities indicate that some KD patients develop upper brainstem damage.

A novel wireless, smartphone-based biofeedback training device for functional defecatory disorders: a pilot study.

BACKGROUND: Functional defecatory disorders (FDDs) are highly prevalent around the world. Biofeedback is an effective treatment for FDDs. Traditionally, this treatment is performed by clinicians in a limited number of hospitals because of procedure-related expenses and a need for a dedicated procedure room. To make the biofeedback therapy more widely available, we have designed a novel wireless, smartphone-based biofeedback device, with the ultimate goal of performing the therapy at home. The aim of this pilot study was to investigate whether the developed device can be employed to treat patients with FDDs in a clinical setting, prior to employing it in a home setting. METHODS: From March 2018 to July 2018, we performed the biofeedback therapy using the newly developed wireless, smartphone-based device in patients with FDDs 30 min daily during weekdays for 2 weeks. A Visual Analogue Scale (VAS) for bowel satisfaction, Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation Quality of Life (PAC-QOL), and a balloon expulsion test were assessed at baseline and after the therapy. RESULTS: Thirteen patients were recruited and ten of them (mean age 70.3 ± 8.9 years, female:male ratio: 3:7) completed the study. Spontaneous bowel movements, complete spontaneous bowel movements, and VAS were all significantly increased after the therapy compared with baseline, respectively (6.5 ± 4.3 vs. 1.5 ± 2.2, p = 0.006; 3.1 ± 2.2 vs. 0.2 ± 0.6, p = 0.002; 49.5 ± 31.0 vs. 12.0 ± 9.2, p = 0.003). There was a significant decrease in the PAC-SYM and PAC-QoL after the biofeedback therapy (0.7 ± 0.6 vs. 1.4 ± 0.3, p = 0.001; 0.7 ± 0. 6 vs. 1.5 ± 0.4, p = 0.001). The therapy reduced the balloon expulsion time significantly (83.9 ± 68.8 s vs. 160.0 ± 36.7 s, p = 0.002). No obvious adverse events related to the procedure itself occurred. CONCLUSIONS: Biofeedback training using the newly developed wireless, smartphone-based device is feasible in the clinic setting, and it seems to be a promising method for improving constipation and related symptoms in patients with FDDs. These findings could be used to develop a much-needed, home-based, suitably powered, randomized, controlled clinical trial.

Bactericidal and antibiofilm properties of Rumex japonicus Houtt. on multidrug-resistant Staphylococcus aureus isolated from milk.

Multidrug-resistant (MDR) Staphylococcus aureus and its biofilm formation have been challenging to control in milk and dairy industries. Biofilms formed by Staph. aureus may result in the failure of antibacterial agents and disinfectants to penetrate the biofilm in an attempt to control contamination. Novel natural antibacterial agents are required to combat MDR bacteria and biofilms. In this study, we evaluated the bactericidal, antibiofilm, and antimotility effects of Rumex japonicus Houtt. (RJH) extract on MDR Staph. aureus isolated from milk. The RJH extract exhibited good antibacterial activity against MDR strains with minimum inhibitory concentrations (MIC) ranging from 0.78 to 6.25 mg/mL and minimum bactericidal concentrations ranging from 3.125 to 12.5 mg/mL. The extract showed strong inhibition of biofilm formation (81.9%) at sub-MIC value and eradication of biofilm at higher concentrations. The motility of Staph. aureus was effectively blocked by the extract. Major compounds emodin, chrysophanol, and physcion were identified in RJH extract using HPLC-linear trap quadrupole (LTQ)/Orbitrap-mass spectrometry. The extract was nontoxic to human epithelial cell lines such as Caco-2 and HT-29 cell lines at concentrations ranging from 0.1 to 0.5 mg/mL, and from 0.1 to 0.75 mg/mL, respectively. These findings suggest that RJH extract could be an alternative to synthetic preservatives in milk and dairy products.

[Appropriate protocol of treatment modulation for seasonal allergic rhinitis caused by cypress pollens].

Objective: To investigate appropriate protocol of treatment modulation for seasonal allergic rhinitis (AR) patients, in order to promote the implementation of personalized medicine. Methods: Total of 124 AR patients allergic to cypress pollens were recruited from January to February 2020 in Department of Allergy in Peking Union Medical College Hospital, 43 males and 81 females with an average age of (41±9) years. The patients were divided into two groups with block randomization method. In the first group, treatment was modulated every two days according to the average daily rhinoconjunctivitis symptom score of the last two days (short-term symptom-score group); while in the second group, therapy regimen was adjusted every week based on the Allergic Rhinitis Control Test (ARCT) score of the last week (long-term ARCT group). The treatment level was up-regulated when the cypress pollen count increased and stayed at a high level (step-up pharmacotherapy stage); and treatment was down-regulated while the pollen count decreased (step-down pharmacotherapy stage). Daily symptom scores, medicine scores, and ARCT scores of the two groups were recorded and compared. Results: During the whole cypress pollen season, the daily rhinoconjunctivitis symptom score of short-term symptom-score group was significantly lower than that in long-term ARCT group(2.4±1.0 vs 2.7±1.0, P<0.01), and the difference between the two groups was more pronounced in the step-up pharmacotherapy stage than that in the step-down pharmacotherapy stage, while there was no statistical difference between the daily medicine scores of the two groups (P>0.05). During the pollen rising period, the ARCT score of short-term symptom-score group was significantly better than that of long-term ARCT group (21(19, 22) vs 20 (17, 21), P=0.049); while in the pollen peak period and decreasing period, the ARCT scores of the two groups showed no statistical difference (P>0.05). The proportion of incompliance with doctor's advice was higher in long-term ARCT group compared to that in short-term symptom-score group (30.1% vs 6.7%, P<0.001). Conclusion: The protocol of treatment modulation for seasonal AR patients allergic to pollens should be developed flexibly according to the variation trend of pollen allergen exposure, so as to implement the idea of personalized medicine.

[Treatment efficacy of dietary supplement Licofor for dry eye associated with meibomian gland dysfunction].

Objective: To evaluate the clinical efficacy of dietary supplement Licofor in the treatment of dry eye associated with meibomian gland dysfunction (MGD). Methods: This was a prospective, randomized controlled clinical trial. Sixty patients [25 males, 35 females, aged (42±13) years] who had dry eye associated with MGD were recruited in Xiangya Hospital of Central South University from December 2018 to October 2019. The patients were equally divided into two groups: 30 cases (60 eyes) in the experimental group and 30 cases (60 eyes) in the control group. All subjects were treated with eye hot compress, artificial tears and antibiotic ointment. After that, the experimental group and control group were received dietary supplementary Licofor or placebo daily for 12 weeks. The symptoms and signs of dry eye, morphology and function of meibomian gland, and inflammatory response were assessed at the beginning, 4th, 8th and 12th week of treatment. Results: After 12 weeks of treatment, statistically significant improvements in ocular surface disease index (OSDI) scores, tear break-up time (TBUT), corneal fluorescein staining (CFS), the morphology of eyelid margin, meibomian gland orifice, meibomian gland expressibility, meibum quality, and periglandular inflammatory cell density were determined in both groups (all P<0.05). In the Licofor group, the improvement of OSDI scores [16.7 (12.5, 20.8) vs 20.8 (18.8, 22.9), P<0.001], the morphology of eyelid margin, meibomian gland orifice and periglandular inflammatory cell density [443 (318, 513) vs 553 (415, 676)/mm2, P=0.002] were more significant (all P<0.05). Conclusion: The combined treatment of licofor and conventional treatment can significantly improve symptoms of dry eye, the morphology of eyelid margin, meibomian gland orifice, meibum quality, and eyelid inflammation response of dry eye associated with MGD.

Artemisia ordosica Polysaccharide Alleviated Lipopolysaccharide-induced Oxidative Stress of Broilers via Nrf2/Keap1 and TLR4/NF-κB Pathway.

Artemisia ordosica is one of the main shrubby perennials belonging to Artemisia species of Asteraceae and could be used in folk Chinese/Mongolian medicine to treat symptoms of various inflammatory ailments. The present study was conducted to investigate the protective effects of dietary Artemisia ordosica polysaccharide (AOP) against lipopolysaccharide (LPS) induced oxidative stress in broilers via Nrf2/Keap1 and TLR4/NF-κB pathway. A total of 192 1-day-old Arbor Acres male broilers were randomly allotted to four treatments with 6 replicates (n = 8): (1) CON group, non-challenged broilers fed basal diet; (2) LPS group, LPS-challenged broilers fed basal diet; (3) AOP group, non-challenged broilers fed basal diet supplemented with 750 mg/kg AOP; (4) LPS+AOP group, LPS-challenged broilers fed basal diet supplemented with 750 mg/kg AOP. The trial included starter phase (d 1-14), stress period Ⅰ (d 15-21), convalescence Ⅰ (d 22-28), stress period Ⅱ (d 29-35) and convalescence Ⅱ (d 36-42). During stress period Ⅰ (on d 15, 17, 19 and 21) and stress period Ⅱ (on d 29, 31, 33 and 35), broilers were injected intra-abdominally either with LPS solution or with an equal amount of sterile saline. The results showed that dietary AOP supplementation alleviated LPS-induced reduction in antioxidant enzyme activity and excessive production of ROS, 8-OHdG and PC in serum of broilers challenged with LPS. Moreover, dietary AOP supplementation alleviated the decrease of T-AOC and activities of SOD, CAT and GPx in liver of broilers challenged with LPS by increasing expression of Nrf2, and inhibiting over-expression of Keap1 both at gene and protein level. Additionally, dietary AOP supplementation decreased the over-production of IL-1ß and IL-6 in liver of broilers challenged by LPS through decreasing mRNA expression of TLR4, MyD88, NF-κB P65, IL-1ß and IL-6, and alleviating the increase of protein expression of TLR4, IKKß, NF-κB P65, IL-1ß, IL-6, and the decrease of protein expression of IkBα. In conclusion, dietary AOP supplementation could alleviate LPS-induced oxidative stress through Nrf2/Keap1 and TLR4/NF-κB pathway.

[The effect on patient life quality of prophylactic treatment to seasonal allergic rhinitis and related transcriptomics research].

Objective: The preseason prophylactic treatment of seasonal allergic rhinitis (AR) caused by pollens could alleviate AR symptoms during the pollen season. This study aimed to evaluate the effect of prophylaxis usage of suplatast tosilate on the life quality of AR patients in the pollen season, and investigate the potential mechanism of action through transcriptomic analysis. Methods: This is a randomized controlled study. AR patients allergic to weed pollens were recruited from Allergy Clinic of Peking Union Medical College Hospital from January 2020 to June 2020, and divided into prophylactic group who started to take suplatast tosilate as prophylaxis 2 weeks before the spread of weed pollens[n=10, 4 men and 6 women with age range of (34±6) years old] and control group who did not use any prophylactic treatment[n=24, 12 men and 12 women with age range of (33±9) years old]. The differences of age (t=0.381, P=0.706) and gender (χ²=0.595, P=0.715) distribution between the patients of two groups were not statistically significant. All the subjects filled in the rhinoconjunctivitis quality of life questionnaire (RQLQ) while onset of AR symptoms, and peripheral blood was drawn for transcriptomic analysis 1 month before and during the pollen season. Differences between groups were statistically analyzed through chi-square test and t test. Results: There was no significant difference in visual analogue scale of rhinitis symptom in the last pollen season between prophylactic group and control group[ 8.0 (6.4, 9.3) vs 7.3 (6.1, 8.0), Z=1.180, P=0.254]. The RQLQ score of prophylactic group was superior to that of control group in the weed pollen season (2.9±0.9 vs 3.7±0.9, t=-2.438, P=0.026). 210 differentially expressed genes of fold change ≥2 were identified, with 147 genes upregulated and 63 genes downregulated in the prophylactic group compared to the control group. Gene Ontology annotation showed that IL-12 and IL-23 related pathways were downregulated in prophylactic group (P=0.006 48). Polymerase Chain Reaction (PCR) verification of differentially expressed genes indicated that the relative expression level of HLA-G in prophylactic group was significantly lower than that in control group (0.23±0.19 vs 1.00±0.49,t=4.016, P=0.006). Conclusion: The prophylactic treatment of suplatast tosilate showed some benefit to the life quality of seasonal AR patients during the pollen season, and the potential mechanism might be related with the downregulation of IL-12 and IL-23 pathways and decreased expression of HLA-G.

[Safety and feasibility of laparoscopic double-flap technique in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction tumors larger than 5 cm].

Objective: To investigate the safety and feasibility of laparoscopic double-flap technique (Kamikawa) in digestive tract reconstruction after proximal gastrectomy for esophagogastric junction (EGJ) leiomyoma and gastrointestinal stromal tumor (GIST) with the maximum diameter >5 cm. Methods: A descriptive case-series study was used to retrospectively analyze the data of patients with EGJ leiomyoma and GIST undergoing laparoscopic-assisted proximal gastrectomy and double-flap technique (Kamikawa) at the Department of Gastrointestinal Surgery, Guangdong Hospital of Traditional Chinese Medicine from September 2017 to March 2019. All the tumors invaded the cardia dentate line, and the maximum diameter was >5 cm. After the exclusion of patients requiring emergency surgery and complicating with severe cardiopulmonary diseases, a total of 4 patients, including 3 males and 1 female with age of 29-49 years, were included in this study. After laparoscopic-assisted proximal gastrectomy, the residual stomach was pulled out of the abdominal cavity and marked with methylene blue at the proximal end 3~4 cm from the anterior wall of the residual stomach in the shape of "H". The gastric wall plasma muscular layer was cut along the "H" shape, and the space between the submucosa and the muscular layer was separated to both sides along the longitudinal incision line to make the seromuscular flap. The residual stomach was put back into the abdominal cavity. Under laparoscopy, 4 stitches were intermittently sutured at the upside of "H" shape and 4-5 cm from the posterior wall of the esophageal stump. The stump of the esophagus was cut open, and the submucosa and mucosa were cut under the "H" shape to enter the gastric cavity. The posterior wall of the esophageal stump was sutured continuously with the gastric stump mucosa and submucosa under laparoscopy. The anterior wall of the esophageal stump was sutured continuously with the whole layer of the residual stomach. The anterior wall of the stomach was sutured to cover the esophagus. The anterior gastric muscle flap was sutured and embedded in the esophagus to complete the reconstruction of digestive tract. The morbidity of intraoperative complications and postoperative reflux esophagitis and anastomosis-related complications were observed. Results: All the 4 patients completed the operation successfully, and there was no conversion to laparotomy. The median operative time was 239 (192-261) minutes, the median Kamikawa anastomosis time was 149 (102-163) minutes, and the median intraoperative blood loss was 35 (20-200) ml. The abdominal drainage tube and gastric tube were removed, and the fluid diet was resumed on the first day after surgery in all the 4 patients. The median postoperative hospitalization time was 6 (6-8) days. Postoperative pathology revealed 3 leiomyomas and 1 GIST. There were no postoperative complications such as anastomotic leakage or stenosis, and no reflux symptoms were observed. The median follow-up time was 22 (11-29) months after the operation, and no reflux esophagitis occurred in any of the 4 patients by gastroscopy. Conclusion: For >5 cm EGJ leiomyoma or GIST, double-flap technique (Kamikawa) used for digestive tract reconstruction after proximal gastrectomy is safe and feasible.

[Impacts of high-voltage electrical burn on serum platelet-related factors and platelet aggregation number in rats and the interventive effect of Xuebijing].

Objective: To explore the effect of high-voltage electrical burn on platelet function and rheological behavior in rats and the interventive effect of Xuebijing. Methods: A total of 280 Sprague Dawley rats of clean grade (aged 8-10 weeks, male and female unlimited) were divided into sham injury group, simple electrical burn group, electrical burn+ saline group, and electrical burn+ Xuebijing group according to the random number table, with 70 rats in each group. Rats in sham injury group were not conducted with electrical current to cause sham injury. Rats in the other three groups were given electrical current with output voltage of 2 kV and current intensity of (1.92 ± 0.24) A for 3 s, which caused high-voltage electrical burn wounds, each with an area of 1 cm×1 cm distributed in the left forelimb at the current inlet and the right hindlimb at the current outlet respectively. Rats in sham injury group and simple electrical burn group were not treated after injury. At post injury minute 2 and on post injury day (PID) 1, 2, 3, 4, 5, and 6, rats in electrical burn+ saline group and electrical burn+ Xuebijing group were intraperitoneally injected with 6 mL/kg saline and 6 mL/kg Xuebijing, respectively. Survival conditions of rats were recorded during the experiment. At 15 min before injury and at post injury hour (PIH) 1, 8, 24, 48, 72, and on PID 7, 10 rats in each group were respectively selected according to the random number table to sacrifice after collection of 5 mL blood under the direct vision of heart. Blood in the volume of 0.05 mL from each rat was taken to make blood smear, and platelet aggregation number was counted under 400 fold field of view using multiple projection microscope. The remaining blood samples were centrifuged to collect supernatant, and the content of platelet-derived growth factor (PDGF), thrombopoietin (TPO), and platelet activating factor (PAF) was detected by enzyme-linked immunosorbent assay. Data were statistically analyzed with analysis of variance for factorial design and Student-Newman-Keuls method. Results: All rats in sham injury group and simple electrical burn group survived during the experiment. One rat in electrical burn+ saline group died on PID 6, and one rat on PID 5 and one rat on PID 6 died in electrical burn+ Xuebijing group. The levels of all indexes among the 4 groups were close at 15 min before injury. The serum content of PDGF, TPO, and PAF and platelet aggregation number of rats in the three electrical burn groups at all time points after injury were higher or more than those in sham injury group, and the first three indexes reached the peak at PIH 8. The serum platelet aggregation number of rats in simple electrical burn group reached the peak at PIH 48, and that in electrical burn+ saline group and electrical burn+ Xuebijing group reached the peak at PIH 72. Among them, the serum content of PDGF of rats in electrical burn+ Xuebijing group at PIH 48, 72 and on PID 7 ((12.8±4.0), (11.6±4.4), (11.0±3.6) ng/mL, respectively) was close to that in sham injury group ((10.4±2.0), (10.4±2.5), (9.8±3.3) ng/mL, respectively, P>0.05). The serum content of TPO of rats in electrical burn+ Xuebijing group at PIH 24, 72 and on PID 7 ((200±52), (192±36), (193±32) ng/mL, respectively) was close to that in sham injury group ((182±30) , (184±41), (183±33) ng/mL, respectively, P>0.05). The serum content of PDGF, TPO, and PAF and platelet aggregation number of rats in electrical burn+ Xuebijing group at every time point after injury was generally lower or less than that in electrical burn+ saline group and simple electrical burn group. Conclusions: Application of Xuebijing treatment after high-voltage electrical burn can decrease the content of PDGF, TPO, and PAF in the serum and reduce the number of platelet aggregation, thereby inhibit platelet activation and improve platelet rheology.