Effects of dietary methionine supplementation from different sources on growth performance and meat quality of barrows and gilts.

Methionine is indispensable for growth and meat formation in pigs. However, it is still unclear that increasing dietary sulphur-containing amino acid (SAA) levels using different methionine sources affects the growth performance and meat quality of barrows and gilts. To investigate this, 144 pigs (half barrows and half gilts) were fed the control (100% SAA, CON), DL-Methionine (125% SAA, DL-Met)-supplemented, or OH-Methionine (125% SAA, OH-Met)-supplemented diets during the 11-110 kg period. The results showed that plasma methionine levels varied among treatments during the experimental phase, with increased plasma methionine levels observed following increased SAA consumption during the 25-45 kg period. In contrast, pigs fed the DL-Met diet had lower plasma methionine levels than those fed the CON diet (95-110 kg). Additionally, gilts fed the DL-Met or OH-Met diets showed decreased drip loss in longissimus lumborum muscle (LM) compared to CON-fed gilts. OH-Met-fed gilts had higher pH45min values than those fed the CON or DL-Met diets, whereas OH-Met-fed barrows had higher L45min values than those fed the CON or DL-Met diets. Moreover, increased consumption of SAA, regardless of the methionine source, tended to decrease the shear force of the LM in pigs. In conclusion, this study indicates that increasing dietary levels of SAA (+25%) appeared to improve the meat quality of gilts by decreasing drip loss and increasing meat tenderness.

Clinical efficacy of targeted therapy, immunotherapy combined with hepatic artery infusion chemotherapy (FOLFOX), and lipiodol embolization in the treatment of unresectable hepatocarcinoma.

To evaluate the clinical efficacy of targeted therapy and immunotherapy combined with hepatic arterial infusion chemotherapy (HAIC) of FOLFOX and lipiodol embolization in the treatment of unresectable hepatocellular carcinoma. Patients included in the study were those who received targeted therapy and immunotherapy combined with HAIC of FOLFOX and lipiodol embolization in Zhongshan People's Hospital from December 2020 to June 2021 for unresectable hepatocellular carcinoma. Evaluation indicators included objective response rate (ORR), median progression-free survival (mPFS), median duration of response (mDOR), 1-year overall survival rate (OS), surgical conversion rate, and adverse events. Treatment response was assessed using Response Evaluation Criteria in Solid Tumors (mRECIST and RECIST v1.1). A total of 35 patients were included in this study, 30 of whom completed treatment evaluation. According to mRECIST evaluation criteria, the objective response rate (ORR) was 83.3% (25/30); the complete response (CR) was 60% (18/30); the partial response (PR) was 23.3% (7/30), and stable disease (SD) was 16.7% (5/30). The mDOR was 10.3 months (95% Cl: 8.27-NE), and the mPFS was 13.2 months (95% CI: 10.3-NE); the surgical conversion rate was 30.0% (9/30). The 1-year OS was 96.7%. There were no serious surgical complications and grade 4 or 5 adverse events of targeted therapy, immunotherapy and HAIC. Some patients had grade 3 adverse reactions in gastrointestinal toxicity or hepatotoxicity, and the adverse reactions were improved after corresponding symptomatic treatment. We concluded that HAIC of FOLFOX and lipiodol embolization combined with targeted therapy and immunotherapy had a significant curative effect in the treatment of unresectable hepatocellular carcinoma, with no serious adverse reactions and a high rate of surgical conversion rate.

[Prognostic significance of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma treated with CHOP-based chemotherapy].

Objective: To validate the prognostic value of NCCN-International Prognostic Index (NCCN-IPI) for patients with peripheral T-cell lymphoma (PTCL) treated with CHOP-based chemotherapy. Methods: A retrospective analysis in 162 PTCL patients who were initially diagnosed and treated in Rui Jin Hospital from January 2003 to May 2013 was conducted. Baseline characteristics were collected, and survival analysis was performed according to the IPI and NCCN-IPI model. Results: The estimated 5-year overall survival (OS) rate and progression free survival (PFS) rate were 33% and 20%, with median OS and PFS of 17.0 months and 9.2 months, respectively. Multivariate analysis indicated ECOG score (PFS: HR=2.418, 95%CI 1.535-3.809, P<0.001; OS: HR=2.347, 95%CI 1.435-3.839, P= 0.001) , specific extra-nodal sites (PFS: HR=1.800, 95%CI 1.216-2.665, P=0.003; OS: HR=1.608, 95% CI 1.054-2.454, P=0.027) and pathology type (PFS: HR=0.424, 95% CI 0.184-0.975, P=0.043; OS: HR=0.276, 95% CI 0.087-0.877, P=0.029) were independent prognostic factors of OS and PFS for the patients with PTCL. The survival rates of low risk patients based on NCCI-IPI were remarkably higher than the counterparts based on IPI (5-year OS 74% vs 54%, χ(2)=5.041, P=0.025, 5-year PFS 50% vs 38%, χ(2)= 5.295, P=0.021) . NCCN-IPI was outstanding to identify the subgroup of low risk patients with PTCL, who may benefit from conventional chemotherapy such as CHOP or CHOP-like regimen. Conclusion: NCCN-IPI is more powerful for low risk PTCL patients and a strong supplement for IPI.

[Efficacy of additional two cycles of rituximab administration for patients with diffuse large B-cell lymphoma in first remission].

Objective: To analyze the efficacy of additional two cycles of rituximab administration for Chinese patients with diffuse large B-cell lymphoma (DLBCL) in first complete remission (CR) after six cycles of standard 21-day rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP21). Methods: Retrospective analysis was performed in 351 patients with DLBCL diagnosed from March 2003 to March 2012. International Prognosis Index (IPI), Revised (R)-IPI and National Comprehensive Cancer Network (NCCN)-IPI were calculated for each patient. Patients were divided into GCB and non-GCB subtype according to Han's Classification. Progression-free survival (PFS) and overall survival (OS) were analyzed using Kaplan-Meier methods. Results: 282 (80.3%) patients achieved CR and 132 (46.8%) of 282 cases received additional two rituximab therapy. The other 150 (53.2%) patients entered into observation on the intention of the patients. No significant difference was observed in baseline characteristics between the two groups. 3-year estimated PFS for additional rituximab group and observation group were 80.0% and 78.1% (P=0.334), while 3-year estimated OS were 89.7% vs. 86.1% (P=0.452). By subgroup analysis, prolonged PFS were observed in R-IPI low-risk and NCCN-IPI low-risk patients after additional two rituximab cycles. Conclusion: For patients with DLBCL in first remission after standard six cycles of R-CHOP21 regimen, additional two cycles of rituximab maintenance did not significantly improve the general prognosis, but low-risk subgroups of R-IPI and NCCN-IPI could benefit from this regimen.

Wuling Capsule for Major Depressive Disorder: A Meta-analysis of Randomised Controlled Trials.

INTRODUCTION: In China, Wuling capsule, a traditional Chinese medicine consisting of Wuling mycelia of Xylaria nigripes (Kl.) Sacc (a rare type of fungus), is used to treat major depressive disorders. A meta-analysis of randomised controlled trials was performed to compare the efficacy and safety of Wuling capsule alone with Wuling capsule-antidepressant combination in the treatment of major depressive disorders. METHODS: Two assessors independently selected studies, extracted data, and conducted quality assessment and data synthesis. Standard mean difference, risk ratio (RR) ± 95% confidence interval (CI), the number needed to treat, and the number needed to harm were analysed. RESULTS: A total of 12 randomised controlled trials (880 patients; mean age ± standard deviation, 39.7 ± 12.5 years; male patients, 41%) were identified, including 4 trials with Wuling capsule alone (n = 340) and 8 with Wuling capsule-antidepressant (sertraline, mianserin, mirtazapine, and paroxetine) combination (n = 540). The mean length of trial was 5.7 ± 1.3 weeks. Meta-analysis of symptomatic improvement at last-observation endpoint and study-defined response and remission revealed no significant differences between the Wuling capsule alone and antidepressant monotherapy. The Wuling capsule-antidepressant cotreatment was superior to antidepressant monotherapy in symptomatic improvement at last-observation endpoint (standard mean difference: -0.46, p = 0.001) as well as study-defined response (68.4% vs. 56.0%, RR = 1.23; p = 0.03) and remission (46.5% vs. 34.5%, RR = 1.35; p = 0.05). Wuling capsule was associated with fewer adverse drug reactions than antidepressant monotherapy. CONCLUSIONS: Adjunctive Wuling capsule may augment the effects of antidepressants and may be associated with fewer adverse drug reactions. More large-scale and rigorously designed randomised controlled trials with large sample size are warranted to clarify the effectiveness of Wuling capsule for major depressive disorders.

The effect of pre-treatment with transcutaneous electrical acupoint stimulation on the quality of recovery after ambulatory breast surgery: a prospective, randomised controlled trial.

Electroacupuncture has been demonstrated to be effective at alleviating pain and postoperative side-effects. Our aim was to investigate whether transcutaneous electric acupoint stimulation, a low-skill alternative to needle-based electroacupuncture, could improve the quality of recovery after ambulatory surgery. Seventy-two women scheduled for cosmetic breast surgery were randomly allocated to transcutaneous electric acupoint stimulation or sham groups. Patients in the transcutaneous electric acupoint stimulation group received 30 min of electrical stimulation at three acupoints located on the hand and forearm before the induction of general anaesthesia. We found significant mean (SD) differences between the transcutaneous electric acupoint stimulation and sham groups in the mean (SD) length of recovery room stay (35.6 (12.9) min vs 48.3 (16.3) min, p = 0.01), time to removal of the laryngeal mask airway (10.2 (2.5) min vs 17.8 (4.4) min, p = 0.01), and time to reorientation of the patient (14.6 (3.2) min vs 26.5 (5.0) min, p = 0.01). Further, postoperative pain scores and the incidence of side-effects were all lower in the transcutaneous electric acupoint stimulation group. In conclusion, transcutaneous electric acupoint stimulation can significantly improve the quality of recovery and decrease the incidence of anaesthesia-related side-effects for patients undergoing ambulatory surgery.

Transcutaneous electric acupoint stimulation reduces intra-operative remifentanil consumption and alleviates postoperative side-effects in patients undergoing sinusotomy: a prospective, randomized, placebo-controlled trial.

BACKGROUND: Although opioids are widely used as analgesics in general anaesthesia, they have unpleasant side-effects and can delay postoperative recovery. Acupuncture and related techniques are effective for acute and chronic pain, and reduces some side-effects. We assessed the effect of transcutaneous electric acupoint stimulation (TEAS) on intra-operative remifentanil consumption and the incidences of anaesthesia-related side-effects. METHODS: Sixty patients undergoing sinusotomy were randomly assigned to TEAS or control group. TEAS consisted of 30 min of stimulation (6-9 mA, 2/10 Hz) on the Hegu (LI4), Neiguan (PC6), and Zusanli (ST36) before anaesthesia. The patients in the control group had the electrodes applied, but received no stimulation. Bispectral index was used to monitor the depth of anaesthesia. Perioperative haemodynamics were recorded, and peripheral blood samples were collected to measure the levels of mediators of surgical stress. The primary end point was intraoperative remifentanil consumption and the secondary endpoints were recovery quality and anaesthesia-related side-effects. RESULTS: Patients in the TEAS group required 39% less remifentanil during surgery than controls [0.0907 (SD 0.026) µg kg(-1) min(-1) vs 0.051 (0.018) µg kg(-1) min(-1)]. There were no differences in intra-operative haemodynamics or surgical stress between groups. However, the time to extubation and recall in the control group was 16.8 (6.8) min and 23.0 (5.0) min, respectively, significantly longer than that in the TEAS group (P<0.01). TEAS also decreased the incidence of dizziness and pruritus within the first 24 h after surgery (P<0.01). CONCLUSION: The use of TEAS significantly reduced intra-operative remifentanil consumption and alleviated postoperative side-effects in patients undergoing sinusotomy. CLINICAL TRIAL REGISTRATION: The trial was registered at clinicaltrials.gov (NCT01700855).

Functional recovery of stepping in rats after a complete neonatal spinal cord transection is not due to regrowth across the lesion site.

Rats receiving a complete spinal cord transection (ST) at a neonatal stage spontaneously can recover significant stepping ability, whereas minimal recovery is attained in rats transected as adults. In addition, neonatally spinal cord transected rats trained to step more readily improve their locomotor ability. We hypothesized that recovery of stepping in rats receiving a complete spinal cord transection at postnatal day 5 (P5) is attributable to changes in the lumbosacral neural circuitry and not to regeneration of axons across the lesion. As expected, stepping performance measured by several kinematics parameters was significantly better in ST (at P5) trained (treadmill stepping for 8 weeks) than age-matched non-trained spinal rats. Anterograde tracing with biotinylated dextran amine showed an absence of labeling of corticospinal or rubrospinal tract axons below the transection. Retrograde tracing with Fast Blue from the spinal cord below the transection showed no labeled neurons in the somatosensory motor cortex of the hindlimb area, red nucleus, spinal vestibular nucleus, and medullary reticular nucleus. Retrograde labeling transsynaptically via injection of pseudorabies virus (Bartha) into the soleus and tibialis anterior muscles showed no labeling in the same brain nuclei. Furthermore, re-transection of the spinal cord at or rostral to the original transection did not affect stepping ability. Combined, these results clearly indicate that there was no regeneration across the lesion after a complete spinal cord transection in neonatal rats and suggest that this is an important model to understand the higher level of locomotor recovery in rats attributable to lumbosacral mechanisms after receiving a complete ST at a neonatal compared to an adult stage.

Next-generation spirobenzazepines: identification of RWJ-676070 as a balanced vasopressin V1a/V2 receptor antagonist for human clinical studies.

We have continued to explore spirobenzazepines as vasopressin receptor antagonists to follow up on RWJ-339489 (2), which had advanced into preclinical development. Further structural modifications were pursued to find a suitable backup compound for human clinical studies. Thus, we identified carboxylic acid derivative 3 (RWJ-676070; JNJ-17158063) as a potent, balanced vasopressin V(1a)/V(2) receptor antagonist with favorable properties for clinical development. Compound 3 is currently undergoing human clinical investigation.

Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis.

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a role in the modulation of food intake and mood. In rodents, the actions of MCH are mediated via the MCHR1 receptor. The goal of this study was to investigate the effects of acute (1 h) and chronic (28 days) p.o. dosing of a novel MCHR1 antagonist, N-[3-(1-{[4-(3,4-difluorophenoxy)-phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847), in three mouse models predictive of antidepressant/anxiolytic-like activity: novelty suppressed feeding (NSF) in 129S6/SvEvTac mice and light/dark paradigm (L/D) and forced swim test (FST) in BALB/cJ mice. A significant increase in the time spent in the light compartment of the L/D box was observed in response to acute and chronic treatment with SNAP 94847. An anxiolytic/antidepressant-like effect was found in the NSF test after acute and chronic treatment, whereas no effect was observed in the FST. Because neurogenesis in the dentate gyrus has been shown to be a requirement for the effects of antidepressants in the NSF test, we investigated whether neurogenesis was required for the effect of SNAP 94847. We showed that chronic treatment with SNAP 94847 stimulated proliferation of progenitors in the dentate gyrus. The efficacy of SNAP 94847 in the NSF test, however, was unaltered in mice in which neurogenesis was suppressed by X-irradiation. These results indicate that SNAP 94847 has a unique anxiolytic-like profile after both acute and chronic administration and that its mechanism of action is distinct from that of selective serotonin reuptake inhibitors and tricyclic antidepressants.

Triterpenoid saponins from Clematis tangutica.

Two new triterpenoid saponins, tanguticoside A and B along with seven known saponins vitalboside B, alpha-hederin, saponin PK, beta-hederin, saponin PJ3, saponin PE, and ciwujianoside A were isolated from aerial part of Clematis tangutica. By chemical and spectral evidences methods, the structures of tanguticoside A and B were elucidated as 3-O-beta-D-glucopyranosylhederagenin 28-O-alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside and 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosylhederagenin 28-O-alpha-D-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside, respectively.

Molecular determinants of the modulation of cyclic nucleotide-activated channels by calmodulin.

The action of calmodulin (CaM) on target proteins is important for a variety of cellular functions. We demonstrate here, however, that the presence of a CaM-binding site on a protein does not necessarily imply a functional effect. The alpha-subunit of the cGMP-gated cation channel of human retinal cones has a CaM-binding site on its cytoplasmic N-terminal region, but the homomeric channel that it forms is not functionally modulated by CaM. Mutational analysis based on comparison to the highly homologous olfactory cyclic nucleotide-gated channel alpha-subunit, which does form a CaM-modulated channel, indicates that residues downstream of the CaM-binding domain on these channels are also important for CaM to have an effect. These findings suggest that a CaM-binding site and complementary structural features in a protein probably evolve independently, and an effect caused by CaM occurs only in the presence of both elements. More generally, the same may be true for other recognized binding sites on proteins for modulators or activators, so that a demonstrated physical interaction does not necessarily imply functional consequence.

Isolation and mapping of a family of putative zinc-finger protein cDNAs from rice.

To understand the functions of rice homologues of the Arabidopsis flowering-time gene CONSTANS (CO) and salt-tolerance gene STO, we performed a similarity search of the single-run sequence data of cDNA clones accumulated by the Rice Genome Research Program, and isolated seven rice cDNA clones (S3574, C60910, S12569, R2931, R1479, R1577, and E10707) coding for proteins containing one of two zinc-finger-like motifs. Comparison of the deduced amino acid sequences between these cDNAs and the CO gene revealed significant similarities (46%-61%) in the region of zinc-finger motifs. A domain having a high content of basic amino acids at the C-terminus of the CO protein was found in the corresponding region of proteins predicted by from cDNAs S3574, C60910, and S12569. Two amino acid sequences, "CCADEAAL" and "FCV(L)EDRA," which were present inside each zinc-finger in the Arabidposis regulatory protein STO, were also found in each of the two zinc-finger regions of proteins predicted from cDNAs R2931, R1479, R1577, and E10707. Using restriction fragment length polymorphism (RFLP) linkage analysis, we determined the chromosomal location of the seven cDNA clones. The position of R2931 on the RFLP linkage map was closely linked to Hd-3, one of the putative quantitative trait loci (QTL) controlling heading date in rice.

[Experimental study on hypoglycemic effect of YTY granules].

OBJECT: To perform experimental pharmacodynamic evaluation of a new TCM antidiabetic drug Yitangyin (YTY). METHODS: Experimkental streptozotocin induced rat diabetes models were subjected YTY treatment and the hypoglycemic effect was evaluated. The proved TCM Yusanxiao (YSX) was used as contrast. RESULTS: The low, middle and high dose YTY groups exhibited significant hypoglycemic effects on the model rats. The efficiency was comparable with YSX. CONCLUSION: The TCM YTY granule is an effective hypoglycmeic agent.

In vitro studies on cellular and molecular mechanisms of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia: As2O3 induces NB4 cell apoptosis with downregulation of Bcl-2 expression and modulation of PML-RAR alpha/PML proteins.

It has been shown recently in China that arsenic trioxide (As2O3) is a very effective treatment for acute promyelocytic leukemia (APL). APL patients resistant to all-trans retinoic acid (ATRA) and conventional chemotherapy can still respond to AS2O3. In this study, we addressed the possible cellular and molecular mechanisms of this treatment by using NB4 cells as a model. The results show that: (1) As2O3 triggers relatively specific NB4 cell apoptosis at micromolar concentration, as proved by morphology, histogramic related nuclear DNA contents, and DNA gel eletrophoresis. (2) As2O3 does not influence bax, bcl-x, c-myc, and p53 gene expression, but downregulates bcl-2 gene expression at both mRNA and protein levels. (3) As2O3 induces a significant modulation of the PML staining pattern in NB4 cells and HL-60 cells. The micropunctates characteristic of PML-RAR alpha in NB4 cells dissappear after treatment with As2O3, whereas a diffuse PML staining occurs in the perinuclear cytoplasmic region. In addition, a low percentage of untreated NB4 cells exhibits an accumulation of PML positive particles in a compartment of cytoplasm. The percentage of these cells can be significantly increased after As2O3 treatment. A similar PML staining pattern is observed in apoptotic cells. (4) ATRA pretreatment does not influence As2O3-induced apoptosis. These results suggest that induction of cell apoptosis can be one of the mechanisms of the therapeutic effect of As2O3. Moreover, this apoptosis induction occurs independently of the retinoid pathway and may be mediated, at least partly, through the modulation of bcl-2, as well as PML-RAR alpha and/ or PML proteins.

Pharmacokinetics and efficacy of low-dose all-trans retinoic acid in the treatment of acute promyelocytic leukemia.

A clinical trial was conducted in order to evaluate the therapeutic effect and side-effects of low-dose ATRA in the treatment of acute promyelocytic leukemia (APL). We compared the pharmacokinetic features in normal individuals with single oral ATRA at 15 mg/m2 and 45 mg/m2, respectively. The results showed that maximal plasma concentration (Cpmax) with oral 15 mg/m2 ATRA was high enough (10(-6) M) to induce APL cell differentiation. Based on these results, 27 cases of de novo APL patients were treated with continuous oral ATRA at the dose of 15-20 mg/m2/day and 24/26 evaluable cases (92%) achieved clinical CR after 13 to 67 days of ATRA treatment. No patient experienced RAS and DIC. The Cpmax with a single dose of ATRA on day 1 of treatment and immediately at CR obtained with continuous ATRA in three cases demonstrated similar values in one patient and an approximately two-fold decrease in two patients. More importantly, compared with a relatively well-matched historic group of 20 APL patients treated with high-dose ATRA, our results suggest that low-dose ATRA is as effective as high-dose in treating APL patients and may provide advantages through decreased hyperleukocytosis and other side-effects.

[Pharmacological studies of Polygonum capitatum Buch-Ham. ex D. Don].

The pharmacological effect of aqueous extract of Polygonum capitatum has been studied. The experimental results show that Polygonum capitatum markedly decreases WBC and RBC in urine of pyelonephritis mode in rats, the death rate of Escherichia coli infected mice, and the temperature of feverish rabbits. It has also been found that after oral administration of Polygonum capitatum the animal urine markedly inhibits the growth of Escherichia coli, but diuretic action of the herb has not been observed.

[Tube pregnancy treated with trichosanthin and followed up by hysterosalpingography].

Twenty cases of unruptured tube pregnancy were treated with Trichosanthin intramuscularly given. Only two cases were eventually operated, so the effective rate was 90%. The hysterosalpingography was taken in 14 of 18 cases who was willing to accept the procedure at 0.5-1.5 year after the conservative treatment. Both tubes were patent in 10 of 14 cases, the rate of patency was 71.4%.

Effects of liuwei dihuang wan [symbol: see text:bd and some other TCM drugs on bone biomechanics and serum 25 (OH)D3 content in rats.

After a relatively long-term injection of hydrocortisone into rats, the strength of bone (anti-stress capacity) reduced evidently, while the rigidity (anti-deformity capacity) increased markedly (ie, bone fragility elevated). At the same time, the content of serum 25(OH)D3 decreased remarkably. After oral administration of Liuwei Dihuang Wan ([see symbol: see text]), anti-stress capability of bone increased evidently and its anti-deformity capability returned to normal; however, there was no elevation of serum 25(OH)D3 content. The effect of Longmu Zhuanggu Chongji ([see symbol: see text]) or Jisheng Shenqi Wan (see symbol: see text]) was lower than that of Liuwei Dihuang Wan. The experiments suggests that Liuwei Dihuang Wan is beneficial to preventing and curing osteoporosis, but no correlation between its mechanism and the metabolism of 25(OH)D3 was demonstrated.