Whole-body PET tracking of a d-dodecapeptide and its radiotheranostic potential for PD-L1 overexpressing tumors

Peptides that are composed of dextrorotary (d)-amino acids have gained increasing attention as a potential therapeutic class. However, our understanding of the in vivo fate of d-peptides is limited. This highlights the need for whole-body, quantitative tracking of d-peptides to better understand how they interact with the living body. Here, we used mouse models to track the movement of a programmed death-ligand 1 (PD-L1)-targeting d-dodecapeptide antagonist (DPA) using positron emission tomography (PET). More specifically, we profiled the metabolic routes of [64Cu]DPA and investigated the tumor engagement of [64Cu/68Ga]DPA in mouse models. Our results revealed that intact [64Cu/68Ga]DPA was primarily eliminated by the kidneys and had a notable accumulation in tumors. Moreover, a single dose of [64Cu]DPA effectively delayed tumor growth and improved the survival of mice. Collectively, these results not only deepen our knowledge of the in vivo fate of d-peptides, but also underscore the utility of d-peptides as radiopharmaceuticals.

Bidirectional regulation of acupuncture: a subgroup analysis of multicenter randomized controlled trial of acupuncture with / 中国针灸

OBJECTIVE@#To explore the bidirectional regulation of acupuncture based on a subgroup analysis of multicenter randomized controlled trial of acupuncture with @*METHODS@#A total of 519 patients were included in the analysis, including 137 patients with constipation type irritable bowel syndrome (IBS-C) (92 cases in the acupuncture group and 45 cases in the polyethylene glycol [PEG] group), and 382 patients with diarrhea type irritable bowel syndrome (IBS-D) (252 cases in the acupuncture group and 130 cases in the pinaverium group). The patients in the acupuncture group were given acupuncture at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Shangjuxu (ST 37), Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) once every other day, 3 times a week. The patients in the PEG group received polyethylene glycol 4000 powder orally, and the pinaverium group received pinaverium bromide tablets orally. All were treated for 6 weeks. The IBS symptom severity score (IBS-SSS) was assessed at baseline, treatment period (2, 4, 6 weeks of treatment) and 12 weeks of follow-up, and the IBS quality of life (IBS-QOL) score was evaluated at the baseline period, 6 weeks of treatment and 12 weeks of follow-up.@*RESULTS@#The total IBS-SSS scores of the two groups of IBS-C patients at 2, 4, 6 weeks of treatment and follow-up of 12 weeks were lower than those in the baseline period (@*CONCLUSION@#Acupuncture with

Correlation between curative effect and 5-HTTLPR polymorphism in treatment of diarrhea-predominant irritable bowel syndrome with acupuncture for regulating / 中国针灸

OBJECTIVE@#To compare the curative effect on diarrhea-predominant irritable bowel syndrome (IBS-D) between acupuncture for regulating @*METHODS@#A total of 231 patients with IBS-D were randomized into an acupuncture group (154 cases) and a western medication group (77 cases) at the ratio of 2 to 1. In the acupuncture group, acupuncture was applied to acupoint regimen for regulating @*RESULTS@#After treatment and in follow-up, the total scores of IBS-SSS in the patients of the two groups were all reduced as compared with those before treatment (@*CONCLUSION@#Acupuncture for regulating

Exosomes in bladder cancer: novel biomarkers and targets / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Exosomes are nanometer-sized vesicles that contain various types of biologically active components, including proteins, nucleic acids, carbohydrates, and lipids, which vary with the type and physiological state of the cell. In recent years, several studies have showed that exosomes can provide new non-invasive diagnostic and prognostic biomarkers in patients affected by cancers, including bladder cancer (BC), and the lipid bilayer membrane structure makes exosomes as promising delivery vehicles for therapeutic applications. Exosomes have the characteristics of high abundance, high stability, tissue specificity, and wide distribution in body fluids, and are secreted as various types by cells in different states, thereby possessing great potential as biomarkers for BC. Herein, we briefly summarize the functions and roles of exosomes in the occurrence and development of BC and the current progress of research on exosomes in BC, while focusing on potential clinical applications of the diagnosis, treatment, and prognosis of BC.

Exploration on the relationship between acupuncture for mind-regulation and flow theory / 中国针灸

Based on the story of Chinese idiom, (a magical and skilled form of craftsmanship) as the breakthrough point, this paper discusses the both (cook) and the experienced acupuncture practitioner have the same high skills and explores the potential relationship between mind-regulation in treatment with acupuncture and flow theory. It is believed that the skills of ancient acupuncture practitioner in mind-regulation with acupuncture is not only a kind of "Tao" mode, but also a state of "flow". By the discussion on mind-regulation and flow theory, modern people may have more clear recognition on the mind regulation in treatment with acupuncture so as to better determine the therapeutic methods of acupuncture for mind-regulation.

Regulatory Effect of Gandou Decoction on Wnt/β-catenin Signaling Pathway in Liver of Wilson Model Copper-loaded Rats / 中国实验方剂学杂志

Objective: To investigate the regulatory effect of Gandou decoction (GDD) on Wnt/β-catenin signaling pathway in hepatic tissue of Wilson disease model copper-loaded rats and its potential mechanism. Method: One hundred and fifteen SD rats were randomly divided into the normal group (n=20) and modeling group. Modeling group was given copper sulfate feed (1 g·kg-1·d-1) and 0.185%copper sulfate solution (0.02 mL·g-1·d-1) for 12 weeks after one week's adaptive feeding, so as to build the copper loaded rats model. After modeling, 95 model rats were randomly divided into model group (n=45), which were fed by modeling method for continuously four weeks; GDD group and penicillamine (PCA) group (n=25 per group). GDD group and PCA group were given GDD(0.4 g·kg-1·d-1) and PCA (0.09 g·kg-1·d-1) by gavage for four weeks. The hepatic tissues of rats in each group were removed after final medication for further research:inductively coupled plasma-atomic emission spectrometry(ICP-AES) was used to detect the content of Cu element in rat livers. Htoxylin eosin(HE) staining was used to detect the pathological changes of rat liver. Immunohistochemistry was used to detect expression of oxidative stress. Western blot was used to detect protein expressions in Wnt/β-catenin of rat livers. Result: Compared with model group, content of Cu element in GDD group was less (PPPβ-catenin, p-glycogen synthase kinase-3β(p-GSK3β),cellular myelocytomatosis oncogene (c-Myc) in GDD and PCA group increased, while p-β-catenin, Dishevelled3, GSK3β protein expressions reduced (PConclusion: GDD can relieve liver damage by promoting excessive copper discharge. GDD decoction can promote the compensatory self-healing of the injured liver tissue by activating Wnt/β-catenin signaling pathway in the hepatic tissue of Wilson disease model copper-loaded rats, so as to reduce the therapeutic effect of hepatocellular injury induced by high copper.

Differences in starting points of active phase and labor duration between preterm and full-term primiparae / 中华围产医学杂志

Objective@#To compare the starting points of the active phase of labor and labor duration between preterm and full-term primiparae and to provide evidence for appropriate labor management.@*Methods@#From January 2013 to December 2016, 925 preterm primiparae (preterm group, 28 to 36+6 weeks) and equal number of full-term primiparae (full-term group, 37 to 41+6 weeks) who delivered in Tianjin Central Hospital of Gynecology Obstetrics were recruited. The starting point of the active labor was defined as the cervical dilatation at the turning point on the cervical dilatation curve where changing from almost flat to the biggest slope. Differences in the starting points and labor duration between the two groups were compared. Statistical analysis was performed using two independent sample t-test, one way analysis of variance and rank-sum test.@*Results@#The duration of the first and second stages [(5.7±2.5) vs (6.8±5.2) h, t=-5.835; (29.9±16.8) vs (34.2±17.2) min, t=-12.637; both P<0.001] and the active phase [M (P95): 1.0 (3.2) vs 1.0 (4.5) h, Z=2.017, P=0.047] of the preterm primiparae were all significantly shorter than those of the full-term primiparae, and the average cervical dilatation rate was significantly accelerated during the active period [M (P5): 6.7 (1.8) vs 5.1 (1.6) cm/h, Z=-2.676, P<0.001]. In the preterm group, women whose starting points of the active phase were at 1 cm, 2 cm, 3 cm, 4 cm, 5 cm and ≥6 cm of cervical dilatation were 25 (2.7%), 275 (29.7%), 258 (27.9%), 203 (21.9%),109 (11.8%) and 55 (5.9%), respectively. While in the full-term group, women whose starting points of the active phase were at 2 cm, 3 cm, 4 cm, 5 cm, 6 cm and >6 cm of cervical dilatation were 74 (8.0%), 208 (22.5%), 287 (31.0%), 168 (18.2%), 127 (13.7%) and 61(6.6%), respectively. In the preterm group, the starting points of the active phase at cervical dilatation≤3 cm, ≤4 cm and ≤5 cm accounted for 60.3% (558/925), 82.3% (761/925) and 94.1% (870/925), respectively. In the full-term group, the percentages of the active phase starting at cervical dilatation≤4 cm, ≤5 cm and ≤6 cm were 61.5% (569/925), 79.7% (737/925) and 93.4% (864/925), respectively.@*Conclusions@#Preterm primiparae may experience shorter labor duration and an earlier start of the active phase than full-term primiparae. The routine labor progression model for full-term primiparae should not be applied to preterm primiparae.

Differences in starting points of active phase and labor duration between preterm and full-term primiparae / 中华围产医学杂志

Objective To compare the starting points of the active phase of labor and labor duration between preterm and full-term primiparae and to provide evidence for appropriate labor management. Methods From January 2013 to December 2016, 925 preterm primiparae (preterm group, 28 to 36+6 weeks) and equal number of full-term primiparae (full-term group, 37 to 41+6 weeks) who delivered in Tianjin Central Hospital of Gynecology Obstetrics were recruited. The starting point of the active labor was defined as the cervical dilatation at the turning point on the cervical dilatation curve where changing from almost flat to the biggest slope. Differences in the starting points and labor duration between the two groups were compared. Statistical analysis was performed using two independent sample t-test, one way analysis of variance and rank-sum test. Results The duration of the first and second stages [(5.7±2.5) vs (6.8±5.2) h, t=－5.835; (29.9±16.8) vs (34.2± 17.2) min, t=－12.637; both P<0.001] and the active phase [M (P95): 1.0 (3.2) vs 1.0 (4.5) h, Z=2.017, P=0.047] of the preterm primiparae were all significantly shorter than those of the full-term primiparae, and the average cervical dilatation rate was significantly accelerated during the active period [M (P5): 6.7 (1.8) vs 5.1 (1.6) cm/h, Z=－2.676, P<0.001]. In the preterm group, women whose starting points of the active phase were at 1 cm, 2 cm, 3 cm, 4 cm, 5 cm and ≥ 6 cm of cervical dilatation were 25 (2.7%), 275 (29.7%), 258 (27.9%), 203 (21.9%), 109 (11.8%) and 55 (5.9%), respectively. While in the full-term group, women whose starting points of the active phase were at 2 cm, 3 cm, 4 cm, 5 cm, 6 cm and >6 cm of cervical dilatation were 74 (8.0%), 208 (22.5%), 287 (31.0%), 168 (18.2%), 127 (13.7%) and 61(6.6%), respectively. In the preterm group, the starting points of the active phase at cervical dilatation≤3 cm, ≤4 cm and ≤5 cm accounted for 60.3% (558/925), 82.3% (761/925) and 94.1% (870/925), respectively. In the full-term group, the percentages of the active phase starting at cervical dilatation≤4 cm, ≤5 cm and ≤6 cm were 61.5% (569/925), 79.7% (737/925) and 93.4% (864/925), respectively. Conclusions Preterm primiparae may experience shorter labor duration and an earlier start of the active phase than full-term primiparae. The routine labor progression model for full-term primiparae should not be applied to preterm primiparae.

Correlation of 5-hydroxytryptamine transporter gene-linked polymorphic region with lifelong premature ejaculation: Progress in studies / 中华男科学杂志

Premature ejaculation (PE), as one of the most common male sexual dysfunctions, has a serious negative impact on the sexual satisfaction of the patients and their sexual partners. Lifelong PE is a most common type and a current focus of research as well. The etiology and pathogenesis of this disease are not yet clear and genetic factors are considered to be closely related to lifelong PE. Studies show that the 5-hydroxytryptamine transporter (5-HTT) gene plays an important role in the development and progression of lifelong premature ejaculation and the 5-HTT-linked polymorphic region (5-HTTLPR) has attracted much attention in recent years. This article presents an overview on the correlation between 5-HTTLPR and lifelong PE.

Acupuncture with regulating mind and spleen for diarrhea irritable bowel syndrome and sleep quality:a randomized controlled trial / 中国针灸

<p><b>OBJECTIVE</b>To compare the effects between acupuncture with regulating mind and spleen and wes-tern medication for diarrhea irritable bowel syndrome (IBS-D).</p><p><b>METHODS</b>Eighty-one patients were randomly at the ratio of 2 to 1 assigned into an acupuncture group (54 cases) and a western medication group (27 cases). Acupuncture with regulating mind and spleen was applied in the acupuncture group for 6 weeks at Baihui (GV 20), Yintang (GV 29), Tianshu (ST 25), Zusanli (ST 36), Shangjuxu (ST 37), Sanyinjiao (SP 6), and Taichong (LR 3), once every other day, 3 times a week. Pinaverium bromide tablet was used orally in the western medication group for 6 weeks, 50 mg a time, 3 times a day. IBS symptom severity score (IBS-SSS) were observed before and after 1-week, 6-week treatment. Pittsburgh sleep quality index (PSQI) was applied before and after 6-week treatment. Also, clinical efficacy was evaluated in the two groups.</p><p><b>RESULTS</b>Three patients dropped out in the acupuncture group, and 1 in the western medication group. Except abdominal distension score after 1-week treatment in the western medication group, single scores and total scores of IBS-SSS apparently reduced in the two groups after 1-week and 6-week treatment (<0.01,<0.05). After 1-week treatment, the abdominal pain score of the acupuncture group was obviously lower than that of the western medication group (<0.05). After 6-week treatment, with abdominal pain relief advantage, other results including the number of pain days, defecation satisfaction,life disturbance degree and total score of the acupuncture group were obviously lower than those of the wes-tern medication group (<0.01,<0.05). After 6-week treatment, the PSQI score and its change before and after treatment in the acupuncture group were superior to those in the western medication group (both<0.05). The relief rate and relief plus obvious effective rate in the acupuncture group were higher than those in the western medication group[51.0% (26/51) vs 19.2% (5/26),<0.01; 64.7% (33/51) vs 34.6% (9/26),<0.05].</p><p><b>CONCLUSIONS</b>Acupuncture with regulating mind and spleen for diarrhea irritable bowel syndrome can more effectively relieve abdominal pain than pinaverium bromide tablet at the early stage. Its total effect and single effects are better at the later stage on abdominal pain, seizure frequency, defecation satisfaction, life disturbance, and sleep quality.</p>

Meta analysis of acupuncture-moxibustion in treatment of irritable bowel syndrome / 中国针灸

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy and safety of acupuncture-moxibustion in treatment of irritable bowel syndrome systematically.</p><p><b>METHODS</b>Clinical randomized controlled trials on treatment of irritable bowel syndrome with acupuncture-moxibustion were collected. Through retrieval of CNKI (1979 - December of 2011) and VIP (1979- December of 2011), randomized and quasi-randomized controlled clinical trials on treatment of irritable bowel syndrome with control study between acupuncture and sham acupuncture or western medication were included. The test bias risk and quality assessment of each experiment were carried out by two researchers in accordance with the Cochrane Handbook 5.1.0 standard. And RevMan 5.1.6 software was adopted for the Meta analysis.</p><p><b>RESULTS</b>Eleven researches were included with totally 969 patients. Meta analysis shows that the effective rate of the combined methods of acupuncture and moxibustion [RR = 1. 27, 95% CI ( 1.09, 1.49)] is superior to conventional western medication treatment.</p><p><b>CONCLUSION</b>Acupuncture-moxibustion for irritable bowel syndrome is better than the conventional western medication treatment.</p>

Observation on theraputic effect of five-needle-in-nape acupuncture for treatment of poststroke pesudobulbar paralysis dysphagia / 中国针灸

<p><b>OBJECTIVE</b>To compare the therapeutic effect of five-needle-in-nape acupuncture treatment and the routine acupuncture treatment for poststroke pesudobulbar paralysis dysphagia.</p><p><b>METHODS</b>Sixty cases were randomly divided into a five-needle-in-nape (FNN) group and a routine acupuncture (RA) group (n=30 in each group). Ya-men (GV 15), Tianzhu (BL10), Zhiqiang acupoint (Extra) were needled and the training of swallowing was practiced when needling in FNN group. Lianquan (CV 23), Tongli (HT 5), Zhaohai (KI 6) were needled in RA group. The course of acupuncture treatment consisted of needling once time every day, six times a week for two weeks. The therapeutic effects were evaluated after two courses of acupuncture treatment.</p><p><b>RESULTS</b>The effective rate was 93.3% in FNN group, better than that of 80.0% in RA group (P < 0.05).</p><p><b>CONCLUSION</b>The therapeutic effect in FNN group was better than that of RA group for poststroke pesudobulbar paralysis dysphagia.</p>