Acupuncture, an effective treatment for post-stroke neurologic dysfunction.

Stroke episodes represent a significant subset of cerebrovascular diseases globally, often resulting in diverse neurological impairments such as hemiparesis, spasticity, dysphagia, sensory dysfunction, cognitive impairment, depression, aphasia, and other sequelae. These dysfunctions markedly diminish patients' quality of life and impose substantial burdens on their families and society. Consequently, the restoration of neurological function post-stroke remains a primary objective of clinical treatment. Acupuncture, a traditional Chinese medicine technique, is endorsed by the World Health Organization (WHO) for stroke treatment due to its distinct advantages in managing cerebrovascular diseases, including ischemic stroke. Numerous clinical studies have substantiated the efficacy of acupuncture in ameliorating neurological dysfunctions following stroke. This review systematically examines the improvements in post-stroke neurological dysfunction attributable to acupuncture treatment and elucidates potential mechanisms of action proposed in recent years. Additionally, this article aims to present novel therapeutic concepts and strategies for the clinical management of post-stroke neurological dysfunction.

Mechanisms of acupuncture for primary dysmenorrhea based on PI3K/Akt/mTOR signaling pathway in rats. / 基于PI3K/Akt/mTORä¿¡å·é€šè·¯æŽ¢è®¨ç”µé’ˆæ²»ç–—åŽŸå‘æ€§ç—›ç»å¤§é¼ çš„æœºåˆ¶.

OBJECTIVES: To observe the effect of electroacupuncture(EA) on phosphatidylinositol-3-kinases(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR) signaling pathway of uterus tissue in rats with primary dysmenorrhea(PDM), so as to investigate its mechanisms underlying improvement of PDM. METHODS: Thirty healthy non-pregnant female SD rats were randomly divided into blank, model and EA groups, with 10 rats in each group. The PDM model was established by subcutaneous injection of estradiol diphenhydrate combined with intraperitoneal injection of oxytocin. For rats of the EA group, EA(50 Hz, a tolerable current intensity) was applied to "Guanyuan"(CV4) and bilateral "Sanyinjiao"(SP6) for 20 min, once a day for 10 consecutive days. The number of writhing, wri-thing score, and writhing latency were observed. The uterine histopathological changes were observed by H.E. staining, and the ultrastructural changes of uterine tissue cells in each group were observed by transmission electron microscopy. The contents of prostaglandin E2(PGE2), prostaglandin F2α(PGF2α) and ratios of PGF2α/PGE2 in the serum and uterine tissue were detected by ELISA. The relative expression levels of PI3K, Akt and mTOR and their phosphorylation proteins in the uterine tissue were detected by Western blot and the ratios were calculated. RESULTS: Compared with the blank group, the number and score of writhing, latency of writhing, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in the serum and uterine tissue, and the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR in the uterine tissue were significantly increased in the model group(P<0.01, P<0.05), while contents of PGE2 in the serum and uterine tissue were reduced(P<0.05). In comparison with the model group, the number of writhing and writhing score, pathological injury score, contents of PGF2α and ratios of PGF2α/PGE2 in both the serum and uterine tissue, the levels of p-PI3K/PI3K, p-Akt/Akt and p-mTOR/mTOR were obviously decreased(P<0.05, P<0.01), whereas the writhing latency was considerably prolonged in the EA group(P<0.01), with elevated contents of PGE2 in the serum and uterine tissue(P<0.05). H.E. staining showed slight dilation of uterine glandular cavity, and severe endometrial edema with extensive cell shedding and a large number of vacuole-like degeneration, apoptosis, pyknosis or fragmentation or disappearance of the nucleus, and neutrophil infiltration in the model group, which were relatively milder in the EA group. Ultrastructural results showed irregular fibroblasts of uterine tissue cells, obvious cytoplasmic edema, reduction in cytoplasmic electron density, seriously irregular nuclei, severe edema of mitochondria with dissolved matrix, fracture and disappearance of mitochondrial crests and vacuolation, and moderate dilation of rough endoplasmic reticulum in the model group, which were milder in the EA group. CONCLUSIONS: EA can improve pain and uterine inflammatory response in PDM rats, which may be associated with its functions in reducing uterine PGF2α and down-regulating PI3K/Akt/mTOR signaling.

[Effects of electroacupuncture on N-methyl-D-aspartate receptor and mitogen activated protein kinase in spinal cord of rats with primary dysmenorrhea].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on the expression levels of N-methyl-D-aspartate receptor (NMDAR), extracellular signal-regulated kinase (ERK)1/2, p38 mitogen activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in the spinal cord of rats with primary dysmenoramia (PDM), so as to explore the underlying mechanism of EA treating PDM. METHODS: Thirty female SD rats were randomly divided into normal group, model group and EA group, with 10 rats in each group. The PDM rat model was established by subcutaneous injection of estradiol benzoate and oxytocin into the thigh. At the same time of modeling, rats in the EA group were treated with EA (50 Hz) at "Sanyinjiao" (SP36) and "Guanyuan" (CV4) once daily, 20 min each time, for 10 consecutive days. The writhing times, writhing score and writhing latency were observed within 30 min after oxytocin injection. The uterine pathological morphology was observed by HE staining, and pathological score was calculated. Serum prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2) were determined by ELISA. The protein expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were detected by Western blot. RESULTS: Compared with the normal group, the writhing times and writhing score were significantly increased (P<0.05); the endometrial epithelial cells showed vacuolar degeneration, death and hyperemia, the uterine pathological score was increased (P<0.05); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly increased (P<0.01), while the content of serum PGE2 was significantly decreased (P<0.01); the expression levels of NMDAR, ERK1/2, p38MAPK and JNK in spinal cord were significantly increased (P<0.05, P<0.01) in the model group. Compared with the model group, the writhing times and writhing score were significantly decreased (P<0.05), the writhing latency was prolonged (P<0.05); the endometrial epithelial cells still showed vacuolar degeneration, death and hyperemia, and the uterine pathological score was decreased (P<0.01); the content of serum PGF2α and the ratio of PGF2α/PGE2 were significantly decreased (P<0.01), while the content of serum PGE2 was significantly increased (P<0.01); the protein expression levels of ERK1/2 and JNK in spinal cord were significantly decreased (P<0.01) in the EA group. CONCLUSION: EA intervention at SP36 and GV4 has obvious analgesic effect on PDM rats, and its mechanisms may be related to reducing serum prostaglandin, alleviating uterine inflammation, and inhibiting the protein expressions of NMDAR, ERK1/2, p38 MAPK and JNK in spinal cord.

[Effects of electroacupuncture on NLRP3 inflammasome and pyroptosis protein GSDMD in uterine tissue in rats with primary dysmenorrhea].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on NLRP3 inflammasome and its downstream protein gastermin D (GSDMD) in rats with primary dysmenorrhea (PDM), and to explore the potential mechanism of EA on the treatment of PDM. METHODS: Forty healthy female SD rats without pregnancy were randomly divided into a control group, a model group, an EA group and an ibuprofen group, 10 rats in each group. PDM model was prepared by injection of estradiol benzoate and oxytocin. Except the control group, the rats in each group were subcutaneously injected with estradiol benzoate for 10 days, and oxytocin was injected on the 11th day. The rats in the EA group were intervened with EA (dense wave, frequency of 50 Hz) at "Guanyuan" (CV 4) and "Sanyinjiao" (SP 6) at the same time of modeling, once a day, 20 min each time, for 10 consecutive days. The rats in the ibuprofen group were treated with 0.8 mL of ibuprofen by gavage (concentration of ibuprofen solution was 1.25 mg/mL) for 10 consecutive days. After modeling, the writhing reaction was observed. After intervention, the HE staining method was used to observe the histological morphology of uterus and evaluate the pathological damage score of uterus; ELISA method was used to detect the serum levels of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α); Western blot method was used to detect the protein expression of NLRP3, apoptosis related spot like protein (ASC), caspase-1, GSDMD, GSDMD-N and inflammatory factors (interleukin [IL]-1ß, IL-18) in uterine tissue. RESULTS: In the model group, a large number of vacuolar degeneration and death of endometrial epithelial cells, spiral arterioles congestion in lamina propria and neutrophil infiltration were observed. In the EA group, there was a small amount of vacuolar degeneration and death of endometrial epithelial cells, a small amount of spiral arterioles congestion in the lamina propria, and a small amount of neutrophils infiltration. In the ibuprofen group, there was very small number of degeneration and death of endometrial epithelial cells, and no obvious arterial congestion was found in lamina propria, and neutrophil infiltration was occasionally seen. Compared with the control group, in the model group the number of writhing was increased (P<0.01), the writhing reaction score and serum level of PGF2α and PGF2α/PGE2 value were increased (P<0.01), the level of PGE2 was decreased (P<0.01). Compared with the model group, in the EA group and the ibuprofen group the number of writhing were decreased (P<0.05), the latency of writhing was prolonged (P<0.01), the writhing reaction scores and serum levels of PGF2α and PGF2α/PGE2 values were decreased (P<0.05, P<0.01), the levels of PGE2 were increased (P<0.01). Compared with the control group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1ß and IL-18 in the uterine tissues of rats was increased in the model group (P<0.01). Compared with the model group, the protein expression of NLRP3, ASC, caspase-1, GSDMD, GSDMD-N, IL-1ß and IL-18 in the uterine tissues of rats was decreased in the EA group and the ibuprofen group (P<0.01, P<0.05). There was no significant difference between the EA group and the ibuprofen group in the above indexes (P>0.05). CONCLUSION: EA could alleviate pain and uterine tissue injury in rats with PDM. The mechanism may be related to the inhibition of the activation of NLRP3 inflammasome in rat uterine tissues, thereby inhibiting pyroptosis and its inflammatory factors release.

[Effect of electroacupuncture intervention on relieving pain and inflammation by suppressing TLR4/NF-κB signaling in rats with primary dysmenorrhea].

OBJECTIVE: To investigate the mechanism of electroacupuncture(EA) intervention in rats with primary dysmenorrhea(PDM) based on the Toll-like receptor 4(TLR4)/nuclear factor(NF)-κB signaling pathway. METHODS: Forty female SD rats were randomly divided into blank control, model, EA and medication groups, with 10 rats in each group. PDM rat model was established by subcutaneous injection of estradiol benzoate combined with intraperitoneal injection of oxytocin. At the same time of model procedures, EA(50 Hz, dense wave) was applied to "Guanyuan" (CV4) and bilateral "Sanyinjiao" (SP6) of rats in the EA group, with needles retained for 20 min, for 10 consecutive days. Rats in the medication group received ibuprofen(125 mg/100 mL, 0.8 mL) by gavage for 10 consecutive days. At the 11th day, writhing behavior of rats was assessed. Uterine morphology was observed by eyes and uterine pathological changes were observed after HE staining. Content of prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in serum and uterine tissues was detected by ELISA; NF-κB p65 positive expression in nucleus was detected by immunofluorescence; protein expression levels of TLR4, NF-κB p65, p-NF-κB p65 and inflammatory factors interleukin (IL) -1ß and IL-18 were detected by Western blot. RESULTS: After modeling, uterus tissues were congested and edematous, with necrosis of luminal epithelium, severe edema and extensive shedding of endometrium, nuclear pyknosis, fragmentation and disappearance, neutrophils infiltration, and slight expansion of glandular cavity, which was milder in the EA and the medication groups. Compared with the blank control group, writhing times, scores and incubation period, HE pathological scores, PGF2α contents in serum and uterine tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB p65, p-NF-κB p65, IL-1ß and IL-18 protein expression levels in uterine tissues of rats in the model group were all significantly increased(P<0.01), while PGE2 contents in serum and uterine tissues were significantly decreased(P<0.01). Compared with the model group, writhing times and scores, HE pathological scores, PGF2α contents in serum and uterine tissues, ratio of NF-κB p65 positive expression in nucleus, TLR4, NF-κB p65, p-NF-κB p65, IL-1ß and IL-18 protein expression levels in uterine tissues of rats in the EA and medication group were all significantly decreased(P<0.01), while writhing incubation period, PGE2 contents in serum and uterine tissues were significantly increased(P<0.05, P<0.01). CONCLUSION: EA intervention could relieve inflammatory response and pain in PDM rats, which may be related to its effect in reducing TLR4 expression, inhibiting NF-κB activation and down-regulating inflammatory factors levels of IL-1ß and IL-18.

Effect of Lactobacillus plantarum WCFS1 on pancreatic and ileal injury in mice with acute necrotizing pancreatitis / 中华胰腺病杂志

Objective:To explore the effect of probiotics Lactiplantibacillus plantarum(LP) WCFS1 by gavage on acute necrotizing pancreatitis (ANP) and associated ileum injury in mice. Methods:Twenty-four healthy male mice were gavaged with broad-spectrum antibiotics for 3 weeks to establish microbiota-depleted mice, and then randomly divided into control group (CON), ANP model group (ANP), LP gavage group (LP) and LP gavage and ANP induced group (LP+ ANP) , with 6 mice in each group. Mice in LP and LP+ ANP group were treated by gavage of LP (1×10 9 CFU/ml, 0.2 ml/day per mouse) for 1 week, while CON and ANP were gavaged with sterile phosphate buffered saline for 1 week instead. The ANP model was induced by intraperitoneal injection with caerulein (100 μg/kg) for 10 times with 1-hour interval between two injections and the 10th injection with lipopolysaccharide(LPS) 5 mg/kg intraperitoneally, and the mice were sacrificed 2 h later. Levels of LP in stool and ileal mucosa were detected by real-time PCR; the pancreas and ileum were collected for pathological examination to observe the extent of tissue inflammation and to score the pathology. Serum amylase activities were determined by enzymatic kinetic chemistry; serum inflammators levels and intestinal permeability were detected by ELISA; levels of inflammators in pancreatic and ileal tissues were detected by real-time PCR; ileal tight-junction proteins (occludin, claudin-1 and ZO-1) were measured by immunofluorescence staining. Results:LP levels in the stool and ileal mucosa of mice were significantly increased after LP gavage, and the differences were statistically significant (913.30±39.12 vs 2.39±1.39, 23.11±0.50 vs 1.38±0.28, all P value <0.05). The pathological scores of pancreatic tissue of CON, LP, ANP and LP+ ANP group were (0.26±0.41), (0.17±0.26), (8.55±0.46) and (6.30±0.45); the serum amylase activities were (219.70±19.73), (217.60±11.30), (2896.24±98.32) and (1837.13±131.60)U/L, IL-1β were (0.87±0.28), (1.4±0.85), (67.41±6.45) and (36.33±5.65)pg/ml, IL-6 were (0.74±0.27), (0.16±0.16), (280586.12±39163.92) and (107912.75±31283.47)pg/ml, IL-10 were (35.52±5.27), (50.99±15.34), (2008.45±184.83) and (3070.35±403.71)pg/ml; the expression level of pancreatic IL-1β mRNA was 1.42±0.39, 0.95±25, 20.53±0.50 and 10.69±1.01, IL-6 mRNA was 1.31±0.44, 0.93±0.023, 21.97±1.71 and 11.54±1.75, IL-10 mRNA was 0.93±0.14, 0.75±0.15, 0.99±0.21 and 1.76±0.19; there was no significant difference between LP and CON group, and pancreatic pathological scores, serum amylase、IL-1β and IL-6 levels, and the expression level of pancreatic IL-1β and IL-6 mRNA were significantly decreased in LP+ ANP group compared with those in ANP group, while serum IL-10 levels and the expression level of pancreatic IL-10 mRNA were significantly increased compared with ANP group, and all the differences were statistically significant (all P values <0.05). The pathological scores of ileal tissue of CON, LP, ANP and LP+ ANP group were 0, 0, (3.17±0.41) and (1.67±0.52); the levels of serum DAO of CON, LP, ANP and LP+ ANP group were (0.03±0.03), (0.02±0.02), (0.50±0.05) and (0.49±0.06)ng/ml; LPS levels were (2.75±0.35), (3.74±0.28), (7.19±0.92) and (5.88±0.38)ng/ml; the expression level of ileal IL-1β mRNA was 1.21±0.20, 1.17±0.09, 1.81±0.25 and 1.63±0.21; IL-6 mRNA was 1.01±0.29, 2.83±0.42, 54.45±8.50 and 16.87±4.42; IL-10 mRNA was 1.12±0.41, 6.09±2.51, 11.65±1.47 and 29.86±2.93. There was no significant difference between LP and CON group, except that the ileal IL-10 mRNA expression was significantly higher than that of CON group. Ileal pathological scores, serum LPS levels and the expression level of ileal IL-6 mRNA were significantly lower in LP+ ANP group than those in ANP group, while the expression level of ileal IL-10 mRNA was significantly higher than that of ANP group; the expression of ileal tight junction proteins (ocludin, claudin-1, ZO-1) was significantly higher than those in ANP group, and all the differences were statistically significant (all P values <0.05). Conclusions:LP WCFS1 gavage could ameliorate the injury of pancreatic and ileal barrier in caerulein-induced ANP mice.

Establishment of mouse pancreatic ductal organoids and exploration of its physiological functions / 中华胰腺病杂志

Objective:To establish culture system for mouse pancreatic ductal organoids and investigate the morphology and physiological functions of the organoids.Methods:Pancreatic tissues were taken from C57BL/6 mice (6-8 weeks) and digested by collagenase Ⅳ. The pancreatic ducts were separated and collected and then the pancreatic organoids were cultured in the complete medium after Matrix gel embedding. Morphological evaluation of the organoids was performed after hematoxylin-eosin staining. The expression and localization of markers for organoids were identified by Western Blot and immunofluorescence staining; and the expression and localization of ion channels and antimicrobial peptides of the organoids were detected by agarose gel electrophoresis and immunofluorescence staining.Results:Mouse pancreatic organoids were successfully established, which could be stably passaged for 10 generations. The organoids grew spherically and formed a duct-like structure. The internal cavity corresponded to the lumen of pancreatic duct tissue. The pancreatic organoids stably expressed stem progenitor cell marker gene SOX9 and ductal epithelial cell-specific gene KRT19, which were both localized in the epithelium. The organoids did not express amylase. The organoids maintained stable expression of epithelial ion channels Clcn1, Kcnma1, CFTR, Slc12a5, Slc26a3, Slc26a6 and Scnn1a, low expression of Ano1 and no expression of Clcn3, Kcna1, Kcna2, Kcnd3, Kcnh1, Atp12a, Slc4a4, Slc9a1, Slc12a2 and Slc26a11; and CFTR highly expressed in epithelial cells. The organoids maintained high expression of antimicrobial peptides Reg3a, CRAMP and glycoprotein 2, low expression of Defb1, Defb2, and Defb3 and no expression of Defa1 and Defa4; and both CRAMP and Reg3a were expressed in the epithelial cells and secreted into the lumen of the organoids.Conclusions:Mouse pancreatic organoids are successfully established, which can be stably passaged. The organoids maintain the characteristics of ductal epithelial cells and can be used as an in vitro model to study the physiology of pancreatic ducts.

Immunometabolism: a new dimension in immunotherapy resistance / 医学前沿

Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.

Intestinal TLR4 deletion exacerbates acute pancreatitis through gut microbiota dysbiosis and Paneth cells deficiency.

Toll-like receptor 4 (TLR4) has been identified as a potentially promising therapeutic target in acute pancreatitis (AP). However, the role of intestinal TLR4 in AP and AP-associated gut injury remains unclear. This study aimed to explore the relationship between intestinal TLR4 and gut microbiota during AP. A mouse AP model was establish by intraperitoneal injection of L-arginine. Pancreatic injury and intestinal barrier function were evaluated in wild-type and intestinal epithelial TLR4 knockout (TLR4ΔIEC) mice. Gut microbiota was analyzed by 16S rRNA sequencing. Quadruple antibiotics were applied to induce microbiota-depleted mice. Differentially expressed genes in gut were detected by RNA sequencing. L. reuteri treatment was carried out in vivo and vitro study. Compared with wild-type mice, AP and AP-associated gut injury were exacerbated in TLR4ΔIEC mice in a gut microbiota-dependent manner. The relative abundance of Lactobacillus and number of Paneth cells remarkably decreased in TLR4ΔIEC mice. The KEGG pathway analysis derived from RNA sequencing suggested that genes affected by intestinal TLR4 deletion were related to the activation of nod-like receptor pathway. Furthermore, L. reuteri treatment could significantly improve the pancreatic and intestinal injury in TLR4ΔIEC mice through promoting Paneth cells in a NOD2-dependent manner. Loss of intestinal epithelial TLR4 exacerbated pancreatic and intestinal damage during AP, which might be attributed to the gut microbiota dysbiosis especially the exhausted Lactobacillus. L. reuteri might maintain intestinal homeostasis and alleviate AP via Paneth cells modulation.Abbreviations: AP Acute pancreatitis, TLR4 Toll-like receptor 4, IL-1ß Interleukin-1ß, IL-6 Interleukin-6, TNF-α Tumor necrosis factor-α, SIRS Systematic inflammatory response syndrome, LPS Lipopolysaccharides, SPF Specific pathogen-free, ZO-1 Zonula occludens-1, CON Control, H&E Hematoxylin and eosin, FISH Fluorescence in situ hybridization, DAPI 4',6-diamidino-2-phenylindole, PCoA Principal co-ordinates analysis, SCFA Short chain fatty acid, LEfSe Linear discriminant analysis Effect Size, ANOVA Analysis of variance, F/B Firmicutes/Bacteroidetes, PCA Principal component analysis, NOD2 Nod-like receptor 2, ABX antibiotics, PCNA proliferating cell nuclear antigen.

Research Progress of Immunotherapy for Non-small Cell Lung Cancer with Drive Gene Mutation / 中国肺癌杂志

Lung cancer is the most lethal malignancy around the world and non-small cell lung cancer (NSCLC) accounts for 80% of all cases. Most of the NSCLC patients has "driver gene mutations" and targeted therapy achieved a relatively good efficacy, but some patients progressed or relapsed after treatment. Previous studies demonstrated that immune checkpoint inhibitor could improve the prognosis of advanced-stage NSCLC and prolong the survival time. However, the efficacy of immune therapy varies in NSCLC patients with different immune and molecular features. The efficacy of immune therapy was controversial in NSCLC patients with driver gene mutation. The present review will summarize the immune characteristics of NSCLC patients with driver mutation and the directions of immunotherapy for patients with driver mutation.
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One-step synthesis of site-specific antibody-drug conjugates by reprograming IgG glycoengineering with LacNAc-based substrates

Glycosite-specific antibody‒drug conjugatess (gsADCs), harnessing Asn297 N-glycan of IgG Fc as the conjugation site for drug payloads, usually require multi-step glycoengineering with two or more enzymes, which limits the substrate diversification and complicates the preparation process. Herein, we report a series of novel disaccharide-based substrates, which reprogram the IgG glycoengineering to one-step synthesis of gsADCs, catalyzed by an endo-N-acetylglucosaminidase (ENGase) of Endo-S2. IgG glycoengineering via ENGases usually has two steps: deglycosylation by wild-type (WT) ENGases and transglycosylation by mutated ENGases. But in the current method, we have found that disaccharide LacNAc oxazoline can be efficiently assembled onto IgG by WT Endo-S2 without hydrolysis of the product, which enables the one-step glycoengineering directly from native antibodies. Further studies on substrate specificity revealed that this approach has excellent tolerance on various modification of 6-Gal motif of LacNAc. Within 1 h, one-step synthesis of gsADC was achieved using the LacNAc-toxin substrates including structures free of bioorthogonal groups. These gsADCs demonstrated good homogeneity, buffer stability, in vitro and in vivo anti-tumor activity. This work presents a novel strategy using LacNAc-based substrates to reprogram the multi-step IgG glycoengineering to a one-step manner for highly efficient synthesis of gsADCs.

Effect of Statin Therapy on Diabetes Retinopathy in People With Type 2 Diabetes Mellitus: A Meta-Analysis.

Objective: We tried to find the relationship between statin and diabetes retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). Methods: We searched the databases of PubMed, EMBASE, and the Cochrane Library for eligible studies reporting on the relationships between statin use and DR, from inception to September 25, 2020. The terms searched including Diabetes Mellitus, Type 2, Hydroxymethylglutaryl-CoA Reductase Inhibitors, and Diabetic Retinopathy. We expressed the results as the odds ratios (ORs) with 95% confidence intervals (CIs) which were calculated using a random-effects model. Results: A total of 6 eligible studies, including 43 826 patients, were included in the meta-analysis. The meta-analysis showed that statin was not associated with elevated risk of DR [OR = 0.96 (95% CI: 0.80-1.16), P = .68]. Similarly, no differences were found between statin and placebo in participants ≥500 [OR = 0.98 (95% CI: 0.80-1.21)] or participants <500 [OR = 0.90 (95% CI: 0.49-1.66)]. Further, we conducted a meta-analysis to study the effect of statin therapy on DR in people with type 2 diabetes according to age and found that statin use was associated with a decreased risk of DR in patients with type 2 diabetes 40 years of age or older [OR = 0.87 (95% CI: 0.82-0.92)]. Conclusion: Our meta-analysis revealed that statin was not associated with elevated risk of DR in patients with T2DM. Moreover, statin use was associated with a lower incidence of DR in patients with type 2 diabetes 40 years of age or older.

C-Reactive Protein, Interleukin-6 and Procalcitonin in Early Assessment of Severity of Acute Pancreatitis / 胃肠病学

Background: Acute pancreatitis (AP) is a common acute abdominal disease in clinical practice. Severe AP (SAP) usually progresses rapidly, leading to systemic inflammatory response syndrome, multiple organ failure, and even death. Early identification of severe cases with timely and effective treatment can improve patient's prognosis and reduce mortality. Aims: To explore the value of single and combined detection of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) in the early assessment of severity of AP. Methods: A total of 472 AP patients hospitalized in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from January 2018 to December 2020 were enrolled retrospectively. The laboratory data within 48 h of admission were extracted, and the patients were allocated into mild AP (MAP) group and SAP group (including moderately severe and severe AP) according to the 2012 revised Atlanta classification. The differences of CRP, IL-6 and PCT between the two groups were statistically analyzed, and the value of single and combined detection of the three indicators for predicting the disease severity was determined by ROC curve analysis. Results: The levels of CRP, IL-6 and PCT in SAP group were significantly higher than those in MAP group (all P< 0.05). ROC curve analysis revealed that the area under the curve (AUC) of single, two and three indicators combined for predicting SAP was all higher than 0.7, which represented a moderately diagnostic accuracy. Three indicators combined demonstrated the highest diagnostic accuracy (AUC=0.826); with an optimal cut-off value, the sensitivity and specificity were 71.4% and 79.3%, respectively. Conclusions: CRP, IL-6 and PCT are meaningful in early assessment of severity of AP. The overall diagnostic value of combined detection of three indicators is superior to single and two indicators combination in predicting SAP.

Update on the treatment of childhood-onset systemic lupus erythematosus / 中华实用儿科临床杂志

Systemic lupus erythematosus (SLE) is a serious multisystem autoimmune disease with different clinical manifestations.Childhood-onset SLE (cSLE) is similar to adult-onset SLE, while its morbidity and mortality are higher than adults, and it is prone to damage important organs.Therefore, early diagnosis and treatment are very important.With the in-depth exploration of the pathogenesis and the development of cell and molecular biology, the progress of drug therapy for SLE has been promoted.Immunosuppression still remains the cornerstone of treatment, and glucocorticoids still plays a leading role.Biologics bring the gospel to SLE patients, and non-specific immunotherapy gains treatment time for refractory and severe SLE patients.Treatment options are led by the level of disease severity.It is of great significance to understand the treatment progress of cSLE and combine theory with practice together to control the disease activity and improve the prognosis.This article reviews recent advances regarding the update on the treatment of cSLE in recent years.

Recent advances in the diagnosis and management of Takayasu arteritis complicated with ocular ischemic syndrome / 中华眼底病杂志

Takayasu arteritis (TA) is a rare, chronic non-specific vasculitis that can lead to ocular hypoperfusion. As a result, ocular ischemic syndrome (OIS), which prominently manifests as Takayasu retinopathy, may develop subsequently. Ocular manifestations mainly consist of progressive painless vision loss and amaurosis fugax in TA patients complicated with OIS. However, due to the lack of specific clinical characteristics, it is of great significance to improve the timely diagnosis aided by multimodal imaging, especially fundus fluorescein angiography. Early diagnosis of OIS is essential for reversal of ocular ischemia and better prognosis of TA patients. Management of OIS patients associated with Takayasu arteritis requires a combination of systemic and ophthalmic treatment. Therefore, the optimal individualized regiment should be determined by disease activity and progression, which are addressed by multi-disciplinary team assessment. Ophthalmologists should further understand the clinical features and the importance of regular ophthalmologic examinations during the disease course, thus to improve the overall survival and visual outcomes.

[Acupuncture at acupoints along the meridians for primary insomnia: a multi-center randomized controlled trial].

OBJECTIVE: To compare the clinical effect differences among different acupoint selection methods for primary insomnia. METHODS: A total of 333 patients with primary insomnia were recruited from 3 study centers and randomly divided into a group A (111 cases, 7 cases dropped off), a group B (111 cases, 5 cases dropped off) and a group C (111 cases, 2 cases dropped off). The patients in the group A were treated with acupuncture at Shenmen (HT 7) and Baihui (GV 20), the patients in the group B were treated with acupuncture at Sanyinjiao (SP 6) and Baihui (GV 20), and the patients in the group C were treated with acupuncture at non-acupoint and Baihui (GV 20). All the treatment was given once a day, 30 min each time; 5 treatments were taken as a course and 5 courses of treatment were given. The Pittsburgh sleep quality index (PSQI) and Athens insomnia scale (AIS) scores were evaluated before and after treatment as well as 4 weeks after treatment. The encephalofluctuograph technology (ET) was observed before and after treatment. RESULTS: Compared before treatment, the PSQI scores after treatment and at follow-up were significantly decreased in three groups (P<0.01), and the decrease in the group A and the group B was greater than that in the group C (P<0.01). Compared before treatment, the AIS scores after treatment and at follow-up was significantly decreased in three groups (P<0.01), and the decrease in the group A was greater than that in the group C (P<0.05). The interclass and between-groups ET before and after treatment had no significant difference (P>0.05). CONCLUSION: The acupuncture at acupoints along the meridians could improve the sleep quality in patients with primary insomnia, and the therapeutic effect of acupoint along the meridians is better than that of non-acupoint.

Second-Order Nonlinear-Optical-Active Selenide Borate YSeBO2: Featuring a [YSeBO2]n Planar Belt.

Chalcogenide borates were very rarely investigated in the past. As the second selenide borate, YSeBO2 obtained by a high-temperature solid-state reaction crystallizes in the noncentrosymmetric orthorhombic space group Cmc21 with a novel structure type. Its structure consists of two basic building units, [BO3]3- planar triangles and [YO3Se4]11- pentagonal bipyramids, and features the [YSeBO2]n planar belt. Second-harmonic-generation measurement shows its phase-matchable activity. YSeBO2 has an optical energy gap of 3.45 eV. Density functional theory calculation is also performed, addressing the electronic structure and nonlinear-optical property.

Research of TLD calibrated in different standard X-ray RQR radiation field in terms of eye lens dose Hp (3) / 中华放射医学与防护杂志

Objective To compare the calibration result of standard X-ray RQR radiation field between SSDL (NIRP) and CEA LIST LNHB (France),and to explore the feasibility of calibrating Hp (3) in standard X-ray RQR radiation field of SSDL (NIRP).Methods Using a column model with a diameter and high of 20 cm,TLD was calibrated in SSDL (NIRP) and CEA LIST LNHB (France) to measure the personal dose equivalent eye lens dose Hp (3),X-ray RQR radiation field included RQR4 (60 kV),RQR7 (90 kV),RQR9 (120 kV),with energy response,angle response and linear response.Results In terms of energy response,the calibration results of TLD in both SSDL (NIRP) and CEA LIST LNHB (France) were in good agreement.The difference between exposure value and response value was less than 10％.In terms of angle response,the calibration result of TLD in CEA LIST LNHB (France) was better in SSDL (NIRP).The difference between exposure value and response value in CEA LIST LNHB (France) was less than 6％,while the difference between exposure value and response value in SSDI (NIRP) was more than 10％ at angle of 20°.In terms of linear response,both calibration result of SSDL (NIRP) and CEA LIST LNHB (France) were in good agreement.Conclusions The standard X-ray RQR field in SSDL (NIRP) can be used for the calibration of Hp (3).

Research of TLD calibrated in different standard X-ray RQR radiation field in terms of eye lens dose Hp(3) / 中华放射医学与防护杂志

Objective@#To compare the calibration result of standard X-ray RQR radiation field between SSDL (NIRP) and CEA LIST LNHB(France), and to explore the feasibility of calibrating Hp(3) in standard X-ray RQR radiation field of SSDL(NIRP).@*Methods@#Using a column model with a diameter and high of 20 cm, TLD was calibrated in SSDL (NIRP) and CEA LIST LNHB (France) to measure the personal dose equivalent eye lens dose Hp(3), X-ray RQR radiation field included RQR4(60 kV), RQR7(90 kV), RQR9(120 kV), with energy response, angle response and linear response.@*Results@#In terms of energy response, the calibration results of TLD in both SSDL (NIRP) and CEA LIST LNHB (France) were in good agreement. The difference between exposure value and response value was less than 10%. In terms of angle response, the calibration result of TLD in CEA LIST LNHB (France) was better in SSDL(NIRP). The difference between exposure value and response value in CEA LIST LNHB (France) was less than 6%, while the difference between exposure value and response value in SSDL(NIRP) was more than 10% at angle of 20°. In terms of linear response, both calibration result of SSDL (NIRP) and CEA LIST LNHB (France) were in good agreement.@*Conclusions@#The standard X-ray RQR field in SSDL (NIRP) can be used for the calibration of Hp(3).

Effect of exosomes from human adipose-derived stem cells on wound healing and migration potential of HaCaT cells: a preliminary experimental study / 中华皮肤科杂志

Objective@#To preliminarily evaluate the effect of exosomes from human adipose-derived stem cells (hADSCs) on the migration of epidermal cells.@*Methods@#hADSCs were isolated from adipose tissues obtained from a healthy woman after liposuction, and subjected to culture. Exosomes were collected from the culture supernatant of hADSCs by using a modified method combining ultracentrifugation with ultrafiltration, and identified and isolated by transmission electron microscopy (TEM) , dynamic light scattering (DLS) and Western blot analysis. Some cultured HaCaT cells were divided into several groups to be treated with hydrogen peroxide (H2O2) at different concentrations of 0, 50, 100, 200, 250, 300, 400, 500, 600, 800 μmol/L for 1 hour, and cell counting kit-8 (CCK8) assay was performed to evaluate the effect of H2O2 on the survival rate of HaCaT cells. Some HaCaT cells were classified into 2 groups to be pretreated with phosphate-buffered saline (PBS) (normal group) or 100 μmol/L H2O2 (injury group) for 0.5 hour; then, HaCaT cells in the 2 groups were separately divided into treatment group and control group to be co-cultured with exosomes or not. Confocal fluorescence microscopy was conducted to confirm the uptake of PKH26-labelled exosomes by HaCaT cells, scratch assay to estimate the wound healing potential, and Transwell assay to evaluate the migratory activity of HaCaT cells. Statistical analysis was carried out by using one-way analysis of variance for comparison among groups, least significant difference (LSD) -t test for multiple comparisons, and Spearman correlation analysis for analyzing correlations.@*Results@#TEM showed that the exosomes isolated from hADSCs were saucer-like nanovesicles with diameters of 60-80 nm. DLS revealed that the purity of the isolated exosomes was 65.88%, and they were stained positively for CD63, Alix and TSG101, which coincided with the basic characteristics of exosomes. CCK8 assay showed that survival rates of HaCaT cells gradually decreased along with the increase of H2O2 concentrations after 1-hour treatment, and were negatively correlated with the concentration of H2O2 (r= -0.91, P < 0.01) . Confocal fluorescence microscopy showed that the isolated exosomes could be endocytosed into impaired HaCaT cells. Scratch assay showed that the gap-filling rates at 12 hours were 40.26% ± 0.64%, 69.57% ± 0.69%, 32.28% ± 0.31% and 69.62% ± 1.68% in the normal control group, normal treatment group, injury control group and injury treatment group respectively, and the injury treatment group showed a significantly increased gap-filling rate compared with the injury control group (t = 37.33, P < 0.01) . Transwell assay showed that the number of migratory cells per × 10 field was 20.85 ± 4.84, 44.8 ± 5.24, 14.95 ± 2.58 and 40.05 ± 7.66 in the normal control group, normal treatment group, injury control group and injury treatment group respectively, and was significantly larger in the injury treatment group than in the injury control group (t = 25.10, P < 0.01) .@*Conclusion@#Exosomes isolated from hADSCs can improve the migration of HaCaT cells after oxidative injury.