Toxicity Attenuation Mechanism on Processing Method for Aconiti Lateralis Radix Praeparata in Guilingji Based on Urine Metabolomics / 中国实验方剂学杂志

ObjectiveMetabolomics was used to reveal the mechanism of Aconiti Lateralis Radix Praeparata（ALRP） in attenuating toxicity by processing from the aspects of amino acid metabolism， oxidative stress and energy metabolism by analyzing multiple metabolic pathways. MethodTwenty-four rats were randomly divided into control group， raw group and processed group， 8 rats in each group. The raw and processed group were given with 0.64 g·kg-1 of raw ALRP and processed ALRP respectively every day， the control group was given with an equal amount of normal saline once a day. After continuous administration for 7 days， the urine， serum and heart tissue of rats were collected. Pathological examination of the heart was carried out using hematoxylin-eosin（HE） staining， and the activities of lactate dehydrogenase（LDH） and creatine kinase-MB（CK-MB） in serum and cardiac tissues were detected by microplate assay and immunoinhibition assay. The effects of ALRP on rat heart before and after processing were compared and analyzed. Ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to perform urine metabolomics analysis， and multivariate statistical analysis was used to screen for differential metabolites related to ALRP in attenuating toxicity by processing， and pathway enrichment analysis was carried out to explore the processing mechanism. ResultHE staining showed that no obvious pathological changes were observed in the heart tissue of the control group， while obvious infiltration of inflammatory cells such as plasma cells and granulocytes was observed in the heart tissue of the raw group， indicating that the raw ALRP had strong cardiotoxicity. There was no significant difference in HE staining of heart tissue between the processed group and the control group， indicating that the toxicity of ALRP was significantly reduced after processing. Compared with the control group， the activities of LDH and CK-MB were significantly increased in serum and heart tissue of the raw group， and those were significantly decreased in serum and heart tissue of the processed group， suggesting that the myocardial toxicity of processed ALRP was reduced. A total of 108 endogenous differential metabolites associated with the raw ALRP were screened using multivariate statistical analysis in positive and negative modes， of which 51 differential metabolites were back-regulated by the processed ALRP. Biological analysis of the key regulatory pathways and associated network changes showed that the pathways related to toxicity of ALRP mainly included tryptophan metabolism， arginine and proline metabolism， phenylalanine metabolism， aminoacyl-tRNA biosynthesis， alanine， aspartate and glutamate metabolism， etc. The metabolic pathways related to the attenuation of processed ALRP mainly included aminoacyl-tRNA biosynthesis， tryptophan metabolism， phenylalanine， tyrosine and tryptophan biosynthesis， phenylalanine metabolism and caffeine metabolism. ConclusionThe processing technology of ALRP in Guilingji can significantly attenuate the cardiotoxicity of raw products， the mechanism mainly involves amino acid metabolism， oxidative stress and energy metabolism， which can provide experimental bases for the research related to the mechanism of toxicity reduction of ALRP by processing and its clinical safety applications.

Investigation on the pharmacological mechanisms of Shirebi granules in treating gouty arthritis with damp-heat syndrome based on crosstalk of Wnt/β-catenin signaling / 药学学报

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Study on release and antioxidant activity of quercetin after loaded by hot alkali hydrolysis modified UiO-66 material / 药学学报

UiO-66 (University of Oslo 66) is a kind of promising material that can improve the release and bioavailability of poorly water-soluble bioactive compounds of traditional Chinese medicine. However, the loading of quercetin in raw UiO-66 was not ideal. In this study, UiO-66-BH (UiO-66-blend-heating) was obtained by heating UiO-66 and KOH solution following blended them. UiO-66-BH maintained the outline of octahedral structure of UiO-66 but with obvious rough and uneven pores on the surface. UiO-66-BH had good adsorption of quercetin with saturation adsorption was 138.92 mg·g-1, the adsorption process belonged to single molecular layer adsorption and was controlled by chemisorption. UiO-66-BH can control the release of quercetin in simulated gastrointestinal fluid, and the drug concentration was significantly higher than that of free quercetin after long-term release (36% vs 9%). Compared with quercetin, the ABTS (2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) ammonium salt) radical scavenging activity of UiO-66-BH@quercetin drug delivery system decreased, while the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity remained almost unchanged. The drug delivery system showed a strong antioxidant effect similar to quercetin. The findings indicated that UiO-66-BH could control release of quercetin and was expected to be used as a drug carrier material for some insoluble active components of traditional Chinese medicine such as quercetin.

Iso-Kikuchi syndrome: report of two cases / 中华皮肤科杂志

To report 2 cases of Iso-Kikuchi syndrome, both of which were congenital. Case 1, a 7-month-old female infant, visited the hospital due to abnormalities in the nail plate of the left index finger for 7 months; case 2, a 3-year-old male child, also visited the hospital due to abnormalities in the nail plate of the left index finger for 3 years. The 2 patients both presented with 2 tiny, independent nail plates on both sides of the nail bed of the left index finger, instead of normal nail plates. Based on their clinical features, the 2 patients were diagnosed with Iso-Kikuchi syndrome (congenital onychodysplasia of the index finger). The mother of case 1 had a history of progesterone use to prevent miscarriage during pregnancy, the mothers of the two patients both suffered from hypothyroidism and continued to receive thyroid hormone replacement therapy during pregnancy, and the mother of case 2 had a history of gestational diabetes. It is still unclear whether these comorbidities and drugs are directly related to the occurrence of Iso-Kikuchi syndrome.

The preliminary experience of immediate radical prostatectomy after the diagnosis of prostate cancer by targeted prostate biopsy combined with intraoperative frozen section / 中华老年医学杂志

Objective:To investigate the practicality and safety of performing a radical prostatectomy(RP)shortly after the diagnosis of prostate cancer using a combination of prostate targeted biopsy and intraoperative frozen section.Methods:Prospective enrollment was conducted for patients suspected of having prostate cancer based on abnormal prostate specific antigen(PSA)levels.The inclusion criteria for the study were as follows: patients aged 80 years or younger with an ECOG score of 1 or lower.Prior to biopsy, patients underwent both prostate magnetic resonance imaging(MRI)and prostate specific membrane antigen positron emission tomography/computed tomography(PSMA PET/CT)to determine the likelihood of prostate cancer with clinical stages within T 2-3aN 0M 0.In order to be included in the study, patients must agree to receive RP after their prostate cancer diagnosis has been confirmed by biopsy.All enrolled patients underwent a targeted prostate biopsy, consisting of 1-2 cores.These specimens were then examined through frozen section analysis.For patients diagnosed with prostate cancer through intraoperative frozen section pathology, RP was immediately performed.In this study, transperineal prostate targeted+ systematic biopsy was utilized for patients with undiagnosed prostate cancer.Additionally, routine pathological examination of specimens was conducted.The study analyzed the baseline data, surgical conditions, pathological results, and follow-up information of patients in a descriptive manner. Results:Seven patients, ranging in age from 54 to 77 years with a mean age of 66.7 years, were enrolled in the study.Their mean PSA level was 12.668 μg/L, ranging from 4.359 to 22.195 μg/L.Of these patients, 4 had a PI-RADS score of 4 and 3 had a score of 5.The maximum diameter of the index lesion was 1.3 cm, ranging from 0.5 to 2.2 cm.PSMA PET/CT scores were 4 in 1 case and 5 in 6 cases.The index lesions detected by PSMA PET/CT were consistent with those detected by MRI, and the maximum standardized uptake value(SUVmax)was 15.7, ranging from 5.3 to 39.4.Prostate cancer was diagnosed through targeted biopsy and intraoperative frozen section pathology.Four cases had a Gleason score of 3+ 3=6, while one case had a Gleason score of 3+ 4=7, another had a score of 4+ 3=7, and the last had a score of 4+ 4=8.All patients underwent RP treatment immediately after the prostate cancer diagnosis.Only one patient had slight adhesion at the apex of the prostate, while the other six patients were evaluated by surgeons as having no obvious adhesion at the apex.All surgeries were completed successfully, with a mean operation time of 149.7(ranging from 108 to 255)minutes.After RP, whole mount pathology results indicated that all cases were prostate adenocarcinoma, with a Gleason score of 3+ 4=7 in four cases and 4+ 3=7 in three cases.The pathological stages were pT2 in three cases and pT3a in four cases, with five cases having negative surgical margins and two cases with positive surgical margins.During the study, all patients were monitored for a period of 5.4 months(ranging from 3 to 7 months)and no complications of Clavien Dino≥Ⅰ were observed.PSA levels were measured at 6 weeks and 3 months after surgery, with readings of 0.020 μg/L(ranging from 0 to 0.079 μg/L)and 0.016 μg/L(ranging from 0 to 0.087 μg/L), respectively.No hormonal therapy or radiotherapy was administered during this time.Four patients were able to recover from urinary continence.Conclusions:Based on a combination of MRI and PSMA PET/CT, it is both safe and feasible to promptly perform RP following the diagnosis of prostate cancer through targeted biopsy for index lesions, along with intraoperative frozen section.

Risk factors for failure of nasal high frequency oscillatory ventilation as initial therapy in very low birth weight infants with respiratory distress syndrome / 中国新生儿科杂志

Objective:To study the risk factors of failure using nasal high frequency oscillatory ventilation (nHFOV) as initial therapy in the treatment of respiratory distress syndrome (RDS) in very low birth weight infants (VLBWIs).Methods:From January 2018 to December 2021, VLBWIs with RDS initially supported by nHFOV in NICU of our hospital were retrospectively analyzed. They were assigned into success and failure groups according to the ventilation efficacy. Demographic data and clinical outcomes of the two groups were compared. Risk factors of initial nHFOV failure were analyzed using binary Logistic regression method.Results:A total of 135 infants were included, including 103 in the success group and 32 in the failure group. The initial nHFOV failure rate was 23.7%. The failure group had lower pH (7.26±0.09 vs. 7.33±0.08) and PaO 2 [61.0 (49.6, 77.2) mmHg vs. 83.6 (64.4, 99.0) mmHg] than the success group ( P<0.05) and higher PaCO 2 than the success group [49.0 (42.3, 58.1) mmHg vs. 43.4 (36.0, 50.0) mmHg] ( P<0.05). Using PaCO 2 as predictor, the area under the curve (AUC) was 0.682 (95% CI 0.575-0.788) and the cut-off value was 44.8 mmHg for nHFOV failure and the AUC was 0.716 (95% CI 0.615-0.817) and the cut-off value was 67.1 mmHg for nHFOV success. The incidences of early onset sepsis (EOS), shock within 3 d and hemodynamically significant patent ductus arteriosus (hsPDA) in the failure group were significantly higher than the success group (40.6% vs. 7.8%, 53.1% vs. 2.9%, 31.3% vs. 13.6%, P<0.05, respectively). Binary logistic regression analysis found that PaO 2<67.1 mmHg ( OR=5.458,95% CI 1.730-17.220) on the first blood gas analysis and shock within 3 d ( OR=26.585,95% CI 3.854-183.396) were independent risk factors for initial nHFOV failure ( P<0.05). Conclusions:The failure of initial nHFOV is correlated with the first blood gas parameters, EOS, hsPDA and shock within 3 d. Shock within 3 d and low PaO 2(<67.1 mmHg) were independent risk factors for initial nHFOV failure.

MicroRNA-204/-211 deficiency aggravates synovial hyperplasia and inflammation in DMM-induced OA mice / 中国药理学通报

Aim To observe the effects of microRNA-204/-211 deficiency on osteoarthritis(OA) induced by medial meniscus amputation (DMM) in mice. Methods 12 C57BL/6J wild-type (WT) mice were randomly divided into sham operation groups and DMM groups, namely WT-control group and WT + DMM group. And twelve microRNA-204/-211 gene knockout (miR-204/-211-dKO) mice were randomly divided into sham operation groups and DMM groups, namely dKO group, and dKO + DMM group. The pain sensitivity of mice was measured by the von Frey test before sacrificing. Three months after the operation, the mice were sacrificed. The knee joints and dorsal root ganglion (DRG) were taken for detection. The subchondral bone structure was detected by micro-CT. Sections of knee joint tissue were stained with toluidine blue, PCNA, type Ⅱ collagen and immunohistochemistry. DRG tissues were detected for related pain factors and inflammatory factors by RT-qPCR. Results Compared with the mice in the WT-Control group, mice in the WT + DMM group showed typical OA symptoms such as osteophyte formation, subchondral osteosclerosis, and decreased pain thresholds. The expression of collagen Ⅱ in cartilage significantly decreased, while the expression of MMP13 significantly increased. The expression of inflammatory and pain-related factors in DRG significantly increased. At the same time, the OA phenotypes of mice in dKO + DMM were more obvious than that of mice in the WT + DMM group, indicating that miR-204/-211 deficiency aggravated the OA induced by DMM in mice. In particular, DMM did not cause synovial hyperplasia and synovial inflammation in WT mice, which could not completely represent the pathological characteristics of OA patients in clinical practice. However, miR-204/-211 deficiency significantly promoted synovial hyperplasia and synovial inflammation of knee joints in DMM mice. Conclusions After DMM operation, miR-204/-211 deficient mice showed not only typical OA phenotypes such as osteophyte formation, subchondral osteosclerosis, cartilage destruction and lower pain threshold, but also synovial hyperplasia and synovitis, which could better represent the pathological characteristics of clinical OA patients. MiR-204/-211 deficient mice with DMM can be used as a new OA model and an ideal animal model for screening anti-OA drugs.

Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes / 中华妇产科杂志

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 μg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 μg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor β1 (TGF-β1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-β1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-β1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-β1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-β1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis / 医学前沿

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H2S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

Advances in the diagnosis and treatment of retinal artery macroaneurysms / 国际眼科杂志(Guoji Yanke Zazhi)

Retinal arterial macroaneurysm(RAM)is a kind of acquired retinal vascular disorder. The pathogenesis of RAM is not yet clear, and it is associated with some systemic conditions, including hypertension, arteriosclerosis and hyperlipidemia. RAM is prone to exudation or bleeding, leading to some other complications in the condition of hypertension due to the weak tube wall, and its clinical manifestations are complex and diverse, which makes it difficult to diagnose. RAM itself has a tendency of self-degeneration, and the prognosis of visual acuity is good if the lesion doesn't involve the macular area. However, when the macula is affected by exudation and/or bleeding, the vision is severely affected and some feasible treatments are needed. Understanding the typical imaging manifestations of RAM is helpful to make a definite diagnosis and give corresponding treatment measures. In this paper, the manifestations of RAM by various examination methods are reviewed and the corresponding treatments of different types of RAM are summarized, aiming to provide reference for the early diagnosis and treatment of RAM in the future.

Feasibility analysis of digital method for measuring supracrestal tissue height crest around implant / 华西口腔医学杂志

OBJECTIVES@#This study aimed to investigate the feasibility of measuring the soft tissue height of bone cristae around implant by digital method.@*METHODS@#A total of 36 patients with dental implants were selected from the Dental Medicine Center of the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from August 2022 to December 2022. A total of 43 dental implants were enrolled. All postoperative cone beam CT (CBCT) imaging data and intraoral digital impressions obtained before surgery were immediately obtained by the patients on the day of completion of oral implant surgery and they were imported into oral implant surgery planning software for image fitting. Then, virtual implants of the same specification were placed in the planting area, and the implant position was adjusted to overlap with the implant shadow in the CBCT image. Supracrestal tissue height (STH) was measured at the implant view interface (digital group). During the operation, implant holes were prepared step by step in accordance with the standard preparation method, and implants were implanted. The upper edge of the implant was flushed with the crest of the alveolar ridge. STH was measured by perio-dontal probing (periodontal probe group). Paired t-test was used to compare the STH differences between the digital and periodontal probe groups. Bland-Altman test was used to analyze the consistency of the two methods. Intra-group correlation coefficient (ICC) was used to verify the reliability of the results measured by different surveyors using di-gital methods.@*RESULTS@#No statistical significance was observed in the STH difference between the two methods (P>0.05). Bland-Altman test showed good consistency between the two methods, but the measurement of mandibular posterior teeth showed that the results of periodontal probe were greater than those of digital method. The ICC and 95%CI of the STH results measured digitally by different surveyors are 0.992 (0.986-0.996).@*CONCLUSIONS@#The digital me-thod is in good agreement with the periodontal probe method in measuring the soft tissue height of the bone cristae around the implant.

Efficacy and safety of ropivacaine combined with alfentanil for analgesia after knee arthroscopic surgery / 中国药房

OBJECTIVE To explore the efficacy and safety of intra-articular injection of ropivacaine combined with alfentanil for postoperative analgesia in patients who underwent knee arthroscopic surgery. METHODS A total of 60 patients who underwent knee arthroscopic surgery were collected from the Central Hospital of Enshi Tujia and Miao Autonomous Prefecture from March to September in 2022， and then divided into trial group and control group with random number table method， with 30 cases in each group. The control group received intra-articular injection of 0.25% ropivacaine 50 mg， and the trial group received intra-articular injection of 0.25% ropivacaine 50 mg+alfentanil 0.15 μg/kg.The first postoperative remedial analgesia time， the total amount of postoperative remedial drugs， numerical rating scale at rest （NRS-R） scores， numerical rating scale at movement （NRS-M） scores， heart rate， mean arterial blood pressure， and pulse oxygen saturation during exercise at different monitoring time points after surgery， the incidence of adverse drug reactions such as hypotension， respiratory depression， nausea， and vomiting after surgery were compared between 2 groups. RESULTS Compared with the control group， the first postoperative remedial analgesia time was significantly longer in the trial group， and the total amount of postoperative remedial drugs was significantly reduced （P＜0.001）. The trial group had lower NRS-R and NRS-M scores at each monitoring time point， with statistically significant differences （P＜0.001）， and there was an interactive effect between time and groups （P＜0.001）. The changes in heart rate， mean arterial blood pressure， and pulse oxygen saturation of patients in the trial group were relatively small， with no statistically significant differences （P＞0.05）， and there was no interactive effect between time and groups （P＞0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups， such as postoperative hypotension， respiratory depression， nausea， vomiting （P＞0.05）. CONCLUSIONS The intra- articular injection of ropivacaine combined with alfentanil shows good efficacy and safety for post-knee arthroscopic analgesia， and significantly prolongs the analgesic duration of ropivacaine.

Application of single sperm sequencing for the preimplantation genetic testing of a Chinese family affected with Spinal muscular atrophy / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M).@*METHODS@#A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus.@*RESULTS@#Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion.@*CONCLUSION@#By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.

Feasibility and safety of bipolar-plasmakinetic transurethral enucleation and resection of the prostate in day surgery mode / 浙江大学学报·医学版

OBJECTIVES@#To evaluate the feasibility and safety of bipolar-plasmakinetic transurethral enucleation and resection of the prostate (B-TUERP) in day surgery.@*METHODS@#From January 2021 to August 2022, 34 patients with benign prostatic hyperplasia (BPH) underwent B-TUERP in day surgery in the First Affiliated Hospital of Anhui Medical University. Patients completed the screening and anesthesia evaluation before admission and received the standard surgery which implements "anatomical enucleation of the prostate" and "absolute bleeding control" on the same day of admission, and by the same doctor. Bladder irrigation was stopped, catheter was removed and the discharge evaluation was performed on the first day after operation. The baseline data, perioperative conditions, time of recovery, treatment outcomes, hospitalization costs, and postoperative complications were analyzed.@*RESULTS@#All operations were successfully conducted. The average age of the patients was (62.2±7.8) years, average prostate volume was (50.2±29.3) mL. The average operation time was (36.5±19.1) min, the average hemoglobin and blood sodium were decreased by (16.2±7.1) g/L and (2.2±2.0) mmol/L, respectively. The average postoperative length of hospital stay, and total length of hospital stay were (17.7±2.2) and (20.8±2.1) h, respectively, and the average hospitalization cost was (13 558±2320) CNY. All patients were discharged on the day after surgery except for one patient who was transferred to a general ward. Three patients received indwelling catheterization after catheter removal. The 3-month follow-up results showed a substantial improvement in the International Prostate Symptom Score, quality of life score and maximum urinary flow rate (all P<0.01). Three patients experienced temporary urinary incontinence, 1 patient experienced urinary tract infection, 4 patients were diagnosed with urethral stricture and 2 patients experienced bladder neck contracture. No complications above Clavien grade Ⅱ occurred.@*CONCLUSIONS@#The preliminary results showed that B-TUERP ambulatory surgery is a safe, feasible, economical and effective treatment for appropriately selected patients with BPH.

Nature-effect transformation mechanism of mulberry leaves and silkworm droppings based on chemical composition analysis / 中国中药杂志

Starting with the relationship between mulberry leaves and silkworm droppings as food and metabolites, this study systematically compared the chemical components, screened out differential components, and quantitatively analyzed the main differential components based on ultra-high performance liquid chromatography with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) and UPLC-Q-TRAP-MS combined with principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Moreover, the in vitro enzymatic transformation of the representative differential components was studied. The results showed that(1) 95 components were identified from mulberry leaves and silkworm droppings, among which 27 components only exist in mulberry leaves and 8 components in silkworm droppings. The main differential components were flavonoid glycosides and chlorogenic acids.(2) Nineteen components with significant difference were quantitatively analyzed, and the components with significant differences and high content were neochlorogenic acid, chlorogenic acid, and rutin.(3) The crude protease in the mid-gut of silkworm significantly metabolized neochlorogenic acid and chlorogenic acid, which may be an important reason for the efficacy change in mulberry leaves and silkworm droppings. This study lays a scientific foundation for the development, utilization, and quality control of mulberry leaves and silkworm droppings. It provides references for clarifying the possible material basis and mechanism of the pungent-cool and dispersing nature of mulberry leaves transforming into the pungent-warm and dampness-resolving nature of silkworm droppings, and offers a new idea for the study of nature-effect transformation mechanism of traditional Chinese medicine.

A prospective cohort study of long-term fasting blood glucose variability and risk of mortality in patients with type 2 diabetes / 中华流行病学杂志

Objective: To investigate the association between long-term fasting blood glucose (FPG) variability and all-cause mortality in patients with type 2 diabetes. Methods: A total of 7 174 type 2 diabetic patients included in National Basic Public Health Service Program in Changshu of Jiangsu Province were recruited as participants. Long-term glucose variability was assessed using standard deviation (SD), coefficient of variation (CV), average real variability (ARV), and variability independent of the mean (VIM) across FPG measurements at the more than three visits. Death information were mainly obtained from the death registry system in Jiangsu. Then Cox proportional hazards regression models were used to estimate the associations of four variability indicators and all-cause mortality's hazard ratios (HRs) and their 95%CIs. Results: Among 55 058.50 person-years of the follow-up, the mean follow-up time was 7.67 years, and 898 deaths occurred during the follow-up period. After adjustment, compared with T1 group, the Cox regression model showed that HRs of T3 group in SD, CV, ARV and VIM were 1.24 (95%CI: 1.03-1.49), 1.20 (95%CI: 1.01-1.43), 1.28 (95%CI: 1.07-1.55) and 1.20 (95%CI:1.01-1.41), respectively. HRs of per 1 SD higher SD, CV, ARV and VIM were 1.13 (95%CI: 1.06-1.21), 1.08 (95%CI: 1.01-1.15), 1.05 (95%CI: 1.00-1.12) and 1.09 (95%CI: 1.02-1.16) for all-cause mortality, respectively. In the stratified analysis, age, gender, hypoglycemic agent and insulin uses had no effect on the above associations (all P for interaction >0.05). Conclusion: Long-term FPG glycemic variability was positively associated with the risk of all-cause mortality in type 2 diabetes patients.

Identification and validation of novel biomarkers for cold-dampness syndrome of rheumatoid arthritis based on integration of multiple bioinformatics methods / 中国中药杂志

This study aims to identify the novel biomarkers of cold-dampness syndrome(RA-Cold) of rheumatoid arthritis(RA) by gene set enrichment analysis(GSEA), weighted gene correlation network analysis(WGCNA), and clinical validation. Firstly, transcriptome sequencing was carried out for the whole blood samples from RA-Cold patients, RA patients with other traditional Chinese medicine(TCM) syndromes, and healthy volunteers. The differentially expressed gene(DEG) sets of RA-Cold were screened by comparison with the RA patients with other TCM syndromes and healthy volunteers. Then, GSEA and WGCNA were carried out to screen the key DEGs as candidate biomarkers for RA-Cold. Experimentally, the expression levels of the candidate biomarkers were determined by RT-qPCR for an independent clinical cohort(not less than 10 cases/group), and the clinical efficacy of the candidates was assessed using the receiver operating characteristic(ROC) curve. The results showed that 3 601 DEGs associated with RA-Cold were obtained, including 106 up-regulated genes and 3 495 down-regulated genes. The DEGs of RA-Cold were mainly enriched in the pathways associated with inflammation-immunity regulation, hormone regulation, substance and energy metabolism, cell function regulation, and synovial pannus formation. GSEA and WGCNA showed that recombinant proteasome 26S subunit, ATPase 2(PSMC2), which ranked in the top 50% in terms of coefficient of variation, representativeness of pathway, and biological modules, was a candidate biomarker of RA-Cold. Furthermore, the validation results based on the clinical independent sample set showed that the F1 value, specificity, accuracy, and precision of PSMC2 for RA-Cold were 70.3%, 61.9%, 64.5%, and 81.3%, respectively, and the area under the curve(AUC) value was 0.96. In summary, this study employed the "GSEA-WGCNA-validation" integrated strategy to identify novel biomarkers of RA-Cold, which helped to improve the TCM clinical diagnosis and treatment of core syndromes in RA and provided an experimental basis for TCM syndrome differentiation.

Predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome / 北京大学学报(医学版)

OBJECTIVE@#To explore the predictive value of four items of new thrombus markers combined with conventional coagulation tests for thrombosis in antiphospholipid syndrome.@*METHODS@#A total of 121 antiphospholipid syndrome (APS) patients who hospitalized at Peking University People's Hospital from March 2022 to January 2023 were selected and divided into thrombus group (50 cases) and nonthrombus group (71 cases) according to whether thrombosis occurred. The differences of laboratory characteristics including antiphospholipid antibodies were compared between the thrombotic and non-thrombotic groups. Chemiluminescent immunoassay was used to detect thrombomodulin (TM), thrombin-antithrombin complex (TAT), Plasmin-α2 plasmin inhibitor complex (PIC), and tissue plasminogen activator inhibitor complex (t-PAIC) in plasma from venous. The independent risk factors of thrombosis in patients with APS were determined using binary Logistic regression. Receiver operating characteristic (ROC) curve analysis was applied to evaluate the efficacy of each index on the prediction of thrombosis.@*RESULTS@#Compared with the patients without thrombosis, the patients with thrombosis were older [49 (32, 64) years vs. 36 (32, 39) years, P < 0.05]. The percentages of male, smoking, hypertension, and global antiphospholipid syndrome score (GAPSS)≥10 in the patients with thrombosis were significantly higher than those in the patients without thrombosis (P < 0.05). The positive rates of anticardiolipin antibody (aCL) and lupus anticoagulant (LA) in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05), and the levels of prothrombin time, activated partial thromboplastin time, fibrinogen, fibrin degradation product in the thrombotic group were significantly higher than those in the non-thrombotic group (P < 0.05).Among the thrombosis group, venous thrombosis accounted for 19 (38.00%), including deep vein thrombosis (16, 84.21%) and pulmonary embolism accounted (5, 26.32%); Arterial thrombosis accounted for 35 (70.00%), including myocardial infarction (6, 17.14%) cerebral infarction (30, 85.71%). The patients in the thrombotic group had significantly greater TM levels than those in the non-thrombotic group (P < 0.05).There were no significant dif-ferences between the two groups in TAT (Z=-1.420, P=0.156), PIC (Z=-0.064, P=0.949), and t-PAIC (Z=-1.487, P=0.137). Univariate and binary Logistic regression analysis of relevant variables showed that advanced age [OR=1.126, P=0.002], elevated TM [OR=1.325, P=0.048], prolonged prothrombin time (PT) [OR=4.127, P=0.008] were independent risk factors for thrombosis in the patients with APS. ROC curve analysis of the above three independent risk factors showed that the combined detection of age, PT and TM had the highest Yoden index (0.727) and sensitivity (83.0%), with a specificity of 89.7%.@*CONCLUSION@#TAT, PIC, TM, and t-PAIC may reflect thrombus formation from the coagulation system, fibrinolysis system, and endothelial system. The combined of age TM and PT is superior to the application of a single marker, which has diagnostic value for the early identification of APS thrombosis.

Significance of anti-Jo-1 antibody's clinical stratification in idiopathic inflammatory myopathy and disease spectrum / 北京大学学报(医学版)

OBJECTIVE@#To investigate the significance of anti-histidyl tRNA synthetase (Jo-1) antibody in idiopathic inflammatory myopathies (IIM) and its diseases spectrum.@*METHODS@#We enrolled all the patients who were tested positive for anti-Jo-1 antibody by immunoblotting in Peking University People's Hospital between 2016 and 2022. And the patients diagnosed with anti-synthetase antibody syndrome (ASS) with negative serum anti-Jo-1 antibody were enrolled as controls. We analyzed the basic information, clinical characteristics, and various inflammatory and immunological indicators of the patients at the onset of illness.@*RESULTS@#A total of 165 patients with positive anti-Jo-1 antibody were enrolled in this study. Among them, 80.5% were diagnosed with connective tissue disease. And 57.6% (95/165) were diagnosed with IIM, including ASS (84/165, 50.9%), immune-mediated necrotizing myopathy (7/165, 4.2%) and dermatomyositis (4/165, 2.4%). There were 23.0% (38/165) diagnosed with other connective tissue disease, mainly including rheumatoid arthritis (11/165, 6.7%), undifferentiated connective tissue disease (5/165, 3.0%), interstitial pneumonia with autoimmune features (5/165, 3.0%), undifferentiated arthritis (4/165, 2.4%), Sjögren's syndrome (3/165, 1.8%), systemic lupus erythematosus (3/165, 1.8%), systemic vasculitis (3/165, 1.8%), and so on. Other cases included 3 (1.8%) malignant tumor patients, 4 (2.4%) infectious cases and so on. The diagnoses were not clear in 9.1% (15 /165) of the cohort. In the analysis of ASS subgroups, the group with positive serum anti-Jo-1 antibody had a younger age of onset than those with negative serum anti-Jo-1 antibody (49.9 years vs. 55.0 years, P=0.026). Clinical manifestations of arthritis (60.7% vs. 33.3%, P=0.002) and myalgia (47.1% vs. 22.2%, P=0.004) were more common in the ASS patients with positive anti-Jo-1 antibody. With the increase of anti-Jo-1 antibody titer, the incidence of the manifestations of arthritis, mechanic hands, Gottron sign and Raynaud phenomenon increased, and the proportion of abnormal creatine kinase and α-hydroxybutyric dehydrogenase index increased in the ASS patients. The incidence of myalgia and myasthenia were significantly more common in this cohort when anti-Jo-1 antibody-positive ASS patients were positive for one and more myositis specific antibodies/myositis associated autoantibodies (P < 0.05).@*CONCLUSION@#The disease spectrum in patients with positive serum anti-Jo-1 antibody includes a variety of diseases, mainly ASS. And anti-Jo-1 antibody can also be found in many connective tissue diseases, malignant tumor, infection and so on.