Evidence-Based Dampness-Heat ZHENG (Syndrome) in Cancer: Current Progress toward Establishing Relevant Animal Model with Pancreatic Tumor / 中国结合医学杂志

Cancer is one of the deadliest diseases affecting the health of human beings. With limited therapeutic options available, complementary and alternative medicine has been widely adopted in cancer management and is increasingly becoming accepted by both patients and healthcare workers alike. Chinese medicine characterized by its unique diagnostic and treatment system is the most widely applied complementary and alternative medicine. It emphasizes symptoms and ZHENG (syndrome)-based treatment combined with contemporary disease diagnosis and further stratifies patients into individualized medicine subgroups. As a representative cancer with the highest degree of malignancy, pancreatic cancer is traditionally classified into the "amassment and accumulation". Emerging perspectives define the core pathogenesis of pancreatic cancer as "dampness-heat" and the respective treatment "clearing heat and resolving dampness" has been demonstrated to prolong survival in pancreatic cancer patients, as has been observed in many other cancers. This clinical advantage encourages an exploration of the essence of dampness-heat ZHENG (DHZ) in cancer and investigation into underlying mechanisms of action of herbal formulations against dampness-heat. However, at present, there is a lack of understanding of the molecular characteristics of DHZ in cancer and no standardized and widely accepted animal model to study this core syndrome in vivo. The shortage of animal models limits the ability to uncover the antitumor mechanisms of herbal medicines and to assess the safety profile of the natural products derived from them. This review summarizes the current research on DHZ in cancer in terms of the clinical aspects, molecular landscape, and animal models. This study aims to provide comprehensive insight that can be used for the establishment of a future standardized ZHENG-based cancer animal model.

Study on fluvoxamine maleate sustained-release pellets and its compression technology / 药学学报

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (24) Taguchi experiment. Using Minitab software to design a DOE experiment with 24 partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Short-term effectiveness of transverse antecubital incision for failed closed reduction of Gartland type Ⅲ supracondylar humerus fractures in children / 中国修复重建外科杂志

OBJECTIVE@#To investigate the short-term effectiveness of transverse antecubital incision in the treatment of failed closed reduction of Gartland type Ⅲ supracondylar humeral fractures (SHFs) in children.@*METHODS@#Between July 2020 and April 2022, 20 children with Gartland type Ⅲ SHFs who failed in closed reduction were treated with internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision. There were 9 boys and 11 girls with an average age of 3.1 years (range, 1.1-6.0 years). The causes of injuries were fall in 12 cases and fall from height in 8 cases. The time from admission to operation ranged from 7 to 18 hours, with an average of 12.4 hours. The healing of the incision and the occurrence of complications such as nerve injury and cubitus varus were observed after operation; the elbow flexion and extension range of motion after removing the gypsum, after removing the Kirschner wire, and at last follow-up were recorded and compared, as well as the elbow flexion and extension and forearm rotation range of motion at last follow-up between healthy and affected sides; the Baumann angle was measured on the X-ray film, and the fracture healing was observed. At last follow-up, the effectiveness was evaluated according to the Flynn elbow function evaluation criteria.@*RESULTS@#All incisions healed by first intention, and there was no skin necrosis, scar contracture, ulnar nerve injury, and cubitus varus. Postoperative pain occurred in the radial-dorsal thumb in 2 cases. The gypsum was removed and elbow flexion and extension exercises were started at 2-4 weeks (mean, 2.7 weeks) after operation, and the Kirschner wire was removed at 4-5 weeks (mean, 4.3 weeks). All the 20 patients were followed up 6-16 months, with an average of 12.4 months. The fracture healing time was 4-5 weeks, with an average of 4.5 weeks, and there was no complication such as delayed healing and myositis ossificans. The flexion and extension range of motion of the elbow joint gradually improved after operation, and there were significant differences between the time after removing the gypsum, after removing the Kirschner wire, and at last follow-up ( P<0.017). There was no significant difference in the flexion and extension of the elbow joint and the forearm rotation range of motion between the healthy and affected sides at last follow-up ( P>0.05). There was no significant difference in Baumann angle between the time of immediate after operation, after removing the Kirschner wire, and at last follow-up ( P>0.05). According to Flynn elbow function evaluation standard, 16 cases were excellent and 4 cases were good, the excellent and good rate was 100%.@*CONCLUSION@#The treatment of Gartland type Ⅲ SHFs in children with failed closed reduction by internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision has the advantages of complete soft tissue hinge behind the fracture for easy reduction and wire fixation, small incision, less complications, fast fracture healing, early functional recovery, reliable reduction and fixation, and can obtain satisfactory results.

Identification of the metabolites from co-cultures of marine Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 / 药学学报

A new siderophore chelate (1) and 8 known compounds were identified from the liquid co-cultures of the marine-derived Streptomyces sp. IMB18-531 and Cladosporium sp. IMB19-099 by a combination of chromatography methods, including C18 reversed-phase medium pressure chromatography, gel column chromatography and HPLC. Their structures were determined by spectroscopic analysis and chemical methods as aluminioxamine E (1), desferrioxamine E (2), ferrioxamine E (3), terragine E (4), capsimicin (5), cyclo(L-prolinyl-L-tyrosine) (6), anthranilic acid (7), (Z)-14-methylpentadec-9-enoic acid (8), and (Z)-hexadec-8-enoic acid (9). Compound 2 showed inhibitory activities against the expression of liver fibrosis related genes COL1A1, MMP2, and TIMP2. Compounds 5, 8, and 9 displayed antibacterial activities against methicillin-resistant Staphylococcus aureus, S. epidermidis and Bacillus subtilis, with MICs of 16-64 μg·mL-1. Compound 5 showed cytotoxicities against human pancreatic cancer MIA Paca-2 and human colon cancer HT-29 cell lines with IC50 of 2.9 and 6.3 μmol·L-1, respectively.

Study on the correlation of cyfra21-1 and modified ultrasound in connective tissue disease associated with interstitial lung disease / 中华风湿病学杂志

Objective:To investigate the correlation between cytokeratin 19 fragment(CYFRA21-1), modified ultrasound B-line and connective tissue disease associated with interstitial lung disease (CTD-ILD).Methods:The data of 112 patients with CTD hospitalized in the Department of Rheumatology and Immunology of the Second Hospital of Fujian Medical University from September 2019 to December 2021 were retrospectively collected. Sixty patients in the CTD-ILD group and 52 patients in the connective tissue disease without interstitial lung disease (CTD-noILD) group were included. The t-test and χ2 test were used to compare the demographic characteristics and tumor-associated antigens of the two groups of patients. Modified ultrasound score and HRCT Warrick score were evaluated by Pearson correlation analysis. In addition, the relationship between CYFRA21-1, modified ultrasound score and Warrick score were evaluated, and the diagnostic efficacy of CYFRA21-1 and modified ultrasound of CTD-ILD was evaluated and analyzed by binary logistic regression analysis. Results:Patients in the CTD-ILD group had higher CYFRA21-1 concentrations than the CTD-no-ILD group[5.74(4.25, 9.79) ng/ml vs. 2.79(2.21, 3.23) ng/ml, Z=45.94, P<0.001], patients in the CTD-ILD group had higher modified ultrasound scores than the CTD-no-ILD group [44.5(36.5, 60.0) vs. 5.0 (3.2, 6.8), P<0.001]. Modified ultrasound score was positively correlated with Warrick score ( r=0.93, P<0.001) and CYRFA21-1 was positively correlated with modified ultrasound score ( r=0.39, P=0.042). The sensitivity of CYFRA21-1 in determining CTD-ILD was 81.7% and the specificity was 92.3% [ AUC (95% CI)=0.88(0.81, 0.95), P<0.001], the sensitivity of modified ultrasound B-line to determine CTD-ILD was 96.4% and the specificity was 92.9% [ AUC (95% CI)=0.99 (0.97, 1.00), P<0.001]. History of smoking[ OR(95% CI)=9.26(1.11, 77.12), P=0.040] and elevated CYFRA21-1 concentration[ OR(95% CI)=19.40(4.89, 76.95), P<0.001] were risk factors for CTD-ILD. Conclusion:CYFRA21-1 is expected to be a serum marker indicating concomitant ILD in patients with CTD. Modified ultrasound B-line to determine concomitant ILD in CTD patients has good diagnostic utility and can reflect the severity of pulmonary fibrosis in CTD-ILD patients.

Clinical centralized safety monitoring and evaluation of traditional Chinese medicine formula granules / 中国中药杂志

Traditional Chinese medicine(TCM) formula granules are highly praised for the advanced, convenient, and modern use of Chinese medicinal materials. The safety of TCM formula granules has long been a concern of regulatory authorities and the medical industry. A multi-center, prospective, open, non-interventional, and centralized monitoring was carried out for the patients treated with TCM formula granules in 252 medical institutions from February 5, 2020 to April 19, 2022. All the case data and the incidence of adverse drug reactions/events were recorded. This study evaluated the safety of TCM formula granules, aiming to provide a reference for the clinically use. A total of 20 547 patients were included in this study. Four adverse events were recorded, including 3 adverse drug reactions with an adverse drug reaction rate of 0.015%, all of which occurred in the digestive system. There was no serious adverse event, and no factors related to adverse drug reactions/events were identified. The incidence of adverse drug reactions/events associated with China Resources Sanjiu Medical & Pharmaceutical Co., Ltd. TCM formula granules was rare, which proved their safety in clinical use. A comprehensive data mining and objective analysis was carried out for the medicines with high frequency in TCM formula granules, the commonly used medicine pairs and combinations, and departmental medication. The drug use characteristics, prescription rules, and departmental use of TCM formula granules were summarized, which can shed light on the prescription compatibility and clinical application.

Research Progress of β-Klotho in Energy Metabolism and Tumor Development / 中国生物化学与分子生物学报

β-Klotho (KLB) is a member of the Klotho protein family, which is mainly distributed in organs and tissues such as the liver, fat, pancreas, and brain. KLB is a single-pass transmembrane protein whose structural characteristics determine that KLB acts as a co-receptor for fibroblast growth factor (FGF) 19/21 targeting the activation of fibroblast growth factor receptor (FGFRs). KLB is involved in the regulation of blood glucose, lipids, body weight, bile acid circulation, and hepatocyte proliferation in the FGF21/19-KLB-FGFRs pathway. This paperwill review the structural characteristics and distribution of KLB, as well as the regulatory mechanism of material energy and its role in tumor formation in the FGF19/21-KLB-FGFRs pathways.

Multi-index analysis of regional brain activity in patients with Alzheimer's disease during resting state / 解剖学报

Objective To investigate the spontaneous neural activity in the brain of patients with Alzheimer' s disease (AD) used 3 indicators of resting state-functional magnetic resonance (rs-fMRI) amplitude of low frequency fluctuation (ALFF), fractional amplitude of low frequency fluctuation (fALFF) and percentage amplitude fluctuation (PerAF). Methods Totally 36 clinically diagnosed AD patients and 40 healthy volunteers were scanned by fMRI in resting state respectively. ALFF, fALFF and PerAF were used to calculate and compare the changes of brain regions between the two groups. Results Compared with the normal control group, mALFF value in AD group increased significantly in bilateral caudate nucleus, medial frontal gyrus, superior frontal gyrus, gyrus rectus, anterior cingulate gyrus, olfactive cortex, left middle frontal gyrus and inferior frontal gyrus (P<0. 05). mALFF values decreased significantly in the right middle temporal gyrus, inferior temporal gyrus, inferior occipital gyrus, middle occipital gyrus, bilateral calcarine, cuneus, lingual gyrus, superior occipital gyrus, vermis, precuneus and other regions (P<0. 05). In AD group, mfALFF value of right inferior temporal gyrus, anterior cerebellar lobe, fusiform gyrus, left superior frontal gyrus, medial frontal gyrus, middle frontal gyrus, inferior frontal gyrus, gyrus rectus and anterior cingulate gyrus increased significantly (P<0. 05); mfALFF values decreased significantly in bilateral lingual gyrus, left calcarine, cuneus, superior occipital gyrus, middle occipital gyrus and vermis (P<0. 05). In AD group, mPerAF value increased significantly in bilateral gyrus rectus, anterior cingulate gyrus, medial frontal gyrus, left superior frontal gyrus, caudate nucleus, middle frontal gyrus, inferior frontal gyrus, olfactive cortex and insula (P<0. 05); mPerAF values decreased significantly in bilateral calcarine, cuneus, superior occipital gyrus, lingual gyrus, precuneus, left fusiform gyrus, inferior occipital gyrus, right superior parietal lobule, angular gyrus, middle temporal gyrus, inferior temporal gyrus and middle occipital gyrus (P < 0. 05). Conclusion The default mode network (DMN) and visual network of AD patients are characterized by abnormal brain activity, with the most significant neural activity in the prefrontal cortex and visual cortex.

Rho A/ROCK signaling pathway involved in hyper responsiveness to aortic contraction in mice with type 2 diabetes / 中国药理学通报

Aim To investigate the mechanism of RhoA/ROCK signaling pathway in abnormal aortic contractility in type 2 diabetes (T2DM) mice. Methods The experiment was divided into two groups, the control group (db/m mice) and the model group (db/db mice). Changes of the response to different methods were measured in aorta rings using a Multi Myograph System. At the same time, the protein expression changes of aortic smooth muscle contraction signaling pathway in mice were determined by Western method. Results Compared with the control group, the blood glucose and body weight levels of the mice in the T2DM group significantly increased, and the cardiac function was abnormal (P <0. 01). The contractile response of the aorta of the diabetic mice induced by the contractile agents Phe, 5-HT and CaCl

CT-Based Weighted Radiomic Score Predicts Tumor Response to Immunotherapy in Non-Small Cell Lung Cancer / 中国医学科学院学报

Objective To develop a CT-based weighted radiomic model that predicts tumor response to programmed death-1(PD-1)/PD-ligand 1(PD-L1)immunotherapy in patients with non-small cell lung cancer.Methods The patients with non-small cell lung cancer treated by PD-1/PD-L1 immune checkpoint inhibitors in the Peking Union Medical College Hospital from June 2015 to February 2022 were retrospectively studied and classified as responders(partial or complete response)and non-responders(stable or progressive disease).Original radiomic features were extracted from multiple intrapulmonary lesions in the contrast-enhanced CT scans of the arterial phase,and then weighted and summed by an attention-based multiple instances learning algorithm.Logistic regression was employed to build a weighted radiomic scoring model and the radiomic score was then calculated.The area under the receiver operating characteristic curve(AUC)was used to compare the weighted radiomic scoring model,PD-L1 model,clinical model,weighted radiomic scoring + PD-L1 model,and comprehensive prediction model.Results A total of 237 patients were included in the study and randomized into a training set(n=165)and a test set(n=72),with the mean ages of(64±9)and(62±8)years,respectively.The AUC of the weighted radiomic scoring model reached 0.85 and 0.80 in the training set and test set,respectively,which was higher than that of the PD-L1-1 model(Z=37.30,P<0.001 and Z=5.69,P=0.017),PD-L1-50 model(Z=38.36,P<0.001 and Z=17.99,P<0.001),and clinical model(Z=11.40,P<0.001 and Z=5.76,P=0.016).The AUC of the weighted scoring model was not different from that of the weighted radiomic scoring + PD-L1 model and the comprehensive prediction model(both P>0.05).Conclusion The weighted radiomic scores based on pre-treatment enhanced CT images can predict tumor responses to immunotherapy in patients with non-small cell lung cancer.

Study on after-effect of electroacupuncture with different time intervals on corticospinal excitability in primary motor cortex / 中国针灸

OBJECTIVES@#To compare the effects of electroacupuncture (EA) with different time intervals on corticospinal excitability of the primary motor cortex (M1) and the upper limb motor function in healthy subjects and observe the after-effect rule of acupuncture.@*METHODS@#Self-comparison before and after intervention design was adopted. Fifteen healthy subjects were included and all of them received three stages of trial observation, namely EA0 group (received one session of EA), EA6h group (received two sessions of EA within 1 day, with an interval of 6 h) and EA48h group (received two sessions of EA within 3 days, with an interval of 48 h). The washout period among stages was 1 week. In each group, the needles were inserted perpendicularly at Hegu (LI 4) on the left side, 23 mm in depth and at a non-acupoint, 0.5 cm nearby to the left side of Hegu (LI 4), separately. Han's acupoint nerve stimulator (HANS-200A) was attached to these two needles, with continuous wave and the frequency of 2 Hz. The stimulation intensity was exerted higher than the exercise threshold (local muscle twitching was visible, and pain was tolerable by healthy subjects, 1-2 mA ). The needles were retained for 30 min. Using the single pulse mode of transcranial magnetic stimulation (TMS) technique, before the first session of EA (T0) and at the moment (T1), in 2 h (T2) and 24 h (T3) after the end of the last session of EA, on the left first dorsal interosseous muscle, the amplitude, latency (LAT), resting motor threshold (rMT) of motor evoked potentials (MEPs) and the completion time of grooved pegboard test (GPT) were detected. Besides, in the EA6h group, TMS was adopted to detect the excitability of M1 (amplitude, LAT and rMT of MEPs) before the last session of EA (T0*).@*RESULTS@#The amplitude of MEPs at T1 and T2 in the EA0 group, at T0* in the EA6h group and at T1, T2 and T3 in the EA48h group was higher when compared with the value at T0 in each group separately (P<0.001). At T1, the amplitude of MEPs in the EA0 group and the EA48h group was higher than that in the EA6h group (P<0.001, P<0.01); at T2, it was higher in the EA0 group when compared with that in the EA6h group (P<0.01); at T3, the amplitude in the EA0 group and the EA6h group was lower than that of the EA48h group (P<0.001). The LAT at T1 was shorter than that at T0 in the three groups (P<0.05), and the changes were not obvious at the rest time points compared with that at T0 (P > 0.05). The GPT completion time of healthy subjects in the EA0 group and the EA48h group at T1, T2 and T3 was reduced in comparison with that at T0 (P<0.001). The completion time at T3 was shorter than that at T0 in the EA6h group (P<0.05); at T2, it was reduced in the EA48h group when compared with that of the EA6h group (P<0.05). There were no significant differences in rMT among the three groups and within each group (P>0.05).@*CONCLUSIONS@#Under physiological conditions, EA has obvious after-effect on corticospinal excitability and upper limb motor function. The short-term interval protocol (6 h) blocks the after-effect of EA to a certain extent, while the long-term interval protocol (48 h) prolongs the after-effect of EA.

The objectification of ashi point diagnosis and treatment / 中国针灸

Ashi points play a significant role in the clinical localization and qualitative diagnosis of acupuncture, as well as in selecting acupoints along the meridians and applying tonifying or reducing techniques. This paper introduces the theoretical basis and existing technical methods of objectification of ashi point diagnosis and treatment. It proposes that using sensory quantitative testing to determine the temperature and tenderness thresholds of ashi points could help to identify the pathological characteristics of "cold" "heat" "deficiency" or "excess" of ashi points. In addition, the possibility of objectification of ashi point diagnosis-treatment plan is explored from three perspectives, precision of selection of ashi point therapy, objectification of effect evaluation of ashi point analgesia, and differentiation of the studies on ashi point analgesic mechanism, aiming to provide new research ideas for the modernization of traditional Chinese acupuncture.

Biomechanical Evaluation of Oblique Lateral Interbody Fusion Combined with Different Internal Fixation Methods for Treating Degenerative Lumbar Scoliosis:A Finite Element Analysis / 医用生物力学

Objective To verify the biomechanical stability of oblique lateral interbody fusion ( OLIF) combinedwith different fixation methods for treating degenerative lumbar scoliosis (DLS) by three-dimensional (3D) finite element analysis. Methods The L1-S1 3D finite element DLS model ( Model 1) was established, and then the OLIF (L2-5) at 3 contiguous levels of fusion and its combination with different internal fixation methods were simulated, namely, stand-alone OLIF model ( Model 2), vertebral screw fixation model ( Model 3), unilateral pedicle screw fixation model (Model 4) and bilateral pedicle screw fixation model (Model 5) were established,respectively. Under upright, flexion, extension, lateral bending and axial rotation states, range of motion (ROM) of fusion segments, as well as cage stress, internal fixation stress, and stress distribution were recorded and analyzed. Results Under six motion states, the overall ROM of fusion segments in Models 2-5 was smaller than that of Model 1. Compared with Model 1, the overall ROM reduction of Model 3 and Model 4 was larger than that of Model 2 and smaller than that of Model 5. Under flexion and extension, the overall ROM reduction of Model 4 and Model 5 was basically equal. Under left and right lateral bending, the overall ROM reduction of Model 3 and Model 5 was basically equal. Under all motion states, the peak stress of Model 3 and Model 4 fusion cage was larger than that of Model 5 and smaller than that of Model 2. The peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 3 increased by 5. 52% , 10. 96% and 7. 99% respectively compared with Model 5 under left lateral bending, and the peak stresses of L2-3, L3-4 and L4-5 fusion cages in Model 4 increased by 8. 70% , 7. 00% and 6. 99% respectively under flexion. Under all motion states, the peak stress of screw rod in Model 5 was smaller than that of Model 3 and Model 4, and the peak stresses of screw rod in Models 3-5 were the smallest in upright state. Conclusions The OLIF with unilateral pedicle screw fixation or vertebral screw fixation can provide favorable biomechanical stability of the fusion segment. The results provide some references for clinical application of OLIF technology in the treatment of DLS.

18FMAGL-4-11 positron emission tomography molecular imaging of monoacylglycerol lipase changes in preclinical liver fibrosis models

Monoacylglycerol lipase (MAGL) is a pivotal enzyme in the endocannabinoid system, which metabolizes 2-arachidonoylglycerol (2-AG) into the proinflammatory eicosanoid precursor arachidonic acid (AA). MAGL and other endogenous cannabinoid (EC) degrading enzymes are involved in the fibrogenic signaling pathways that induce hepatic stellate cell (HSC) activation and ECM accumulation during chronic liver disease. Our group recently developed an 18F-labeled MAGL inhibitor ([18F]MAGL-4-11) for PET imaging and demonstrated highly specific binding in vitro and in vivo. In this study, we determined [18F]MAGL-4-11 PET enabled imaging MAGL levels in the bile duct ligation (BDL) and carbon tetrachloride (CCl4) models of liver cirrhosis; we also assessed the hepatic gene expression of the enzymes involved with EC system including MAGL, NAPE-PLD, FAAH and DAGL that as a function of disease severity in these models; [18F]MAGL-4-11 autoradiography was performed to assess tracer binding in frozen liver sections both in animal and human. [18F]MAGL-4-11 demonstrated reduced PET signals in early stages of fibrosis and further significantly decreased with disease progression compared with control mice. We confirmed MAGL and FAAH expression decreases with fibrosis severity, while its levels in normal liver tissue are high; in contrast, the EC synthetic enzymes NAPE-PLD and DAGL are enhanced in these different fibrosis models. In vitro autoradiography further supported that [18F]MAGL-4-11 bound specifically to MAGL in both animal and human fibrotic liver tissues. Our PET ligand [18F]MAGL-4-11 shows excellent sensitivity and specificity for MAGL visualization in vivo and accurately reflects the histological stages of liver fibrosis in preclinical models and human liver tissues.

Effects of different extracts of Dendrobium officinale on rats with chronic pharyngitis induced by pepper water combined with ammonia / 中国中药杂志

Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.

Constructions of the scale of difficulty in the extraction of impacted mandibular third molars by using Delphi method / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the relevant indicators affecting difficulty in the extraction of impacted mandibular third molars and score difficulty of different operation and risk indicators, so as to build an intuitive and accurate scale to help operators make more accurate analysis and prediction of difficulty before the operation.@*METHODS@#Based on literature and the clinical review, the difficulty indicators of tooth extraction were summarized. Firstly, 10 doctors from Peking University School and Hospital of Stomatology who had been engaged in alveolar surgery for a long time established an expert nominal group, and then rated whether the summarized indicators needed to be retained in the form of face-to-face questionnaires. A level 1 and 2 item frame for evaluating difficulty in the tooth extraction was formed after discussion; Then Delphi method was used to send a questionnaire to 30 experts by e-mail. After two rounds of scoring and modification, the scale of difficulty in the extraction of impacted mandibular third molars was formed.@*RESULTS@#The recycling rate of two rounds of questionnaires was 100.0%, which showed that the experts were very enthusiastic about the study; The authority coefficients (Cr) of the two rounds of Delphi expert consultation were both 0.92, which showed that the results were representative and authoritative. After two rounds of grading and revision, the variable coefficient (CV) decreased and the Kendall's concordance coefficient (W) increased, which were statistically significant: In the first round, the CV was 0.24 and W was 0.56 (P < 0.001), and in the second, the CV was 0.19 and W was 0.72 (P < 0.001), which indicated that there was a good convergence among the expert opinions. Finally, a scale of difficulty in the tooth extraction containing 12 items at level A and 37 items at level B was formed, including operation difficulty indicators, risk difficulty indicators and common difficulty indicators.@*CONCLUSION@#Based on comprehensive literature retrieval, the study has put forward the concept that difficulty in the extraction of impacted mandibular third molars is composed of operation difficulty and risk difficulty. Using Delphi method, the long-term clinical experience and professional knowledge of experts are transformed into quantitative indicators as a scoring scale. The scale has certain representativeness and authority.

Clinical Efficacy of Gandou Fumu Granules on Wilson Disease with Liver-kidney Deficiency and Phlegm-blood Stasis / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of Gandou Fumu granules （GDFM） in the treatment of Wilson disease （WD） with liver-kidney deficiency and phlegm-blood stasis. MethodNinety WD patients in The First Affiliated Hospital of Anhui University of Chinese Medicine were randomly divided into a control group （45 cases） and a treatment group （45 cases）. All patients were treated with sodium 2，3-dimercaptopropane-1-sulfonate （DMPS）， while those in the treatment group received additional GDFM. All patients were treated for four courses （32 days）. The traditional Chinese medicine （TCM） syndrome scores，clinical effective rate，24 h urinary copper，ceruloplasmin （CER），tumor necrosis factor-α（TNF-α），interleukin-1β（IL-1β），interleukin-6 （IL-6），superoxide dismutase （SOD），glutathione peroxidase （GSH-Px） and malondialdehyde （MDA） levels of the two groups before and after treatment were observed. ResultAfter treatment， the TCM syndrome scores of the two groups decreased （P<0.01），and the score of TCM syndrome in the treatment group was lower than that of the control group （P<0.01）. The total effective rate of the treatment group was 82.22% （37/45）， higher than 57.78% （26/45） of the control group （χ2=6.402，P<0.05）. There was no significant difference in CER before and after treatment in both groups. The post-treatment 24 hour urinary copper increased （P<0.01）， which was higher in the treatment group than that in the control group （P<0.05）. The TNF-α，IL-1β， and IL-6 levels were significantly reduced in both groups after treatment（P<0.01），and the above indicators in the treatment group were significantly lower than those in the control group （P<0.01）. After treatment，the SOD level increased and the MDA level decreased in the control group （P<0.01）， while no significant difference in GSH-Px level was observed. The SOD and GSH-Px levels increased and the MDA level decreased in the treatment group （P<0.01）. After treatment， SOD and GSH-Px levels of the treatment group were higher than those in the control group， while the MDA level was lower than that in the control group（P<0.05，P<0.01）. ConclusionGDFM can improve the TCM syndrome score and clinical efficacy，enhance the copper removing effect，and inhibit the inflammatory response and antioxidative stress in the treatment of WD with liver and kidney deficiency and phlegm-blood stasis.

Effect of Gandou Decoction on Mitophagy in Toxic Milk （TX） Mouse Model of Wilson Disease Based on Pink1/Parkin Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Gandou decoction （GDD） on the mitophagy of hippocampal neurons in toxic milk （TX） mouse model of Wilson disease and explore the protective mechanism of GDD against neuron injury through the PTEN induced kinase 1 （Pink1） /E3 ubiquitin ligase （Parkin） pathway. MethodSixty mice were randomly divided into a blank group， a model group， a penicillamine group （0.09 g·kg-1）， and low- （5.5 g·kg-1）， medium- （11 g·kg-1）， and high-dose （22 g·kg-1） GDD groups， and treated correspondingly by gavage for 8 weeks. Morris water maze， traction test， and pole test were used for the evaluation of animal behaviors. Hematoxylin-eosin （HE） staining and transmission electron microscopy were used to observe cell apoptosis， ultrastructure， autophagy， and mitochondrial structure. The levels of superoxide dismutase （SOD）， reactive oxygen species （ROS）， and malondialdehyde （MDA） were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of Pink1， Parkin， autophagy-associated protein Beclin-1， microtubule-associated protein 1 light chain 3Ⅱ （LC3Ⅱ）， and p62. Western blot was conducted to detect the protein expression of Pink1， Parkin， Beclin-1， LC3Ⅱ/Ⅰ， and p62. ResultCompared with the blank group， the model group showed prolonged escape latency， decreased times of platform crossing， lower score in the traction test， and longer pole climbing time （P<0.01）. Compared with the model group， the medium- and high-dose GDD groups and the penicillamine group showed shortened escape latencies， increased times of platform crossing， higher scores in the traction test， and shortened pole climbing time （P<0.01）. Compared with the blank group， the model group displayed severely damaged neurons and increased autophagosomes. Compared with the model group， the medium- and high-dose GDD groups and the penicillamine group showed improved neuron damage and reduced autophagosomes. The levels of ROS and MDA were higher and SOD was lower in the model group than those in the blank group （P<0.01）， while the levels of the above indicators were reversed by GDD intervention as compared with the model group （P<0.01）. Compared with the blank group， the model group exhibited up-regulated mRNA and protein expression of Pink1， Parkin， LC3Ⅱ， and Beclin-1 and down-regulated p62 （P<0.05）. Compared with the model group， the medium- and high-dose GDD groups showed reduced mRNA and protein expression of Pink1， Parkin， LC3Ⅱ， and Beclin-1 and increased p62 （P<0.05， P<0.01）. ConclusionGDD can significantly inhibit the excessive mitophagy in neurons of TX mice and protect neurons from damage. The mechanism may be related to the regulation of the Pink1/Parkin pathway.

Correlation between dietary approaches to stop hypertension pattern and central obesity affected by PM2.5 exposure / 环境与职业医学

Background There is a lack of evidence on whether exposure to PM2.5 and its constituents would affect the relationship between the dietary approaches to stop hypertension (DASH) and central obesity. Objective To investigate the effect of exposure to PM2.5 and its constituents on the correlation between the DASH dietary pattern and the prevalence of central obesity. Methods The data were obtained from the baseline survey of the "Xinjiang Multi-Ethnic Natural Population Cohort Construction and Health Follow-Up Study" in Urumqi. A DASH score was calculated according to intake frequency of 8 food groups, and summed from intake frequency of recommended food groups scored from 1 to 5 from low to high, and intake frequency of restricted food groups scored from 1 to 5 from high to low. A higher DASH score indicates better compliance with the DASH dietary pattern. We estimated exposure using satellite-derived PM2.5 and a chemical transport model (GEOS-Chem) for its constituents, including organic carbon (OC), black carbon (BC), sulfate (SO42−), nitrate (NO3−), ammonium (NH4+), and soil dust. Central obesity was defined by waist circumference: ≥90 cm for men or ≥85 cm for women according to Criteria of weight for adults (WS/T 428—2013). A logistic regression model was used to analyze the effects of the DASH dietary pattern as well as PM2.5 and its constituents on central obesity, and a stratified analysis was used to explore the effects of PM2.5 and its constituents on the association between the DASH dietary pattern and central obesity. Results The study included 9 565 urban residents, aged (62.30±9.42) years, with a central obesity prevalence rate of 60.75%. After adjusting for selected confounders, the DASH score Q5 group had a 17.5% lower risk of central obesity than the Q1 group (OR=0.825, 95%CI: 0.720-0.947). PM2.5 and its constituents OC, BC, SO42−, NH4+, and soil dust were positively associated with the prevalence of central obesity, but no association was observed between constituent NO3− exposure and central obesity. The stratified analysis revealed that the prevalence of central obesity was reduced in the DASH score Q5 group in participants exposed to low concentrations of PM2.5 and its constituents NO3−, NH4+, and soil dust, while the protective effect of the DASH pattern on central obesity disappeared in subjects exposed to high concentrations of PM2.5 and its constituents NO3−, NH4+, and soil dust. Conclusion Exposure to PM2.5 and its constituents NO3−, NH4+, and soil dust could attenuate the protective effect of the DASH pattern on central obesity.

Research advances in tibial insertion of posterior cruciate ligament and location of tibial tunnel / 中华创伤骨科杂志

Posterior cruciate ligament (PCL) plays an important role in maintaining the stability of knee. PCL injury is often accompanied by serious axial and rotational instability, and severe PCL injury is likely to be combined with injuries to the anterior cruciate ligament, medial collateral ligament and other tissues which are often repaired by necessary posterior cruciate ligament reconstruction (PCLR) to restore their physiological functions. However, PCLR research is not as common as the research into the anterior cruciate ligament reconstruction, not only due to controversies in the anatomy and mechanics of PCL but also due to a higher failure rate and more complications following PCLR. This situation is closely related to the anatomical characteristics of the PCL tibial insertion. The present review deals with the anatomy, mechanics and clinical research of the PCL tibial insertion in order to provide more references for PCLR operators.