Research progress of needle-free injection technology / 药学学报

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone / 药学学报

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Resveratrol inhibits autophagy and promotes apoptosis in uveal melanoma cells via miR-512-3P/DUSPl axis / 中国药理学通报

Aim To investigate the regulatory role and mechanism of resveratrol in inhibiting autophagy and promoting apoptosis in choroidal melanoma cells. Methods Choroidal melanoma cells (MUM2B) were divided into control and experimental groups, and treated with different concentrations of resveratrol (0, 10, 20,40,60,80 μmol ·L

Anzhen hospital expert experience on perioperative treatment principles of cardiovascular surgery for patients infected with COVID-19 / 中华胸心血管外科杂志

The end of the COVID-19 infection peak in 2022 prompts a backlog of cardiovascular surgical patients to gradually return to the hospital, resulting in a surge in cardiovascular surgeries. However, against the backdrop of the COVID-19 pandemic, the clinical practice of cardiovascular surgery faces many problems. Therefore, organized by Beijing Anzhen Hospital, experts in cardiovascular surgery and related fields have formulated hospital expert experience on perioperative treatment principles of cardiovascular surgery for patients infected with COVID-19. This article summarizes the clinical decision-making of patients requiring cardiovascular surgery after COVID-19 infection, and advises on the corresponding recommendations according to the existing evidence-based medical evidence as well as the actual clinical practice experience of relevant experts. The main content of the article includes special requirements for cardiovascular surgical treatment indications in patients with COVID-19 infection, selection of surgical timing, special requirements of preoperative, intraoperative and postoperative management, etc., which aims to provide COVID-19-infected patients with guidance on rational decision-making when receiving cardiovascular surgery.

Analysis of clinical characteristics of multiple myeloma patients combined with kidney injury and risk factors for kidney injury / 白血病·淋巴瘤

Objective:To investigate the clinical characteristics of patients with multiple myeloma (MM) combined with kidney injury and the risk factors associated with the occurrence of kidney injury.Methods:The clinical data of 96 newly treated MM patients in Heze Municipal Hospital from January 2017 to June 2021 were retrospectively analyzed, and the patients were divided into the kidney injury group (33 cases) and the non-kidney injury group (63 cases) based on whether the blood creatinine was >177 μmol/L at the time of diagnosis. The general data and laboratory results of the two groups were compared. The risk factors for kidney injury in MM patients were analyzed by logistic regression method, and the receiver operating characteristic (ROC) curve was drawn to assess the predictive value of each risk factor for the occurrence of kidney injury in MM patients.Results:Compared with the non-kidney injury group, hemoglobin was lower in the kidney injury group, and white blood cell count, blood uric acid, urea nitrogen, β 2-microglobulin (β 2-MG), cystatin C, the proportion of patients with light chain type, and the proportion of patients with international staging system (ISS) stage Ⅲ were higher in the kidney injury group, and the differences were statistically significant (all P < 0.05). Thirty-four patients underwent fluorescence in situ hybridization (FISH) test, and 22 cases (64.7%) had abnormal results. In the non-kidney injury group, genetic testing were performed in 26 cases, and the results were abnormal in 14 cases, including 11 cases (42.3%) of IgH rearrangement, 4 cases (15.4%) of RB1 deletion, 4 cases (15.4%) of 1q21 amplification, and 1 case (3.8%) of P53 deletion; in the kidney injury group, 8 cases underwent genetic testing, and all results were abnormal, including 6 cases (75.0%) of IgH rearrangement, 5 cases (40.0%) of RB1 deletion, and 2 cases (25.0%) of 1q21 amplification. The rate of RB1 mutation in the kidney injury group was higher than that in the non-kidney injury group, and the difference was statistically significant ( χ2 = 4.43, P = 0.035). Logistic regression analysis showed that elevated blood uric acid ( OR = 1.009, 95% CI 1.002-1.016, P = 0.015) and ISS stage Ⅲ ( OR = 16.401, 95% CI 1.174-229.164, P = 0.038), elevated white blood cell count ( OR = 1.833, 95% CI 1.020-3.294, P = 0.043), elevated β 2-MG ( OR = 1.320, 95% CI 1.009-1.728, P = 0.043), and decreased hemoglobin ( OR = 0.900, 95% CI 0.832-0.922, P = 0.008) were independent risk factors for the development of kidney injury in MM patients. According to the area under the ROC curve (AUC), blood uric acid (AUC = 0.775, 95% CI 0.675-0.875, P < 0.001), white blood cell count (AUC = 0.696, 95% CI 0.583-0.809, P = 0.002), β 2-MG (AUC = 0.822, 95% CI 0.732-0.911, P < 0.001), hemoglobin (AUC = 0.755, 95% CI 0.652-0.857, P < 0.001), and ISS stage Ⅲ (AUC = 0.763, 95% CI 0.669-0.856, P < 0.001) had predictive value for kidney injury in MM. Conclusions:MM patients have a high incidence of combined kidney injury, and active monitoring and control of risk factors may improve the outcome and prognosis of patients.

Whole-course management strategies for gastroesophageal reflux disease: an evidence mapping study based on clinical practice guidelines / 中华胃肠外科杂志

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases with high incidence, complicated clinical symptoms, difficulties in standard treatment, and heavy medical burden. At present, some GERD-relevant clinical practice guidelines (CPGs) have been issued by different countries and academic organizations, but some recommendations were inconsistent, which has caused some problems for the current clinical whole-course management of GERD. To summarize the relevant evidence among the CPGs on GERD and formulate the whole- course management strategies, we included GERD-relevant CPGs published or updated after 2010 by searching websites of guidelines, relevant professional societies, and electronic databases. We extracted the recommendations and summarized the evidence from the aspects of symptoms, epidemiology, diagnosis and treatment, which was presented in the form of evidence mapping. We included 24 CPGs, including three in Chinese and 21 in English. The clinical practice management strategies of GERD were formulated based on the evidence from the aspects of clinical symptoms, diagnostic methods, medical treatment, anti-reflux surgery and endoscopic treatment, psychological treatment, and traditional Chinese medicine treatment.

Characteristics of Silent Alpha Thalassemia Gene in Child-Bearing Adults in Guangdong / 中国实验血液学杂志

OBJECTIVE@#To investigate characteristics of silent alpha thalassemia genes in child-bearing adults in Guangdong, in order to provide data for the prevention and control of hemoglobin H disease.@*METHODS@#A total of 8 752 cases were collected from January 2016 to December 2020. Gap-PCR was used to detect the deletional of α-thalassemia mutations (-α3.7, -α4.2), while PCR reverse dot blot hybridization assay (RDB) was used to detect the non-deletional α-thalassemia mutations (Hb CS, Hb QS and Hb Westmead).@*RESULTS@#Among 8 752 subjects, 717 cases of silent α-thalassemia were detected, the detection rate was 8.19%, including 555 cases of deletional α-thalassemia (77.41%) and 162 cases of non-deletional α-thalassemia 22.59%. The mean corpuscular volume (MCV) of deletional silent α-thalassemia was (82.09±4.10) fl, and mean corpuscular hemoglobin (MCH) was (27.03±1.37) pg, which both were over the diagnostic cut-off value for thalassemia. The MCV of non-deletional silent α-thalassemia was (81.07±4.93) fl, and MCH was (26.77±2.20) pg. According to the diagnostic criteria, if using MCV<82 fl or (and) MCH<27 pg as a positive criteria for screening thalassemia in the childbearing age, the screening sensitivity was 53.14% and different in different genotype, among which ααQS/αα was 100%, -α3.7/αα, -α4.2/αα, ααCS/αα and ααWS/αα was 62.15%, 63.41%, 44.83% and 39.62%, respectively. Namely, nearly half the carriers of such mutations might have escaped detection as a result of their screening strategy.@*CONCLUSION@#When a couple is preparing for pregnancy, if one of them has been determined to be mild α-thalassemia or hemoglobin H disease, other half is necessary to carry out silent α thalassemia detection to prevent the birth of children with hemoglobin H disease even if MCV>82 fl and MCH>27 pg.

Effects and mechanism of Morus alba L. (Sangzhi) alkaloids combined with metformin on glucose metabolism in diabetic KKAy mice / 药学学报

To investigate the effects and mechanism of the combination of Morus alba L. (Sangzhi) alkaloids(SZ-A) and metformin (Met) on glucose metabolism in type 2 diabetic mice, KKAy mice were divided into four groups according to the glucose and lipid indexes: control group (control), Morus alba L. (Sangzhi) alkaloids group (SZ-A, 100 mg·kg-1), metformin group (Met, 100 mg·kg-1) and combined administration group (combination, Comb, 100 mg·kg-1 SZ-A + 100 mg·kg-1 Met). All groups were administered by gavage once daily for 7 weeks accompanied with monitoring food intake, water intake, body weight as well as glycemia. Additionally, oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and oral sodium pyruvate tolerance test (OPTT) were performed at week 2, week 5, week 6, respectively. The experiments were approved by the Institutional Animal Care and Use Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (00004332). We determined the weight and lipid content of liver, and then performed the histopathological analysis after sacrificed. Furthermore, Western blot assay was used to detect the protein levels of key molecules of PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue. Compared to the SZ-A or Met monotherapy group, SZ-A + Met significantly improved the glucose metabolism disorder, which was showed in reduced food intake, water intake, the level of fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin A1c (HbA1c) of KKAy mice, as well as improved glucose tolerance, enhanced insulin sensitivity and inhibited gluconeogenesis. In addition, SZ-A + Met obviously up-regulated the protein expression levels in PI3K/PDK1/Akt/GLUT signaling pathway in liver, muscle and adipose tissue of KKAy mice. Moreover, the liver lipid accumulation and blood aminotransferase level of KKAy mice in the combined administration group were significantly reduced. Therefore, we concluded that the combination of SZ-A and Met improved glucose metabolism and inhibited the occurrence and development of T2DM via promoting glucose uptake and utilization, suggesting that the combination of SZ-A and Met is a more useful treatment for T2DM.

Role of TGF-β/Smad signaling pathway in pulmonary fibrosis after rheumatoid arthritis in mice / 中国药理学通报

Aim To investigate the role of TGF-β/Smad signaling pathway in rheumatoid arthritis (RA) - associated postinterstitial pulmonary fibrosis in mice. Methods The mouse model of RA was constructed by subcutaneous administration of complete Freund's adjuvant (CFA) and chicken II collagen (Col-II) to the tail root of mice. The blank group was given the same amount of distilled water, and the control group was given the same amount of glacial acetic acid (solvent). The degree of toe swelling (joint swelling degree and arthritis index) was monitored to evaluate the mouse modeling. The pathological changes of mouse lung tissues were observed by HE and Masson staining. The expression of TGF-β in lung tissues were observed by immunohistochemical staining. The level of hydroxyproline in lung tissues was measured by chemiluminescence method. The expressions of Smad2, Smad3 and phosphorylated p-Smad2 and phosphorylated p-Smad3 in lung tissues were detected by Western blot. Results Compared with blank group and solvent group, the joint swelling and arthritis index of model group significantly increased. Twenty-one days after administration, HE staining showed inflammatory changes in lung interstitium of the model group, Masson staining showed collagen fiber deposition and obvious fibrosis in lung interstitium of the model group, and immunohistochemical staining showed that the expression of TGF-β in cytoplasm of lung interstitial cells of the model group increased, which was brown and yellow. Meanwhile, hydroxyproline was significantly raised in lung tissue homogenate of the model group. Further WB analysis showed that compared with blank group and solvent group, the expression of p-Smad2 and pSmad3 in lung tissues of the model group was significantly up-regulated (P < 0. 05, P < 0. 01). Conclusions RA can give rise to pulmonary fibrosis, and the expressions of p-Smad2 and p-Smad3 are up-regulated, which is be pivotal in pulmonary fibrosis and RA-related post-interstitial pulmonary fibrosis.

The effect and mechanism of metformin on peripheral neuropathy in type 1 diabetic rats / 药学学报

Diabetic peripheral neuropathy (DPN) is one of the most common microvascular complications occurring in both type 1 and type 2 diabetes mellitus patients, which often results in patients suffering from severe hyperalgesia and allodynia. Up to now, the clinical therapeutic effect of DPN is still unsatisfactory. Metformin is an anti-diabetic drug that has been safely and widely used for the treatment of type 2 diabetes for decades. Studies have shown that metformin can improve pain caused by DPN, but its effects on the nerve conduction velocity and morphology of the sciatic nerve of DPN, and the mechanism for improving DPN are not clear. Therefore, the STZ-induced model of type 1 DPN in SD rats was used to study the effects of metformin on DPN, and to preliminarily explore its mechanism in this study. All animal experiments were carried out with approval of the Experimental Animal Welfare Ethics Committee of the Institute of Materia Medica (Chinese Academy of Medical Sciences and Peking Union Medical College). After the model was established successfully, STZ diabetic rats were randomly divided into a model group and a metformin treatment group, and 10 normal SD rats were selected as the normal control group, and the rats were intragastrically administered for 12 weeks. The results showed that metformin significantly reduced blood glucose, glycosylated hemoglobin, food consumption and water consumption in STZ rats. Metformin markedly increased the motor nerve conduction velocity and mechanical stabbing pain threshold, prolonged the hot plate latency threshold, and improved the pathological morphological abnormalities of the sciatic nerve in STZ rats. In addition, metformin increased the content of glutathione (GSH), enhanced the activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT), and reduced the content of malondialdehyde (MDA) in serum and sciatic nerve of STZ diabetic rats, as well as regulating the expression of genes related to oxidative stress in the sciatic nerve. Metformin obviously reduced the levels of pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β and IL-6 in the serum in STZ rats, and inhibited the gene expression of these inflammatory factors in the sciatic nerve. In summary, metformin significantly increased nerve conduction velocity, improved sciatic nerve morphological abnormalities and pain in DPN rats, which may be related to its effect in improving oxidative stress and reducing inflammation.

Clinical observation of polymyxin B in the treatment of CRKP-BSI in patients with hematological malignancies / 中国药房

OBJECTIVE To analyze the efficacy and safety of polymyxin B in the treatment of carbapenem-resistant Klebsiella pneumoniae （CRKP）-bloodstream infection （BSI） in patients with hematologic malignancies. METHODS The medical records of patients with hematologic malignancies with CRKP-BSI who received polymyxin B for at least 3 days in our hospital from September 2019 to June 2021 were retrospectively analyzed. All patients were initially treated with a triple therapy namely polymyxin B+tigecycline+carbapenems for anti-infection therapy. RESULTS A total of 10 patients were enrolled as the study subjects. Eleven strains of CRKP were cultured in blood， including 10 strains of CRKP produced Klebsiella pneumoniae carbapenemase（KPC） and 1 strain of CRKP produced both KPC and metal-beta-lactamase； 9 strains were sensitive to colistin， 7 strains were sensitive to tigecycline， 5 strains were sensitive to amikacin and 2 strains were sensitive to compound sulfamethoxazole. All patients were accompanied by neutropenia， with an average duration of （14.1±6.4） days. They were all characterized by fever， chills and fatigue. After treatment， 6 patients were cured and discharged， 4 patients died of ineffective treatment of septic shock. No serious adverse events related to polymyxin B occurred in all patients. CONCLUSIONS Polymyxin B can be used as a therapeutic drug for CRKP-BSI in patients with hematological malignancies. No serious adverse event related to polymyxin B occurs during the treatment.

Panscleritis After Blunt Ocular Trauma in A Child with Epididymitis / 中国医学科学杂志(英文版)

We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground. Etiologic diagnosis played a key role in this case. Systemic examinations ruled out systemic autoimmune diseases, tumors, and infections as the cause of scleritis and suggested that the disease was caused by a local delayed-type hypersensitivity (DTH) induced by ocular trauma and was non-infectious. Still, the right epididymitis was infectious. Both conditions were treated successfully using steroids and antibiotics, respectively. Thus, early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.

Efficacy and safety of Regan Syrup in treatment of common cold (wind-heat syndrome):a multicenter, randomized, double-blind, double-dummy, placebo and positive drug-controlled, parallel, phase Ⅱb clinical trial / 中国中药杂志

Regan Syrup has the effect of clearing heat, releasing exterior, benefiting pharynx and relieving cough, and previous phase Ⅱ clinical trial showed that the efficacy of Regan Syrup high-dose and low-dose groups was better than that of the placebo group, and there was no statistically significant difference in the safety between the three groups. The present study was conducted to further investigate the efficacy and safety of the recommended dose(20 mL) of Regan Syrup in the treatment of common cold(wind-heat syndrome). Patients who met the inclusion and exclusion criteria were selected and divided into the test group(Regan Syrup+Shufeng Jiedu Capsules placebo), positive drug group(Regan Syrup placebo+Shufeng Jiedu Capsules) and placebo group(Regan Syrup placebo+Shufeng Jiedu Capsules placebo) at a 1∶1∶1 using a block randomization method. The course of treatment was 3 days. A total of 119 subjects were included from six study centers, 39 in the test group, 40 in the positive drug group and 40 in the placebo group. The onset time of antipyretic effect was shorter in the test group than in the placebo group(P≤0.01) and the positive drug group, but the difference between the test group and the positive drug group was not significant. The test group was superior to the positive drug group in terms of fever resolution(P<0.05), and had a shorter onset time of fever resolution than the placebo group, but without obvious difference between the two groups. Compared to the positive drug group, the test group had shortened disappearance time of all symptoms(P≤0.000 1). In addition, the test group was better than the positive drug group and the placebo group in relieving symptoms of sore throat and fever(P<0.05), and in terms of clinical efficacy, the recovery rate of common cold(wind-heat syndrome) was improved in the test group compared to that in the placebo group(P<0.05). On the fourth day after treatment, the total TCM syndrome score in both test group and positive drug group was lower than that in the placebo group(P<0.05). There was no significant difference in the incidence of adverse events between three groups and none of them experienced any serious adverse events related to the study drug. The results indicated that Regan Syrup could shorten the onset time of antipyretic effect, reduce the time of fever resolution, alleviate the symptoms such as sore throat and fever caused by wind-heat cold, reduce the total score of Chinese medicine symptoms, and improve the clinical recovery rate with good safety.

Proteomic Research on Characteristic Processing Materials of Porcine Cardiac Blood and Porcine Blood from Menghe Medical School and Their Effect on Anti-microglial Inflammatory Damage of Salviae Miltiorrhizae Radix et Rhizoma / 中国实验方剂学杂志

ObjectiveProteomics was used to investigate the protein differences between porcine cardiac blood（PCB） and porcine blood（PB） from Menghe medical school and to compare the effects of both on the microglial inflammation of Salviae Miltiorrhizae Radix et Rhizoma（DS）. MethodNanoliquid chromatography-quadrupole orbitrap mass spectrometry（nLC-MS/MS） and bioinformatics were utilized to compare the proteomic differences of PCB and PB in simulated gastrointestinal digestion. Furthermore， Western blot was used to verify the contents of some shared proteins and differential proteins identified in PCB and PB. In addition， BV2 neuroinflammation model constructed by corticosterone（CORT） and lipopolysaccharide（LPS） was applied to detect the intervention effects of PCB and PB on the levels of tumor necrosis factor（TNF）-α and interleukin（IL）-6 in BV2 inflammatory cells of DS. ResultA total of 69 common proteins and 68 differential proteins were identified in PCB and PB， among which the common proteins included transferrin（Tf） with brain-targeting effect， and the differential proteins in the two were 41 and 27， respectively. Western blot validation showed that the difference in the content of the same protein Tf between PCB and PB was not statistically significant， while the difference in the contents of the specific proteins of creatine kinase M and heart-type fatty acid binding protein（H-FABP） were statistically significant（P<0.05）. Moreover， in vitro experimental studies revealed that compared with the same concentration of DS group， in addition to the 100 mg·L-1 PB-DS group， PCB-DS and PB-DS groups could significantly inhibit the levels of TNF-α and IL-6 in BV2 inflammatory cells（P<0.05， P<0.01）， and PCB-DS group had more significant anti-inflammatory effect than PB-DS group with the same concentration（P<0.05， P<0.01）. ConclusionBoth of PCB and PB can enhance the inhibitory effect of DS on the release of inflammatory factors， thus playing a neuroprotective role， and PCB promotes DS inhibition more significantly， which may be due to the existence of the two involved in energy metabolism-related differential proteins， which can lay a foundation for revealing the scientific connotation of the processing of PCB-DS and PB-DS.

The function and drug development progress of free fatty acid receptor 1 in chronic inflammatory diseases / 药学学报

As a member of G protein coupled-receptors superfamily, free fatty acid receptor 1 (FFAR1), is also known as GPR40, has been shown to regulate numerous pathophysiological processes in a variety of tissues and organs. The activated FFAR1 has a variety of biological functions. For instance, it can not only regulate metabolism of fatty acids and glucose, but also play an important role in immune inflammatory response, it may be a potential drug target for the treatment of various chronic inflammatory diseases. In this review, we focus on the recent researches of FFAR1's action in the regulation of pathophysiological processes, its molecular mechanism and new agonists development. At the same time, this review will take the discovery of series FFAR1 agonists as examples, and display the applied prospects of FFAR1.

Investigation on oral health knowledge, attitude and behavior of hemiplegic patients / 中国康复理论与实践

ObjectiveTo investigate and analyze the knowledge, attitude and behavior of oral health for hemiplegic patients. MethodsFrom August 15 to September 15, 2019, patients with hemiplegia caused by central nervous system damages such as stroke and traumatic brain injury in Beijing Bo'ai Hospital were investigated their demographic information, oral health behavior, oral health knowledge, oral health attitude and utilization of oral health services through paper questionnaires. ResultsA total of 200 questionnaires were sent out and 184 valid questionnaires were collected. There were 103 patients with good brushing habits, and the highest proportion was in independent walkers (χ2 = 6.564，P = 0.038). The average score of oral health knowledge was 5.3, and the average accuracy of oral health knowledge was 75.7%. The average score of oral health attitude was 3.3, and the average positive attitude was 81.8%. Both the knowledge and attuite scores were not significant in different characteristics (Z < 5.299, P > 0.05). There were 59 patients visiting institute of stomatology in past twelve months, and there was no significant difference among genders and travel modes (χ2 < 4.707, P > 0.05). ConclusionThe brushing habits is well in independent walkers. The oral health knowledge and attitude of hemiplegia patients need to be improved, and the utilization of oral health services is low.

Bi-directional Control of Synaptic Input Summation and Spike Generation by GABAergic Inputs at the Axon Initial Segment / 神经科学通报·英文版

Differing from other subtypes of inhibitory interneuron, chandelier or axo-axonic cells form depolarizing GABAergic synapses exclusively onto the axon initial segment (AIS) of targeted pyramidal cells (PCs). However, the debate whether these AIS-GABAergic inputs produce excitation or inhibition in neuronal processing is not resolved. Using realistic NEURON modeling and electrophysiological recording of cortical layer-5 PCs, we quantitatively demonstrate that the onset-timing of AIS-GABAergic input, relative to dendritic excitatory glutamatergic inputs, determines its bi-directional regulation of the efficacy of synaptic integration and spike generation in a PC. More specifically, AIS-GABAergic inputs promote the boosting effect of voltage-activated Na+ channels on summed synaptic excitation when they precede glutamatergic inputs by >15 ms, while for nearly concurrent excitatory inputs, they primarily produce a shunting inhibition at the AIS. Thus, our findings offer an integrative mechanism by which AIS-targeting interneurons exert sophisticated regulation of the input-output function in targeted PCs.

Evaluation of p16/Ki-67 double-stained immunohistochemistry in diagnosis of human papilloma virus-positive oropharyngeal squamous cell carcinoma / 中华口腔医学杂志

Objective: To explore the diagnostic value of p16/Ki-67 double-stained immunohistochemistry in the diagnosis of human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma(opscc) and find out the optimal index to improve the accuracy of HPV detection. Methods: A total of 153 cases, from May 2014 to May 2020, diagnosed OPSCC in Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, were selected. This cohort included 130 males and 23 females, aged (58.6±10.0) years old. HPV RNA in situ hybridization was chosen as the gold standard to detect their HPV status. p16 immunohistochemistry and p16/Ki-67 double-stained immunohistochemistry were performed on all cases, and the p16/Ki-67 double positive index including 20%, 40%, and 60% were used as the thresholds to compare their sensitivity, specificity, and positive prediction value (PPV), negative prediction value (NPV) and prognosis prediction ability. Results: Among the 153 patients with OPSCC, 114 were HPV-negative and 39 were HPV-positive, and the HPV infection rate of OPSCC patients was 25.5% (39/153). Only 58.1% (36/62) of single p16 positive cases were HPV-positive, and the prognosis of patients could not be distinguished using p16 immunohistochemistry only. Using p16/Ki-67 double staining, the accuracy of HPV positive diagnosis has been improved. The HPV diagnostic ability was the highest when the p16/Ki-67 double positive index was 40% (sensitivity=86.8%, specificity=94.8%, PPV=84.6%, NPV=95.6%, area under the curve=0.897), which could distinguish the prognosis of patients (P=0.012). Conclusions: The p16/Ki-67 double-stained immunohistochemistry can improve the accuracy of HPV positive diagnosis rate and diagnosis of HPV-positive oropharyngeal cancer is the most accurate when the double-positive index is 40% as the threshold to judge HPV status and could serve as better surrogate marker for HPV detection.

The role of the national oral health program in the development of oral health service and related thinkings / 中华口腔医学杂志

Conception of public health was firstly put forward by American professor Winslow. Ensuring and promoting the health of general population is the key connotation for the definition of public health. Oral disease has become a public health problem. Caries which preventable and curable is the most common oral disease and the etiology is also clear. Oral health comprehensive intervention program for children in central and western regions was set up in 2008 by Chinese government. The program included sealing on the first permanent molar and oral health education towards primary school children covering mid-west area. This was the first oral health program invested by government and managed by Chinese Stomatological Association. Six years later, the program was popularized to the whole nation, and renamed as national oral health comprehensive intervention program for children in China. The program had made deep impact on development of oral health service in China. The study tries to analyze the challenges of oral health service through reviewing the background, content, organization and effectiveness of the program, aiming to provide suggestions on policy, financing, system, ability and technology for the future development.

Role of brown adipose tissue in phlegm-dampness metabolic syndrome based on infrared thermal imaging / 中国中药杂志

This study aimed to explore the infrared manifestation and role of brown adipose tissue(BAT) in phlegm-dampness me-tabolic syndrome(MS), and to provide objective basis for clinical diagnosis and treatment of phlegm-dampness MS. Subjects were selected from the department of endocrinology and ward in the South District of Guang'anmen Hospital, China Academy of Chinese Medical Sciences from August 2021 to April 2022, including 20 in healthy control group, 40 in non phlegm-dampness MS group and 40 in phlegm-dampness MS group. General information, height and weight of the subjects were collected and body mass index(BMI) was calculated. Waist circumference(WC), systolic blood pressure(SBP) and diastolic blood pressure(DBP) was measured. Triglyceride(TG), high density lipoprotein cholesterol(HDL-C), fasting blood glucose(FBG), fasting insulin(FINS), leptin(LP), adiponectin(ADP) and fibroblast growth factor-21(FGF-21) were detected. The infrared thermal image of the supraclavicular region(SCR) of the subjects before and after cold stimulation test was collected by infrared thermal imager and the changes of infrared thermal image in the three groups were observed. In addition, the differences in the average body surface temperature of SCR among the three groups were compared, and the changes of BAT in SCR were analyzed. The results showed compared with the conditions in healthy control group, the levels of WC, SBP, DBP, TG and FPG in MS groups were increased(P<0.01), and the HDL-C level was decreased(P<0.01). Compared with non phlegm-dampness MS group, phlegm-dampness MS group had higher conversion score of phlegm dampness physique(P<0.01). According to the infrared heat map, there was no difference in the average body surface temperature of SCR among the three groups before cold stimulation. while after cold stimulation, the average body surface temperature of SCR in MS groups was lower than that in healthy control group(P<0.05). After cold stimulation, the maximum temperature of SCR and its arrival time in the three groups were as follows: healthy control group(3 min)>non phlegm-dampness MS group(4 min)>phlegm-dampness MS group(5 min). The thermal deviation of SCR was increased and the average body surface temperature of left and right sides were higher(P<0.01) in healthy control group and non phlegm-dampness MS group, while the thermal deviation of SCR did not change significantly in the phlegm-dampness MS group. Compared with that in healthy control group, the elevated temperature between left and right sides was lower(P<0.01, P<0.05), and compared with that in non phlegm-dampness MS group, the elevated temperature of left side was lower(P<0.05). The changes of the average body surface temperature of SCR in the three groups were in the order of healthy control group>non phlegm-dampness MS group>phlegm-dampness MS group. Compared with the conditions in healthy control group and non phlegm-dampness MS group, FINS, BMI and FGF-21 levels were increased(P<0.01,P<0.05), while ADP level was decreased(P<0.01, P<0.05) in phlegm-dampness MS group. Moreover, the LP level in phlegm-dampness MS group was higher than that in non phlegm-dampness MS group(P<0.01). It was observed in clinical trials that after cold stimulation, the average body surface temperature of SCR in MS patients was lower than that of the healthy people; the thermal deviation of SCR did not change significantly in the phlegm-dampness MS patients, and the difference in their elevated temperature was lower than that in the other two groups. These characteristics provided objective basis for clinical diagnosis and treatment of phlegm-dampness MS. With abnormal BAT related indicators, it was inferred that the content or activity of BAT in SCR of phlegm-dampness MS patients were reduced. There was a high correlation between BAT and phlegm-dampness MS, and thus BAT might become an important potential target for the intervention in phlegm-dampness MS.