Improvement effects of Runchang granules on the constipation in mice and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.

Mast cells in oral lichen planus and oral lichenoid lesions related to dental amalgam contact

Abstract The aim of this study was to analyze the expression of mast cell markers toluidine blue, c-kit, and tryptase and presence of mononuclear inflammatory cells in oral lichen planus (OLP) and oral lichenoid lesions related to dental amalgam. Nineteen specimens of OLP, OLLC, and healthy oral mucosa were selected. Mononuclear inflammatory cells were analyzed. Histochemical and immunohistochemical analyses were performed using toluidine blue, anti-c-kit and anti-tryptase reagents, and the results were quantified in areas A and B of connective tissue. Mast cells of all OLP and OLLC samples were positive for toluidine blue, c-kit, and tryptase. The density of toluidine blue+, c-kit+ and tryptase+ mast cells was higher in tissue with OLP and OLLC compared with healthy controls (p < 0.05). No difference was noted in mast cells density between OLP and OLLC (p > 0.05). The density of tryptase+ mast cells was higher in the subepithelial region (area A) than the region below it (Area B) in OLLC (p = 0.047). The mononuclear inflammatory cell density was higher in OLLC compared to OLP, but without statistical significance (p > 0.05). A positive statistical correlation was found between mononuclear immune cells and density of c-kit+ and tryptase+ mast cells in OLP (r = 0.943 and r = 0.886, respectively). Our data demonstrate that the etiopathogenesis process of OLP and OLLC modulates the expansion and degranulation of mast cells; mast cells density, however, was similar between OLP and OLLC. The distribution of mast cells appears to vary along the lamina propria.

Clinical application of a novel urinary cytology detection system for bladder cancer / 现代泌尿外科杂志

【Objective】 To investigate the diagnostic efficacy of a novel bladder cancer detection system utilizing a urine cell processing kit for urine sample preservation and detection. 【Methods】 Patients with primary persistent gross hematuria and high recurrence risk of bladder cancer after transurethral resection of bladder tumor were prospectively enrolled between Dec.2021 and Mar.2022. Urine specimens were either added to (experimental group) or not added to (control group) the urine cell processing kit and were fixed on Day 0, Day 3 and Day 7. The sensitivity and specificity of the two groups were compared after the cells were fixed, produced, stained and read with body fluid cytology total staining technique. 【Results】 The sensitivity and specificity of the experimental group on Day 0 were 82.50% (33/40) and 87.50% (14/16), respectively; those of the control group were 79.49% (31/39) and 82.35% (14/17), respectively. On Day 3, the sensitivity and specificity of the experimental group were 76.32% (29/38)and 81.25% (13/16), respectively; those of the control group were 52.78% (19/36) and 78.57% (11/14), respectively. On Day 7, the sensitivity and specificity of the experimental group were 71.43% (25/35) and 72.22% (13/18), respectively; those of the control group were 35.71% (10/28) and 60.00% (9/15), respectively. The sensitivity of the experimental group on Day 3 and Day 7 was significantly higher than that of the control group (P<0.05). 【Conclusion】 This bladder cancer urine cytology detection system provides clear diagnostic advantages and can be used as an auxiliary examination before cystoscopy for patients with hematuria and those at high risk of bladder cancer recurrence. It can also be used as a bladder cancer screening tool for pre-screening a large sample of people in order to achieve early diagnosis and treatment of bladder cancer.

Study on the change of neutralizing antibody level in plasma donors after a third shot of inactivated novel coronavirus vaccine / 中国输血杂志

【Objective】 To investigate the trend of neutralizing antibody level in plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine. 【Methods】 Three commercial ELISA kits for novel coronavirus neutralization antibody detection, manufactured by Company A, B and C, were chosen and screened by Pseudotype Neutralization Test from December 2021 to June 2022. A total of 410 plasma samples from 64 plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine and there after donated plasma within six months were detected by the selected ELISA kit from July to October, 2022. The data were analyzed by Excel 2013 and SPSS 26 software. 【Results】 The high-throughput ELISA kit for SARS-CoV-2 neutralizing antibody detection, manufactured by Company A, was selected for further antibody titer detection. The mixed plasma titers were 1 337.34, 1 148.89, 852.19, 681.38, 556.44 and 457.19 U/mL from 1 to 6 months, respectively, after the 3rd shot of vaccine. The neutralizing antibody titer level began to increase around 7 days after the 3rd shot of vaccine injection and peaked (peak range: 264.07-2 208.39 U/mL, median: 569.34 U/mL) at 1 month (range: 9-43 days, median: 22 days), and then gradually decreased (P<0.05). 【Conclusion】 The neutralizing antibody titer of plasma donors who received the 3rd shot of inactivated novel coronavirus vaccine began to rise around 7 days after vaccination, which reached the peak value at around 1 month and then gradually decreased.

Clinicopathological analysis of primary nasopharyngeal melanomas in elderly patients / 中华老年医学杂志

Objective:To investigate the clinicopathologic features and molecular genetics characteristics of sinonasal tract mucosal malignant melanomas(STMMMs)in elderly patients.Methods:The clinicopathological features, immunohistochemical features and BRAF, C-KIT, NRAS mutations of STMMM in ten elderly patients were retrospectively analyzed.Results:Among the 10 patients, 5 were female and 5 were male.The patients were aged 65-81 years, with an average age of(72.5 ± 8.5)years.The lesions in 7 cases were located in the nasal cavity and paranasal sinuses, and in the other 3 cases were located in the nasopharynx.The morphologies of tumor cells under microscope was complex and diverse, showing plasma cell-like, rhabdomyoblast-like, small cell-like, epithelial-like, and spindle cell-like morphologies.Immunohistochemically, HMB-45 and S-100 were generally positive in 10 cases, and the positive rate of Melan A was 70.0%.The genes detection data showed no mutations in BRAF or NRAS genes in all the 10 cases, while C-KIT exon 11 c. 1666_1667insA mutation was found in one case, and the remaining 9 cases were wild-type for C-KIT.All the 10 cases were followed up for 4~50 months.Three cases survived so far.Conclusions:STMMM in elderly patients are rare and easy to be misdiagnosed.Immunohistochemistry and genetic testing provide guidance for accurate diagnosis and targeted therapy.

Establishment of national reference panel for coxsackievirus A16 nucleic acid detection kit / 中国生物制品学杂志

@#ObjectiveTo establish the national reference panel for coxsackievirus A16(CA16)nucleic acid detection kit and related quality standard.MethodsThe CA16 positive and negative samples were collected and screened,and then were filled and lyophilized to establish the national reference panel for CA16 nucleic acid detection kit. According to the cooperative calibration results of various reagent manufacturers,the quality standard of reference panel was determined.Meanwhile,the homogeneity and stability of the national reference panel were well studied.ResultsThe national reference panel of CA16 nucleic acid detection kit consisted of 9 positive samples,8 negative samples,1 limit-detecting sample and1 precision sample. The quality standard was as follows:the coincidence rate of positive samples was no less than 8/9;The coincidence rate of negative samples was 8/8;The minimum detection limit required that the dilution of limit-detecting sample was no less than 1∶103;The precision required that the coefficient of variation(CV)of Ct value of 10 precision samples diluted 100 times was no higher than 5% and the results were all positive. The homogeneity of the reference panel met the requirement,and the stability was not affected by the storage at room temperature(25 ℃)for 24 hours and repeated freezing and thawing three times.ConclusionThe first national reference panel of CA16 nucleic acid detection kit and the related quality standard have been established,which provided a reference for the quality control and evaluation of the related reagents.

Development of uniform antigen content detection kit for recombinant SARS-CoV-2 protein vaccines / 中国生物制品学杂志

@#Objective To prepare and verify a uniform antigen content detection kit for recombinant protein vaccines against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2). Methods Using goat anti-S protein polyclonal antibody prepared by National Institutes for Food and Drug Control(NIFDC) as coating antibody,one of four monoclonal antibodies(14C8,15F9,17A7 and 20D8)with high receptor-binding domain(RBD)binding activity and broad-spectrum resistance against major variants as HRP-labeled antibody,a uniform double-antibody sandwich ELISA kit for antigen content detection of recombinant SARS-CoV-2 vaccine was prepared,and the dilution of coating antibody(1∶125 ～ 1∶4 000)and enzymelabeled antibody(1∶250 ～ 1∶32 000)were optimized by chessboard titration. The specificity,linear range,accuracy,precision and durability of the kit were verified. The prepared uniform detection kits were distributed to 12 laboratories to detect15 batches of recombinant SARS-CoV-2 protein vaccine stock solutions(including 11 batches of stock solutions designed with WT strain and 4 batches of designed with Beta,Gamma and Delta variants as reference sequence)from different expression systems(CHO cells,Pichia pastoris,Sf9 cells or E. coli)and target proteins(RBD or S protein)prepared by each laboratory.Results Monoclonal antibody 20D8 was used as the enzyme-labeled antibody with the optimal dilution of 1 : 4 000,and the optimal dilution of coating antibody was 1 : 500. The uniform detection kit showed no cross reaction with recombinant S protein of severe acute respiratory syndrome(SARS)and Middle East respiratory syndrome(MERS). The first generation national standard for recombinant SARS-CoV-2 protein vaccine antigen(national standard for short)showed a concentration of 0. 16 ～ 2. 50 U/mL with a good linear relationship with A450/630,and the linear equation was:y = 0. 791 x-0. 100 4,R2= 0. 993 7;The recoveries of 0. 16 ～ 2. 50 U/mL national standard in 6 repeated tests were 95% ～ 104% and the coefficients of variation(CVs)were less than 15%;The CVs in 3 repeated tests by 2 experimenters at different time were 4. 4% ～6. 6% and the recoveries were in the range of 80% ～ 120% under different temperature and time conditions. The antigen content of 15 batches of recombinant SARS-CoV-2 protein vaccine stock solutions showed good parallelism with the national standard. Conclusion The uniform detection kit for antigen content developed in this study had good specificity,accuracy,precision and durability,and might be used for the detection of antigen content of recombinant SARS-CoV-2 protein vaccines.

Effect of moxibustion on immune function homeostasis in rats with diarrhea irritable bowel syndrome based on SCF/c-kit signaling pathway / 中国针灸

OBJECTIVE@#To observe the effects of moxibustion on the stem cell factor (SCF)/tyrosine kinase receptor (c-kit) signaling pathway and immune function in rats with diarrhea irritable bowel syndrome (IBS-D), and to explore the mechanism of moxibustion for IBS-D.@*METHODS@#Among 52 young rats born from 6 healthy pregnant SPF rats, 12 rats were randomly selected into the normal group, and the remaining 40 rats were treated with the three-factor combination method of maternal separation, acetic acid enema and chronic restraint stress to establish the IBS-D rat model. Thirty-six rats with successful IBS-D model were randomly divided into a model group, a moxibustion group, and a medication group, 12 rats in each group. The rats in the moxibustion group were treated with suspension moxibustion at "Tianshu" (ST 25) and "Shangjuxu" (ST 37); the rats in the medication group were treated with intragastric administration of rifaximin suspension (150 mg/kg). All the treatments were given once a day for 7 consecutive days. The body mass, loose stool rate (LSR), the minimum volume threshold when abdominal withdrawal reflex (AWR) scored 3 were measured before acetic acid enema (35 days old), after modeling (45 days old), and after intervention (53 days old). After intervention (53 days old), HE staining was used to observe the morphology of colon tissue, and spleen and thymus coefficients were measured; ELISA method was used to detect serum inflammatory factors (tumor necrosis factor a [TNF-a], interleukin [IL]-10, IL-8), T-lymphocyte subsets (CD+4, CD+8, CD+45), value of CD+4/CD+8 and immune globulin (IgA, IgG, IgM); real-time PCR method and Western blot method was used to detect the expression of SCF, c-kit mRNA and protein in colon tissue; immunofluorescence staining method were used to detect positive expression of SCF and c-kit.@*RESULTS@#After intervention, compared with the normal group, in the model group, the body mass and the minimum volume threshold when AWR scored 3 were decreased (P<0.01), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD+4, CD+45, CD+4/CD+8, IgA, IgG, IgM were increased (P<0.01), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were decreased (P<0.01), and the positive expression of SCF and c-kit was decreased (P<0.01). Compared with the model group, in the moxibustion group and the medication group, the body mass and the minimum volume threshold when AWR scored 3 were increased (P<0.01, P<0.05), LSR, spleen and thymus coefficients, serum levels of TNF-α, IL-8, CD+4, CD+8, CD+45, CD+4/CD+8, IgA, IgG, IgM were decreased (P<0.01, P<0.05), serum IL-10 level and protein and mRNA expression of SCF and c-kit in colon tissue were increased (P<0.01), and the positive expression of SCF and c-kit was increased (P<0.01). Compared with the medication group, in the moxibustion group, the level of serum CD+4 was decreased (P<0.05), the value of CD+4/CD+8 was increased (P<0.01), and there was no significant difference in other indexes (P>0.05). The expression of SCF and c-kit mRNA was positively correlated with the minimum volume threshold when AWR scored 3 and IL-10 (P<0.01), and negatively correlated with remaining indexes (P<0.01, P<0.05).@*CONCLUSION@#Moxibustion could reduce visceral hypersensitivity, improve symptoms of abdominal pain and diarrhea in IBS-D rats, and its mechanism may be related to up-regulation of the expression of SCF/c-kit signaling pathway and improvement of IBS-D immune function.

An institution-based study on Hematological profile of Dengue patients at a tertiary care hospital in Konkan region of Maharashtra

Background: Dengue is the most rapidly spreading mosquito-borne viral fever especially in coastal regions due to heavy rainfalls. It is important to understand the hemato-pathological changes associated with dengue infections to avoid dreaded hematological complications. These hematological changes can be used as diagnostic aid in remote rural set-ups wherein rapid dengue diagnostic kits are not available. Objective: This retrospective study was carried out from 1st January 2018 to 31st August 2021 with an objective to analyze the hematological profile of serologically diagnosed dengue patients. Materials and Methods: A cross sectional, observational, retrospective study was carried out at a tertiary care center at Dervan, Konkan region of Maharashtra over a period of three years and eight months. Commercially available ‘Dengue Day 1 test kit’ was used to detect NS1 antigen and IgM and IgG antibodies. Patients with positive NS1 antigen and/or IgM or IgG antibody were included while patients with other febrile illnesses like typhoid, malaria were excluded from this study. Patient’s venous blood was collected in plain bulb for serology and in EDTA bulb for hematological profile (CBC/blood smear). This profile included hemoglobin, hematocrit (HCT), RBC indices like MCV, MCH And MCHC, total leucocyte count (TLC), Differential leucocyte count (DLC) and platelet count (PC). Results: A total of 330 patients were diagnosed as dengue cases based on rapid card test. Majority of the patients were positive for NS1 antigen (60%) followed by IgM antibody (27.87%). Male: female ratio was 1.8:1. Age of the patients were in the range of 10-65 years whereas majority of NS1 positivity was seen in the age group of 21-30 years. Hemoglobin levels among these patients ranged from 3.1-19.9 g/dl. 27.47% cases had hemoglobin level of more than 15 g/dl and 16.96% patients had hemoglobin level <10 g/dl. 225 out of 330 patients showed hematocrit (HCT) >35% above the average reference value. HCT ranging from 20-35% was seen in 72/330 (21.82%) patients. 143/330 (43.34%) cases showed TLC <4000/cumm (leukopenia). 51.07% patients showed relative lymphocytosis with 15.15% of these cases showing reactive lymphocytosis. Maximum cases showed thrombocytopenia (69.32%). 31.21% showed grade 1 thrombocytopenia that is, platelets between 75000-150000/cumm. This grade was followed sequentially by Grade III, II and IV thrombocytopenia cases. Conclusion: This study highlights important hematological parameters on different serological dengue diagnosis made on rapid card test. This study will help diagnose dengue disease in remote, rural set-ups wherein rapid diagnostic kits are not available.

Concordancia entre métodos diagnósticos de infección por SARS-CoV-2 en niños asistidos en el departamento de urgencias de un hospital pediátrico / Agreement between diagnostic methods for SARS-CoV-2 infection in children seen at the Emergency Department of a children's hospital

Introducción. Los inmunoensayos de detección rápida de antígenos (TRA) del SARS-CoV-2, son considerados adecuados para el diagnóstico en el punto de atención. El objetivo fue conocer la concordancia entre la reacción en cadena de la polimerasa en tiempo real con transcriptasa inversa (RT-qPCR, por su sigla en inglés) y los TRA en población pediátrica. Población y métodos. Se reclutaron todos los pacientes entre 1 mes y 17 años 11 meses de edad atendidos en la Unidad Febril de Urgencia de un hospital pediátrico entre el 11 de junio y el 3 de octubre de 2021. Se utilizó el TRA Panbio COVID-19 Ag® (Abbott Diagnostic) y, comométodo de referencia, la RT-qPCR (según el protocolo de los Centros para el Control y la Prevención de Enfermedades). Resultados. Se incluyeron 6491 pacientes. La prevalencia de COVID-19 fue del 2,8 %. El92,1 % de los sujetos presentaron síntomas. La sensibilidad, la especificidad y el índice kappa de concordancia para el TRA fueron del 71,0 %, 99,9 % y 0,813, respectivamente. El índice kappa yla sensibilidad del TRA fueron significativamentemayores en el grupo de 13 a 17 años (0,89 y 82,4 %,respectivamente) cuando se los comparó con los grupos de 0 a 5 y de 6 a 12 años. Esto podría deberse a la menor carga viral observada en los pacientes menores de 12 años. Conclusión. Si bien los TRA permiten acortar el tiempo de obtención de los resultados y mejorar la estrategia de aislamiento de pacientes con COVID-19, la sensibilidad en niños menores de 12 años o asintomáticos no se encontraría dentro de los rangos recomendados, sobre todo enperíodos de baja prevalencia de la enfermedad.

Introduction. Rapid antigen tests (RAgTs) for SARS-CoV-2 are considered adequate for diagnosis at the point of care. Our objective was to establish the agreement between reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and RAgTs in the pediatric population. Population and methods. All patients aged 1 month to 17 years and 11 months seen at the Emergency Fever Unit of a children's hospital between 6-11-2021 and 10-3-2021 were recruited. The Panbio COVID-19 Ag® test (Abbott Diagnostic) was compared to the reference method RT-qPCR (as per the protocol suggested by the United States Centers for Disease Control and Prevention). Results. A total of 6491 patients were included. The prevalence of COVID-19 was 2.8%. Symptoms were observed in 92.1%. Sensitivity, specificity, and the kappa index of agreement for the RAgT were 71.0%, 99.9%, and 0.813, respectively. The kappa index and the RAgT sensitivity were significantly higher in the group aged 13­17 years (0.89 and 82.4%, respectively) compared to the groups aged 0­5 and 6­12 years. This may be due to the lower viral load observed in patients younger than 12 years. Conclusion. Although RAgTs shorten the time to result and improve the isolation strategy for COVID-19 patients, their sensitivity in children younger than 12 years or asymptomatic children is not within the recommended ranges, especially during periods of low disease prevalence.

Toolkit for delivering the 3Es and 6As tobacco interventions in dental care

Tobacco use is one of the major public health problems in India and also the single most important remediable public health problem. Tobacco cessation is the need of the hour. The dentists have a unique opportunity and professional obligation to be a positive influence in reducing the economic and social burden inflicted by tobacco use on dental and general health. However, dentists, in general, have not widely embraced tobacco cessation in practice. In this article, an evidence-based model (an adaptation of the World Health Organization “5As” tobacco cessation model) is presented for the dentist to help patients avoid tobacco initiation, to encourage and assist patients in tobacco cessation

Evaluation of the effects of different 14C-urea breath test products in the diagnosis of Helicobacter pylori infection / 中华消化杂志

Objective:To evaluate the effects of the cassette 14C-urea breath test kit, scintillation sampling bottle (solid-state scintillation method) and liquid scintillation 14C-urea breath test kit in the diagnosis of Helicobacter pylori ( H. pylori) infection. Methods:From January 7 to October 28, 2020, 239 patients were enrolled who visited Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, the Second Affiliated Hospital of Zhejiang University School of Medicine and the First Affiliated Hospital of Nanchang University. All subjects first received 14C-urea breath test.Within >1 to <7 days after gas collection, mucosal tissues were taken under gastroscopy for gold standard test, including biopsy and rapid urease test (RUT). If both biopsy and RUT indicated H. pylori positive, the result of gold standard test was H. pylori positive, and if both were negative, the result of gold standard test was H. pylori negative. If the results of biopsy and RUT were inconsistent, they were not included in the subsequent analysis. Based on the results of gold standard test, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the cassette 14C-urea breath test kit, scintillation sampling bottle, and liquid scintillation 14C-urea breath test kit in the diagnosis of H. pylori infection were analyzed. The safety of the test was evaluated by whether there were any adverse events during the test. Descriptive methods were used for statistical analysis. Results:Among the 239 subjects, 12 cases did not complete the test, 227 subjects finally completed the test. The test completion rate was 95.0% (227/239). No.008 patient was only included in the analysis of cassette 14C-urea breath test kit and scintillation sampling bottle because of lacking the result of liquid scintillation breath test. The results of gold standard test showed that among 227 patients, 87 cases were H. pylori positive, 118 cases were H. pylori negative. The results of biopsy and RUT were inconsistent in 22 cases, so they were not included in the subsequent analysis. Excluding No.008 patient, the results of gold standard test showed that 86 cases were H. pylori positive and 118 cases were negative. Based on the results of gold standard test, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of cassette 14C-urea breath test kit, scintillation sampling bottle, and the liquid scintillation 14C-urea breath test kit in the diagnosis of H. pylori infection were 91.9%, 100.0%, 96.6%, 100.0% and 94.4%, respectively; 95.4%, 97.5%, 96.6%, 96.5% and 96.6%, respectively; and 96.5%, 99.2%, 98.0%, 98.8% and 97.5%, respectively. Only one adverse event (right upper abdominal pain after eating) occurred. Combined with the patients condition, the adverse event was determined as the onset of chronic cholecystitis and it might not be related to the test medication. Conclusions:Cassette 14C-urea breath test kit, scintillation sampling bottle, and liquid scintillation 14C-urea breath test kit have reliable performance, good safety, and high sensitivity, specificity and accuracy in the diagnosis of H. pylori infection, which are worthy of clinical application.

Electroacupuncture can alter bladder c-Kit expression in rats with urination disorders after a spinal cord injury / 中华物理医学与康复杂志

Objective:To observe any effects of electroacupuncture (EA) on urodynamics and bladder c-Kit expression in rats with urination disorders after spinal cord injury (SCI).Methods:Complete spinal cord injury models were created in female Sprague-Dawley rats by transecting the spine at the thoracic or sacral level. On day 22 after the injury, the rats with successful modeling were randomized into a thoracic spinal cord injury (TSCI) group, a TSCI+ EA group, a sacral spinal cord injury (SSCI) group and an SSCI+ EA group, each of 10. Both EA groups were given 15 minutes of EA at the Guanyuan (CV4) and Sanyinjiao (SP6) points daily for 14 days. After the intervention, urination function was evaluated using bladder volume, compliance and residual urine volume. Hematoxylin and eosin staining was used to observe any morphological changes in bladder tissues. The gene and protein expression of c-Kit in bladder tissues were detected using real-time quantitative polymerase chain reactions and western blotting.Results:Compared with the sham group, the bladder volume and compliance of the TSCI group decreased significantly, while the average residual urine volume increased significantly. In the SSCI group the average residual urine volume, bladder volume and compliance all increased significantly. The modeling altered the morphology of the bladder in all of the SCI rats. The average expression of c-Kit mRNA and protein increased significantly in TSCI group, but both decreased significantly in the SSCI group. EA improved the histological structure of the SCI rats′ bladders.Conclusions:EA can bi-directionally regulate bladder c-Kit expression, and that is a possible mechanism for improving urinary incontinence and urine retention after an SCI.

Effect of C-KIT gene mutation on the prognosis of acute myeloid leukemia associated with core-binding factor in children: a Meta-analysis / 白血病·淋巴瘤

Objective:To systematically evaluate the relationship between C-KIT gene mutation and the prognosis of childhood core-binding factor-related acute myeloid leukemia (CBF-AML).Methods:The PubMed database was searched with "KIT" "Acute Myeloid Leukemia" and "Children"; the Chinese Journal Full-text Database (CNKI), Chinese Biomedical Literature Database (CBM), VIP database and Wanfang database were also searched with "KIT" "Acute Myeloid Leukemia" and "Children", and the search time was from the establishment of the database to October 1, 2020. After strict screening, the literature was included in the analysis; according to the presence or absence of genetic changes, the included cases was divided into C-KIT mutation group and wild group, and the complete remission (CR) rate, event-free survival (EFS) rate, and overall survival (OS) rate of the two groups were analyzed.Results:Six articles were collected, including 4 articles in English and 2 articles in Chinese, with a total of 667 patients. There was a statistically significant difference in the EFS rate between the C-KIT mutation group and wild group in children with CBF-AML ( HR = 2.40, 95% CI 1.47-3.89, P = 0.001); there was no significant difference in the CR rate and OS rate ( OR = 0.93, 95% CI 0.48-1.80, P = 0.830; HR = 1.92, 95% CI 0.96-3.83, P = 0.065) between the two groups. Conclusions:C-KIT gene mutation may be a risk factor for poor prognosis in children with CBF-AML.

Chemo-photothermal immunotherapy for eradication of orthotopic tumors and inhibition of metastasis by intratumoral injection of polydopamine versatile hydrogels

Cancer remains one of the leading causes of death globally and metastasis always leads to treatment failure. Here, we develop a versatile hydrogel loading photothermal agents, chemotherapeutics, and immune-adjuvants to eradicate orthotopic tumors and inhibit metastasis by combinational therapy. Hydrogel networks were synthesized via the thiol-Michael addition of polydopamine (PDA) with thiolated hyaluronic acid. PDA acted as a cross-linking agent and endowed the hydrogel with excellent photothermal property. Meanwhile, a chemotherapeutic agent, doxorubicin (DOX), was loaded in the hydrogel via π‒π stacking with PDA and an immune-adjuvant, CpG-ODN, was loaded via electrostatic interaction. The release of DOX from the hydrogel was initially slow but accelerated due to near infrared light irradiation. The hydrogels showed remarkably synergistic effect against 4T1 cancer cells and stimulated plenty of cytokines secreting from RAW264.7 cells. Moreover, the hydrogels eradicated orthotopic murine breast cancer xenografts and strongly inhibited metastasis after intratumoral injection and light irradiation. The high anticancer efficiency of this chemo-photothermal immunotherapy resulted from the strong synergistic effect of the versatile hydrogels, including the evoked host immune response. The combinational strategy of chemo-photothermal immunotherapy is promising for highly effective treatment of breast cancer.

Targeting a cryptic allosteric site of SIRT6 with small-molecule inhibitors that inhibit the migration of pancreatic cancer cells

SIRT6 belongs to the conserved NAD+-dependent deacetylase superfamily and mediates multiple biological and pathological processes. Targeting SIRT6 by allosteric modulators represents a novel direction for therapeutics, which can overcome the selectivity problem caused by the structural similarity of orthosteric sites among deacetylases. Here, developing a reversed allosteric strategy AlloReverse, we identified a cryptic allosteric site, Pocket Z, which was only induced by the bi-directional allosteric signal triggered upon orthosteric binding of NAD+. Based on Pocket Z, we discovered an SIRT6 allosteric inhibitor named JYQ-42. JYQ-42 selectively targets SIRT6 among other histone deacetylases and effectively inhibits SIRT6 deacetylation, with an IC50 of 2.33 μmol/L. JYQ-42 significantly suppresses SIRT6-mediated cancer cell migration and pro-inflammatory cytokine production. JYQ-42, to our knowledge, is the most potent and selective allosteric SIRT6 inhibitor. This study provides a novel strategy for allosteric drug design and will help in the challenging development of therapeutic agents that can selectively bind SIRT6.

Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylation-mediated mitophagy

Parkin, an E3 ubiquitin ligase, plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy. Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level, but the underlying mechanism is poorly understood. Here, our study demonstrated that inhibition of histone deacetylase (HDAC) by treatment of HDACis activates mitophagy through mediating Parkin acetylation, leading to inhibition of cervical cancer cell proliferation. Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer, indicating the low acetylation level of Parkin. Using mass spectrometry, Parkin is identified to interact with two upstream molecules, acetylase acetyl-CoA acetyltransferase 1 (ACAT1) and deacetylase HDAC2. Under treatment of suberoylanilide hydroxamic acid (SAHA), Parkin is acetylated at lysine residues 129, 220 and 349, located in different domains of Parkin protein. In in vitro experiments, combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1 (PINK1) and the function of Parkin in mitophagy induction and tumor suppression. In tumor xenografts, the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA. Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis, which offers a new mitophagy modulation strategy for cancer therapy.

The development of a local sexual assault investigation kit: The Philippine experience

Objectives@#This paper presents the development of a local sexual assault investigation kit (SAK) that doctors in the Philippines could use to collect biological samples from victims of sexual abuse, including child patients, that would be used for DNA testing. The study also reports on a management system via courier service to protect the integrity of the samples that could be eventually used as evidence in court from the collection site to the laboratory with sufficient backup measures. @*Methods@#Women and Child Protection Units (WCPU) from Manila, Baguio, Cebu, and Davao partnered with the DNA Analysis Laboratory, Natural Sciences Research Institute of UP Diliman (NSRI-UPD) DNA Analysis Laboratory in testing the utility of a prototype SAK for the collection of biological samples from child patients. From January 2002 to March 2006, samples were collected from patients who went to WCPU within 72 hours post-contact and consented to participate in the study. WCPU doctors collected biological samples guided by the patient’s narratives and packaged the samples while following detailed documentation and chain of custody procedures. SAKs were then sent via a designated courier service from WCPU to the NSRI-UPD DNA Analysis Laboratory for DNA testing. The WCPU kept half of the samples collected, following recommendations made during sectoral consultations that included members of the Research Group of the Philippine Judicial Academy, prosecutors, and defense counsels. Case samples were packed well by the WCPU and received at the NSRI-UPD DNA Analysis Laboratory. Due to budget limitations, only the internal genitalia and patients’ reference buccal swabs were subjected to DNA tests as reported by Maiquilla et al.1 The remaining SAK components and case records were kept in a dedicated and secure storage facility. DNA testing reports were sent to the WCPU, which released them to the child patients and their legal guardians. @*Results@#One hundred fifty-four female children aged 2-18 years old and their legal guardians agreed to participate in the study. Based on the initial interviews of the social workers who conducted the evaluation, all the participants came from families with very low socioeconomic status. The WCPU doctors then complied with prescribed procedures. To date, NSRI-UPD DNA Analysis Laboratory records show that a subpoena for expert testimony had been issued in only one case out of the 63 cases (1.6%) that were positive for male DNA. No further information was available on the final decision in this case due to the absence of any order from the judge granting the laboratory access to court records. Likewise, WCPUs did not have any information on the remaining 62 cases that could have used the DNA test results as evidence if a case had been filed in court. @*Conclusion@#This study is the first to report the development and validation of a sexual assault investigation kit in the Philippines aimed at helping medical doctors in collecting and preserving critical biological samples for DNA testing. Using a dedicated courier service to send SAK from collecting agencies to the laboratory for DNA testing was successfully tested and resulted in faster delivery and significantly reduced overall cost. While DNA testing remains the most powerful tool for human identification and the technology has been available in the Philippines since 1997, certain factors have prevented it from being used routinely in sexual assault investigations, including those involving children.

Update on Diagnosis and Treatment of Gastrointestinal Stromal Tumors / 肿瘤防治研究

In recent years, with the emergence of new research evidence, the domestic and foreign guidelines in the field of gastrointestinal stromal tumors (GISTs) have been updated. The adjusted contents cover almost every link of GISTs management, from GISTs diagnosis, biological behavior, surgical treatment to targeted drug treatment. Since 2020, the NCCN of the United States has separated the contents related to GISTs from the clinical practice guide for soft tissue sarcoma for the first time to form 2021 V.1 versions. The CSCO has also adjusted and upgraded the previous consensus of Chinese experts on the diagnosis and treatment of GISTs to 2020 and 2021 versions of the guidelines for the diagnosis and treatment of GISTs. This opens a new model of accurate diagnosis and treatment of GISTs under the guidance of evidence-based medicine. The listing of new targeted drugs afatinib and ripretinib is expected to get rid of the drug-resistant treatment dilemma of metastatic GISTs, enrich the back-line treatment camp, provide more opportunities for surgical intervention, and then bring survival benefits to patients with advanced GISTs.

Discovery of novel diarylamides as orally active diuretics targeting urea transporters

Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,