Exploration of the relationship between the storage time of leukodepleted red blood cell and transfusion adverse reactions / 中国输血杂志

【Objective】 To explore the relationship between the storage time of leukodepleted red blood cells and transfusion adverse reactions by analyzing the occurrence of transfusion adverse reactions of patients after leukodepleted red blood cells transfusion from four hospitals. 【Methods】 By using the electronic medical record management system, the collection and transfusion dates of leukodepleted red blood cells from four hospitals in Enshi Prefecture from 2018 to 2022, as well as the information on transfusion adverse reactions, were retrieved. 【Results】 From 2018 to 2022, a total of 697 61 bags of leukodepleted red blood cells were transfused in four hospitals, resulting in 166 cases of transfusion adverse reactions, among which 93 were allergic reactions, 63 were non hemolytic febrile reactions, and 10 were others, with a total incidence rate of transfusion adverse reactions at 0.24%. The average storage time of leukodepleted red blood cells with and without transfusion adverse reactions was (20.25±6.31) and (19.88±5.50) days, respectively. With a storage time of 7 days as the threshold, the incidence of transfusion adverse reactions was the lowest for a storage time of 15~21 days. The incidence of transfusion adverse reactions of leukodepleted red blood cells in two groups (with storage days ≤21 days and >21 days) was not statistically significant(P>0.05). 【Conclusion】 Allergic reactions were the main type of transfusion adverse reaction caused by leukodepleted red blood cells, and the incidence of transfusion adverse reactions decreased and then increased with the prolongation of the storage time of leukodepleted red blood cells. There was no significant difference in the incidence of transfusion adverse reactions with leukodepleted red blood cells stored for ≤ 21 days and >21 days.

Application of the “TST-IGRA” two-step method in screening close contacts of active tuberculosis patients among three high schools / 公共卫生与预防医学

Objective To explore the application of the TST-IGRA two-step method in the screening of close contacts of active tuberculosis patients among three high schools in Jinshan District in 2020-2021，and to provide evidence for improving the prevention and control of tuberculosis in schools. Methods Three school tuberculosis outbreaks in Jingshan District from 2020 to 2021 were included in the present study. After excluding active tuberculosis, tuberculin skin test and γ-interferon release assay (IGRA) were conducted to screen latent infection of Mycobacterium tuberculosis in close contacts, and the necessity of the two-step method was analyzed. Results A total of 362 close contacts were screened in the three outbreaks, and 350 people were tested by TST. Comparing the results of TST and IGRA among different types of close contacts, it was found that the positive rate of TST in teachers was higher than that in students（54.84% vs 20.38%，P<0.05）. The positive rate of TST among students from high-burden areas of pulmonary tuberculosis in Shanghai was higher than that of local students（24.71% vs 18.80%，P<0.05). IGRA detection was performed on those with moderate and strong positive TST results, and the results showed that the positive rate of IGRA in those with strong positive TST results was only 17.7%, with Kappa value of 0.3. Conclusion The prevention and control of tuberculosis in school should strengthen the annual health examination of teachers and staff, promote timely medical treatment for suspected tuberculosis symptoms, reasonably increase the screening frequency of students in high-burden areas of tuberculosis in Shanghai, and collect students’ previous history of tuberculosis exposure. When screening close contacts, after excluding active tuberculosis, it is recommended that TST and IGRA should be combined to determine latent Mycobacterium tuberculosis infection and achieve accurate intervention.

Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer / 药物分析学报

Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.

Analysis on the registration of Chinese patent medicines in Canada and its referantial significance to the international registration of Traditional Chinese Medicines / 国际中医中药杂志

By searching for the Canadian Licensed Natural Health Products Database, (LNHPD), this paper analyzed the characteristics and current status of 92 Chinese patent medicines successfully registered and listed in Canada, and found that the enterprises of successfully registered enterprises are mainly located in areas with better development condition of Traditional Chinese Medicine (TCM) such as Beijing, Guangdong and Tianjin; The successfully registered Chinese patent medicines include 64 kinds of single medicine or medicine with single active ingredient (69.6%) and 28 kinds of compound medicine (30.4%), the forms of the dosage are mainly tablets and capsules, which have the characteristics of accuracy in dosage and stable physicochemical properties. There are also granules, solutions, powders and other dosage forms, which can be preserved for a long time and have low requirements on technic and environment. These Chinese patent medicines are mainly used to treat respiratory and circulatory system diseases, some are used to treat urogenital and digestive system diseases, and few are used to treat difficuilt diseases like tumors, diabetes. There are some other health care products. It is suggested to strengthen the connection between domestic standards of TCM registration and international standards, and promote the scientific and technological capacity of relevant enterprises, and encourage enterprises to strengthen international registration of advantageous products, so as to accelerate the speed of international development of TCM in China.

Efficacy and safety of bladder neck resection combined with local steroid injection in the treatment of bladder neck contracture after TURP / 中华泌尿外科杂志

Objective:To investigate the efficacy and safety of bladder neck resection combined with multipoint injection of triamcinolone acetonide in the treatment of bladder neck contractures (BNC) after transurethral resection prostate (TURP).Methods:The data of 25 patients with BNC after TUPR who underwent transurethral surgery in West China Hospital of Sichuan University from July 2019 to November 2021 were retrospectively analyzed, and the patients were divided into 2 groups according to the treatment method. There were 15 cases in the steroid injection group, with an average age of (67.5±8.8) years, 1 case of diabetes, and 2 cases of hypertension. And the average postoperative time after TURP was (21.9±29.1) months, the preoperative International Prostate Symptom Score (IPSS) was (30.0±3.5) points, quality of life (QOL) score was (5.7±0.5) points. There were 10 cases in the non-steroid injection group, with an average age of (65.2±10.5) years, 1 case of diabetes, and 2 cases of hypertension. And the average postoperative time of TURP was (29.3±33.5) months, and the preoperative IPSS was (30.4±2.6) points, QOL score was (5.8±0.4) points. There was no significant difference between the two groups ( P>0.05). In the steroid injection group, bladder neck resection combined with multipoint injection of triamcinolone acetonide was performed. The patients were in the lithotomy position, and a scope was placed through the urethra into the distal end of the narrow urethra under direct vision for observation, and a supersmooth guide wire was placed. The narrow section is then incised at 6 o'clock. After replacing the resectoscope, the urethral stricture scar was excised until the normal tissue of the bladder neck was exposed. Hemostasis by electrocoagulation resulted in no active bleeding from the urethra after resection. After the bladder injection needle was inserted, 80 mg (12 ml) of triamcinolone acetonide injection was injected in 6 equally spaced needles at the direction of the bladder neck from 3 to 9 o'clock. A supersmooth guide wire was placed, and a three-channel silicone urinary catheter was indwelled along the guide wire. The non-steroid injection group underwent simple bladder neck resection. Re-examination of urethroscopy at 3 and 6 months after operation showed that the patient had obvious dysuria and the microscopic examination showed that the recurrence of bladder neck stenosis was defined as the recurrence of stenosis. The efficacy, complications, and recurrence-free survival rates of the two groups were compared. Predictors of postoperative BNC recurrence were analyzed. Results:The operations in both groups were successfully completed. The operation time of the steroid injection group and the non-steroid injection group were (36.0±17.8) min and (48.5±57.9) min respectively ( P=0.438), and the intraoperative blood loss was (1.9±3.0) ml and (12.0±31.1) ml ( P=0.221)respectively. The length of hospital stay was (5.8±1.2) d and (4.4±2.5) d, respectively ( P=0.070). There was 1 case of transient hematuria and 1 case of epididymitis in the steroid injection group, and 1 case of transient hematuria and 1 case of transient dysuria in the non-steroid injection group ( P>0.05), all of which were relieved after symptomatic treatment. The IPSS of steroid injection group and non-steroid injection group were (11.0±5.6) points and (12.4±3.9) points at 3 months after operation, and (10.1±4.9) points and (14.7±7.7) points at 6 months after operation, respectively. QOL at 3 months after operation was (1.7±1.2) points and (2.1±1.5) points, respectively, and at 6 months after operation, it was (1.5±1.3) points and (3.0±2.0) points, respectively. There was statistical significance ( P<0.05). There were 1 case and 2 cases of recurrence in the steroid injection group and non-steroid injection group at 3 months after operation ( P=0.543), and 1 case and 5 cases at 6 months after operation ( P=0.023). The difference in survival curve between the two groups was statistically significant ( P=0.013). Combined steroid therapy ( OR=14.000, 95% CI1.299-150.889, P=0.030), time after scar resection ( OR=1.138, 95% CI1.017-1.273, P=0.025), postoperative IPSS( OR=1.302, 95% CI1.018-1.666, P=0.036), postoperative QOL score ( OR=4.280, 95% CI1.523-12.030, P=0.006) were the predictors of stenosis recurrence 6 months after surgery. Conclusion:Bladder neck scar resection combined with steroid injection could be safe and effective in the treatment of BNC after TURP, and local steroid injection may help reduce the recurrence rate of postoperative stenosis.

Site-specific labelling and biological evaluation of PD-L1 targeted single-domain antibody / 中华核医学与分子影像杂志

Objective:To synthesize a novel site-specifically labelled probe 68Ga-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA)-Cys-Asp-Val (CDV)-Nb109 and explore its potential for detection of the programmed cell death ligand 1 (PD-L1) expression level in different tumors. Methods:Firstly, CDV was inserted into the tail of the sequence of Nb109 by genetic engineering. Then the precursor DOTA-CDV-Nb109 was prepared by mixing the maleimide-DOTA and the single-domain antibody CDV-Nb109 (amount of substance ratio 1∶1) via the maleimide-cysteine site-specific coupling strategy. Subsequently, the DOTA-CDV-Nb109 was labeled with 68Ga and purified by PD-10 column. Human melanoma A375, human PD-L1 transfected melanoma A375-hPD-L1 and human glioma U87 tumor-bearing mice models were established, and the diagnostic value of 68Ga-DOTA-CDV-Nb109 was evaluated by stability assay, cellular uptake, and microPET imaging. One-way analysis of variance and the least significant difference t test were used to analyze the data. Results:The probe 68Ga-DOTA-CDV-Nb109 was obtained with the radiochemical yield of (69.79±4.69)%, radiochemical purity more than 97%, and molar activity of (12.85±1.51) GBq/μmol. 68Ga-DOTA-CDV-Nb109 had strong binding affinity for A375-hPD-L1 with the dissociation constant ( Kd) of (66.43±17.89) nmol/L. The uptake of 68Ga-DOTA-CDV-Nb109 in A375-hPD-L1 and U87 cells were (3.17±0.15) percentage of the added radioactivity dose (%AD) and (2.08±0.03) %AD respectively, which were significantly higher than that in A375 cells ((1.21±0.14) %AD; F=82.87, t values: 15.23, 9.98, P values: <0.001, 0.003). The tumor uptake of the probe in A375-hPD-L1 ((5.21±0.35) percentage of injected dose per ml (%ID/ml)) and U87 tumor-bearing mice ((3.44±0.69) %ID/ml) were significantly higher than that in A375 tumor-bearing mice ((2.17±0.36) %ID/ml; F=249.72, t values: 35.70, 3.43, both P<0.001). Conclusion:The site-specifically labelled probe 68Ga-DOTA-CDV-Nb109, which can non-invasively and dynamically monitor the change of PD-L1 expression level in different tumors and help screen patients who can benefit from PD-L1 immune checkpoint blocking therapy, is successfully synthesized with high radiochemical purity.

To study the use of different assessment methods in predicting perioperative outcomes in patients with acute cholecystitis and decompensated cirrhosis / 中华肝胆外科杂志

Objective:To study the use of different assessment methods in predicting perioperative outcomes in patients with acute cholecystitis and decompensated cirrhosis.Methods:A retrospective study was performed on 28 patients with acute cholecystitis and decompensated cirrhosis (MELD ≥ 15) who underwent laparoscopic surgical intervention from January 2016 to August 2020 at the Third People Hospital of Xinjiang Uygur Autonomous Region. These patients were divided into 2 groups according to the severity of acute cholecystitis grading in the Tokyo Guidelines 2018 (TG18): TG18 grade Ⅰ for the mild cholecystitis group ( n=15) and TG18 grade Ⅱ and grade Ⅲ for the moderate and severe cholecystitis group ( n=13). 16 patients with a MELD score ranging from 5 to 15 and with TG18 grade Ⅰ were used as the control group. The operation-related conditions, surgical injuries and surgical complications were compared among the three groups. Results:Of 44 patients with acute cholecystitis and decompensated cirrhosis included in this study, there were 28 males and 16 females, aged (57.3±5.9) years. Significantly more patients in the moderate and severe cholecystitis group (13/13) suffered from cholecystitis due to stone impaction than the control group (11/16) and the mild cholecystitis group (10/15) ( P<0.05). When compared to the control group, patients in the mild cholecystitis group and the moderate and severe cholecystitis group had significant increases in operative time, intraoperative bleeding, amount of abdominal drainage, abdominal drainage time, delayed feeding time and hospital stay ( P<0.05). These perioperative outcomes were further and significantly increased in the moderate and severe cholecystitis group when compared to the mild cholecystitis group ( P<0.05). The blood bilirubin levels, blood creatinine levels and MELD scores after surgery were significantly better in both the mild cholecystitis group and the moderate and severe cholecystitis group on postoperative day 3 when compared to those before treatment ( P<0.05). The Child score was significantly better in the control group after surgery than that before surgery ( P<0.05). The grade Ⅰ-Ⅱ surgical complication rate was significantly higher in the moderate and severe cholecystitis group (11/13) than the mild cholecystitis group (5/15, χ 2=7.479), and the control group (4/16, χ 2=10.208) ( P<0.05). There were no significant differences in the grade Ⅲ-Ⅴ surgical complication rates among the three groups (all P>0.05). The overall surgical complication rate was significantly higher in the moderate and severe cholecystitis group (12/13) than the mild cholecystitis group (7/15, χ 2=7.385), and the control group (5/16, χ 2=11.023), (all P<0.05). Conclusions:The MELD score when combined with the severity grading for acute cholecystitis of the TG18 was effective to evaluate the perioperative risks of patients with acute cholecystitis and decompensated cirrhosis. Patients with a MELD score ≥ 15 and TG18 Ⅱ or Ⅲ had significantly higher risks after minimally invasive surgery.

Effect of cinobufagin on transient outward potassium current in dorsal root ganglion cells of rats with cancer-induced bone pain / 南方医科大学学报

OBJECTIVE@#To observe the effect of cinobufagin on transient outward potassium current () in rat dorsal root ganglion cells of cancer-induced bone pain (CIBP) and explore the possible analgesic mechanism of cinobufagin.@*METHODS@#Whole cell patch clamp technique was used to examine the effect of cionbufagin on in acutely isolated dorsal root ganglion (DRG) cells from normal SD rats and rats with bone cancer pain.@*RESULTS@#The DRG cells from rats with CIBP showed obviously decreased current density, an activation curve shift to the right, and an inactivation curve shift to the left. Cinobufagin treatment significantly increased the current density and reversed the changes in the activation and inactivation curves in the DRG cells.@*CONCLUSIONS@# current is decreased in DRG neurons from rats with CIBP. Cinobufagin can regulate the activation and inactivation of current in the DRG cells, which may be related to its analgesic mechanism.

Progress in research on the role of cannabinoid receptor 1 signaling pathway in epilepsy / 中华神经科杂志

Epilepsy,a group of chronic neurological disorders characterized by spontaneous and recurrent seizures and learning and memory impairments,results in transient brain dysfunction due to sudden abnormal discharge of brain neurons.The pathogenesis of epilepsy is very complicated and has not yet been fully elucidated.The imbalance between excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) neurotransmitters in the central nervous system and changes in ionic functions of N-methyl-D-aspartate receptors directly induce epileptic seizures.The endocannabinoid system plays an important role in retrograde synaptic transmission and exerts the anti-epileptic effect in cannabinoid receptor 1 (CBR1) dependent manner by regulating the synaptic transmission of glutamatergic and GABAergic neurons and homeostatsis of ionic channel function.Elucidating the specific mechanism of action of CBR1 signaling pathway in epilepsy,can provide an effective theoretical basis and novel drug's target for clinical treatment of epilepsy.

Progress in research on the role of cannabinoid receptor signaling pathway in Huntington's disease / 中华神经科杂志

Huntington's disease (HD),a single-gene autosomal dominant neurodegenerative disease,is pathologically characterized by the great loss of striatal neurons in the brain.Clinical manifestations of HD show involuntary dance-like movements,cognitive function and neuropsychiatric symptoms.The pathogenesis of HD is concerned with the protein expression of mutant huntingtin which leads to the selective degeneration of medium spiny neurons in the striatum and the onset of the disease.Cannabinoid receptor (CBR) plays a key role in the release of neurotransmitters,synaptic plasticity,gene expression and modulation of.neuronal activity through the CBR1 and CBR2 signaling pathways.Recent studies have found that CBR-mediated phosphoinositide3-kinases/protein kinase B/mammalian target of rapamycin complex1/brain derived neurotrophic factor,neuropeptide Y/neuronal nitric oxide synthase signaling pathway play a vital role in the regulation.of striatal neuroprotection in HD.This review reveals the research progress of CBR1 related signaling pathways in HD,which provides new theoretical basis and drug targets for the prevention and treatment of HD.