Universal chimeric Fcγ receptor T cells with appropriate affinity for IgG1 antibody exhibit optimal antitumor efficacy

Developing universal CARs with improved flexible targeting and controllable activities is urgently needed. While several studies have suggested the potential of CD16a in tandem with monoclonal antibodies to construct universal CAR-T cells, the weak affinity between them is one of the limiting factors for efficacy. Herein, we systematically investigated the impact of Fcγ receptor (FcγR) affinity on CAR-T cells properties by constructing universal CARs using Fcγ receptors with different affinities for IgG1 antibodies, namely CD16a, CD32a, and CD64. We demonstrated that the activities of these universal CAR-T cells on tumor cells could be redirected and regulated by IgG1 antibodies. In xenografted mice, 64CAR chimeric Jurkat cells with the highest affinity showed significant antitumor effects in combination with herceptin in the HER2 low expression U251 MG model. However, in the CD20 high expression Raji model, 64CAR caused excessive activation of CAR-T cells, which resulted in cytokine release syndrome (CRS) and the decline of antitumor activity, and 32CAR with a moderate affinity brought the best efficacy. Our work extended the knowledge about FcγR-based universal CAR-T cells and suggested that only the FcγRCAR with an appropriate affinity can offer the optimal antitumor advantages of CAR-T cells.

Evaluation of ICUs and weight of quality control indicators: an exploratory study based on Chinese ICU quality data from 2015 to 2020 / 医学前沿

This study aimed to explore key quality control factors that affected the prognosis of intensive care unit (ICU) patients in Chinese mainland over six years (2015-2020). The data for this study were from 31 provincial and municipal hospitals (3425 hospital ICUs) and included 2 110 685 ICU patients, for a total of 27 607 376 ICU hospitalization days. We found that 15 initially established quality control indicators were good predictors of patient prognosis, including percentage of ICU patients out of all inpatients (%), percentage of ICU bed occupancy of total inpatient bed occupancy (%), percentage of all ICU inpatients with an APACHE II score ⩾15 (%), three-hour (surviving sepsis campaign) SSC bundle compliance (%), six-hour SSC bundle compliance (%), rate of microbe detection before antibiotics (%), percentage of drug deep venous thrombosis (DVT) prophylaxis (%), percentage of unplanned endotracheal extubations (%), percentage of patients reintubated within 48 hours (%), unplanned transfers to the ICU (%), 48-h ICU readmission rate (%), ventilator associated pneumonia (VAP) (per 1000 ventilator days), catheter related blood stream infection (CRBSI) (per 1000 catheter days), catheter-associated urinary tract infections (CAUTI) (per 1000 catheter days), in-hospital mortality (%). When exploratory factor analysis was applied, the 15 indicators were divided into 6 core elements that varied in weight regarding quality evaluation: nosocomial infection management (21.35%), compliance with the Surviving Sepsis Campaign guidelines (17.97%), ICU resources (17.46%), airway management (15.53%), prevention of deep-vein thrombosis (14.07%), and severity of patient condition (13.61%). Based on the different weights of the core elements associated with the 15 indicators, we developed an integrated quality scoring system defined as F score=21.35%xnosocomial infection management + 17.97%xcompliance with SSC guidelines + 17.46%×ICU resources + 15.53%×airway management + 14.07%×DVT prevention + 13.61%×severity of patient condition. This evidence-based quality scoring system will help in assessing the key elements of quality management and establish a foundation for further optimization of the quality control indicator system.

Research Progress on Epigenetics in Endometriosis / 中国医学科学院学报

Epigenetics refers to heritable changes in gene expression and function without alterations in gene sequences,including DNA methylation,histone modification,and non-coding RNAs.Endometriosis is a benign gynecological disease that affects the fertility and health of reproductive-age women,the etiology of which remains unclear.The recent studies have demonstrated that epigenetics plays a key role in the occurrence and development of endometriosis.This article reviews the research progress in the regulatory mechanism and application of epigenetics in endometriosis.

Clinical effect of laparoscopy for the treatment of biliary stricture after biliary dilatation operation / 中华外科杂志

Objective: To investigate the safety and effect of laparoscopy for the treatment of biliary stricture after the biliary dilatation operation. Methods: The clinical data of 78 patients,including 27 males and 51 females aged (48.6±14.2)years(range:17 to 76 years),who presented biliary stricture after biliary dilatation operation from January 2017 to June 2021 in the Department of Minimally Invasive Hepatobiliary Surgery,Hunan Provincial People's Hospital,were retrospectively collected,with 38 cases in the laparoscopy group and 40 cases in the laparotomy group. Of the 78 patients,there were 67 cases of cholangiojejunostomy stricture and 11 cases of stricture of the high intrahepatic bile duct. Statistical methods such as t-test and χ2 test were carried out to compare perioperative clinical data and follow-up information between the two groups. Results: Less intraoperative blood loss((102.6±76.4)ml vs. (162.5±105.9) ml, t=-2.874,P=0.005),shorter postoperative stay length of stay((10.5±3.7)days vs. (14.5±6.4)days, t=-3.379,P=0.001) and shorter waiting time for postoperative anal exhaust((2.0±0.6)days vs. (2.5±0.9)days, t=-2.827,P=0.006) were found in the laparoscopy group than that in the laparotomy group,with statistically significant differences. While there was no statistically difference in the operative time((252.8±54.7)minutes vs. (257.4±68.6)minutes,t=-0.331,P=0.742). Postoperative review and follow-up did not show statistically significant differences between the two groups in the residual stone rate(5.3%(2/38) vs. 5.0%(2/40)) and the incidence of recurrent biliary stricture(5.3%(2/38) vs. 7.5%(3/40))(both P>0.05). Conclusion: Laparoscopy may be safe and effective in the treatment of biliary stricture after the biliary dilatation operation,with less trauma,faster recovery compared to laparotomy.

Relationship between the inserting sites of Fu's subcutaneous needling and traditional acupoints: revelation to acupuncture and moxibustion / 中国针灸

Focusing on the phenomenon of "de-acupoints" of the needle insertion sites in Fu's subcutaneous needling (FSN), the authors allocated the evolution and characteristics of the needle insertion sites of FSN. From six aspects, named morphology and structure, location, nomenclature, numbers and meridian tropism, indications and acupuncture manipulations, the comparison was made between the insertion sites of FSN and traditional acupoints. It is believed: ①The needle insertion sites of FSN has the basic attributes of acupoint, which not only refers to the operation site, but also indicates the reaction of disease; moreover, it is the treatment site with significant therapeutic effect. ②The optimized sites of insertion in FSN should be named differently and their locations and numbers should be specified relatively. ③The insertion sites of FSN should be further intersected and integrated with traditional acupoints, and a part of traditional acupoints should become the insertion sites of FSN. ④Accepting and integrating the insertion sites of FSN, and expanding the scope of traditional acupoints may be the new project in the research of traditional acupoints.

Investigation of a suspected outbreak of carbapenem-resistant Klebsiella pneumonia infection / 上海预防医学

ObjectiveTo investigate a suspected outbreak of healthcare-associated infection （HAI） caused by carbapenem-resistant Klebsiella pneumonia （CRKP） in a secondary grade-A hospital， analyze the infection source and transmission route， and put forward corresponding preventive and control measures. MethodsEpidemiological investigation was conducted on 5 patients with CRKP infection in department of neurosurgery during December 23‒30， 2021. Specimens were collected with the environmental microbiology monitoring procedure. CRKP isolated from the environmental samples were analyzed by multilocus sequence typing （MLST） method. Comprehensive measures were taken to control the CRKP infection. ResultsThe 5 infected patients were located in 3 rooms， and all were diagnosed as HAI. The antimicrobial susceptibility testing results from the specimens of 3 CRKP infected patients were the same. Through environmental microbiology monitoring， CRKP strains were detected from the faucet handle and sink specimens in 3 rooms. The results of MLST analysis showed that the faucet handle and sink specimens in room 2 and 3 were ST11 type. The environmental specimen in room 1 was ST23 type. The suspected outbreak was effectively controlled after comprehensive interventions. ConclusionHAI suspected outbreak might be caused by the environmental contamination from the pathogens of CRKP-infected patients as well as the contaminated hands of medical staff and accompanying family members. Strengthening the publicity， education and management of medical staff and accompanying staff， early identification of infection outbreaks， and timely comprehensive control measures are the keys to controlling multidrug-resistant nosocomial infection outbreaks.

Lethal mitochondrial trifunctional protein deficiency caused by HADHB gene variation: a case report / 中华围产医学杂志

This article reported a male neonate with lethal mitochondrial trifunctional protein deficiency (MTPD) caused by compound heterozygous variations in the HADHB gene. The patient presented with poor milk intake complicated by abnormal myocardial enzymes within 24 h after birth and was transferred to the Children's Hospital of Nanjing Medical University on day 4. Physical examination revealed no obvious abnormalities on admission. Laboratory examination showed increased creatine kinase isoenzyme and cardiac troponin levels, and electrocardiogram suggested sinus tachycardia and low QRS voltage in limb leads. Blood screening for metabolic abnormalities showed high levels of tetradecenyl carnitine and various 3-hydroxycarnitines. Heterozygous mutations of c.739C>T(p.Arg247Cys) and c.607C>T(p.Arg203Ter,272) were detected in the HADHB gene in the boy, which were pathogenic variants included in the Human Gene Mutation Database. Followed up to three months of age, the boy was readmitted to hospital due to poor milk intake for one week and poor response for 2 d after catching a cold. After admission, he quickly developed multiple organs dysfunction such as heart failure and respiratory failure, and then died. Lethal MTPD is rare with no effective treatment and poor prognosis. Lethal MTPD should be highly suspected when unexplained cardiomyopathy, hypoglycemia, acidosis and other metabolic abnormalities appear in the neonatal period, and an early diagnosis could be confirmed with genetic testing in the neonatal period.

Effect of probiotics on the cognitive function of patients with schizophrenia / 中国医师杂志

Objective:To explore the effect of probiotics on the cognitive function of patients with schizophrenia.Methods:100 schizophrenic patients admitted to Shanghai Jinshan District Mental Health Center from January 2019 to January 2021 were randomly divided into the conventional group (treated with atypical antipsychotics combined with placebo, 50 cases) and the intervention group (treated with atypical antipsychotics combined with probiotics, 50 cases). Before treatment and 3 months after treatment, the feces of the patients were taken for DNA detection to compare the composition of intestinal flora. The cognitive function of the patients was assessed by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and the mental state of the patients was assessed by the Positive and Negative Symptom Scale(PANSS). The incidence of adverse drug reactions was compared between the two groups.Results:Before treatment, the relative abundance of Fusobacteria, Proteus and Actinobacteria in the two groups had no statistical significant difference (all P>0.05); After 3 months of treatment, the relative abundance of Fusobacteria, Proteus and Actinobacteria in the two groups decreased compared with that before treatment, and the decline was more significant in the intervention group (all P<0.05). Before treatment, there was no significant difference in immediate memory, visual span, speech function, attention function, delayed memory and RBANS between the two groups (all P>0.05); After 3 months of treatment, the scores of immediate memory, visual span, speech function, attention function, delayed memory and RBANS in the two groups were higher than those before treatment, and the increase was more significant in the intervention group (all P<0.05). Before treatment, there was no significant difference in PANSS scores between the two groups ( P>0.05); After 3 months of treatment, PANSS scores in both groups decreased compared with those before treatment, and the decrease degree in the intervention group was higher than that in the conventional group (all P<0.05). During the three months of treatment, there was no significant difference in the incidence of adverse drug reactions between the two groups ( P>0.05). Conclusions:Probiotics are used in adjuvant therapy for patients with schizophrenia, which can regulate the patients′ intestinal flora, improve patients′ cognitive function and mental disorders, and do not increase the incidence of adverse drug reactions. They have significant clinical efficacy and high treatment safety.

Clinical characteristics of 151 COVID-19 cases in a designated hospital in a district of Shanghai， 2022 / 上海预防医学

ObjectiveTo analyze the clinical characteristics of 151 local COVID-19 patients in Shanghai， 2022. MethodsThe clinical data of 151 COVID-19 patients admitted to a district-level designated hospital in Shanghai from April 13 to May 10， 2022 were reviewed， and their clinical manifestations， laboratory tests， lung imaging， treatment and outcomes were analyzed. ResultsThe 151 patients ranged from 3 to 97 years old， with a median age of 72 years. Most of them were clustered cases in the communities and families. The main clinical types were mild （95 cases， 62.9%） and general （47 cases， 31.1%）. Most of the 9 severe/critical patients （6.0%） were elderly and complicated with multiple comorbidities. The proportion of people who had not been vaccinated was as high as 66.9%， and the proportion of those among severe/critically ill patients who had not been vaccinated was even higher. The most common first symptoms were expectoration in 71 cases （47.0%）， fever in 51 cases （33.8%） and dry cough in 30 cases （19.9%）. The counts of white blood cells and neutrophils in mild or general group were mostly normal or decreased， and in the severe/critical group increased significantly （P<0.001）. Increase of troponin， D-dimer， creatinine， and myoglobin； and decrease of lymphocytes in severe/critical group were more common than the other clinical types （P<0.05）. The proportions of use of antibiotics， antiviral drugs， thymalfasin and heparin in severe/critical and general patients were significantly higher than those in mild patients （P<0.05）. Among the cured and discharged patients （138 cases， 91.4%）， the median number of days for COVID-19 viral nucleic acid to turn negative after treatment was 12 days. The negative conversion days of mild patients were significantly shorter than those of general patients and severe/critical patients （P<0.01）. Four （2.6%） death patients were all over 80 years old， unvaccinated， combined with multiple comorbidities， and eventually died of those serious comorbidities. ConclusionCOVID-19 patients at the district-level designated hospital are mainly clustered cases， and the proportion of patients who do not receive COVID-19 vaccine is high. Most of the hospitalized patients are mild， but advanced age， multiple underlying diseases， and lack of vaccination are high-risk factors for developing severe disease. Early assessment and comprehensive treatment are the key to improve prognosis.

Application of augmented reality and mixed reality navigation technology in laparoscopic limited right hepatectomy / 中华外科杂志

Objective: To investigate the application effect of augmented reality and mixed reality navigation technology in three-dimensional(3D) laparoscopic narrow right hepatectomy(LRH). Methods: A retrospective analysis was performed on the clinical data of 5 patients with hepatic malignancy admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from September 2020 to June 2021,all of whom were males,aged from 42 to 74 years.Preoperative evaluation was performed using the self-developed 3D abdominal medical image visualization system; if all the 5 patients were to receive right hemihepatectomy,the remnant liver volume would be insufficient,so LRH were planned.During the operation,the independently developed 3D laparoscopic augmented reality and mixed reality surgical navigation system was used to perform real-time multi-modal image fusion and interaction between the preoperative 3D model and 3D laparoscopic scene.Meanwhile,intraoperative ultrasound assisted indocyanine green fluorescence was used to determine the surgical path.In this way,the LRH under the guidance of augmented reality and mixed reality navigation was completed.The predicted liver resection volume was evaluated before surgery,actual resected liver volume,surgical indicators and postoperative complications were analyzed. Results: All the 5 patients completed LRH under the guidance of augmented reality and mixed reality navigation technology,with no conversion to laparotomy.The median operative time was 300 minutes(range:270 to 360 minutes),no intraoperative blood transfusion was performed,and the median postoperative hospital stay was 8 days(range:7 to 9 days).There were no perioperative deaths,or postoperative complications such as liver failure,bleeding,or biliary fistula. Conclusion: For patients who need to undergo LRH,the use of augmented and mixed reality navigation technology can safely and effectively guide the implementation of surgery,retain more functional liver volume,improve surgical safety,and reduce postoperative complications.

How to change from traditional surgery to intelligent navigation surgery? / 中华外科杂志

After more than 20 years of multidisciplinary integration of medical science and technology,as well as research and practice in innovative diagnosis and treatment,digital medicine 4.0 has made a profound and important impact on the development of traditional surgery. To combine traditional surgery with digital medicine 4.0 technology is the direction of surgery development in the future.New technologies represented by digital intelligent navigation surgery have been deeply explored and widely applied in the diagnosis and treatment of many surgical diseases. With the innovative development and application of artificial intelligence,Big Data and mixed reality technology,the surgery will develop in ways similar to aerospace automatic and intelligent navigation,leading to the advent of digital medicine 5.0.

Mechanism of Tripterygium wilfordii in Treatment of Triple Negative Breast Cancer Based on Network Pharmacology and Experimental Validation / 中国实验方剂学杂志

ObjectiveTo explore the active ingredients， therapeutic targets， and relative signaling pathways of Tripterygium wilfordii in the treatment of triple negative breast cancer （TNBC） based on network pharmacology， and to verify the mechanism through in vitro cell model. MethodThe active ingredients of T. wilfordii were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）. The targets of TNBC were obtained from DisGeNET and GeneCards. Venny was used to identify the potential therapeutic targets of T. wilfordii against TNBC. Protein-protein interaction （PPI） network was constructed with String database. Gene ontology （GO） annotation and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment were carried out with DAVID to predict the mechanisms of potential targets. The molecular docking between triptolide and key targets were performed with AutoDock Vina. The effect of triptolide （0， 5， 10， 20， 30， 40， 50， 60， 80 nmol·L-1） on the proliferation of MDA-MB-231 cells was determined through methyl thiazolyl tetrazolium （MTT） assay. The effect of triptolide （0， 12.5， 25， 50 nmol·L-1） on the apoptosis of MDA-MB-231 cells was detected with Hoechst 33342 staining. Western blot was performed to detect the effect of triptolide （0， 25， 50 nmol·L-1） on the expression levels of key targets. ResultT. wilfordii had 23 active ingredients related to 55 potential targets of TNBC. GO and KEGG enrichment revealed that the potential targets were associated with 103 biological processes， 15 cellular components， and 35 molecular functions， and were involved in 140 signaling pathways including atherosclerosis and apoptosis. The results of molecular docking demonstrated that triptolide could bind with the targets including threonine kinase 1 （Akt1）， vascular endothelial growth factor A （VEGFA）， cellular tumor antigen p53 （p53）， transcription factor AP-1 （JUN）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， mitogen-activated protein kinase 8 （MAPK8）， prostaglandin G/H synthase 2 （PTGS2）， and Caspase-3. According to the results of MTT assay， triptolide （20， 30， 40， 50， 60， 80 nmol·L-1） inhibited the proliferation of MDA-MB-231 cells compared with blank control （P<0.05， P<0.01）. Hoechst 33342 staining showed that triptolide （12， 25， 50 nmol·L-1） induced the apoptosis of MDA-MB-231 cells compared with black control （P<0.05， P<0.01）. Western blot showcased that 50 nmol·L-1 triptolide down-regulated the relative expression levels of p-Akt， TNF-α， and VEGFA， while 25 and 50 nmol·L-1 triptolide up-regulated the relative expression level of p53 in a dose-dependent manner compared with the blank control （P<0.05， P<0.01）. ConclusionT. wilfordii has multiple ingredients， targets， and pathways in the treatment of TNBC. It may regulate p53， VEGFA， TNF-α and other key targets to induce cell apoptosis and suppress angiogenesis and inflammatory response， which provides a scientific basis for the further investigation and clinical application of T. wilfordii.

Study on Reentry Evaluation Mode for Blood Donors Used to be HBV Reactive in Jiangsu Province / 中国实验血液学杂志

OBJECTIVE@#To evaluate the risk of reentry in HBV reactive blood donors and feasibility of HBV reentry strategy.@*METHODS@#HBsAg+ or HBV DNA+ donors who had been quarantined for more than 6 months in Jiangsu Province could propose for reentry application. Blood samples were routinely screened by dual-ELISA for HBsAg, anti-HCV, HIV Ab/Ag, and anti- Treponema pallidum and those non-reactive ones were tested by minipool nucleic acid testing (NAT) for three times. To identify occult HBV donors, samples of NAT non-reactive were further tested by electrochemiluminescence immunoassay (ECLIA) for HBV seromarkers (including HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb). Donors of only 4 ECLIA patterns were accepted to reentry, including all 5 HBV seromarkers negative, anti-HBs only but having history of hepatitis B vaccine injection, HBcAb only, HBsAb+ / HBcAb+ with HBsAb more than 200 IU/L. Additionally, the detection rate of HBV infection was compared between routine screening mode and ECLIA, as well as the reentry qualified rate of HBsAg+ and HBV DNA+ blood donors.@*RESULTS@#From Oct. 2016 to Aug. 2019, a total of 737 HBV reactive donors had applied for reentry, including 667 HBsAg+ reactive and 70 HBV DNA+ reactive donors. Among 3 screening methods, the highest HBV detection rate (43.15%, 318/737) was observed on ECLIA, while only 4.75% (35/737) on ELISA and 3.12% (23/737) on NAT, respectively. Among 4 qualified patterns of HBV serological markers, the highest proportion was found in the all negative group (22.90%, 155/677), followed by the group with HBsAb+ only and history of hepatitis B vaccine injection (19.35%, 131/677), and the median concentration of HBsAb was 237.7 IU/L. The unqualified rate of HBV DNA+ donors was 82.86%, which was significantly higher than 47.98% of HBsAg+ donors.@*CONCLUSION@#Routine screening tests merely based on ELISA and NAT could miss occult HBV donors and may not be sufficient for blood safety. HBsAb concentration and vaccine injection history should be included in the evaluation of HBV reactive donors who intend to apply for reentry. There is a relatively larger residual risk of occult HBV infection in blood donors quarantined for HBV DNA reactive.

Early risk factors for death in neonates with persistent pulmonary hypertension of the newborn treated with inhaled nitric oxide / 中国当代儿科杂志

OBJECTIVES@#To evaluate the early risk factors for death in neonates with persistent pulmonary hypertension of the newborn (PPHN) treated with inhaled nitric oxide (iNO).@*METHODS@#A retrospective analysis was performed on 105 infants with PPHN (gestational age ≥34 weeks and age <7 days on admission) who received iNO treatment in the Department of Neonatology, Children's Hospital of Nanjing Medical University, from July 2017 to March 2021. Related general information and clinical data were collected. According to the clinical outcome at discharge, the infants were divided into a survival group with 79 infants and a death group with 26 infants. Univariate and multivariate Cox regression analyses were used to evaluate the risk factors for death in infants with PPHN treated with iNO. The receiver operating characteristic (ROC) curve was used to calculate the cut-off values of the factors in predicting the death risk.@*RESULTS@#A total of 105 infants with PPHN treated with iNO were included, among whom 26 died (26/105, 24.8%). The multivariate Cox regression analysis showed that no early response to iNO (HR=8.500, 95%CI: 3.024-23.887, P<0.001), 1-minute Apgar score ≤3 points (HR=10.094, 95%CI: 2.577-39.534, P=0.001), a low value of minimum PaO2/FiO2 within 12 hours after admission (HR=0.067, 95%CI: 0.009-0.481, P=0.007), and a low value of minimum pH within 12 hours after admission (HR=0.049, 95%CI: 0.004-0.545, P=0.014) were independent risk factors for death. The ROC curve analysis showed that the lowest PaO2/FiO2 value within 12 hours after admission had an area under the ROC curve of 0.783 in predicting death risk, with a sensitivity of 84.6% and a specificity of 73.4% at the cut-off value of 50, and the lowest pH value within 12 hours after admission had an area under the ROC curve of 0.746, with a sensitivity of 76.9% and a specificity of 65.8% at the cut-off value of 7.2.@*CONCLUSIONS@#Infants with PPHN requiring iNO treatment tend to have a high mortality rate. No early response to iNO, 1-minute Apgar score ≤3 points, the lowest PaO2/FiO2 value <50 within 12 hours after admission, and the lowest pH value <7.2 within 12 hours after admission are the early risk factors for death in such infants. Monitoring and evaluation of the above indicators will help to identify high-risk infants in the early stage.

~1H-qNMR quantification of total ginsenosides in Shenmai Injection / 中国中药杂志

A content determination method based on ~1H-qNMR was developed for the determination of total ginsenosides in Shenmai Injection. The parameters were optimized with CD_3OD as the solvent, dimethyl terephthalate as the internal standard, the peak at δ 8.11 as the internal standard peak, and the peaks at δ 1.68 and δ 0.79 as quantitative peaks of total ginsenosides. The developed ~1H-qNMR-based method was validated methodologically. The results showed that the method could achieve accurate measurement of total ginsenosides in Shenmai Injection in the range of 0.167 6-3.091 1 mmol·L~(-1). The developed ~1H-qNMR-based method for total ginsenosides is simple in operation, short in analysis time, strong in specificity, independent of accompanying standard curve, and small in sample volume, which can serve as a reliable mean for the quality control of Shenmai Injection. This study is expected to provide new ideas for the development of quantification methods of total ginsenosides.

Fingerprint of Shenmai Injection based on ~1H-NMR technique / 中国中药杂志

Shenmai Injection is a Chinese medicinal injection prepared from Ginseng Radix et Rhizoma Rubra and Ophiopogonis Radix, which is widely used in clinical practice for the treatment and adjuvant therapy of cardiovascular diseases with significant pharmacological effects. Proton nuclear magnetic resonance spectroscopy(~1H-NMR) has the advantages of simple and nondestructive sample pretreatment, fast analysis, abundant chemical information, quantification and no need to follow the standard curve. It is widely used in the analysis and research of complex mixtures of traditional Chinese medicine, clinical blood and urine samples. In this study, the ~1H-NMR fingerprint of Shenmai Injection was established. Thirty-two chemical components were identified, including seven amino acids, eight small molecular organic acids, one alkaloid, four sugars, two nucleosides, seven saponins, and three other components. Pearson's correlation coefficient and multivariate analysis of variance(principal component analysis combined with hierarchical cluster analysis) were applied based on the ~1H-NMR fingerprint to evaluate the quality consistency. The results showed high-quality consistency of 82 batches of Shenmai Injection. This study confirms that the ~1H-NMR fingerprint has great potential in the application of quality control of Chinese medicinal injection.

Quality evaluation of ginsenoside reference substances based on qNMR spectroscopy / 中国中药杂志

The present study established a quality evaluation method for ginsenoside reference substances based on quantitative nuclear magnetic resonance(qNMR) spectroscopy. ~1H-NMR spectra were collected on Bruker Avance Ⅲ 500 MHz NMR spectrometer equipped with a 5 mm BBO probe. The acquire parameters were set up as follows: pulse sequence of 30°, D_1=20 s, probe temperature= 303 K, and the scan number = 32. Dimethyl terephthalate, a high-quality ~1H-qNMR standard, was used as the internal standard and measured by the absolute quantitative method. Methyl peaks of comparatively good sensitivity were selected for quantification, and linear fitting deconvolution was adopted to improve the accuracy of integration results. The qNMR spectroscopy-based method was established and validated, which was then used for the quality evaluation of ginsenoside Rg_1, ginsenoside Re, ginsenoside Rb_1, ginsenoside Rd, and notoginsenoside R_1. The results suggested that the content of these ginsenoside reference standards obtained from the qNMR spectroscopy-based method was lower than that detected by the normalization method in HPLC provided by the manufacturers. In conclusion, the qNMR spectroscopy-based method can ensure the quality of ginsenoside reference substances and provide powerful support for the accurate quality evaluation of Chinese medicine and its preparations. The qNMR spectroscopy-based method is simple, rapid, and accurate, which can be developed for the quantitative assay of Chinese medicine standard references.

Quantitative NMR spectroscopy and its application in quality control of Chinese medicinal injection / 中国中药杂志

Chinese medicinal injection, made of active components extracted from Chinese medicine or Chinese medicinal compound, is a novel dosage form of Chinese patent medicine in China and is pivotal in the traditional Chinese medicine(TCM) industry. The quality control standard of Chinese medicinal injection determines its safety and efficacy. The quantitative nuclear magnetic resonance(qNMR) spectroscopy is a non-targeted, non-invasive, and non-destructive technique with high reproducibility, short measurement time, convenient sample preparation, a broad range of linearity, and no requirement on the reference substance of tested components, which is advantageous as compared with traditional chromatographic methods, and it can provide information about the molecular composition of the tested samples. Therefore, in light of multiple challenges in the quality control of Chinese medicinal injection, such as complex composition, difficulties in quantitative analysis, and the shortage of reference substances, the application of qNMR spectroscopy combined with chemometrics techniques was proposed for the quality evaluation of Chinese medicine reference substances, Chinese medicinal injection, and intermediates in the production process, as well as for the stability analysis of Chinese medicinal injection. This study is expected to provide references for the application of qNMR spectroscopy in the quality control of Chinese medicinal injection.

Efficacy and safety of sacral neuromodulation variable-frequency stimulation in the treatment of refractory lower urinary tract dysfunction / 中华泌尿外科杂志

This study prospectively collected the clinical data of patients who received sacral neuromodulation(SNM)variable-frequency stimulation (VFS) mode from June 2020 to December 2020, in order to explore the efficacy and safety of VFS mode in the treatment of refractory lower urinary tract dysfunction. The inclusion criteria were as follows: ①SNM was implanted; ②age ≥18 years old; ③The traditional constant-frequency stimulation (CFS) mode has poor therapeutic effect, and can not be improved after repeated adjustment of stimulation parameters; ④Patients with overactive bladder (OAB) symptoms, who fail to respond to conservative treatment or are intolerant to conservative treatment; ⑤The drugs that affect the lower urinary tract symptoms and pelvic function should not be increased or decreased during the trial; ⑥provision of informed consent. A total of six patients meeting the criteria were included in the study, with three males and three females. The age ranged from 47 to 74 years, with an average age of 55 years. Among those patients, three cases were diagnosed of OAB, two cases were diagnosed of interstitial cystitis, and one case was diagnosed of neurogenic bladder. All patients had received CFS-SNM for an average of 20.6 months before upgrading to VFS mode, and suffered from severe frequency of urination at the same time. Compared with the severity of symptoms during the baseline period and the CFS period, a trend of improvement was found among four patients during the VFS period. The severity of symptoms was mainly based on the average daily urination frequency and OAB-Q score. For the two patients with interstitial cystitis, OAB symptoms worsened during the VFS period, while the VAS score did not change significantly. In general, VFS-SNM is not inferior to CFS-SNM in improving the symptoms of frequent micturition. For patients with interstitial cystitis, multiple sets of VFS parameters can be tried under the premise of satisfactory pain management.

Risk factors of hemodynamically significant patent ductus arteriosus in extremely preterm infants / 中国新生儿科杂志

Objective:To study the risk factors of hemodynamically significant patent ductus arteriosus (hsPDA) in extremely preterm infants (EPI).Method:From July 2017 to April 2020, EPI (gestational age <28 weeks) admitted to the Department of Neonatology of our hospital were included and analyzed retrospectively. According to whether hsPDA existed or not, the infants were assigned into non-hsPDA group and hsPDA group. Demographic findings and possible risk factors of hsPDA were collected.The cumulative fluid overload (FO) within 3 days after birth was calculated. Univariate and multivariate analysis were used to determine the risk factors of hsPDA.Result:A total of 79 infants with gestational age of (27.0±0.9) weeks and birth weight of (987±173)g were enrolled, including 23 cases in non-hsPDA group and 56 cases in hsPDA group. Univariate analysis showed that thrombocytopenia ( P=0.044), respiratory distress syndrome (RDS) treated with pulmonary surfactant (PS) ( P=0.006) and high FO level ( P=0.002) were associated with hsPDA. Multivariate analysis showed that RDS treated with PS ( OR=5.933, 95% CI 1.360~25.883, P=0.018) and high FO level ( OR=1.261, 95% CI 1.063~1.496, P=0.008) were independent risk factors for hsPDA in EPIs. ROC curve analysis showed that the cut-off value of FO was -0.2%, with 85.7% sensitivity and 56.5% specificity distinguishing the presence of hsPDA (AUC=0.712, Youden index=0.422). Conclusion:High level of FO within the first 3 days of life and RDS treated with PS are independent risk factors for hsPDA in EPI. After PS treatment, hemodynamic changes of infants with RDS should be monitored closely. During early fluid management of EPI, FO should be strictly monitored to avoid high FO level.