Development and prospects of predicting drug polymorphs technology / 药学学报

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Effects of Gegen Qinlian Decoction on NLRP3 inflammatome signaling pathway in liver of mice with type 2 diabetes mellitus / 国际中医中药杂志

Objective:To observe the effects of different doses of Gegen Qinlian Decoction on nucleotide oligomeric domain-like receptor protein 3 (NLRP3)/Caspase-1/IL1β inflammatory signaling pathway in liver of db/db mice with type 2 diabetes mellitus (T2DM).Methods:Totally 75 SPF male db/db mice were randomly divided into model group, metformin group (0.2 g/kg), Gegen Qinlian Decoction high-, medium-, and low-dosage groups (61.80, 30.90, 15.45 g/kg), with 15 mice in each group. Another 15 db/m male mice were selected as blank control group. Each administration group was given relevant medicine for gavage, while the blank group and model group were given 0.9% sodium chloride solution for gavage, once a day, for 12 weeks. The body weight, fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) contents of each group were measured after treatment. The mRNA expression levels of NLRP3, Caspase-1 and interleukin-1β (IL-1β) in liver were detected by real-time quantitative PCR. The expression levels of NLRP3, Caspase-1, IL-1β and IL-18 in liver tissues were detected by Western Blot. HE staining was used to observe the morphology of liver tissues.Results:Compared with model group, body weight, fasting blood glucose and HbA1c contents of mice in Gegen Qinlian Decoction high- and medium-dosage groups and metformin groups decreased ( P<0.05), the body weight and fasting blood glucose levels of mice in Gegen Qinlian Decoction low-dosage group decreased ( P<0.05); the mRNA levels of NLRP3 and IL-1β in liver tissues of all treatment groups decreased ( P<0.05), the mRNA level of Caspase-1 in liver tissue decreased in Gegen Qinlian Decoction high- and medium-dosage groups ( P<0.05); the expression of NLRP3, Caspase-1, and IL-18 in liver tissue of each treatment group decreased ( P<0.05), while the expression of IL-1β in Gegen Qinlian Decoction high- and medium-dosage groups and the metformin group decreased ( P<0.05); compared with the metformin group, the body weight and fasting blood glucose of mice in the Gegen Qinlian Decoction high-dosage decreased ( P<0.05), while the HbA1c levels in the Qinlian Decoction high- and medium-dosage decreased ( P<0.05); the expressions of NLRP3, Caspase-1 and IL-18 in liver tissues of Gegen Qinlian Decoction high-dosage group decreased ( P<0.05), the expression of IL-1β, NLRP3, Caspase-1, IL-1β, and IL-18 decreased ( P<0.05); HE staining showed that the pathological changes of liver tissue were reduced in all treatment groups. Conclusion:Gegen Qinlian Decoction may reduce blood sugar by inhibiting the activation of NLRP3/Caspase-1/IL-1β inflammatory signaling pathway in liver of db/db mice, thereby improving the inflammatory damage of T2DM.

Association between coagulation function indicators and placental abruption among preeclampsia-eclampsia pregnant women / 中华预防医学杂志

Objective: To explore the association between coagulation function indicators and placental abruption (PA) in different trimesters of pregnancy among preeclampsia-eclampsia pregnant women. Methods: From February 2018 to December 2020, pregnant women who participated in the China birth cohort study and were diagnosed with preeclampsia, eclampsia and chronic hypertension with superimposed preeclampsia in Beijing Obstetrics and Gynecology Hospital were enrolled in this study. The baseline and follow-up information were collected by questionnaire survey, and the coagulation function indicators in the first and third trimesters were obtained through medical records. The Cox proportional hazards model was used to analyze the association between the coagulation function indicators and PA. A restrictive cubic spline curve was used to draw the dose-response curve between the relevant coagulation function indicators and PA. Results: A total of 1 340 participants were included in this study. The age was (32.50±4.24) and the incidence of PA was 4.4% (59/1 340). After adjusting for relevant factors, Cox proportional hazards model showed that compared with the high-level classification of fibrinogen (FIB), participants within the middle-(HR=3.28, 95%CI: 1.27-8.48) and low-level (HR=3.84, 95%CI: 1.40-10.53) classification during the first trimester and within the low-level classification (HR=4.18, 95%CI: 1.68-10.39) during the third trimester were more likely to experience PA. Compared with the middle-level classification of pro-thrombin time (PT), the risk of PA in the participants within the low-level classification (HR=2.67, 95%CI: 1.48-4.82) was significantly higher in the third trimester. The restrictive cubic spline analysis showed a linear negative association between FIB and PA in the first and third trimesters, while PT and PA showed an approximately L-shaped association . Conclusion: Among pregnant women diagnosed with preeclampsia-eclampsia, the middle-and low-level classification of FIB in the first and third trimesters and the low-level classification of PT in the third trimester could increase the risk of PA.

Analysis of incidence and associated factors of preterm birth based on pre-pregnancy body mass index stratification / 中华预防医学杂志

Objective: To analyze the incidence of preterm birth based on pre-pregnancy body mass index (BMI) stratification and explore the associated factors of preterm birth among pregnant women at different BMI stratifications. Methods: From February 2018 to December 2020, pregnant women who participated in China Birth Cohort Study (CBCS) and gave birth at Beijing Obstetrics and Gynecology Hospital were enrolled as the study subjects. Electronic Data Capture System and standard structured questionnaires were used to collect data related to pre-pregnancy, pregnancy, and delivery for pregnant women. Pregnant women were divided into the low-weight group, normal-weight group and overweight group based on their pre-pregnancy BMI. A Cox proportional hazards model was used to analyze the associated factors of preterm birth among pregnant women with different BMI before pregnancy. Results: A total of 27 195 singleton pregnant women were included, with a preterm birth rate of 5.08% (1 381/27 195). The preterm birth rates in the low-weight group, normal-weight group and overweight group were 4.29% (138/3 219), 4.63% (852/18 390) and 7.00% (391/5 586) respectively (P<0.001). After adjusting for relevant factors, the Cox proportional hazards model showed that the risk of preterm birth in the overweight group was 1.457 times higher than that in the normal-weight group (95%CI: 1.292-1.643). Preeclampsia-eclampsia (HR=2.701, 95%CI: 1.318-5.537) was the associated factor for preterm birth in the low-weight group. Advanced maternal age (HR=1.232, 95%CI: 1.054-1.441), history of preterm birth (HR=4.647, 95%CI: 3.314-6.515), vaginal bleeding in early pregnancy (HR=1.613, 95%CI: 1.380-1.884), and preeclampsia-eclampsia (HR=3.553, 95%CI: 2.866-4.404) were associated factors for preterm birth in the normal-weight group. Advanced maternal age (HR=1.473, 95%CI: 1.193-1.818), history of preterm birth (HR=3.209, 95%CI: 1.960-5.253), vaginal bleeding in early pregnancy (HR=1.636, 95%CI: 1.301-2.058), preeclampsia-eclampsia (HR=2.873, 95%CI:2.265-3.643), and pre-gestational diabetes mellitus (HR=1.867, 95%CI: 1.283-2.717) were associated factors for preterm birth in the overweight group. Conclusion: Pre-pregnancy overweight is an associated factor for preterm birth, and there are significant differences in the associated factors of preterm birth among pregnant women with different BMI before pregnancy.

Clinical Analysis of Patients with Blastic Plasmacytoid Dendritic Cell Neoplasm / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics, treatment, and prognosis of patients with blastic plasmacytoid dendritic cell neoplasm(BPDCN).@*METHODS@#Clinical data of 5 patients diagnosed with BPDCN in Wuhan First Hospital and Wuhan Tongji Hospital from June 2016 to November 2021 were retrospectively analyzed.@*RESULTS@#Among the 5 patients, 3 were male and 2 were female, with a median age of 28(10-52) years old. Four patients showed obvious skin damage at the initial diagnosis; the other one showed clinical manifestations of acute leukemia rather than obvious skin damage at the initial diagnosis, but infiltrated skin when the disease relapsed after treatment. Other infiltration sites of lesions included bone marrow (2/5), peripheral blood (2/5), lymph nodes (3/5), liver and spleen (2/5). All patients had no clinical manifestation of central nervous system infiltration. Tumor cell specific immune markers CD4, CD56, CD123 were all positive, and the median Ki-67 index was 70%. TET2, ASXL1 and NRAS gene mutations were found respectively in 3 patients by next-generation sequencing technique (NGS). ALL-like, AML-like and invasive NK/T cell lymphoma-like first-line induction chemotherapy regimens were used for the patients. One patient died of severe complications during the early stage of chemotherapy, 3 patients were evaluated as CR, and 1 patient was evaluated as PR. 2 patients were recurred and progressed after induction of chemotherapy, and one of them was evaluated as CR after re-treatment. One patient received autologous hematopoietic stem cell transplantation (auto-HSCT) and got long-term survival (OS 87 months). 3 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT), of which one died of transplantation related complications, and 2 cases survived. The median follow-up time of 4 patients with evaluable efficacy was 28.5(9-84) months, the median OS time was 31.5(10-87) months.@*CONCLUSION@#BPDCN is a highly heterogeneous malignant tumor with a poor prognosis. HSCT, especially allo-HSCT can significantly improve the prognosis of BPDCN patients.

Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version) / 中国中药杂志

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Effect of Gegen Qinliantang on SIRT1/FoxO1 Autophagy Pathway in db/db Diabetic Mice / 中国实验方剂学杂志

ObjectiveTo validate the alleviating effect of Gegen Qinliantang （GGQLT） on insulin resistance in db/db diabetic mice by regulating the silent information regulator 1 （SIRT1）/forkhead transcription factor O1 （FoxO1） autophagy pathway. MethodSeventy-five SPF-grade spontaneous type 2 diabetic db/db mice and 15 control db/m mice were selected and maintained on regular feed for one week before measuring blood glucose. They were randomly divided into six groups， with 15 mice in each group. The groups included a normal group （physiological saline， 0.2 g·kg-1）， a metformin group （0.2 g·kg-1）， high-， medium-， and low-dose GGQLT groups （31.9， 19.1， 6.9 g·kg-1）， and a model group （physiological saline， 0.2 g·kg-1）. They were orally treated with corresponding drugs for eight weeks， once daily. Fasting blood glucose （FBG） was measured using a Roche glucometer. Serum levels of high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG）， and total cholesterol （TC） were measured using an automated biochemical analyzer. Fasting serum insulin （INS） levels were determined using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） was calculated. Western blot was used to detect the expression of Beclin-1， microtubule-associated protein 1 light chain 3 （LC3）， and SIRT1/FoxO1 autophagy pathway-related proteins in liver tissues. Immunohistochemistry was performed to assess the expression of SIRT1， FoxO1， Beclin-1， and LC3B proteins in liver tissues. Transmission electron microscopy was used to observe the formation of autophagosomes in the liver. ResultCompared with the normal group， the model group showed significant increases in FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.01）， and significant increases in the expression of SIRT1， Beclin-1， LC3， and FoxO1 proteins in liver tissues （P<0.01）. Transmission electron microscopy revealed the highest number of autophagosomes in the model group. Compared with the model group， the metformin group and the low-， medium-， and high-dose GGQLT groups showed significant decreases in serum FBG， FINS， HOMA-IR， TC， TG， LDL-C， and HDL-C levels （P<0.05， P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， LC3 （P<0.05， P<0.01）， and up-regulated FoxO1 protein （P<0.01）. Transmission electron microscopy showed a reduction in the degree of autophagy in the treatment groups. Compared with the metformin group， the medium- and high-dose GGQLT groups showed significant decreases in FBG， FINS， and TG levels （P<0.01）， significant decreases in the expression of SIRT1， Beclin-1， and LC3 in liver tissues （P<0.05， P<0.01）， and reduced FoxO1 protein （P<0.01）. The high-dose GGQLT group showed reduced HOMA-IR， TC， LDL-C， and HDL-C levels （P<0.05， P<0.01）. Transmission electron microscopy revealed a significant reduction in autophagosomes in the medium- and high-dose GGQLT groups. ConclusionGGQLT can significantly improve glucose and lipid metabolism disorders， alleviate insulin resistance in db/db mice， and prevent and treat type 2 diabetes by activating the SIRT1/FoxO1 autophagy pathway.

Analysis of clinical features of seven patients with granular parakeratosis after benzalkonium chloride exposure / 中华皮肤科杂志

Objective:To summarize clinical manifestations and histopathological features of granular parakeratosis (GP) after exposure to benzalkonium chloride.Methods:A retrospective analysis was performed on 7 GP cases with a history of benzalkonium chloride exposure in the Department of Dermatology at Wuhan No.1 Hospital from April to August 2022. Data were collected on the general condition, skin lesion manifestations, pathological examination, treatment, and follow-up of the patients, and retrospectively analyzed.Results:The 7 adult patients with GP typically presented with erythema and brown scales in the intertriginous area, exhibiting an annular distribution pattern. All the 7 patients reported recent exposure to disinfectants containing benzalkonium chloride. A total of 10 skin biopsies were taken from the 7 patients. Histopathological examination showed characteristic hyperkeratosis and fine blue-gray parakeratotic granules in the stratum corneum. All skin lesions improved 1 month after cessation of exposure to benzalkonium chloride.Conclusion:GP has a distinct clinical pattern and histopathological manifestations, and a history of exposure to benzalkonium chloride can be helpful for the diagnosis of GP.

Diagnosis and treatment of a head-neck separation type of Monteggia equivalent fractures in children / 中华创伤骨科杂志

Objective:To explore the clinical characteristics and treatment of a head-neck separation type of Monteggia equivalent fractures in children.Methods:From March 2016 to February 2019, 12 children sought medical attention at Pediatric Orthopedic Hospital, Honghui Hospital Affiliated to Xi'an Jiaotong University for a head-neck separation type of Monteggia equivalent fractures. They were 8 boys and 4 girls, aged from 3 to 14 years (average, 8.3 years). All cases were treated with closed reduction, deformity correction and plaster fixation at emergency department after X-ray examination. In line with the treatment principles for Monteggia fractures, after the ulnar length was first restored and stabilized, a proper fixation method was chosen according to the location and type of the ulnar fracture, followed by treatment of the radial neck fracture. The fracture union and complications were evaluated according to the X-ray films after operation, and the therapeutic efficacy was evaluated according to the Mayo elbow performance score (MEPS) at the final follow-up.Results:The head-neck separation type of Monteggia equivalent fractures in children was characterized by a fracture of ulnar diaphysis or metaphysis and a fracture of the radial neck with complete separation of the head and neck, a longitudinal axis of the radius off the capitellum center at the distal fracture end but normal proximal humeroradial relationship. The fractures were classified into 2 types depending on the angulation direction of the ulnar fracture and the direction of distal displacement of the radial neck fracture: 7 cases belonged to the extension-valgus type and 5 cases to the flexion-varus type. The 12 patients were followed up for 8 to 38 months (average, 16.0 months). Of the ulnar fractures, one was treated with closed reduction and Kirschner wire fixation, 4 with elastic intramedullary nail fixation, 5 with plate fixation, one untreated, and one with manual reduction only. Of the radial neck fractures, 11 were treated with closed reduction and elastic intramedullary nail fixation, and one with open reduction and K-wires fixation. All fractures got united after 8 to 12 weeks (mean, 9.6 weeks). The time for removal of internal fixation ranged from 12 to 50 weeks (mean, 31.2 weeks). Avascular necrosis occurred in one case and bulk formation of proximal metaphysis in another. By the MEPS at the final follow-up, the therapeutic efficacy was excellent in 10 cases, good in one and fair in one.Conclusions:The head-neck separation type of Monteggia equivalent fractures in children is different from common Monteggia fractures or radial neck fractures, because its clinical manifestations are characterized by a fracture of ulnar diaphysis or metaphysis and a fracture of the radial neck with complete separation of the head and neck, a longitudinal axis of the radius off the capitellum center at the distal fracture end but normal proximal humeroradial relationship. The treatment options for ulnar fractures include closed reduction with Kirschner wire fixation, elastic intramedullary nailing, open reduction and bone plate fixation or no fixation, while radial neck fractures are mostly treated by closed reduction and elastic intramedullary nailing. Early functional exercise can lead to satisfactory clinical outcomes.

Progress in MRI evaluation of hip development after closed reduction for developmental dysplasia of the hip / 中华骨科杂志

This article reviews the various studies of MRI in developmental dysplasia of the hip (DDH), focusing on the research progress of MRI in evaluating the developmental trend of hip joint after DDH closed reduction, in order to find reliable indicators for predicting the development of the hip joint after closed reduction of DDH. Due to the advantages of MRI in identifying cartilage and soft tissue, more and more studies have performed MRI before and after DDH treatment to evaluate its specific role. This article has made a corresponding summary, for example, using MRI to identify obstacles that affect the reduction of dislocated hip joints such as fibrofatty tissue hyperplasia/thickening, joint effusion, labrum inversion, iliopsoas muscle atrophy, etc; using MRI to observe the cartilage shaping of the femoral head before and after closed reduction treatment of DDH; using MRI to verify the validity of intraoperative arthrography in assessing the position of femoral head and socket or directly observe the relationship of femoral head and socket with MRI; using hip MR angiography to evaluate the acetabular labrum injury in DDH patients. In addition, the results of bias-corrected studies on MRI-assessed hip-related observations are also summarized. In general, the application of MRI in the diagnosis and treatment of DDH is becoming more and more mature and perfect, and has been advocated by many scholars as a routine auxiliary examination for DDH. However, there is still no consensus on how to evaluate and predict the developmental outcome of the hip joint after closed reduction of DDH. This article summarizes the current progress from three aspects. We summarize the results of many measurements on MRI, which represent cartilage acetabular coverage and are used to predict acetabular growth and development; the research results on the use of MRI to explore the impact of the labrum on the development of the hip joint are summarized; the related research results of MRI evaluation of avascular necrosis of the femoral head after closed reduction are summarized. The above content can provide some reference for the current clinical work and research.

TCM Intervention in Progression of Esophageal Precancerous Lesions into Esophageal Cancer： A Review / 中国实验方剂学杂志

China has a high incidence of esophageal cancer，more than 90% of which are esophageal squamous cell carcinoma （ESCC）. Abnormal proliferation，migration and new microvessels of intraepithelial neoplasia cells are the important pathogenic links in the transformation from esophageal intraepithelial neoplasia （EIN） to ESCC. Studies on the progression of esophageal precancerous lesions into esophageal cancer mostly focus on environment and genetic susceptibility，such as inflammatory factors，abnormal vascular endothelial growth factor （VEGF） signaling pathway transduction，p53 gene mutation，and DNA methylation. Some pharmacology studies have confirmed that traditional Chinese medicine （TCM） can inhibit inflammatory factors，regulate abnormal signaling pathways and improve the microenvironment. A large number of patients with esophageal cancer have been found to be in advanced stage，and the 5-year survival rate is low even after active treatment. The quality of life of patients in advanced stage is worrying due to esophageal obstruction and lung infection，and therefore， early prevention is important. Early intervention in patients with esophageal precancerous lesions is in line with clinical needs and embodies the TCM theory of “treating disease before its onset.” The mechanism of action and clinical efficacy of TCM has been gradually confirmed and promoted， with certain clinical significance. To explore simple，economical and effective TCM intervention measures conforms to the clinical diagnosis and treatment standards and the modernization of TCM.

Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions / 中国中药杂志

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.

Series of group standards of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions / 中国中药杂志

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".

Clinical characteristics and treatment of complex fracture-dislocations of the elbow in children / 中华骨科杂志

Objective:To summarize and discuss the concept and clinical manifestations of complex fracture-dislocations of the elbow in children, and compare its injury characteristics, treatment and clinical effect with adults.Methods:From September 2015 to January 2020, 34 patients seen and treated at our institution for complex fracture-dislocations of the elbow were identified, and their medical records and radiographs were reviewed retrospectively. The inclusion criteria were elbow dislocation combined with one or more fractures at the proximal ulna and radius. There were 25 boys and 9 girls, with an average age of 8.3±3.2 years. The left arm was involved in 27 cases, and the right arm was involved in 7 cases. The causes of injury included falling from a scooter in 16 cases, falling from height in 10 cases, cycling in 5 cases and traffic accident in 3 cases. All patients were treated with closed reduction and the application of plaster under local anaesthesia in the emergency room. Then, X-ray, CT and MRI were performed to evaluate the fracture-dislocation and ligament injury. The following treatment plan was comprehensively evaluated according to the size and displacement of the combined fracture block and the stability of the elbow, for example, open reduction with K-wires and tension band or plate fixation for olecranon fracture, open reduction with loop plate fixation for coronal process fracture, closed reduction or open reduction with K-wires or elasticstable intramedullary nail for radial neck fracture.Results:Among the 34 patients, there were 16 cases of transolecranon fracture-dislocation, 1 case of varus posteromedial rotational instability, 4 cases of valgus posterolateral rotatory instability and 13 cases of divergent dislocation of elbow. All patients were followed up for 13(8, 15) months, and the average fracture healing time was 3.5±0.8 weeks, with no failure of internal fixation. In 2 cases of elbow dislocation combined radial neck fracture, one case had ischemic necrosis of the radial head and one case had early closure of epiphyseal plate of the proximal radius. At the last follow-up, all patients had no subluxation, dislocation or instability of the elbow. The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score (MEPS) as excellent in 25 cases, good in 5 cases, fair in 3 cases, and poor in one case, with excellent and good rate 88%.Conclusion:The complex fracture-dislocations of the elbow is rare in children. We have the opinion that the clinical characteristics are dislocation combined with one or more fractures of the proximal ulna and radius. Compared with adults, its pathological characteristics and the scope of injury are similar, but most of the injuries are mild. The clinical manifestations are mainly transolecranon fracture-dislocation and divergent dislocation of elbow. Good results can be achieved in most cases through open reduction with internal fixation for fractures.

Epidemiological investigation of a coronavirus disease 2019 epidemic and emergency response in Shanghai / 上海预防医学

Objective To analyze the epidemiological investigation results and emergency response to a coronavirus disease 2019 （COVID-19） epidemic in Shanghai. Methods Descriptive epidemiological method was used to describe the epidemiological characteristics， such as population， time and spatial distribution of a COVID-19 epidemic on January 20， 2021 in Huangpu District of Shanghai. The advantages and disadvantages of the emergency response to this epidemic were analyzed. Results All of the 22 cases were found by active screening， which included high-risk population screening （18.2%， 4/22）， medium-risk area screening （9.1%， 2/22）， and close contact population screening （72.7%，16/22）. The first 2 cases were detected by routine nucleic acid screening for staff in two hospitals. The confirmed cases appeared mostly during the first 3 days of the epidemic （45.5%，10/22）， and mainly distributed in the neighborhood C of Huangpu district. There were 6 key locations or regions of Huangpu District involved in this epidemic， and different control measures were adopted in these different regions according to the risk assessments. After precise epidemic prevention and control， it took only 14 days from the first to the last confirmed case of this epidemic （from January 21， 2021 to February 4， 2021）， and no new related cases appeared afterwards. Conclusion Active screening and early finding of COVID-19 cases play a key role in timely control of the epidemic， with the smallest cost， the highest efficiency and the most limited urban impact.

Transolecranon fracture-dislocation of the elbow in children - pathological characteristics and strategy for diagnosis and treatment / 中华创伤骨科杂志

Objective:To discuss the pathological characteristics and strategy for diagnosis and treatment of the transolecranon fracture-dislocation of the elbow in children.Methods:Retrospectively reviewed were the 15 patients who had been treated at Hospital of Pediatric Orthopedics, Xi'an Honghui Hospital from October 2016 to March 2019 for transolecranon fracture-dislocation of the elbow. They were 11 boys and 4 girls, with an average age of 8.3 years (from 5 to 14 years) and 10 left and 5 right arms injured. Type Ⅰ (simple fracture) was found in 11 cases and type Ⅱ (comminuted fracture) in 4 cases in 3 of which the coronoid process was affected. Of them, 14 were treated successfully with closed reduction and plaster fixation under local anesthesia in emergency but one was unsuccessfully. Of the 11 simple fractures, 10 received tension band fixation with Kirschner wire and a short oblique one underwent bone plate fixation; the 4 comminuted fractures were treated by fixation with a combination of Kirschner wire and bone plate.Results:The 15 patients obtained follow-up for 8 to 15 months (average, 11 months). The final follow-up observed fine anatomical relationship of the elbow in all patients, and no such complications as relapse of radial head dislocation, avascular necrosis of the trochlea or early closure of the epiphyseal plate. The transolecranon fracture-dislocation of the elbow obtained bony union in all patients after 5 to 7 weeks (average, 5.6 weeks). The therapeutic efficacy was evaluated at the final follow-up by the Mayo elbow performance score as excellent in 11 cases, as good in 3 and as fair in one.Conclusions:As a type of complicated fracture-dislocation of the elbow, the transolecranon fracture-dislocation of the elbow is rare in children, mainly manifested as simple ones. Treatment options depend on the type of fracture-dislocation. Only anatomical reduction of the olecranon fracture and restoration of a normal trochlear notch can lead to a stable humeroradial joint and thus fine clinical efficacy.

Value of diagnosis and efficacy evaluation of folate receptor-positive circulating tumor cells in patients with small cell lung cancer / 肿瘤研究与临床

Objective:To analyze the value of folate receptor-positive circulating tumor cells (FR +-CTC) in the diagnosis and efficacy evaluation of patients with small cell lung cancer (SCLC). Methods:The data of 59 patients with SCLC and 14 patients with benign pulmonary diseases treated in China-Japan Friendship Hospital from May 2017 to October 2019 were retrospectively analyzed. Folate receptor targeted detection was used to detect the level of FR +-CTC in the blood of SCLC patients. The levels of serum progastrin-releasing peptide (Pro-GRP), neuron-specific enolase (NSE), cytokeratin 19 fragment 21-1 (Cyfra21-1) , and carcinoembryonic antigen (CEA) were detected by using chemiluminescence. The median ( P25, P75) was used as all the detection indexes. Mann-Whitney U test was used for pairwise comparison, Spearman correlation test was used to analyze the correlation between two variables, and receiver operator characteristic (ROC) curve was used to evaluate the diagnostic efficacy. Results:The level of FR +-CTC in 59 patients with SCLC was 11.00 FU/3 ml (7.10 FU/3 ml, 14.50 FU/3 ml), and the positive rate of FR +-CTC in patients with SCLC was 66.10% (30/59); the level of FR +-CTC in 14 patients with benign pulmonary diseases was 6.75 FU/3 ml (5.03 FU/3 ml, 7.85 FU/3 ml), and the positive rate of FR +-CTC in 14 patients with benign pulmonary diseases was 14.29% (2/14). The level of FR +-CTC in patients with SCLC was higher than that in patients with benign pulmonary diseases, and the difference was statistically different ( U = 33.50, P < 0.01). The expression level of FR +-CTC was not related to age, gender and smoking history in SCLC patients (all P>0.05). The expression level of FR +-CTC in patients with extensive-stage was higher than that in patients with limited-stage, and the difference was statistically significant ( P < 0.05). Tumor markers Pro-GRP, NSE, Cyfra21-1 and CEA were compared with FR +-CTC, and the ROC curve was drawn; the results showed that FR +-CTC had better sensitivity (71.2%) and specificity (92.90%) in the diagnosis of SCLC. For SCLC patients who received chemotherapy, the decrease range of FR +-CTC in patients with partial remission and stable disease was greater than that in patients with the progression of disease, and the differences were statistically significant (all P < 0.05). Conclusion:FR +-CTC can assist the diagnosis and disease staging of SCLC. For patients receiving chemotherapy, continuous detection of circulating tumor cells can help to evaluate the efficacy of chemotherapy and provide a reference for the choice of clinical treatment.

Clinical application of nanopore sequencing in detecting bacterial infections in lower respiratory tract / 中华检验医学杂志

Objective:To establish the method for detecting lower respiratory infections (LRIs) bacterialpathogens using nanopore sequencing, and evaluate the feasibility of this method.Methods:Bronchoalveolar lavage fluid (BALF) samples from 33 patients with LRIs who visited the Department of Respiratory and Critical Care Medicine of Beijing Hospital from July 2019 to September 2020 were collected.Nanopore 16S amplicon sequencing were performed on these samples. In order to evaluate the clinical value of the nanopore sequencing, χ 2 test was used to analyze the pathogen differences between the detection rate and pathogen types results found with using the nanopore 16S sequencing and the results found with bacterial culture. Results:The process and method of nanopore sequencing used in the detection of the LRIs pathogens were established. The pathogen detection rate of the 16S sequencing was higher than that of the traditional bacterial culture (75.8% [25/33], 45.5% [15/33], χ2=5.140, P<0.05). From the 25 positive samples found with nanopore 16S sequencing, 16 pathogens were detected, including Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, Streptomonas maltophilia, Acinetobacter baumannii, and Acinetobacter junii, Staphylococcus aureus, Klebsiella pneumoniae, Enterococcus faecalis, Enterococcus gallinarum, Corynebacterium striatum, Mycobacterium paraintracellulare, Serratia marcescens, Achromobacter insuavis, Citrobacter murliniae and Mycoplasma pneumoniae. More than 6 pathogens were tested in clinical culture, including Haemophilus parainfluenzae, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae and Streptomonas maltophilia (χ2=7.949, P<0.05). 16S sequencing aligned to species level sequences accounted for 80.0 (60.0, 86.0)% of the genus level. The results obtained by using16S sequencing and bacterial culture were consistent in 11 (33.3%) samples. Conclusions:Nanopore 16S amplicon sequencing can quickly identify pathogenic bacteria from BALF in LRIs patients. Nanopore 16S amplicon sequencing has a high detection rate, it can detect more pathogens than traditional bacterial culture, and it can also identify most bacteria to the species level. This technology is a very promising platform with broad application prospects.

Clinical Observation of Effects of Modified Xiangsha Liujunzi Tang Application on Adverse Reaction of Moderately/Highly Emetogenic Chemotherapy for Gastrointestinal Tumors / 中国实验方剂学杂志

Objective:To investigate the effects of external application of modified Xiangsha Liujunzi Tang in improving gastrointestinal reaction，immune function， and quality of life in patients with gastrointestinal tumors after moderately/highly emetogenic chemotherapy. Method:A total of 140 inpatients （from January 2018 to May 2021） with gastrointestinal malignancies diagnosed by the Oncology Department of Integrated Traditional Chinese and Western Medicine of China-Japan Friendship Hospital and treated with moderately/highly emetogenic chemotherapy were randomly divided into an experimental group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70） according to the Good Clinical Practice （GCP）. Participants were given routine antiemetic treatment once 20 minutes before chemotherapy （tropisetron 5 mg + dexamethasone 5 mg or methylprednisolone 40 mg）. On this basis， the patients in the experimental group were treated with external application of modified Xiangsha Liujunzi Tang for 1 week on the second day after chemotherapy （the selected points were Zhongwan， Neiguan and Zusanli， 6 hours a day， and the application was changed every day）， and the patients in the control group were applied with comfort patch at the same time. The gastrointestinal reaction grade， subset concentration of lymphocytes， and Karnofsky score in two groups before and one week after chemotherapy were recorded， and all data were analyzed by SPSS 19.0 statistical software. Result:The grades of chemotherapy-related gastrointestinal reaction in two groups after treatment decreased as compared with that before treatment （<italic>P</italic><0.05）. The experimental group was superior to the control group after treatment in terms of grade decrease （<italic>P</italic><0.05）. The total response rate of the experimental group was 81.43% （57/70）， higher than 62.86% （44/70） in the control group （<italic>χ</italic>²=9.73， <italic>P</italic><0.05）. Stratified analysis was performed on the experimental group. Compared with the conditions before treatment， the grade of gastrointestinal reaction in patients with esophageal cancer and colorectal cancer of the experimental group decreased after treatment （<italic>P</italic><0.05）， and that in patients of different genders decreased after treatment （<italic>P</italic><0.05）. The results of immune function showed that there was no significant difference in the concentrations of CD3⁺， CD4⁺， CD8⁺， and NK cell subsets of the control group before and after treatment， while the concentrations of CD3⁺， CD4⁺， and NK cell subsets of the experimental group were higher than those before treatment and even superior to those in the control group （<italic>P</italic><0.05）. The Karnofsky score of quality of life in the experimental group was higher than that in the control group， with quality of life improved （<italic>P</italic><0.05）. Conclusion:External application of modified Xiangsha Liujunzi can improve the gastrointestinal reaction，immune function， and quality of life of patients with gastrointestinal tumors after moderately/highly emetogenic chemotherapy.

Treatment of nonunion of lateral humeral condyle complicated with cubitus valgus with primary fixation in situ and secondary supracondylar varus osteotomy / 中华创伤骨科杂志

Objective:To evaluate the treatment of nonunion of lateral humeral condyle complicated with cubitus valgus with primary fixation in situ and secondary supracondylar varus osteotomy.Methods:A retrospective analysis was made of the 8 children who had been treated for nonunion of lateral humeral condyle complicated with cubitus valgus at Department of Pediatric Orthopedics, Honghui Hospital from January 2016 to March 2018. They were 5 boys and 3 girls with 5 left and 3 right sides involved. Their age at injury ranged from 6 to 14 years (average, 10 years) and the duration from injury to operation from 2 to 6 years (average, 4 years). At the primary stage, the fragments were fixated in situ with compressive cannulated screws after cleaning the nonunion ends, followed by iliac autograft. At the secondary stage, the humeral supracondylar varus osteotomy was performed after the nonunion was healed and the elbow range of motion recovered. The therapeutic effects were assessed by comparing the elbow range of motion, carrying angle and Mayo elbow performance score (MEPS) between preoperation and the final follow-up.Results:All the patients were followed up for an average of 44.5 months (range, from 27 to 64 months). The average healing time for obsolete nonunion of lateral humeral condyle was 81.3 days (range, from 55 to 120 days) after the primary operation and that for supracondylar varus osteotomy 51.1 days (range, from 45 to 60 days) after the secondary operation. The elbow range of motion was 129.0°±4.6° before operation and 138.0°±5.4° at the final follow-up, showing a significant difference ( P<0.001). The average carrying angle at the healthy side in 8 children was 5.4° (range, from 3° to 8°). The carrying angle at the affected side was 31.9°±4.7° (range, from 25° to 42°) before operation and 4.0°±2.2°(range, from 1° to 8°) at the final follow-up, showing a significant difference ( P<0.05). Their preoperative MEPS was 57.5 ± 6.5 (4 good cases and 4 poor ones) but 95.9±3.4 (6 excellent cases and 2 good ones) at the final follow-up, showing a significant difference ( P<0.05). Conclusions:Treatment of nonunion of lateral humeral condyle complicated with cubitus valgus can be effectively carried out by cleaning fibrous tissue in the nonunion gap, iliac autograft and fragments fixation in situ with compressive cannulated screws at the primary stage and supracondylar varus osteotomy at the secondary stage. Intraoperative preservation of the blood supply to the nonunited fragments is the key to successful management.