A 63-year-old female patient with multiple systemic metastases from lung adenocarcinoma was treated with befotertinib (75 mg orally once daily) and other symptomatic supportive treatments. Before treatments, her platelet count (PLT) was 177×10 9/L. After 35 days of medication, the patient had a transient loss of consciousness with chest tightness and shortness of breath. Computed tomography pulmonary angiography showed multiple embolism in bilateral pulmonary arteries. Laboratory tests showed that D-dimer was 35.16 g/L, and PLT was 34×10 9/L. The pulmonary embolism and throm-bocytopenia were considered to be caused possibly by befotertinib. Befotertinib was stopped, and enoxaparin sodium injection and rivaroxaban were given successively for anticoagulation. Thirteen days later, the chest tightness and shortness of breath were significantly improved, D-dimer was 0.57 g/L, and the PLT was 123×10 9/L.

A 63-year-old female patient with multiple systemic metastases from lung adenocarcinoma was treated with befotertinib (75 mg orally once daily) and other symptomatic supportive treatments. Before treatments, her platelet count (PLT) was 177×10 9/L. After 35 days of medication, the patient had a transient loss of consciousness with chest tightness and shortness of breath. Computed tomography pulmonary angiography showed multiple embolism in bilateral pulmonary arteries. Laboratory tests showed that D-dimer was 35.16 g/L, and PLT was 34×10 9/L. The pulmonary embolism and throm-bocytopenia were considered to be caused possibly by befotertinib. Befotertinib was stopped, and enoxaparin sodium injection and rivaroxaban were given successively for anticoagulation. Thirteen days later, the chest tightness and shortness of breath were significantly improved, D-dimer was 0.57 g/L, and the PLT was 123×10 9/L.

Technological innovation and achievement transformation are the key to the organic combination of innovation-driven development strategy and high-quality health development, and play an important role in comprehensively promoting the construction of " healthy China". The author made a comprehensive analysis of the practice of scientific and technological innovation and achievement transformation in health care over the past 40 years of reform and opening up, and summarized the various stages based on the time dimension. On this basis, the author analyzed the opportunities and challenges faced by technological innovation and achievement transformation in health care, and put forward development suggestions.

OBJEC TIVE To establish the qu ality standard of Hylocereus undatus ，and to provide reference for its quality control. METHODS The sample of H. undatus medicinal materials was collected for character observation ，powder microscopic identification and thin-layer chromatography （TLC）identification. Moisture content ，total ash ，acid-insoluble ash ，water-soluble extracts and alcohol-soluble extracts were determined according to the corresponding methods in the general provisions of the 2020 edition of Chinese Pharmacopoeia （part Ⅳ）. The contents of kaempferol and isorhamnetin in H. undatus were determined by high performance liquid chromatography. RESULTS The medicinal materials of H. undatus were in brown or yellowish brown irregular long bundles ；the calyx tubes were twisted in bundles ；the scales on the outside of the flower were shrunken ，and many stamens were inserted on the inside. The powder was brown-green or brown-yellow ，and pollen grains ，ducts and non-glandular hairs were found.In the TLC diagram of test sample ，fluorescent spots of the same color were displayed on the corresponding position of the chromatogram of substance control （kaempferol， isorhamnetin） and reference material. The moisture content ， total ash ， acid-insoluble ash ，water-soluble extract and alcohol-soluble extract of the 15 batches of samples ranged from 10.70％ to 12.23％， 7.48％ to 11.29％，0.25％ to 0.70％，30.34％ to 49.91％，and 25.27％ to 36.92％，respectively. The average values were 11.44％，9.51％，0.46％，40.13％，32.33％，respectively. The contents of kaempferol and isorhamnetin were 1.787-3.785 and 0.597-2.211 mg/g，respectively. CONCLUSIONS This study add microscopic identification ，TLC identification and inspection items such as moisture content ，ash and extract on the basis of the existing quality standards of H. undatus . It is preliminarily proposed that the moisture content in H. undatus shall not exceed 13.0％ and total ash content shall not exceed 12.0％，and the water-soluble extract and alcohol-soluble extract shall not be less than 30.0％ and 25.0％ respectively；the contents of kaempferol and isorhamnetin shall not be less than 1.780 and 0.590 mg/g，respectively. The established quality standard can be used for quality control of H. undatus .

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective:To study the combined use of endoscopic balloon dilation with endoscopic biliary brushings in diagnosis of bile duct strictures.Methods:A prospective single center study was conducted at the Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology. All patients with suspected malignant bile duct strictures shown on CT or MRI imaging from January 2018 to January 2020 were reviewed. All patients gave informed consent to the endascopic retrograde cholangiopancreatography procedures. Their clinical and follow-up data were analyzed. All patients underwent endoscopic balloon dilation of bile duct strictures. Before and after balloon dilation, biliary brush cytology was performed, and the results were used to classify the patients into the control group and the experimental group. Pathological examination of the brush cytology samples was carried out by a single chief pathologist. Presence of cancer cells or significant heterogeneous cells indicated a positive brush cytology test. Negative patients who still highly consider cholangiocarcinoma and agree to surgery and whose gross specimen is confirmed to be malignant after surgery should be considered as false negative by brush examination; it is difficult to judge that patients with cholangiocarcinoma have progress after 2 months of follow-up should be considered as false negative by brush examination. Any progression of disease indicated that the brush test was wrong and the test was again classified as false negative. Only when there was no progression of strictures was the possibility of a benign biliary stricture being considered. The advantage test (McNemar test) was used to analyze the difference between the two diagnostic methods.Results:Of 39 patients who were included in this study, there were 26 males and 13 females, with an age of (68.0 ± 5.2) years. Cholangiocarcinoma was diagnosed by histopathology, surgery or at 2 months follow-up in 35 patients. In the control group, 17 patients had a positive brush test (sensitivity rate was 48.6%, 17/35). In the experimental group, 26 patients had a positive brush test (sensitivity rate was 74.2%, 26/35). In addition, 2 patients in the control group had a positive brush test, while in the experimental group, a negative brush test. A total of 28 patients were positive in the two groups. The sensitivity rate of the brush test was 80.0% (28/35). There were significant differences between the two groups ( P<0.05). Conclusion:Endoscopic balloon dilation combined with endoscopic biliary brushings improved the sensitivity of pathological diagnosis of cholangiocarcinoma, and endoscopic biliary brushings before and after balloon dilation improved the sensitivity of diagnosis.

We provide an overview of the detailed information on the application and fundings of the National Natural Science Foundation of China in reproductive system/perinatology/neonatology in 2018 to facilitate future applications for researchers and physicians in this area in 2019.In-depth analysis was performed from different aspects among all the applications;areas for improving in the format and compiling of the application form were pointed out together with practical suggestions;possible interesting topics in future application were also implicated.

Objective To clone and identify the heat shock factors(HSFs)of Schistosoma japonicum and analyze its molec?ular structure and alternative splicing pattern. Methods The New Zealand rabbits were infected with the cercariae of Schistoso?ma japonicum and were killed and dissected 42 days post?infection,and the adult worms of S. japonicum and the livers of the rabbits were harvested. Then,the total RNA was extracted by using Trizol reagent. The Sj?hsf open reading frame(ORF)and the alternative splicing fragments were amplified by RT?PCR from the female,male and egg samples,then cloned and verified by enzyme digestion and sequencing. DNAMAN 8.0,InterPro,Mega 6 combined with the Internet databases were utilized to clarify the gene structure,functional domains,alternative splicing pattern,and the homology and phylogenetic tree of HSFs. Re?sults Sj?hsf ORF and the alternative splicing fragments were amplified from the female,male and egg samples of S. japonicum by RT?PCR. After cloning,the positive recombinant plasmids pBSjHSFf?F,pBSjHSFf?M,pBSjHSFf?E containing Sj?hsf ORF, pBSjHSFs?F,pBSjHSFs?M,pBSjHSFs?E with Sj?hsf alternative splicing fragments were identified by enzyme digestion and se?quencing. Three alternative splicing Sj?hsf isoforms were observed through sequence analysis:Sj?hsf?isoform1(2 050 bp),Sj?hsf ?isoform2(2 086 bp)and Sj?hsf?isoform3(2 111 bp);the GenBank accession numbers were KU954546,KX119143 and KX119144,respectively. All the three isoforms located in the same Contig SJC_S000780 of S. japonicum genome and all ex?pressed at female,male and egg stages,but Sj?hsf?isoform1 with a high?level expression. Sj?HSF?isoform1(671 aa)and Sj?HSF?isoform2(683 aa)had DBD(DNA binding domain),HR?A/B and HR?C domains,while Sj?HSF?isoform3(282 aa)stopped in advance without HR?C domain. Phylogenetic tree analysis of HSFs illustrated that Sj?HSFs belonged to HSF1 family,with a close phylogenetic relationship to Sm?HSFs. Conclusions There are three alternative splicing isoforms of Sj?HSF existing in the female,male and egg stages of S. japonicum,but Sj?HSF?isoform1 expresses in a high?level. This study lays the foundation for further study on molecular mechanisms of Sj?HSFs in regulating the heat shock response system.

OBJECTIVETo examine the expression profile and immunofluorescence localization of the major egg antigen p40 of Schistosoma japonicum (Sjp40) during granuloma formation in the liver of infected New Zealand white rabbits.

METHODSNew Zealand white rabbits were infected with S. japonicum cercariae, and the livers were harvested at 29 and 45 days post-infection (dpi). The total RNA of the liver tissues was extracted for expression profiling of Sjp40 by quantitative reverse transcription-PCR (qRT-PCR) with GAPDH of S. japonicum as the endogenous reference gene. The expression of Sjp40 in the liver were detected by Western blotting using anti-Sjp40 monoclonal antibody (mAb) 9G7 or anti-Toxoplasma gondii tSAG1 mAb Y3A8 (control) as the primary antibody. Paraffin sections of the liver were prepared for observing egg granuloma formation using HE staining and for indirect immunofluorescence assay of Sjp40 location in the trapped eggs and egg granulomas.

RESULTSThe level of Sjp40 mRNA in the eggs trapped in rabbit livers was significantly higher at 45 dpi than that at 29 dpi (P<0.05), and Western blotting confirmed the presence of Sjp40 protein in the rabbit livers at both 29 and 45 dpi. Immunofluorescence assay demonstrated localized expression of Sjp40 in the immature eggs in the rabbit liver at 29 dpi, but at 45 dpi fluorescence was detected in clusters of mature eggs containing miracidium and in the surrounding egg granulomas.

CONCLUSIONSThe transcriptional levels of Sjp40 significantly increased with the maturation of eggs trapped in the rabbit livers. Sjp40 protein spread from the eggs to the surrounding egg granuloma at 45 dpi when acute liver granulomatous lesions occur, suggesting that Sjp40 plays a key role in egg granulomas formation in the livers of infected New Zealand white rabbits.

Animals ; Antibodies, Monoclonal ; Antigens, Helminth ; metabolism ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Granuloma ; parasitology ; Helminth Proteins ; metabolism ; Liver ; parasitology ; RNA, Messenger ; Rabbits ; Schistosoma japonicum ; Schistosomiasis japonica

Objective To examine the expression profile and immunofluorescence localization of the major egg antigen p40 of Schistosoma japonicum (Sjp40) during granuloma formation in the liver of infected New Zealand white rabbits. Methods New Zealand white rabbits were infected with S. japonicum cercariae, and the livers were harvested at 29 and 45 days post-infection (dpi). The total RNA of the liver tissues was extracted for expression profiling of Sjp40 by quantitative reverse transcription-PCR (qRT-PCR) with GAPDH of S. japonicum as the endogenous reference gene. The expression of Sjp40 in the liver were detected by Western blotting using anti-Sjp40 monoclonal antibody (mAb) 9G7 or anti-Toxoplasma gondii tSAG1 mAb Y3A8 (control) as the primary antibody. Paraffin sections of the liver were prepared for observing egg granuloma formation using HE staining and for indirect immunofluorescence assay of Sjp40 location in the trapped eggs and egg granulomas. Results The level of Sjp40 mRNA in the eggs trapped in rabbit livers was significantly higher at 45 dpi than that at 29 dpi (P<0.05), and Western blotting confirmed the presence of Sjp40 protein in the rabbit livers at both 29 and 45 dpi. Immunofluorescence assay demonstrated localized expression of Sjp40 in the immature eggs in the rabbit liver at 29 dpi, but at 45 dpi fluorescence was detected in clusters of mature eggs containing miracidium and in the surrounding egg granulomas. Conclusion The transcriptional levels of Sjp40 significantly increased with the maturation of eggs trapped in the rabbit livers. Sjp40 protein spread from the eggs to the surrounding egg granuloma at 45 dpi when acute liver granulomatous lesions occur, suggesting that Sjp40 plays a key role in egg granulomas formation in the livers of infected New Zealand white rabbits.