Clinical efficacy of wearing base curve aspheric orthokeratology lens in the control of myopia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the clinical efficacy of wearing base curve aspheric orthokeratology(OK)lens in the control of myopia.METHODS: A prospective study was conducted. A total of 94 cases(94 eyes)of myopia aged 8～13 years old who were fitted with orthokeratology(OK)lens in our hospital from January 2020 to July 2021 were selected(for patients who received OK lens in one eye, the eye is selected as the observation eye, and for patients who receive OK lens in both eyes, the right eye is used as the observation eye). Patients were divided into two groups according to the design of the OK lens, with 46 cases wearing base curve aspheric OK lens in study group and 48 cases wearing base curve spheric OK lens in control group. The study group and the control group were further divided into low myopia group(-3.00D< SE ≤-0.75D)and moderate myopia group(-6.00D< SE ≤-3.00D)according to the baseline spherical equivalent(SE), with 52 cases(52 eyes)in the low myopia group and 42 cases(42 eyes)in the moderate myopia group. Uncorrected visual acuity(UCVA)was evaluated at 1d, 1wk, 1, 3, 6 and 9mo after wearing lenses, and axial length were measured at 6mo and 1a after wearing lenses respectively.RESULTS: All patients completed follow-up, and there was no significant differences in UCVA(LogMAR)between the study group(-0.12±0.08)and the control group(-0.17±0.07)after wearing the OK lens for 1mo(P>0.05); the mean axial length elongation between the two groups had no significant differences after wearing lenses for 6mo and 1a(all P>0.05). In the low myopia group, the axial length elongation of the study group was 0.19±0.17mm after wearing OK lens for 1a, which was significantly lower than that of the control group(0.31±0.18mm; P<0.05); while in the moderate myopia group, the axial length elongation was 0.22±0.18mm, and it had no significant differences with that in the control group(0.19±0.12mm; P>0.05). There was no significant differences in axial length elongation between the low myopia group and the moderate myopia group in study group after wearing lenses for 6mo and 1a(P>0.05), while there was differences in axial length elongation between low myopia group and moderate myopia group in the control group after wearing lenses for 6mo(0.15±0.13 vs. 0.05±0.12mm)and 1a(0.31±0.18 vs. 0.19±0.12mm; all P<0.05).CONCLUSION: Wearing base curve aspheric OK lens can effectively improve the UCVA and control the elongation of axial length. For patients with low myopia, base curve aspheric OK lens had a better efficacy in controlling the elongation of axial length than the spheric OK lens.

Mechanism of Xuebijing Injection in treatment of sepsis-associated ARDS based on network pharmacology and in vitro experiment / 中国中药杂志

The aim of this study was to investigate the effect and molecular mechanism of Xuebijing Injection in the treatment of sepsis-associated acute respiratory distress syndrome(ARDS) based on network pharmacology and in vitro experiment. The active components of Xuebijing Injection were screened and the targets were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The targets of sepsis-associated ARDS were searched against GeneCards, DisGeNet, OMIM, and TTD. Weishengxin platform was used to map the targets of the main active components in Xuebijing Injection and the targets of sepsis-associated ARDS, and Venn diagram was established to identify the common targets. Cytoscape 3.9.1 was used to build the "drug-active components-common targets-disease" network. The common targets were imported into STRING for the building of the protein-protein interaction(PPI) network, which was then imported into Cytoscape 3.9.1 for visualization. DAVID 6.8 was used for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment of the common targets, and then Weishe-ngxin platform was used for visualization of the enrichment results. The top 20 KEGG signaling pathways were selected and imported into Cytoscape 3.9.1 to establish the KEGG network. Finally, molecular docking and in vitro cell experiment were performed to verify the prediction results. A total of 115 active components and 217 targets of Xuebijing Injection and 360 targets of sepsis-associated ARDS were obtained, among which 63 common targets were shared by Xuebijing Injection and the disease. The core targets included interleukin-1 beta(IL-1β), IL-6, albumin(ALB), serine/threonine-protein kinase(AKT1), and vascular endothelial growth factor A(VEGFA). A total of 453 GO terms were annotated, including 361 terms of biological processes(BP), 33 terms of cellular components(CC), and 59 terms of molecular functions(MF). The terms mainly involved cellular response to lipopolysaccharide, negative regulation of apoptotic process, lipopolysaccharide-mediated signaling pathway, positive regulation of transcription from RNA polyme-rase Ⅱ promoter, response to hypoxia, and inflammatory response. The KEGG enrichment revealed 85 pathways. After diseases and generalized pathways were eliminated, hypoxia-inducible factor-1(HIF-1), tumor necrosis factor(TNF), nuclear factor-kappa B(NF-κB), Toll-like receptor, and NOD-like receptor signaling pathways were screened out. Molecular docking showed that the main active components of Xuebijing Injection had good binding activity with the core targets. The in vitro experiment confirmed that Xuebijing Injection suppressed the HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways, inhibited cell apoptosis and reactive oxygen species generation, and down-regulated the expression of TNF-α, IL-1β, and IL-6 in cells. In conclusion, Xuebijing Injection can regulate apoptosis and response to inflammation and oxidative stress by acting on HIF-1, TNF, NF-κB, Toll-like receptor, and NOD-like receptor signaling pathways to treat sepsis-associated ARDS.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial / 中华医学杂志(英文版)

BACKGROUND@#LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer.@*METHODS@#We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels.@*RESULTS@#On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]).@*CONCLUSION@#LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile.@*TRIAL REGISTRATION@#ClinicalTrials.gov, NCT04563936.

Searching for potential biomarkers reflecting early injury and progressive of podocytes in nephropathy based on cellular metabolomics combined with ROC analysis / 药学学报

The pathogenesis of the nephrotic syndrome is complex and the pathological types are diverse, so the minor symptoms in its early phases are difficult to detect. Renal biopsy is the gold indicator for the diagnosis of renal pathology and progression, but poor patient compliance shows, and the optimal treatment time is often delayed. Therefore, the discovery of biomarkers for early diagnosis and disease progression monitoring is of great clinical significance. In this study, doxorubicin-injured podocyte models were used to simulate human kidney disease at different stages of progression. LC-MS-based metabolomic technology combined with statistical methods was used to screen and identify the potential biomarkers associated with early injury or progression of podocytes. The results of cell viability, apoptosis tests and podocyte structural protein analysis showed that the model was successfully constructed, and the degree of podocyte injury was significantly different between the two modeling methods. According to VIP > 1 and P < 0.05 based on the orthogonal partial least squares discriminant analysis (OPLS-DA) model, nine differential metabolites reflecting early podocyte injury and twelve differential metabolites reflecting the injury progression were screened, respectively. ROC analysis was adopted to focus on the potential biomarkers that can reflecting the early podocyte injury including L-tryptophan, guanosine triphosphate (GTP), 5′-thymidylic acid (dTMP) and thymidine, and the biomarkers reflecting the injury progression of podocytes composed of L-phenylalanine, L-tyrosine acid, uridine 5′-diphosphate (UDP) and guanosine 5′-diphosphate (GDP) AUC > 0.85. It indicated that these eight metabolites may have high sensitivity and diagnostic ability. This study provides a reference for the research on biomarkers of progressive diseases.

Neoadjuvant immune combination therapy for muscle-invasive bladder cancer / 中华泌尿外科杂志

Neoadjuvant therapy leads to the eradication of micrometastasis, thereby providing survival benefit to patients with muscle-invasive bladder cancer (MIBC). In the recent years, multiple clinical trials have corroborated the safety and durability of immune checkpoint inhibitors in the treatment of MIBC. Notably, there is a significantly higher response rate (e.g. pathologic complete response) and comparable occurrence of adverse events in patients treated with neoadjuvant dual immunotherapy, immunotherapy combined with chemotherapy or targeted therapy as compared with that treated with neoadjuvant single-agent immunotherapy. With an overview of breakthroughs in the past years, we believe that immune combination therapy is of great promise and expected to revolutionize the landscape of neoadjuvant therapy of MIBC.

A new pair of coumarin-like enantiomeric isomers from Gerbera piloselloides / 药学学报

Ten compounds were isolated from the 95% ethanol extract of the whole plant of Gerbera piloselloides by silica gel column chromatography, MCI column chromatography and semi-preparative HPLC methods. Their structures were identified on the basis of physicochemical properties, spectral data (UV, IR, MS and NMR), circular dichroism (CD) spectra and single crystal X-ray diffraction analysis as 3′R-gerpilosecoumarin A (1a), 3′S-gerpilosecoumarin A (1b), gymnastone (2), gerberinside (3), divaricataester C (4), luteolin (5), caffeic acid methyl ester (6), ethyl chlorogenate (7), 6-(β-D-glucopyranosyloxy)-7-methoxy-5-benzoranpropanoic acid methyl ester (8) and glucozaluzanin C (9). Among them, new compounds 1a and 1b were new compounds and optical enantiomers, which were obtained by chiral resolution, and their absolute configurations were determined by quantum chemical calculation ECD. Compounds 1 and 1a/1b significantly increased the survival of IEC-6 in rat small intestinal crypt epithelial cells after LPS injury.

Contribution to global implementation of WHO guideline on control and elimination of human schistosomiasis by learning successful experiences from the national schistosomiasis control program in China / 中国血吸虫病防治杂志

Schistosomiasis is a parasitic disease that seriously hinders socioeconomic developments and threatens public health security. To achieve the global elimination of schistosomiasis as a public health problem by 2030, WHO released the guideline on control and elimination of human schistosomiasis on February, 2022, with aims to provide evidence-based recommendations for schistosomiasis morbidity control, elimination of schistosomiasis as a public health problem, and ultimate interruption of schistosomiasis transmission in disease-endemic countries. Following concerted efforts for decades, great achievements have been obtained for schistosomiasis control in China where the disease was historically highly prevalent, and the country is moving towards schistosomiasis elimination. This article reviews the successful experiences from the national schistosmiasis control program in China, and summarizes their contributions to the formulation and implementation of the WHO guideline on control and elimination of human schistosomiasis. With the progress of the "Belt and Road" initiative, the world is looking forward to more China's solutions on schistosomiasis control.

Effects of Bushen Yiqi Huoxue Decoction in Treatment of Patients with Diminished Ovarian Reserve: A Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To explore the therapeutic effect of Bushen Yiqi Huoxue Decoction BYHD) in patients with diminished ovarian reserve (DOR).@*METHODS@#A total of 180 patients with DOR diagnosed from December 2013 to December 2014 were equally assigned into progynova and duphaston (E+D) group, Zuogui Pill group and BYHD group with 60 cases in each by computerized randomization. Patients received E+D, Zuogui Pill or BYHD for 12 months, respectively. Follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), anti-Müllerian hormone (AMH), antral follicle count (AFC), ovarian volume, endometrial thickness, and the resistance indices (RIs) of ovarian arteries and uterine arteries were observed before and after treatment.@*RESULTS@#Nine women (4 from the E+D group, 3 from the Zuogui Pill group, and 2 from the BYHD group) withdrew from the study. After 6 months, Zuogui Pill and BYHD significantly decreased FSH and LH and increased endometrial thickness and AMH (all P<0.01). BYHD also resulted in E2 elevation (P<0.05), ovary enlargement (P<0.05), AFC increase (P<0.01), and RI of ovarian arteries decrease (P<0.05). After 12 months, further improvements were observed in the Zuogui Pill and BYHD groups (all P<0.01), but BYHD showed better outcomes, with lower FSH, larger ovaries and a thicker endometrium compared with the Zuogui Pill group (all P<0.01). However, E+D only significantly increased endometrial thickness (P<0.01) and no significant improvements were observed in the RI of uterine arteries in the three groups.@*CONCLUSIONS@#BYHD had a favorable therapeutic effect in patients with DOR by rebalancing hormone levels, promoting ovulation, and repairing the thin endometrium. The combination of tonifying Shen (Kidney), benefiting qi and activating blood circulation may be a promising therapeutic strategy for DOR.

Clinical analysis of 30 cases of basal ganglia germinoma in children / 北京大学学报(医学版)

OBJECTIVE@#To summarize and analyze the clinical characteristics of children with basal ganglia germinoma and to improve the level of early clinical diagnosis.@*METHODS@#The clinical data of children diagnosed with basal ganglia germinoma admitted to the Pediatric Surgery Ward of Peking University First Hospital from January 2013 to December 2020 were retrospectively analyzed, and descriptive statistics were used to analyze the clinical characteristics of children with basal ganglia germinoma.@*RESULTS@#A total of 30 patients were included in the study, 28 were male, 2 were female, the mean age at onset was (9.7±2.2) years, the median disease duration was 7 months, 27 had unilateral disease, and 3 had bilateral disease. The clinical manifestations were decreased limb muscle strength, cognitive function disorders, polydipsia, precocious puberty, intracranial hypertension, dysphonia and swallowing dysfunction. The serum and cerebrospinal fluid tumor marker alpha-fetoprotein (AFP) were normal in the 30 patients, and the serum and cerebrospinal fluid tumor marker β-human chorionic gonadotropin (β-HCG) were normal in 8 patients.The serum β-HCG was normal in 11 patients but the cerebrospinal fluid β-HCG was slightly elevated, and the serum and cerebrospinal fluid β-HCG were slightly elevated in 11 patients. A total of 33 lesions with irregular shapes were found by imaging examination, including 15 (45.5%) patchy lesions, 10 (30.3%) patchy lesions, and 8 (24.2%) round-like high-density lesions. Tumors showed obvious high-density shadows on computed tomography (CT) scan. Magnetic resonance imaging (MRI) scan of the tumors showed low or isointensity on T1WI and isointensity on T2WI, accompanied by mild peritumoral edema, hemispheric atrophy, cerebral peduncle atrophy, calcification, cystic degeneration, ventricular dilatation and wallerian degeneration. On contrast-enhanced scans, the tumor showed no enhancement or heterogeneous enhancement.@*CONCLUSION@#The main age of onset of germ cell tumors in the basal ganglia in children is about 10 years old, and males are absolutely dominant. The clinical features and imaging manifestations have certain characteristics. With both combined, the early diagnosis of germ cell tumors in the basal ganglia can be improved.

Clinical significance of No.11p posterior lymph nodes dissection in gastric cancer surgery / 中华胃肠外科杂志

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.

Efficacy and Mechanism of Qingre Lishi Prescription in Treating Children with Acute Bacterial Lower Urinary Tract Infection of Bladder Damp-heat Syndrome / 中国实验方剂学杂志

Objective:To observe the efficacy of Qingre Lishi prescription in treating children with acute bacterial lower urinary tract infection of bladder damp-heat syndrome， and to explore its mechanism of action. Method:Eighty children with acute bacterial lower urinary tract infection of late bladder damp-heat syndrome who were admitted to the Affiliated Hospital of Changchun University of Chinese Medicine were divided into control group and observation group， 40 cases in each group. Patients in control group were given Bazhengsan for oral treatment on basis of basic treatment， while patients in observation group were given Qingre Lishi prescription for oral administration plus external washing treatment. After two weeks of treatment， the clinical and etiological effect， traditional Chinese medicine （TCM） syndrome scores， antipyretic time and urinary negative time， adverse reactions， and urine pathogens （<italic>Escherichia coli， Enterococcus faecalis， Strange proteus， Klebsiella pneumoniae</italic>）， serum inflammatory factor indicators ［tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， calcium lowering PCT， white blood cell count （WBC） and serum C-reactive protein （CRP）］， immune function indicators ［T cell subsets （CD3⁺， CD4⁺， CD8⁺） and complement （C3， C4）］ were comapred between two groups. Result:The clinical efficacy of observation group was 92.50% （37/40）， which was significantly higher than 65.00% （26/40） in control group （<italic>χ²</italic>=9.038， <italic>P</italic><0.01）， the etiological efficacy of observation group was 87.50% （35/40）， which was significantly higher than 60.00% （24/40） in control group （<italic>χ²</italic>=7.813， <italic>P</italic><0.01）. After treatment， the scores of TCM syndromes of the two groups were significantly reduced （<italic>P</italic><0.05）. The scores of fever， frequent urination， urgent urination， painful urination， difficulty urinating and abdominal pain in two groups were significantly lower than those before treatment （<italic>P</italic><0.05）， and the TCM syndrome scores in observation group were lower than those in control group （<italic>P</italic><0.05）， the antipyretic time and urinary bacteria turning negative time of observation group were significantly lower than those in control group （<italic>P</italic><0.05）， the <italic>Escherichia coli， Enterococcus faecalis， Proteus mirabilis， Klebsiella pneumoniae</italic> pathogenic bacteria detected in both groups were both significantly lower than those before treatment （<italic>P</italic><0.05）. After treatment， the levels of inflammatory factors such as TNF-<italic>α</italic>， IL-6， IL-8， PCT， WBC and CRP in two groups were significantly lower than those before treatment （<italic>P</italic><0.05）， the immune function of the two groups was significantly improved， and the levels of CD3⁺， CD4⁺， C3， and C4 in observation group were higher than those in control group（<italic>P</italic><0.05）， and the CD8⁺ level was lower than that in control group （<italic>P</italic><0.05）. The incidence of adverse reactions had no significant difference between two groups. Conclusion:Qingre Lishi prescription has good clinical effect in treating children with acute bacterial lower urinary tract infection with bladder damp-heat syndrome. It can improve TCM syndromes and clinical symptoms. Its mechanism is related to inhibiting pathogenic bacteria， reducing inflammation， and improving immune function， and it has good security.

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial / 医学前沿

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.

The "Traditional Chinese medicine regulating liver regeneration" treatment plan for reducing mortality of patients with hepatitis B-related liver failure based on real-world clinical data / 医学前沿

On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of "traditional Chinese medicine (TCM) regulating liver regeneration." A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of "TCM regulating liver regeneration" (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups (P < 0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.

Immunogenicity of Whole / 生物医学与环境科学（英文）

Objectives@#To evaluate the immunogenicity of @*Methods@#Protein extracts from @*Results@#Immunization with @*Conclusion@#This is the advanced study to investigate the immunogenicity of

Drug-resistant gene polymorphisms in Plasmodium falciparum isolated from Bioko Island, Equatorial Guinea in 2018 and 2019 / 中国血吸虫病防治杂志

Objective To investigate the genetic polymorphisms of Plasmodium falciparum multidrug resistance protein 1 (PfMDR1), chloroquine resistance transporter (PfCRT) and Kelch 13 (PfK13) genes in Bioko Island, Equatorial Guinea, so as to provide insights into the development of the malaria control strategy in local areas. Methods A total of 85 peripheral blood samples were collected from patients with Plasmodium falciparum infections in Bioko Island, Equatorial Guinea in 2018 and 2019, and genomic DNA was extracted. The PfMDR1, PfCRT and PfK13 genes were amplified using a nested PCR assay. The amplification products were sequenced, and the gene sequences were aligned. Results There were no mutations associated with artemisinin resistance in PfK13 gene in Bioko Island, Equatorial Guinea, while drug-resistant mutations were detected in PfMDR1 and PfCRT genes, and the proportions of PfMDR1_N86Y, PfMDR1_Y184F and PfCRT_K76T mutations were 35.29% (30/85), 72.94% (62/85) and 24.71% (21/85), respectively. Conclusion There are mutations in PfMDR1, PfCRT and PfK13 genes in P. falciparum isolates from Bioko Island, Equatorial Guinea.

Efficacy of tyrosine kinase inhibitors in metastatic renal cell carcinoma with rhabdoid or sarcomatoid differentiation: a single-center retrospective analysis / 中华泌尿外科杂志

Objective:To investigate the efficacy of tyrosine kinase inhibitors (TKI) in the treatment of metastatic renal cell carcinoma with rhabdoid differentiation(mRCC-R) or sarcomatoid differentiation(mRCC-S)and the survival of the patients.Methods:The clinicopathological and postoperative follow-up data of 5 patients with mRCC-R and 9 with mRCC-S confirmed by pathology from February 2016 to December 2018 in Tianjin Medical University Cancer Hospital were reviewed. There were 3 male and 2 female patients in mRCC-R group, with the average age of (60.2±7.1)years old. The clinic manifestation included back or abdominal pain in 2 cases, loss of appetite and weight in one case and founding during physical examination in 2 cases, with the average maximum diameter was (8.8±4.1)cm. The site of tumor included left kidney in 3 cases and right kidney in 2 cases. Lung metastasis was found in 4 cases. Lung and peritoneum metastasis was found in one case. There were 8 male and 1 female patients in mRCC-S group, with the average age of (58.0±8.0)years old. The clinic manifestation included back or abdominal pain in one case, loss of weight in one case, gross hematuria in one case and founding during physical examination in 6 cases. The average diameter of tumor was (8.9±3.5)cm. The site of tumor included left kidney in 4 cases and right kidney in 5 cases. Postoperative metastasis included lung in 3 cases, bone in one case, retroperitoneal lymph node in one case, brain in one case, lung associated with bone in one case. All of the patients were pathologically diagnosed with renal clear cell carcinoma. After metastasis, 5 cases of mRCC-R and 6 cases of mRCC-S were treated with Sorafenib, 2 cases of mRCC-S were treated with Sunitinib, and 1 case of mRCC-S was treated with Axitinib. The efficacy of TKI for the two specific pathological types and for single pathological type at the early postoperative period (within 3 months) and 3 months later was compared. Meanwhile, subgroup analysis was performed on the efficacy of TKI and survival of patients with same metastatic sites in the two groups.Results:The mean overall survival(OS) of mRCC-R and mRCC-S treated with TKI was (26.5±5.5)months and (20.7±4.7) months( P=0.329), and the mean progression-free survival (PFS) was (21.9±5.5) months and (6.3±2.1)months( P=0.013), respectively. Comparing the efficacy of using TKI in the early postoperative period and after 3 months, the mean OS was (27.5±6.5)months and (16.8±6.1)months ( P=0.619), and the mean PFS was (12.3±3.3)months and (3.3±1.7)months ( P=0.096), respectively. There was only 1 patient with mRCC-R who used TKI within 3 months after surgery, and the result was disease progressed and eventually died, OS was 3 months. Comparing the efficacy of TKI in mRCC-R and mRCC-S with lung metastasis alone, the mean OS was (33.3±2.2) months and (19.5±8.9)months ( P=0.118), and the mean PFS was (27.3±3.1) months and (7.8±4.2) months ( P=0.009), respectively. Patients with liver, bone or brain metastasis only occurred in mRCC-S, so it is unable to identify the efficacy of TKI in the two groups. Conclusions:The efficacy of TKI in the treatment of mRCC-R was better than mRCC-S, and there was statistically significant difference in PFS, especially in patients with lung metastasis alone in the two groups. There was no significant difference in the efficacy between patients with mRCC-R who took TKI in the early postoperative period (within 3 months)and those who took TKI after 3 months.

Performance of a recombinase - aided amplification assay for detection of Schistosoma japonicum infections in Oncomelania hupensis / 中国血吸虫病防治杂志

Objective To evaluate the efficiency of a recombinase-aided amplification (RAA) assay for the detection of Schistosoma japonicum infections in Oncomelania hupensis snails. Methods A group test was employed. Fifty Oncomelania snails were collected as a detection sample. The detection samples without infected snails were designated as negative specimens, while the detection samples that contained different numbers of infected snails were designated as positive specimens. A total of 10 negative specimens, 10 positive specimens containing 1 infected snail, 20 positive specimens containing 2 infected snails and 10 positive specimens containing 3 infected snails were assigned. Following random grouping, 40 specimens were subject to the florescent RAA assay using a blind method. The miradium shedding method served as a gold standard, and the sensitivity, specificity, Youden’s index and coincidence rate of the florescent RAA assay were estimated. In addition, 20 samples consisted of 5 negative specimens and 15 positive specimens with 1, 2 and 3 infected snails respectively were grouped randomly. The same specimens were detected using the crushing method and fluorescent RAA assay with the blind method in a paired-design manner. Then, the test results were compared and analyzed. Results Florescent RAA assay detected 29 positives in the 30 specimens containing different numbers of infected snails, with a sensitivity of 96.67%, and 8 negatives in the 10 detection specimens without infected snails, with a specificity of 80.00%, showing a Youden’s index of 0.77. The coincidence rate was 100% among 10 repeated assays for a detection specimen. In addition, there was no significant difference in the detection of infected snails between the florescent RAA assay and the crushing method (χ2 = 0, P > 0.05), and the actual coincidence rates of the florescent RAA assay and crushing method were 95.00% (19/20) and 90.00% (18/20) with the real results, respectively. Conclusion Fluorescent RAA assay has a favorable efficiency for the detection of S. japonicum infections in Oncomelania snails, which shows a potential in screening of S. japonicum-infected Oncomelania snails.

Safety and effectiveness of left atrial appendage occlusion in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis / 中华心血管病杂志

Objective: To evaluate the safety and effectiveness of left atrial appendage occlusion (LAAO) in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis. Methods: Six patients with AF and end-stage renal disease(ESRD)on long term hemodialysis who underwent LAAO from March 2017 to March 2021 in Beijing Anzhen Hospital were enrolled. Baseline characteristics such as age, sex, types of arrhythmia, stroke and bleeding score, and continuous dialysis time were collected. Four patients underwent LAAO, two patients underwent the combined procedure of catheter ablation and LAAO. Perioperative treatment and serious complications were recorded. Transesophageal echocardiography was repeated at 45 days and 60 days after the procedure. Telephone follow-up was conducted at 3, 6 and 12 months after the procedure, and every 6 months thereafter. Thromboembolism and major bleeding events and survival were evaluated. Results: The average age was (66.7±17.0) years old, and 5 were male (5/6). There were 4 patients with paroxysmal AF (4/6), and 2 patients with persistent AF (2/6). The mean CHA2DS2-VASc score was (4.8±1.5), and the HAS-BLED score was (3.5±1.4). The duration of hemodialysis was 2.6 (1.1, 8.3) years. Successfully Watchman implantation was achieved in all patients. There were no severe perioperative complications, and no device related thrombosis or leaks were observed by transesophageal echocardiography. During a mean of 22.0 (12.0, 32.0) months follow-up, there was no thromboembolism or major bleeding events. A total of 2 patients died, one from sudden cardiac death, and another one from heart failure. Conclusions: LAAO may be a safe and effective therapeutic option for prevention of thromboembolism in patients with atrial fibrillation and end-stage renal disease undergoing long-term hemodialysis, further studies with larger patient cohort are needed to confirm our results.

Construction of yeast cell factories for production of azadirachtin precursor tirucalla-7,24-dien-3β-ol / 中国中药杂志

Azadirachtin, as a botanical insecticide, is a highly oxidized limonoid triterpenoid existing in the seeds of Azadirachta indica. However, due to the low content in the seeds, the production of azadirachtin by seed extraction has low yield. Chemical synthesis of azadirachtin is characterized by complex process and low yield. Synthetic biology provides an alternative for the supply of azadirach-tin. In this study, two oxidosqualene cyclases AiOSC1 and MaOSC1 respectively derived from A. indica and Melia azedarach were identified in yeast. A yeast strain producing tirucalla-7,24-dien-3β-ol was constructed by integration of AiOSC1, Arabidopsis thaliana-derived squalene synthase gene(AtAQS2), and Saccharomyces cerevisiae-derived truncated 3-hydroxy-3-methyl-glutaryl coenzyme A reductase gene(PgtHMGR) into the delta site of yeast. Then, the function of MaCYP71BQ5 was successfully verified in yeast after this gene was introduced into the constructed yeast strain. This study not only laid a foundation for the biosynthesis of tirucalla-7,24-dien-3β-ol, but also provided a chassis cell for the functional identification of cytochrome oxidases(CYP450 s) in azadirachtin biosynthesis pathway.

Systematic evaluation on efficacy and safety of Gingko Ketone Ester Dropping Pills in treatment of angina pectoris and coronary heart disease / 中国中药杂志

To systemically evaluate the efficacy and safety of Gingko Ketone Ester Dropping Pills in treating angina pectoris and co-ronary heart disease. CNKI, Wanfang, SinoMed, PubMed, Cochrane Library and EMbase databases were retrieved on computer, and the randomized clinical trial(RCT) on Gingko Ketone Ester Dropping Pills in treating angina pectoris and coronary heart disease, which were published from the database establishment to December 31, 2019, were comprehensively collected. Literature screening, data extraction and quality evaluation were conducted independently by two researchers according to inclusion and exclusion criteria. Literature methodology quality evaluation was conducted with use of the Cochrane Handbook 5.3.0(bias risk assessment tool). Meta-analysis was performed with RevMan 5.3.0 software. A total of 10 RCTs were included. The results of the Meta-analysis showed that as compared with conventional Western medicine alone, the application of Gingko Ketone Ester Dropping Pills combined with conventional Western medicine treatment further improved the total effective rate and electrocardiogram effect(RR=1.43,95%CI[1.20,1.71],P<0.000 1). There were statistically significant differences in the number of angina attacks, the duration of angina and the amount of nitroglycerin used. In terms of safety indicators, four studies reported adverse reactions in the experimental group, including facial flu-shing, tachycardia, dizziness, dyspnea, nausea and other symptoms. Based on the existing findings, in the treatment of angina pectoris and coronary heart disease, Gingko Ketone Ester Dropping Pills combined with conventional Western medicine can improve the clinical total effective rate, electrocardiogram effect, number of angina attacks, duration of angina and the amount of nitroglycerin used. However, in the included studies, due to some methodological quality problems which would impact the reliability of literature results more high-quality randomized controlled trials are still needed for further verification.