Analysis of pretreatment drug resistance and polymorphic sites in CRF08_BC strains among HIV-1 patients / 中华微生物学和免疫学杂志

Objective:To investigate the prevalence of pretreatment drug resistance and the genetic polymorphism of CRF08_BC strains among HIV-1 patients in China.Methods:This cross-sectional survey involved the plasma samples of HIV patients in a national pretreatment HIV drug resistance survey conducted in 2018. RNA was extracted from the samples. The fragments containing protease and partial reverse transcriptase (PR/RT) regions were obtained and sequenced. Drug resistance was analyzed using Stanford HIVdb Program. Differences in polymorphic mutations between drug-resistant and non-drug-resistant HIV-1 strains were analyzed by Chi-square test or Fisher′s exact test. The association between drug-resistant and polymorphic mutations was evaluated using CorMut R package. Molecular transmission networks were constructed using HIV-TRACE software. Results:Totally 465 partial pol sequences were obtained from individuals with CRF08_BC infection in 25 provinces and cities. The total pretreatment drug resistance rate was 17.8% (83/465). The pretreatment drug resistance rates to non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) were 16.6% (77/465), 1.1% (5/465) and 0.9% (4/465), respectively. The resistance rate to rilpivirine (RPV) was the highest (15.7%, 73/465). The most common mutation was E138A (11.6%, 54/465). There were six polymorphic mutations (S162C, K102Q, T200A, V179E, I202V, T200M) that co-variated with E138A. The molecular transmission network showed that patients infected with CRF08_BC strains carrying the resistant mutations at position E138 mainly gathered in clusters in Yunnan and Sichuan, and the highest degree of connection was in Lincang, Yunnan. Conclusions:In China, HIV-1 CRF08_BC-infected patients showed a high rate of pretreatment resistance to one of the second-generation NNRTIs, namely RPV. Further researches were warranted to evaluate the impacts of co-mutations of the E138A mutation and polymorphic sites on HIV resistance and replicative capacity.

Cohort study on the change trend of astigmatism among preschool children in Baiyun district, Guangzhou from 2018 to 2021 / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore the characteristics of astigmatism in preschool children before, during and after the COVID-19 epidemic, so as to provide a reference for further prevention and control of children's vision.METHODS: In the consecutive four years from January 2018 to December 2021, a retrospective analysis of vision data was conducted on 2 273 preschool children(4 546 eyes)younger than 4 years old who participated in children's vision screening test in Baiyun district, Guangzhou. They were divided into 1-year old group(ages<1-year old, 420 cases), 2-year old group(1-year ≤ ages <2-year, 543 cases), 3-year old group(2-year ≤ages <3-year, 614 cases), and 4-year old group(3-year ≤ ages<4-year, 696 cases)according to ages. The analysis included astigmatic degrees of children's eyes as well as their conditions of astigmatism.RESULTS: In 2018, the astigmatic degrees of the both eyes of 1-year-old group were higher than those of other groups(P<0.05). The binocular astigmatic degrees of the preschool children in four groups were obviously higher in 2020 than 2019(P<0.05), while they were significantly decreased in 2021 when compared with 2020(P<0.05). From 2019 to 2020, the increase of astigmatic degrees of the right eye is more considerable than the left eye of preschool children in those four groups(P<0.001). Furthermore, the morbidity of astigmatism basically echoes with the changing tendency of astigmatic degrees from 2018 to 2021.CONCLUSIONS: Preschool children in Baiyun district, Guangzhou, have the highest degree of astigmatism and the fastest progression rate within 1 year old. Before COVID-19 epidemic, the changes in astigmatism and prevalence were relatively stable; during COVID-19 epidemic, the astigmatism and prevalence increased significantly and the astigmatic degrees of right eye increased more than that of the left eye; after the normalization of epidemic prevention and control, the astigmatism and prevalence decreased significantly.

Adjuvant chemotherapy versus adjuvant concurrent chemoradiotherapy after radical surgery for early-stage cervical cancer: a randomized, non-inferiority, multicenter trial / 医学前沿

We conducted a prospective study to assess the non-inferiority of adjuvant chemotherapy alone versus adjuvant concurrent chemoradiotherapy (CCRT) as an alternative strategy for patients with early-stage (FIGO 2009 stage IB-IIA) cervical cancer having risk factors after surgery. The condition was assessed in terms of prognosis, adverse effects, and quality of life. This randomized trial involved nine centers across China. Eligible patients were randomized to receive adjuvant chemotherapy or CCRT after surgery. The primary end-point was progression-free survival (PFS). From December 2012 to December 2014, 337 patients were subjected to randomization. Final analysis included 329 patients, including 165 in the adjuvant chemotherapy group and 164 in the adjuvant CCRT group. The median follow-up was 72.1 months. The three-year PFS rates were both 91.9%, and the five-year OS was 90.6% versus 90.0% in adjuvant chemotherapy and CCRT groups, respectively. No significant differences were observed in the PFS or OS between groups. The adjusted HR for PFS was 0.854 (95% confidence interval 0.415-1.757; P = 0.667) favoring adjuvant chemotherapy, excluding the predefined non-inferiority boundary of 1.9. The chemotherapy group showed a tendency toward good quality of life. In comparison with post-operative adjuvant CCRT, adjuvant chemotherapy treatment showed non-inferior efficacy in patients with early-stage cervical cancer having pathological risk factors. Adjuvant chemotherapy alone is a favorable alternative post-operative treatment.

Clinical features and microsurgical reconstruction of congenital unilateral absence of the vas deferens with obstructive azoospermia: a tertiary care center experience / 亚洲男科学杂志(英文版)

Patients with congenital unilateral absence of the vas deferens (CUAVD) manifest diverse symptoms from normospermia to azoospermia. Treatment for CUAVD patients with obstructive azoospermia (OA) is complicated, and there is a lack of relevant reports. In this study, we describe the clinical features and evaluate the treatments and outcomes of CUAVD patients with OA. From December 2015 to December 2020, 33 patients were diagnosed as CUAVD with OA in Shanghai General Hospital (Shanghai, China). Patient information, ultrasound findings, semen analysis, hormone profiles, and treatment information were collected, and the clinical outcomes were evaluated. Of 33 patients, 29 patients were retrospectively analyzed. Vasoepididymostomy (VE) or cross VE was performed in 12 patients, the patency rate was 41.7% (5/12), and natural pregnancy was achieved in one of the patients. The other 17 patients underwent testicular sperm extraction as the distal vas deferens (contralateral side) was obstructed. These findings showed that VE or cross VE remains an alternative treatment for CUAVD patients with OA, even with a relatively low rate of patency and natural pregnancy.

Effects of miR-515-5p on the proliferation and metastasis of ovarian cancer cell A2780 by regulating the expression of chondroitin sulfate proteoglycan 4 and its mechanism / 解剖学报

Objective To investigate the targeted regulation of miR-515-5p on chondroitin sulfate proteoglycan 4 (CSPG4) and its effect on the proliferation and metastasis of ovarian cancer cell A2780. Methods The target genes of miR-515-5p were predicted by bioinformatics tools. Real-time PCR and Western blotting were used to detect the expression of miR-515-5p and CSPG4 in 65 cases ovarian cancer tissues and adjacent tissues. Ovarian cancer cells A2780 were divided into miR-NC group, miR-515-5p group, si-NC group, si-CSPG4 group, miR-515-5p + pcDNA group, miR-515-5p + pcDNA-CSPG4 group. MTT assay was used to detect cell proliferation. Transell was applied to detect cell migration and invasion, and Western blotting was selected to detect cyclinD1, P21, matrix metalloproteinase (MMP)-2 and MMP-9 protein expression. The double luciferase reporter gene experiment and Western blotting confirmed the regulation effect of miR-515-5p on CSPG4 gene. Results Bioinformatics analysis showed that CSPG4 was one of the potential target genes of miR-515-5p. Compared with the adjacent tissues, the expression of miR-515-5p was lower in ovarian cancer tissues, and the expression of CSPG4 was higher (P< 0. 05). Compared with the miR-NC group, the expression of cyclinD1, MMP-2 and MMP-9 protein was lower in A2780 cells of miR-515-5p group, the expression of P21 protein was higher, the cell viability was lower, and the number of cell migration and invasion was lower (P<0. 05). Compared with the si-NC group, the expression of cyclinD1, MMP-2 and MMP-9 proteins were lower in A2780 cells in si-CSPG4 group, P21 protein was higher, cell viability was lower, and the number of cell migration and invasion was lower (P<0. 05). Compared with the miR-515-5p + pcDNA group, the expression of cyclinD1, MMP-2 and MMP-9 proteins was higher in A2780 cells of miR-515-5p + pcDNA-CSPG4 group, the expression of P21 protein was lower, and the cell viability was higher, the number of cell migration and invasion was higher (P<0. 05). MiR-515-5p targeted and negatively regulated CSPG4 expression. Conclusion MiR-515-5p could inhibit the proliferation and metastasis of ovarian cancer cell A2780 by targeting CSPG4.

6-desulfated heparin inhibits heparan sulfate shedding and epithelial cell damage during bleomycin induced pulmonary injury / 中国药理学通报

Aim To study the effect of different hepa- ry.Methods First, heparin derivatives with different rin sulfation patterns on bleomycin induced lung inju- sulfation patterns,6-desulfated heparin (6-DeH) and N-acetvlated heparin ( N-AcH ) , were synthesized.Secondly, the effect of these compounds on BLM-in¬duced bronchial epithelial cell ( BEARS-2B) injury was evaluated via lactate dehydrogenase activity, MTT experiment, Annexin V/ PI staining and Hoechst 33258 staining.Then , immunofluorescence staining and West¬ern blotting were used to investigate the shedding of Svndecan-1 and the activation of c-Met by 6-DeH/Akt j j signaling pathway.Finally, a BLM-induced lung injury mouse model was used to further verify the protective effect of 6-DeH by HE staining, Svndecan-1 immunos- taining,bodv weight change,and survival rate.Results In the BLM-induced BEARS-2B injury model, 6- DeH was selected as the best candidate, which exerted their effect by competitively binding to BLM, thereby reducing the damage of heparan sulfate barrier (Svnde- can-1 ) on cell surface, and improving cell survival by activating the downstream c-Met/Akt pathway.In the BLM-induced lung injury mouse model, it was further confirmed that 6-DeH reduced the shedding of Svnde- can-1 in the early stage, and delayed the lung injury and fibrosis process.Conclusions 6-DeH protects the bronchial epithelial cells against BLM-induced lung in¬jur)' through inhibiting the shedding of Svndecan-1 and activating the c-Met/Akt signaling pathway.

Study of intermolecular interactions of piroxicam polymorphs / 药学学报

Piroxicam has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Analysis of the intermolecular interactions is essential to reveal the formation mechanism and differences of polymorphs. In this paper, Hirshfeld surface analysis and semi-empirical methods were used to calculate and analyze the intermolecular interactions in seven polymorphic forms of piroxicam. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions, among which H…H, O…H/H…O and N…H/H…N interactions account for 95% of the total energy. There are differences in the proportion and distribution of the forces of different crystal forms. The energy calculation shows that the lattice energy of the hydrate is significantly lower than that of the anhydrous forms, and in the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis was found that within the distance of 3.8 Å from the center of the piroxicam molecule, different crystalline forms of piroxicam molecule have different interaction energies with surrounding molecules.

Applying the OMOP Common Data Model to Facilitate Benefit-Risk Assessments of Medicinal Products Using Real-World Data from Singapore and South Korea / 대한의료정보학회지

Objectives@#The aim of this study was to characterize the benefits of converting Electronic Medical Records (EMRs) to a common data model (CDM) and to assess the potential of CDM-converted data to rapidly generate insights for benefit-risk assessments in post-market regulatory evaluation and decisions. @*Methods@#EMRs from January 2013 to December 2016 were mapped onto the Observational Medical Outcomes Partnership-CDM (OMOP-CDM) schema. Vocabulary mappings were applied to convert source data values into OMOP-CDM-endorsed terminologies. Existing analytic codes used in a prior OMOP-CDM drug utilization study were modified to conduct an illustrative analysis of oral anticoagulants used for atrial fibrillation in Singapore and South Korea, resembling a typical benefit-risk assessment. A novel visualization is proposed to represent the comparative effectiveness, safety and utilization of the drugs. @*Results@#Over 90% of records were mapped onto the OMOP-CDM. The CDM data structures and analytic code templates simplified the querying of data for the analysis. In total, 2,419 patients from Singapore and South Korea fulfilled the study criteria, the majority of whom were warfarin users. After 3 months of follow-up, differences in cumulative incidence of bleeding and thromboembolic events were observable via the proposed visualization, surfacing insights as to the agent of preference in a given clinical setting, which may meaningfully inform regulatory decision-making. @*Conclusions@#While the structure of the OMOP-CDM and its accessory tools facilitate real-world data analysis, extending them to fulfil regulatory analytic purposes in the post-market setting, such as benefit-risk assessments, may require layering on additional analytic tools and visualization techniques.

Primary carcinoid of testis: a case report / 中华泌尿外科杂志

Carcinoid is a rare clinical disease, especially primary carcinoid of testis. On December 11, 2019, a patient with primary testicular carcinoid was admitted to the Fourth Hospital of Hebei Medical University. The physical examination, color Doppler ultrasound and scrotal CT showed that left testicular tumor. The patient underwent radical orchiectomy and sent for pathology examination on December 14, 2019. Gastroscopy, enteroscopy and CT examination of pelvic and abdominal cavity showed no obvious abnormalities. Postoperative pathology combined with immunohistochemistry was diagnosed as primary carcinoid of testis. The patient was followed up for 23 months with no recurrence.

Functional discovery and production technology for natural bioactive peptides / 生物工程学报

Bioactive peptides play important roles in promoting human health, such as lowering blood pressure, blood sugar and blood lipid, anti-obesity, and anti-cancer. Thus, exploring functional bioactive peptides and developing efficient production technologies are of crucial importance. Herein, we review the development of function discovery and production technology for natural bioactive peptides. Presently, the top-down and bottom-up approaches are mainly used for the function discovery and production of natural active peptides. The top-down approach includes the direct extraction and identification for functional discovery, and the direct extraction, enzymatic hydrolysis and microbial fermentation for production. The bottom-up approach includes the polypeptide modification and database mining for functional discovery, and the chemical synthesis, enzyme synthesis, recombinant expression and cell-free synthesis for production. The top-down approach is usually associated with complicated process, lower efficiency, higher cost, harder quality control, and uncertain functionality, while the bottom-up approach is more suitable for the development of peptide drugs but difficult to be used for functional foods. With the technology development of sequencing and mass spectrometry, it is easier to obtain the proteomic information of various organisms at the molecular level. Based on the proteomic information, the top-down and bottom-up approaches can be combined to overcome the disadvantages of using these two approaches alone, thus providing a new strategy for the rapid development and production of natural active peptides.

Wuzhi Tablet protects against APAP-induced liver injury at different pretreated intervals in mice / 药学学报

Acetaminophen (APAP, also known as paracetamol)-induced liver injury is the leading cause of drug-induced liver injury in the world. Wuzhi Tablet (WZ, an ethanol extract of Schisandra sphenanthera) is widely used in clinical practice to protect liver function. Our previous studies have shown that pretreatment with WZ for 3 days can significantly protect against APAP-induced liver injury; however, the effect of different intervals between APAP and WZ treatment on APAP-induced liver injury remains unclear. In this study, the change in liver injury indexes, APAP metabolites, and the activity of cytochrome P450 (CYP450) enzymes after treatment with WZ and APAP at different intervals were determined. The animal experiment was reviewed and approved by the Animal Ethics Committee of Sun Yat-sen University. The results show that 0 h, 0.5 h, and 2 h pretreatment with WZ significantly protected against APAP-induced liver injury in mice, as evidenced by a significant decrease in biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malonaldehyde (MDA). WZ inhibited the metabolic activation of APAP mediated by CYP450 enzymes and reduced the formation of APAP metabolites. This study further demonstrates that pretreatment with WZ at different intervals (0 h, 0.5 h, and 2 h before APAP dosing) exerts a significant hepatoprotective effect against APAP-induced liver injury, and a single-dose of WZ inhibits the activity of CYP450 enzymes related to APAP metabolic activation, thereby protecting against APAP-induced hepatotoxicity.

Technology development and instrumentation of a high-throughput and automated microbial microdroplet culture system for microbial evolution and screening / 生物工程学报

Since microdroplets are able to be generated rapidly in large amount and each droplet can be well controlled as an independent micro-cultivator, droplet microfluidic technology can be potentially used in the culture of microorganisms, and provide the microbial culture with high throughput manner. But its application mostly stays in the laboratory-level building and using for scientific research, and the wide use of droplet microfluidics in microbial technology has been limited by the key problems that the operation for microdroplets needs high technical requirements with wide affecting factors and the difficulties in integration of automatic microdroplet instrumentation. In this study, by realizing and integrating the complicated operations of droplet generation, cultivation, detection, splitting, fusion and sorting, we design a miniaturized, fully automated and high-throughput microbial microdroplet culture system (MMC). The MMC can be widely used in microbial growth curve test, laboratory adaptive evolution, single factor and multi-level analysis of microbial culture, metabolite detection and so on, and provide a powerful instrument platform for customized microbial evolution and screening aiming at efficient strain engineering.

Effect of compound nutrients on behavior and fatigue in mice with high temperature exercise / 中国职业医学

OBJECTIVE: To explore the effects of high temperature on learning and memory ability, behavioral activity, and fatigue as well as the intervention effect of compound nutrients on the exercising mice. METHODS: Thirty specific pathogen-free healthy male Kunming mice were randomly divided into the normal-temperature exercise, high-temperature exercise, and high-temperature exercise supplement groups, with 10 mice in each group. The mice in these three groups performed treadmill exercise for one hour every day, six days per week, and continued for four weeks. The mice in the high-temperature exercise supplement group were fed with 0.3 mL of compound nutrients 30 minutes before each treadmill exercise, whereas the mice in the normal-temperature exercise and the high-temperature exercise groups were fed with an equal volume of distilled water. At the end of the treadmill exercise, the mice were subjected to experiments on their neurological behaviors. The serum of mice in each group were collected to detect the lactic acid level, urea nitrogen level, and creatine kinase activity. The liver and gastrocnemius muscle tissues were then taken for detecting the levels of liver glycogen and muscle glycogen.RESULTS: Compared with the mice in the normal-temperature exercise group, the escape latency of the mice in the high-temperature exercise group was prolonged(P<0.05), whereas the number of platform crossings, percentage of target quadrant time, and distance were reduced(all P<0.05). Compared with the mice in the high-temperature exercise group, the escape latency of the mice in the high-temperature exercise supplement group was shortened(P<0.05), whereas the number of platform crossings, percentage of target quadrant time, and distance were increased(all P<0.05). Compared with the mice in the normal-temperature exercise group, the first fall time and grip strength of the mice in the high-temperature exercise group were reduced(all P<0.05), whereas the number of falls was increased(P<0.05). Compared with the mice in the high-temperature exercise group, the first fall time and grip strength of the mice in the high-temperature exercise supplement group were increased(all P<0.05), whereas the number of falls was reduced(P<0.05). Compared with the mice in the normal-temperature exercise group, the serum lactic acid level, urea nitrogen level, and creatine kinase activity of the mice in the high-temperature exercise group were increased(all P<0.05), whereas the levels of liver glycogen and muscle glycogen were decreased(all P<0.05). Compared with the mice in the high-temperature exercise group, the serum lactic acid level, urea nitrogen level, and creatine kinase activity of the mice in the high-temperature exercise supplement group were decreased(all P<0.05), whereas the levels of liver glycogen and muscle glycogen were increased(all P<0.05). CONCLUSION: High temperature exercise can lead to decreased learning and memory ability and behavioral activity in mice, resulting in exercise-induced fatigue. Supplemental compound nutrients can prevent these changes.

Transcriptional profiling and network pharmacology analysis identify the potential biomarkers from Chinese herbal formula Huosu Yangwei Formula treated gastric cancer in vivo / 中国天然药物

Huosu Yangwei (HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD, AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.

Modified stepwise mini-incision microdissection testicular sperm extraction: a useful technique for patients with a history of orchidopexy affected by non-obstructive azoospermia / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Non-obstructive azoospermia (NOA), which is defined as the absence of spermatozoa in the ejaculate secondary to impaired spermatogenesis within the testis, may be caused by a variety of etiologies, including varicocele-induced testicular damage, cryptorchidism, prior testicular torsion, post-pubertal mumps orchitis, gonadotoxic effects from medications, genetic abnormalities, chemotherapy/radiation, and other unknown causes currently classified as idiopathic (Cocuzza et al., 2013). The microdissection testicular sperm extraction (micro-TESE) technique involves a meticulous microsurgical exploration of the testicular parenchyma to identify and selectively extract larger seminiferous tubules that carry a higher probability of complete spermatogenesis (Schlegel, 1999). The Cornell group evaluated the efficacy of micro-TESE in 152 NOA patients with an associated history of cryptorchidism. In their series, spermatozoa were successfully retrieved in 116/181 attempts (64%), and the resulting pregnancy rate was 50% with a delivery rate of 38% (Dabaja and Schlegel, 2013). Franco et al. (2016) described a stepwise micro-TESE approach in NOA patients, which was considered to reduce the cost, time, and effort associated with the surgery. Alrabeeah et al. (2016) further reported that a mini-incision micro-TESE, carried through a 1-cm equatorial testicular incision, can be useful for micro-TESE candidates, particularly in patients with cryptozoospermia. We conducted a retrospective study of 20 consecutive NOA patients with a history of orchidopexy from May 2015 to March 2017.

Estradiol is an independent risk factor for organic erectile dysfunction in eugonadal young men / 亚洲男科学杂志(英文版)

Erectile dysfunction attributable to testosterone deficiency is less common in young males, and the effect of estradiol on erectile function in eugonadal young males is unclear. We analyzed data from 195 male participants, including 143 eugonadal patients with erectile dysfunction and 52 healthy men. To distinguish psychogenic and organic erectile dysfunction, penile rigidity was measured using the nocturnal penile tumescence rigidity test. Serum levels of sexual hormones were quantified by electrochemiluminescence, and penile vascular status was assessed by penile color Doppler ultrasound. Both serum estradiol levels and the ratio of estradiol to testosterone were higher in patients with organic erectile dysfunction than in patients with psychogenic erectile dysfunction or healthy controls. Organic erectile dysfunction was negatively associated with estradiol levels and the ratio of estradiol to testosterone, and estradiol was the only significant risk factor for organic erectile dysfunction (odds ratio: 1.094; 95% confidence interval: 1.042-1.149, P = 0.000). Moreover, serum estradiol levels were negatively correlated with penile rigidity. Serum estradiol levels were higher and penile rigidity was lower in patients with venous erectile dysfunction than in patients with nonvascular erectile dysfunction. We conclude that elevated serum estradiol levels may impair erectile function and may be involved in the pathogenesis of organic erectile dysfunction in eugonadal young men.

Effect of baicalin on expression of fibrogenic factors TGF-β1, mmp2 and timp2 in tissue of mice with pulmonary fibrosis / 中国中药杂志

To investigate the effect of baicalin extracted from Qinbai Qingfei Concentrated Pills on the expressions of TGF-β1, mmp2 and timp2 in mice with pulmonary fibrosis induced by bleomycin. The Biacore technique was used to detect the specific binding between Qinbai Qingfei Concentrated Pills and TGF-β1, and the affinity components were enriched, regenerated and recovered by Biacore fishing. Then ultra-performance liquid chromatography and quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) were used to determine whether the monomer was baicalin. Biacore was used to verify the affinity kinetics of baicalin, which was validated by pharmacodynamics in vivo. Totally 30 BALB/C mice were randomly divided into three groups: baicalin group, blank group and model group. The blank group was given sodium chloride injection(0.08 mL·kg~(-1)), while the model group and the baicalin group were injected with 4 mg·kg~(-1) bleomycin. The localization of TGF-β1, mmp2 and timp2 protein in the cells and the mRNA expressions of TGF-β1, mmp2 and timp2 were detected by RT-PCR 14 days later. The results of Biacore affinity analysis showed that the peak of binding response between Qinbai Qingfei Concentrated Pills and TGF-β1 protein reached 1 524.0 RU, with specific binding. The affinity constant K_D of baicalin and TGF-β1 was 1.620 06 μmol·L~(-1), which was determined by SPR kinetic analysis, suggesting a stable binding between baicalin and TGF-β1, which verified the results of angulation. The results of immunohistochemistry showed that the deposition of cellulose in baicalin group was significantly less than that in model group, the mRNA expressions of TGF-β1, mmp2 and timp2 were decreased in baicalin solution compared with the model group. Baicalin combined with TGF-β1 could inhibit the expressions of mmp2 and timp2 and delay the progress of pulmonary fibrosis.

Efficacy and safety of the long-acting fusion inhibitor albuvirtide in antiretroviral-experienced adults with human immunodeficiency virus-1: interim analysis of the randomized, controlled, phase 3, non-inferiority TALENT study / 中华医学杂志(英文版)

BACKGROUND@#Albuvirtide is a once-weekly injectable human immunodeficiency virus (HIV)-1 fusion inhibitor. We present interim data for a phase 3 trial assessing the safety and efficacy of albuvirtide plus lopinavir-ritonavir in HIV-1-infected adults already treated with antiretroviral drugs.@*METHODS@#We carried out a 48-week, randomized, controlled, open-label non-inferiority trial at 12 sites in China. Adults on the World Health Organization (WHO)-recommended first-line treatment for >6 months with a plasma viral load >1000 copies/mL were enrolled and randomly assigned (1:1) to receive albuvirtide (once weekly) plus ritonavir-boosted lopinavir (ABT group) or the WHO-recommended second-line treatment (NRTI group). The primary endpoint was the proportion of patients with a plasma viral load below 50 copies/mL at 48 weeks. Non-inferiority was prespecified with a margin of 12%.@*RESULTS@#At the time of analysis, week 24 data were available for 83 and 92 patients, and week 48 data were available for 46 and 50 patients in the albuvirtide and NRTI groups, respectively. At 48 weeks, 80.4% of patients in the ABT group and 66.0% of those in the NRTI group had HIV-1 RNA levels below 50 copies/mL, meeting the criteria for non-inferiority. For the per-protocol population, the superiority of albuvirtide over NRTI was demonstrated. The frequency of grade 3 to 4 adverse events was similar in the two groups; the most common adverse events were diarrhea, upper respiratory tract infections, and grade 3 to 4 increases in triglyceride concentration. Renal function was significantly more impaired at 12 weeks in the patients of the NRTI group who received tenofovir disoproxil fumarate than in those of the ABT group.@*CONCLUSIONS@#The TALENT study is the first phase 3 trial of an injectable long-acting HIV drug. This interim analysis indicates that once-weekly albuvirtide in combination with ritonavir-boosted lopinavir is well tolerated and non-inferior to the WHO-recommended second-line regimen in patients with first-line treatment failure.@*TRIAL REGISTRATION@#ClinicalTrials.gov Identifier: NCT02369965; https://www.clinicaltrials.gov.Chinese Clinical Trial Registry No. ChiCTR-TRC-14004276; http://www.chictr.org.cn/enindex.aspx.

Microsurgical subinguinal varicocelectomy with spermatic cord double traction and vein stripping / 亚洲男科学杂志(英文版)

We retrospectively reviewed data for 286 patients with varicocele who underwent microsurgical subinguinal varicocelectomy from March 2015 to May 2017 in Shanghai General Hospital (Shanghai, China). In this surgical approach, the testis was delivered, and the gubernacular and external cremasteric veins were stripped. In addition, the spermatic cord was delivered downward with continuous double traction away from the external ring. The remaining procedure was similar to the conventional approach. We followed patients for at least 3 months and evaluated postoperative semen parameters, pain symptoms, and complications. We excluded data for 32 men due to inadequate follow-up (<3 months). Of the remaining 254 patients, 73 had oligoasthenospermia, 121 had nonobstructive azoospermia, and 60 had symptomatic varicoceles. Total progressive sperm counts increased in the oligoasthenospermic patients from a median preoperative value of 9.15 × 106 ml-1 to 25.33 × 106 ml-1 (n= 34), and 35.6% (26/73) initially oligoasthenospermic men contributed to unassisted pregnancies. Sperm returned to the ejaculate in 12.4% (15/121) azoospermia patients. In patients with scrotal pain (n = 60), 43 (71.7%) reported complete resolution of pain, 16 (26.7%) reported partial resolution, and 1 (1.7%) reported no change. No patients experienced varicocele recurrence. This double-traction strategy avoids opening the external oblique aponeurosis, and results in less damage and faster recovery. In addition, the stripping strategy eliminates potential damage to the testis caused by the varicose veins. Our results showed that microsurgical subinguinal varicocelectomy using spermatic cord double traction in conjunction with testicular delivery for vein stripping is a safe and effective approach for varicocele repair.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis / 中华医学杂志(英文版)

BACKGROUND@#Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients.@*METHODS@#From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores.@*RESULTS@#Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation.@*CONCLUSIONS@#LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.