Research progress of needle-free injection technology / 药学学报

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

Effect of type of carrier material on the in vitro properties of solid dispersions of progesterone / 药学学报

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

A new suberin from roots of Ephedra sinica Stapf / 药学学报

Six compounds were isolated from the roots of Ephedra sinica Stapf using various chromatographic techniques such as silica gel column chromatography, thin layer chromatography and semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as (Z)-docosanylferulate (1), (E)-docosanylferulate (2), bis (2-ethylheptyl) phythalate (3), 2,2′-oxybis (1,4-di-tert-butylbenzene) (4), diisobutyl phthalate (5), bis (2-ethylhexyl) phthalate (6). Among them, compound 1 is a new compound, compounds 2-4 were first isolated from Ephedra. A corticosterone-induced PC-12 cell injury model was used for compound activity screening. The results showed that compounds 1 and 5 significantly improved corticosterone-induced PC-12 cell injury and significantly increased 5-HT7 receptor protein expression in the cells, indicating potential antidepressant activity.

Nuclear factor-KB signaling pathway and gender differences in alcoholic liver fibrosis / 解剖学报

Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E

Effects of Tao Hong Si Wu decoction on IncRNA expression in rats with occlusion of middle cerebral artery / 中国药理学通报

Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.

Changes of binocular surface indexes after unilateral endoscopic dacryocystorhinostomy / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the effect of unilateral endoscopic dacryocystorhinostomy on binocular surface indexes.METHODS: Totally 45 cases with monocular primary acquired nasolacrimal duct obstruction(PANDO)who successfully underwent endoscopic dacryocystorhinostomy between 1 December 2022 and 31 July 2023 were enrolled in the study. Ocular surface indexes, including the non-invasive tear break-up time(NIBUT), Sjögren's International Collaborative Clinical Alliance ocular staining score(SICCA OSS), Korb score of lid wiper and Schirmer test scores, were collected preoperatively and at 0.5, 1 and 3 mo post-operatively. Subsequently, various indexes were compared at each time point between the operated and healthy eyes pre- and post-operatively.RESULTS: There was no significant differences between operated and healthy eyes in NIBUT, SICCA OSS, Korb scores and Schirmer test(all P>0.05). Furthermore, the Korb scores of operated eye at 0.5, 1 and 3 mo post-operatively were significantly lower than the preoperative value(P=0.034, 0.044, 0.027). Moreover, the Schirmer test score of the operated eye at 1 mo post-operatively was significantly lower than the preoperative value(P=0.0461).CONCLUSION:After a successful endoscopic dacryocystorhinostomy, tear drainage is restored, however, ocular surface damage worsens. These changes typically peak at 1 mo post-operatively before gradually improving.

Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad / 中华肝脏病杂志

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.

Possible Risk Factors for Bone Marrow Fibroplasia in Patients with Polycythemia Vera / 中国实验血液学杂志

OBJECTIVE@#To understand the biological characteristics of polycythemia vera (PV) patients with myeloid fibroplasia, and further analyze the risk factors affecting myeloid fibroplasia in PV patients, so as to provide ideas for predicting the occurrence of myeloid fibroplasia in PV patients.@*METHODS@#Forty patients with PV in the Department of Hematology, Xiyuan Hospital of China Academy of Chinese Medical Sciences were collected and divided into two groups, with (hyperplasia group) and without (Non-proliferative group) hyperplasia of bone marrow fibers. The differences of basic clinical characteristics, blood routine, biochemistry, bone marrow cells, coagulation function and other indicators between the two groups were compared, and the independent risk factors affecting the proliferation of bone marrow fibrous tissue in PV patients were further analyzed by multivariate regression.@*RESULTS@#Compared with Non-proliferative group, the JAK2 mutation rate (95% vs 70%，P=0.037), eosinophilic cell count (0.19 vs 0.11, P=0.047) and eosinophilic percentage (1.84 vs 1.27, P=0.001) in PV patients with hyperplasia were significantly increased, triglycerides (1.55 vs 1.91, P=0.038) and low-density lipoprotein (1.50 vs 3.08, P=0.000) were significantly reduced, bone marrow hematopoietic volume (0.85 vs 0.6, P=0.001), granulocyte/erythrocyte ratio (3.40 vs 1.89, P=0.033), lymphocyte/erythrocyte ratio (0.60 vs 0.42, P=0.033), and granulocyte+lymphocyte/erythrocyte ratio (3.72 vs 2.37, P=0.026) were significantly increased, thrombin time (18.84 vs 18.12, P=0.043) was significantly prolonged. Multivariate regression analysis results showed that peripheral blood eosinophil ≥2% and low-density lipoprotein ≤2 mmol/L were independent risk factors for bone marrow fibrous tissue hyperplasia in PV patients (P<0.05).@*CONCLUSION@#Increased proportion of peripheral blood eosinophils and decreased low density lipoprotein are risk factors for bone marrow fibrous tissue hyperplasia in PV patients.

Limited internal fixation combined with a hinged external fixator in treatment of peri-elbow bone infection / 中国修复重建外科杂志

OBJECTIVE@#To evaluate the effectiveness of limited internal fixation combined with a hinged external fixator in the treatment of peri-elbow bone infection.@*METHODS@#The clinical data of 19 patients with peri-elbow bone infection treated with limited internal fixation combined with a hinged external fixator between May 2018 and May 2021 were retrospectively analyzed. There were 15 males and 4 females with an average age of 44.6 years (range, 28-61 years). There were 13 cases of distal humerus fractures and 6 cases of proximal ulna fractures. All the 19 cases were infected after internal fixation of fracture, and 2 cases were complicated with radial nerve injury. According to Cierny-Mader anatomical classification, 11 cases were type Ⅱ, 6 cases were type Ⅲ, and 2 cases were type Ⅳ. The duration of bone infection was 1-3 years. After primary debridement, the bone defect was (3.04±0.28) cm, and the antibiotic bone cement was implanted into the defect area, and the external fixator was installed; 3 cases were repaired with latissimus dorsi myocutaneous flap, and 2 cases were repaired with lateral brachial fascial flap. Bone defects repair and reconstruction were performed after 6-8 weeks of infection control. The wound healing was observed, and white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reaction protein (CRP) were reexamined regularly after operation to evaluate the infection control. X-ray films of the affected limb were taken regularly after operation to observe the bone healing in the defect area. At last follow-up, the flexion and extension range of motion and the total range of motion of the elbow joint were observed and recorded, and compared with those before operation, and the function of the elbow joint was evaluated by Mayo score.@*RESULTS@#All patients were followed up 12-34 months (mean, 26.2 months). The wounds healed in 5 cases after skin flap repair. Two cases of recurrent infection were effectively controlled by debridement again and replacement of antibiotic bone cement. The infection control rate was 89.47% (17/19) in the first stage. Two patients with radial nerve injury had poor muscle strength of the affected limb, and the muscle strength of the affected limb recovered from grade Ⅲ to about grade Ⅳ after rehabilitation exercise. During the follow-up period, there was no complication such as incision ulceration, exudation, bone nonunion, infection recurrence, or infection in the bone harvesting area. Bone healing time ranged from 16 to 37 weeks, with an average of 24.2 weeks. WBC, ESR, CRP, PCT, and elbow flexion, extension, and total range of motions significantly improved at last follow-up ( P<0.05). According to Mayo elbow scoring system, the results were excellent in 14 cases, good in 3 cases, and fair in 2 cases, and the excellent and good rate was 89.47%.@*CONCLUSION@#Limited internal fixation combined with a hinged external fixator in the treatment of the peri-elbow bone infection can effectively control infection and restore the function of the elbow joint.

Radiation dose and fractionation regimen for limited stage small cell lung cancer: a survey of current practice patterns of Chinese radiation oncologists / 中华放射肿瘤学杂志

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.

Application of debate-based immersive experiential teaching in the nursing practice teaching of stomatology / 中华医学教育探索杂志

Objective:To investigate the application of debate-based immersive experiential teaching in the nursing practice teaching of stomatology.Methods:A total of 82 nursing interns of stomatology in Beijing Tongren Hospital, Capital Medical University, were selected as research subjects and were then divided into control group and observation group using the lottery method, with 41 interns in each group. The interns in the control group received traditional teaching, while those in the observation group received debate-based immersive experiential teaching. The two groups were compared in terms of the scores of comprehensive evaluation indices, nursing thinking ability, empathy ability, and recognition of teaching. SPSS 22.0 was used to perform the chi-square test and the t-test. Results:Compared with the control group, the observation group had significant increases in the scores of theoretical examination, operation examination, nursing medical record writing, reading report writing, basic nursing, communication ability, and comprehensive performance and the total score of these dimensions ( P<0.05). Compared with the control group, the observation group also had significant increases in the scores of nursing thinking ability and empathy ability ( P<0.05). The observation group had a significantly higher degree of recognition of teaching than the control group ( P<0.05). Conclusion:In the nursing practice teaching of stomatology, debate-based immersive experiential teaching can improve the comprehensive ability, nursing thinking ability, and empathy ability of interns, with a relatively high degree of recognition of teaching.

Longitudinal study of psychological distress trajectory and influencing factors in patients with primary acute myocardial infarction / 中国实用护理杂志

Objective:To explore the changes and influencing factors of psychological distress in patients with primary acute myocardial infarction (AMI) in different periods, and to provide reference for the management of psychological distress in patients with primary AMI.Methods:This was a longitudinal, prospective, observational study. From June 2021 to September 2022, 118 patients with primary AMI in Peking Union Medical College Hospital and Peking University First Hospital were selected as the research objects. The psychological distress level of patients was investigated on the points of 24 hours after illness (T 1), before discharge (T 2), 1 month after discharge (T 3), 3 months after discharge (T 4), 6 months after discharge (T 5) and 12 months after discharge (T 6), and the influencing factors were analyzed. Results:The detection rate of psychological distress in 6 follow-up survey nodes was 66.95% (79/118), 48.31% (57/118), 29.66% (35/118), 24.58% (29/118), 19.49% (23/118) and 15.25% (18/118) respectively. Education level, family per capita income and disease awareness had significant effects on the psychological distress of patients with primary AMI at the time points from T 1 to T 6 ( β values were - 1.262 to - 0.212, all P<0.05). Conclusions:The level of psychological distress in primary AMI patients decreased with time. Nursing staff should pay attention to the trajectory and influencing factors of psychological pain, and formulate targeted intervention measures to reduce the level of psychological pain and promote the comprehensive rehabilitation of patients.

Analysis of epidemiology and clinical characteristics of patients with poisons purchase online / 中华急诊医学杂志

Objective:To explore the clinical characteristics of poisoned patients with poisons purchase online.Methods:A retrospective case-control study was conducted on poisoned patients purchased poisons online from 1st January 2021 to 31th May 2022 in the Emergency Department of the First Affiliated Hospital of Nanjing Medical University. The clinical data including sex, age, way of medical treatment, cause of poisoning, exposure routes, category of toxic drugs, gastric lavage, toxic detection and prognosis of patients were collected and compared with those patients obtained poisons at stores as the control group.Results:Totally 318 poisoned patients were included in this study, of which 44 (13.8%) were obtained poisons online. Compared with the patients obtained poisons at stores, the patients obtained poisons online were younger ( P<0.001), and had higher proportion of suicide intention ( P=0.006), more oral route exposure ( P=0.029), and more proportions of receiving gastric lavage before transfer to the hospital ( P=0.001). Pesticides and fertilizers with organic heterocycles were the main types of poisons in the online group, and there was no statistical difference in the distribution of poisons compared with the control group. Mixed drug poisoning was the leading cause in both online group (27.8%) and control group (38.8%) in drug overdose poisoned types, followed by dextromethorphan (16.7%) and estazolam (15.5%) in the online group. Conclusions:Young people are the main group getting poisons through the Internet. Health education should be strengthened for this group, and online shopping platforms should pay attention to the poisoning risk of potential overdose drugs or poisons transactions.

Textual research classic decoction Danggui Yinzi by ancient and modern literatures / 国际中医中药杂志

The Danggui Yinzi, as one of the classic prescriptions, was first recorded in Yan's Jisheng Prescription and is mainly used to treat various skin diseases with blood deficiency and wind dryness. By referring to ancient books and modern literature researches, this study analyzed and summarized the literature of Danggui Yinzi from the aspects of prescription origin, composition, addition and subtractive changes of flavor, dosage and decocting and taking method, discrimination of prescription and efficacy, raw material and processing of medicinal materials, and modern clinical application. Textual researches explored more than 80 ancient literature and 170 modern literature and showed its content included Angelicae Sinensis Radix, Paeoniae Radix Alba, Chuanxiong Rhizoma, Rehmannia Radix, Tribuli Fructus, Saposhnikoviae Radix, Schizonepetae Spica, Polygoni Multiflora Radix, Astragali Radix, Glycyrrhizae Radix et Rhizoma. It was cooked by water. It was used for the patients with skin diseases and Chinese pattern of blood deficiency wind drying. It has showed a wide range of applications, and similar application in ancient and modern time. This paper provides a more comprehensive reference for the research and development of compound preparation of Danggui Yinzi.

Pretreatment Effects of Cutting Balloon on Coronary Artery Calcification Based on Finite Element Analysis / 医用生物力学

Objective To investigates the applicability of cutting balloon in the pretreatment of superficial coronary artery calcified lesions, so as to decrease the occurrence of serious consequences in the treatment of calcified lesions. Methods The effect of cutting balloon on calcified plaques with different curvatures, thickness, and length was analyzed using the finite element method, with normal balloon as a control. The thickness of calcified plaque was set to 0.3 mm and 0.4 mm, and the length was set to 2 mm and 4 mm. The calcification degree was set to 120°, 180°, 270°and 360° according to the intravenous ultrasound (IVUS) calcification severity grading, with a total of 16 types of calcified plaques. The brittle fracture module was used to simulate calcification fracture of calcified plaques, and virtual stent implantation was carried out based on pretreatment simulation. The effect of pretreatment was evaluated by calcification fracture condition and stent roundness. Results For superficial calcification lesions, in lesions less than 120°, the balloon could not remove the calcification plaque obstruction, and the stent roundness rate was 82.75%. In 180° calcified lesions with thickness of less than 0.3 mm, the calcification was broken by cutting balloon under 1 215.9 kPa expansion pressure, and the post-stent roundness rate was 74.42%; normal balloon could not cause calcification fracture under safe expansion pressure (1 418.55 kPa). In 270°calcified lesions with thickness less than 0.3 mm, the normal balloon produced 3 fractures under 1 013.25 kPa expansion pressure. The cutting balloon produced 2 fractures under 1 013.25 kPa expansion pressure, and the balloon could not fracture the circular calcified lesions with thickness of 0.3 mm. Conclusions Cutting balloon is recommended for 180°calcified lesions with thickness less than 0.3 mm, the normal balloon is recommended for 270°calcified lesions, and balloon pretreatment is not recommended for annular lesions with thickness greater than 0.3 mm.

Research progress of taste masking and evaluation technology of medicine / 中国药科大学学报

@#Most drugs taste bitter and irritating, resulting in poor compliance of patients, and the bad odor affects the therapeutic effect. The successful research and development of a drug should not only conform to the five quality characteristics of effectiveness, stability, safety, uniformity and economy, but also the compliance of patients to drugs with bad odor. The development of taste masking techniques is critical for bitter drugs.This review describes the principles, advantages and drawbacks of traditional taste masking techniques, and introduces the mechanism and application of novel taste masking techniques, such as melt granulation, hot melt extrusion, 3D printing, drug complex preparation, and bitter taste inhibitors. The in vitro evaluation methods of drug taste masking effect, such as functional magnetic resonance imaging, in vitro dissolution, and electronic tongue technology, are described. And introduce in vivo evaluation methods, such as animal and human taste, in the field of taste masking effect. A new strategy of BP neural network prediction model for drug taste evaluation is proposed, with a view to providing theoretical reference for the future research on drug taste masking.

Expanded Applications of Traditional Chinese Medicine Four Examination Techniques in Asymptomatic Spleen-Stomach Diseases / 中医杂志

Asymptomatic spleen-stomach diseases refer to diseases without related symptoms and signs of abdo-minal pain， bloating， diarrhea an others in patients， but showing lesions or pathological changes discovered by modern medical techniques such as endoscopy， CT， MRI. The four examination techniques of traditional Chinese medicine （TCM） are based on symptoms and signs of patients， which are the advantage of TCM but also have certain limitations. In the context of the increasingly modernized diagnosis and treatment in TCM， it is proposed to expand the application of the four examination techniques from three aspects including microcosmic syndrome differentiation， data sharing， and artificial intelligence in asymptomatic spleen-stomach diseases， in order to achieve the goals of dynamically observing the disease process， collecting disease data in multiple dimensions， and intelligently processing disease data. This will strengthen the modern requirements of early diagnosis and treatment in TCM， and highlight the advantages of TCM in “treating disease before it arises and treating the symptoms beforehand”.

Association between Serum Amyloid A Levels and Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

Background@#To date, consistent data have not been reported on the association between serum amyloid A (SAA) levels and type 2 diabetes mellitus (T2DM). The purpose of this study was to systematically summarize their relationship. @*Methods@#Databases including PubMed, Cochrane Library, Embase, Web of Science, and MEDLINE were searched until August 2021. Cross-sectional and case-control studies were included. @*Results@#Twenty-one studies with 1,780 cases and 2,070 controls were identified. SAA levels were significantly higher in T2DM patients than in healthy groups (standardized mean difference [SMD], 0.68; 95% confidence interval [CI], 0.39 to 0.98). A subgroup analysis showed that the mean age of participants and the continent that participants were from were related to differences in SAA levels between cases and controls. Furthermore, in T2DM patients, SAA levels were positively associated with body mass index (r=0.34; 95% CI, 0.03 to 0.66), triglycerides (r=0.12; 95% CI, 0.01 to 0.24), fasting plasma glucose (r=0.26; 95% CI, 0.07 to 0.45), hemoglobin A1c (r=0.24; 95% CI, 0.16 to 0.33), homeostasis model assessment for insulin resistance (r=0.22; 95% CI, 0.10 to 0.34), C-reactive protein (r=0.77; 95% CI, 0.62 to 0.91), and interleukin-6 (r=0.42; 95% CI, 0.31 to 0.54), but negatively linked with highdensity lipoprotein cholesterol (r=–0.23; 95% CI, –0.44 to –0.03). @*Conclusion@#The meta-analysis suggests that high SAA levels may be associated with the presence of T2DM, as well as lipid metabolism homeostasis and the inflammatory response.

Phosphodiesterase 5 Inhibitors Attenuate Unilateral Ureteral Obstruction-Induced Renal Fibrosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether phosphodiesterase （PDE） 5 inhibitors sildenafil （SIL） or LW1646 prevented renal interstitial fibrosis induced by unilateral ureteral obstruction （UUO）. MethodsMale C57BL/6 mice were randomly divided into four groups （n =6）， namely the Sham group， 7UUO group， 7UUO+SIL group and 7UUO+LW1646 group. Sildenafil （SIL） or LW1646， or vehicle was administered 1 hour before surgery， and the mice were continuously treated once daily （i. g.， 50 mg/kg） for 7 days. The obstructed kidneys were harvested on day 7. Hematoxylin-eosin （HE） and Masson’s staining was used to examine renal histology. Immunoblotting and RT-qPCR were used to detect the expression levels of protein and mRNA for fibrosis， apoptosis， endoplasmic reticulum （ER） stress， autophagy， and pro-fibrotic factors. Human proximal tubule epithelial cells （HK-2） were treated with TGF-β1 for 48 hours or tunicamycin for 24 hours， respectively， to evaluate whether cyclic guanosine monophosphate （cGMP） or PDE5 inhibitors prevents ER stress and pro-fibrotic responses. ResultsAt the 7th days after UUO， the body weight of the mice showed a significant decrease （P< 0.000 1） compared with that in the sham group. The obstructed kidneys showed a significant tubular dilation and interstitial inflammation. The levels of protein and mRNA expression in apoptosis， ER stress， autophagy-related protein and pro-fibrotic factors were also markedly increased in UUO mice （P <0.05）. In contrast， SIL or LW1646 treatment was associated with attenuated tubular dilation， infiltration of inflammatory cells and collagen content in the obstructed kidney of the mice. The protein and mRNA expression levels of renal TGF-β1 were markedly decreased， and the protein expression levels of apoptosis， endoplasmic reticulum stress， and autophagy markers were also significantly downregulated by PDE5 inhibitors. In HK-2 cells， TGF-β1 induced increased expression levels of fibronectin and BiP， which was at least partially reversed by cGMP， a product of PDE inhibition. Additionally， PDE5 inhibitors were found to modulate aberrant levels of autophagy and apoptosis. ConclusionIn conclusion， PDE5 inhibitors， in particular， LW1646， can alleviate the progression of fibrosis by improving ER stress， apoptosis and autophagy as well as downregulating protein and mRNA expression of TGF-β1.

Analysis of the relationship between embryo quality at different developmental stages and secondary sex ratio of single live births / 中华妇产科杂志

Objective: To investigate the effect of embryo quality at different developmental stages on the secondary sex ratio (SSR) of single live birth neonates. Methods: Data for patients with singleton live births after embryo transferred between January 2016 and January 2022 were retrospectively analyzed. The effect of embryo quality at different development stages on the SSR of 11 713 singleton live births were investigated. The association of SSR and embryo quality at different development stages was examined in univariate analysis and in a multivariate logistic regression model, after adjustment for confounders, using two models (Ⅰ and Ⅱ). Results: The age of both male and female, body mass index of both male and female, basal follicle stimulating hormone and estradiol, smoking of male, methods of insemination, methods of sperm extraction, types of transfer cycle and the number of embryo transferred were not related with SSR (all P>0.05). After adjustment for confounders, the probability of a male live birth was higher after transfer of good-quality blastula than after transfer of poorer-quality blastula (model Ⅰ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001; model Ⅱ: aOR=0.73, 95%CI: 0.65-0.82, P<0.001). The quality of cleavage stage embryo was not associated with SSR (model Ⅰ: aOR=0.99, 95%CI: 0.87-1.13, P=0.937; model Ⅱ: aOR=0.99, 95%CI: 0.87-1.13, P=0.899). Conclusions: The SSR of singleton live births after embryo transfer is not correlated with the quality of cleavage stage embryo, but is correlated with the quality of blastula. Good-quality blastula transfer is more likely to result in a male live birth.