To investigate the impact of preoperative serum follicle-stimulating hormone (FSH) levels on the probability of testicular sperm retrieval, we conducted a study of nonobstructive azoospermic (NOA) men with different testicular volumes (TVs) who underwent microdissection testicular sperm extraction (micro-TESE). A total of 177 NOA patients undergoing micro-TESE for the first time from April 2019 to November 2022 in Shenzhen Zhongshan Obstetrics and Gynecology Hospital (formerly Shenzhen Zhongshan Urology Hospital, Shenzhen, China) were retrospectively reviewed. The subjects were divided into four groups based on average TV quartiles. Serum hormone levels in each TV group were compared between positive and negative sperm retrieval subgroups. Overall sperm retrieval rate was 57.6%. FSH levels (median [interquartile range]) were higher in the positive sperm retrieval subgroup compared with the negative outcome subgroup when average TV was <5 ml (first quartile [Q1: TV <3 ml]: 43.32 [17.92] IU l -1 vs 32.95 [18.56] IU l -1 , P = 0.048; second quartile [Q2: 3 ml ≤ TV <5 ml]: 31.31 [15.37] IU l -1 vs 25.59 [18.40] IU l -1 , P = 0.042). Elevated serum FSH levels were associated with successful micro-TESE sperm retrieval in NOA men whose average TVs were <5 ml (adjusted odds ratio [OR]: 1.06 per unit increase; 95% confidence interval [CI]: 1.01-1.11; P = 0.011). In men with TVs ≥5 ml, larger TVs were associated with lower odds of sperm retrieval (adjusted OR: 0.84 per 1 ml increase; 95% CI: 0.71-0.98; P = 0.029). In conclusion, elevated serum FSH levels were associated with positive sperm retrieval in micro-TESE in NOA men with TVs <5 ml. In men with TV ≥5 ml, increases in average TVs were associated with lower odds of sperm retrieval.
Humans ; Male ; Azoospermia/surgery* ; Sperm Retrieval/statistics & numerical data* ; Adult ; Follicle Stimulating Hormone/blood* ; Retrospective Studies ; Testis/pathology* ; Microdissection ; Organ Size

Objective To explore the effect of phillyrin(KD-1)on lung injury in rats with influenza virus pneumonia and its regulatory mechanism on the sphingosine kinases 1(SphK1)/sphingosine 1-phosphate(S1P)/S1P receptors 1(S1PR1)signal pathway.Methods Wistar male rats were divided into control group(gavage with equal amount of 0.9％NaCl),model group(gavage with equal amount of 0.9％NaCl),positive drug group(gavage with 0.02 g·kg-1 ribaverin),PF-543 group(gavage with 10 mg·kg-1 SphK1 inhibitor PF-543 Citrate)and experimental-L,-H groups(gavage with 6.5,13 mg·kg-1 KD-1,respectively).Except the control group,the other rats were treated with influenza virus nasal drip to establish influenza virus infection pneumonia model.The lung index of rats was measured;Hematoxylin-eosin(HE)staining was applied to observe the pathological damage of lung tissue in rats;the contents of interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α)and IL-6 in bronchoalveolar lavage fluid(BALF)were detected by enzyme linked immunosorbent assay(ELISA);Western blot was applied to detect the expression levels of SphK1,S1P and S1PR1 proteins in rat lung tissue.Results The lung indices of experimental-L,-H groups,PF-543 group,positive drug group,model group and control group were(7.62±0.51),(5.34±0.46),(6.53±0.52),(5.48±0.43),(12.46±0.87)and(4.41±0.32)mg·g-1;IL-1β content were(47.26±2.05),(25.18±1.58),(35.75±1.50),(27.31±1.67),(62.37±2.51)and(13.28±1.04)ng·L-1;the contents of TNF-α were(76.58±4.73),(51.82±3.90),(64.81±4.15),(53.06±3.86),(98.47±4.92)and(42.71±3.52)ng·L-1;IL-6 content were(57.62±4.29),(39.06±3.86),(48.75±3.83),(41.23±3.61),(76.92±5.24)and(28.56±3.17)ng·L-1;SphK1 protein expression were 1.07±0.08,0.51±0.04,0.65±0.05,0.53±0.04,1.28±0.09 and 0.36±0.03;S1P protein expression were 1.21±0.10,0.57±0.05,0.73±0.06,0.58±0.05,1.39±0.11 and 0.39±0.03;S1PR1 protein expression were 0.45±0.03,0.83±0.07,0.64±0.05,0.81±0.07,0.28±0.02 and 1.03±0.07,respectively.Compared with the control group,the above indexes in the model group had statistical significance(all P＜0.05);compared with the model group,the above indexes in experimental-L,-H groups,PF-543 group and positive drug group had statistical significance(all P＜0.05).Conclusion KD-1 may alleviate lung injury in rats with influenza virus pneumonia by inhibiting the SphK1/S1 P/S1 PR1 signal pathway.

Objective To investigate the effect and mechanism of andrographolide(AG)on lipopolysaccharide(LPS)-induced ferroptosis in renal tubular epithelial cells(HK-2 cells).Methods HK-2 cells were treated with LPS to simulate the in vitro HK-2 injury model of sepsis.The cells were further treated with AG of 5,10,20,40 μmol/L and randomly divided into control group,LPS group,LPS+dimethyl sulfoxide group(DMSO group),and AG group.Cell viability was detected by the CCK-8 method,and the optimal concentrations of LPS and AG were screened.Cell morphological change,the levels of kidney injury markers,including neutrophil gelatinase-associated lipocalin(NGAL),kidney injury molecule-1(KIM-1),malondialdehyde(MDA),glutathione(GSH)and reactive oxygen species(ROS),as well as the expression levels of ferroptosis regulatory proteins such as solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and ferritin in each group were compared,and the pro-tective effect of AG treatment on the cells was evaluated.Results Compared with the control group,the cell viabi-lity and GSH content decreased significantly in HK-2 cells treated with 10 μg/mL LPS;cell shrinkage and adhesion ability were poor;the contents of oxidative products MDA and ROS,as well as the levels of kidney injury markers NGAL and KIM-1 increased significantly,while expression levels of SLC7A11 and GPX4 protein decreased;ferritin expression level increased;differences were all statistically significant(all P＜0.05).Compared with LPS group,the cell viability,GSH content,as well as protein expression levels of SLC7A11 and GPX4 increased significantly after AG intervention,while ferritin expression level decreased,differences were all significant(all P＜0.05).MDA content,ROS fluorescence intensity,and the levels of kidney injury markers NGAL and KIM-1 decreased sig-nificantly,difference were all significant(all P＜0.05).Conclusion AG has a protective effect on LPS-induced HK-2 cell injury,possibly by activating SLC7A11/GPX4 pathway,reducing oxidative stress,up-regulating antioxi-dant enzyme activity,and alleviating ferroptosis.

BACKGROUND:Numerous clinical and basic studies have shown that electroacupuncture can improve the function of neurogenic bladder after suprasacral spinal cord injury. OBJECTIVE:To observe the effects of electroacupuncture on bladder function and connective tissue growth factor expression in rats with suprasacral spinal cord injury. METHODS:Forty-eight female Sprague-Dawley rats were randomly divided into four groups(n=12 per group):the blank group did not receive any treatment;the sham-operated group only exposed the T8 subvertebral spinal cord;in the model group established,a T8 subvertebral spinal cord transection injury model was established;in the electroacupuncture group,the T8 subvertebral spinal cord transection injury model was established,and electroacupuncture intervention at Ciliao(BL32),Zhongji(RN03)and Sanyinjiao(SP06)was given at 19 days after modeling,20 minutes once a day,for 10 continuous days.After the intervention,the relevant indicators were detected. RESULTS AND CONCLUSION:Urodynamics:Compared with the blank group,the leakage point pressure,maximum bladder capacity and maximum bladder pressure of rats in the model group increased(P<0.05).Compared with the model group,the leakage point pressure,maximum bladder capacity and maximum bladder pressure of rats in the electroacupuncture group decreased(P<0.05).Hematoxylin-eosin staining:Compared with the blank group,the bladder epithelial cells in the model group were arranged in a disordered manner,the lamina propria was destroyed,the detrusor muscle bundles were hypertrophied,the muscle fibers were arranged in a disordered manner,and the tissue edema was obvious.Compared with the model group,the bladder epithelial cells in the electroacupuncture group were arranged in a regular and orderly manner,and the degree of bladder fibrosis and tissue edema was relatively reduced.Masson staining:The degree of bladder detrusor muscle fibrosis was severe in the model group and it was lighter in the electroacupuncture group than in the model group.Transmission electron microscopy:Mitochondria in the bladder tissue in the model group were swollen and vacuolated,the morphology of the detrusor muscle was twisted and distorted,and the muscle gap was widened.Compared with the model group,mitochondria in the electroacupuncture group had a slightly clearer contour and were less vacuolated,and the muscle gap was narrowed.Western blot detection:The protein expression of connective tissue growth factor in the detrusor muscle of the bladder was elevated in the model group compared with the blank group(P<0.05).Compared with the model group,the protein expression of connective tissue growth factor in the bladder detrusor muscle was decreased in the electroacupuncture group(P<0.05).To conclude,electroacupuncture at Ciliao(BL32),Zhongji(RN03)and Sanyinjiao(SP06)acupoints can improve the morphology,structure and function of the bladder in rats with suprasacral spinal cord injury,and the mechanism of action may be related to the down-regulation of connective tissue growth factor protein expression in the detrusor muscle.

Amorphous solid dispersion (ASD) is one of the most effective formulation approaches to enhance the water solubility and oral bioavailability of poorly water-soluble drugs. However, maintenance of physical stability of amorphous drug is one of the main challenges in the development of ASD. Crystallization is a process of nucleation and crystal growth. The nucleation is the key factor that influences the physical stability of the ASD. However, a theoretical framework to describe the way to inhibit the nucleation of amorphous drug is not yet available. We reviewed the methods and theories of nucleation for amorphous drug. Meanwhile, we also summarized the research progress on the mechanism of additives influence on nucleation and environmental factors on nucleation. This review aims to enhance the better understanding mechanism of nucleation of amorphous drug and controlling over the crystal nucleation during the ASD formulation development.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]

Aim To investigate the protective effects of dendrobium polysaccharide(DOP)against paraceta-mol(APAP)-induced liver injury in mice and eluci-date its underlying mechanism.Methods Healthy male Kunming mice were randomly assigned to the fol-lowing groups:control group,APAP model group,low,medium,high-dose DOP intervention group(225,450,900 mg·kg-1),and DOP control group.The APAP model group was given 300 mg·kg-1 per day,the DOP intervention group was given DOP for 2 h and then APAP was given,and the remaining groups received an equal volume of normal saline daily for sev-en consecutive days.After the final administration,se-rum and liver samples from the mice were collected and tested after 20 hours.Liver morphology and liver coef-ficient were examined.Liver histopathological altera-tions and apoptosis were examined using HE staining and TUNEL staining.Additionally,medium biochemi-cal indexes were assessed in serum and liver tissue u-sing kits.The levels of oxidative stress,inflammation,and apoptosis-related proteins in liver tissue were de-termined using Western blotting.Results In the APAP model group,liver coefficient increased signifi-cantly,the number of liver vacuolar necrosis and apop-tosis cells increased,and the serum ALT and AST lev-els significantly increased.Compared with the APAP group,the liver coefficient,serum ALT and AST levels were significantly reduced,and the liver pathology was improved after DOP intervention,especially in the 900 mg·kg-1 group.The levels of oxidative stress and in-flammation in the APAP group increased,and the ex-pression of apoptosis,inflammation and oxidative stress related proteins in liver was unbalanced.DOP inter-vention,especially in the 900 mg·kg-1 group,could significantly reverse the oxidative stress,apoptosis and inflammatory response induced by APAP in liver,and increase the expression levels of Nrf2 and HO-1,but reduce the expression levels of NLRP3 and HMGB1.Conclusions The hepatoprotective mechanism of DOP is mainly due to its antioxidant and anti-inflammatory response,which may be related to the activation of Nrf2/HO-1 pathway and the inhibition of HMGB1/NL-RP3 pathway by DOP.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Objective: To observe the clinical effect of Qiliqiangxin capsule combined with recombinant human brain natriuretic peptide in acute left heart failure patients 7 days after onset as well as the effects of plasma MDA and ET-1. Methods: In total, 240 hospitalized patients with acute left heart failure from October 2017 to May 2021 were selected from the Department of Emergency and Critical Care Center of Beijing Anzhen Hospital, Capital Medical University and the Department of Cardiology of the Jilin Provincial People's Hospital. They were randomly divided into routine treatment group and combined treatment group, with 120 cases in each group. The routine treatment group was treated with vasodilation, diuresis, cardiotonic and recombinant human brain natriuretic peptide. The combined treatment group was treated with Qiliqiangxin capsules based on the routine treatment group. One week later, the changes in clinical efficacy, ejection fraction, left ventricular commoid diameter, and plasma BNP, MDA, and ET-1 were compared between the two groups before and after treatment. SPSS 11.5 statistical software was used. The measurement data was expressed in x¯±s, the independent sample t-test was used for comparison between groups, and the paired t-test was used for comparison before and after treatment within groups. Counting data was expressed as case (%), and the rank sum test was used for inter-group comparison. Result: In terms of clinical efficacy, the total effective rate of the combined treatment group was significantly higher than that of the conventional treatment group, and the difference was statistically significant (P<0.05). Compared with the routine treatment group, the left ventricular ejection fraction in the combined treatment group was significantly increased (P<0.05). The levels of plasma BNP, MDA and ET-1 were significantly decreased (P<0.05). Conclusion: Qiliqiangxin capsule combined with rhBNP treatment can effectively improve the clinical symptoms of acute heart failure, as well as reduce the lipid peroxidation product MDA content and endothetin ET-1 level in blood. The clinical application value of the Qiliqiangxin capsule needs to be further confirmed by further trials.
Humans ; Heart Failure/physiopathology* ; Natriuretic Peptide, Brain/therapeutic use* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Cardiotonic Agents/therapeutic use* ; Drugs, Chinese Herbal/therapeutic use* ; Recombinant Proteins/therapeutic use* ; Cardiovascular Agents/therapeutic use* ; Drug Therapy, Combination

Objective: Cancer immunotherapy can lead to various side effects, termed immune-related adverse events (irAE). This study summarized and analyzed the clinical and pathological characteristics of immune-mediated liver injury caused by immune checkpoint inhibitors (ILICI). Methods: This is a retrospective case series study involving 11 patients diagnosed with ILICI at the Peking Union Medical College Hospital from November 2019 to November 2021. Patient demographic information and clinical data, including gender, age, ILICI onset, clinical and radiological manifestations, pathological features, treatment, and resumption of ICI were retrospectively collected and analyzed. Results: The patients were primarily males (9/11) with a median age of 65 (range: 32-73) years. ICI mainly resulted in either partial remission (4/11) or stable disease (3/11). ILICI occurred after a median of two cycles of anti-programmed cell death-1 (PD-1) therapy, with a median time from the initial and last anti-PD-1 therapy to ILICI onset of 57 days and 17 days, respectively. ILICI was mostly severe (3/11) or very severe (6/11). While the clinical and radiological manifestations were non-specific, the pathological features were active lobular hepatitis and portal inflammation, with prominent CD8⁺T lymphocyte infiltration. The basic treatment was hepatoprotective drugs (10/11). Glucocorticoids were used as the primary therapy (9/11) but were ineffective in 4 of 9 cases. Of these, 3 of 9 cases received combined treatment with mycophenolate mofetil (MMF), only one of whom achieved remission. By the end of the study, 2 of 11 cases had resumed ICI and neither had experienced an ILICI relapse. Conclusion: The ILICI patients in this study had a corresponding history of ICI treatment and pathological features. The main treatment included hepatoprotective drugs and glucocorticoids. Immunosuppressive drugs were added for some cases but had poor efficacy.
Male ; Humans ; Adult ; Middle Aged ; Aged ; Immune Checkpoint Inhibitors/adverse effects* ; Retrospective Studies ; Antineoplastic Agents, Immunological/adverse effects* ; Liver ; Glucocorticoids/therapeutic use*