ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

ObjectiveTo observe the clinical efficacy of the stasis-dispelling and detoxifying therapy in endometriosis （EMs） patients with the syndrome of kidney deficiency and blood stasis and the effects of this therapy on the expression levels of proteins related to the c-Jun N-terminal kinase （JNK） signaling pathway. MethodsA total of 72 patients with EMs due to kidney deficiency and blood stasis who met the criteria at the Integrated Traditional Chinese and Western Medicine Center for Reproduction and Genetics of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from March 2024 to February 2025 were selected and randomized into a treatment group and a control group， with 36 patients in each group. Another 36 patients undergoing in vitro fertilization-embryo transfer （IVF-ET） due to male factors alone were selected as the blank group. The treatment group took the Zishen Quyu Jiedu formula orally， while the control group and the blank group took placebos. The treatment course encompassed the cycle before ovarian stimulation and the oocyte retrieval cycle. The TCM syndrome score of kidney deficiency and blood stasis， as well as the serum level of cancer antigen 125 （CA125）， were evaluated at the time of enrollment （before treatment） and on the trigger day （after treatment）. Serum levels of sex hormones were measured on day 2 of the menstrual cycle. On the trigger day， the duration and dosage of gonadotropin （Gn） administration and the serum levels of hormones on the day of human chorionic gonadotropin （HCG） injection were assessed. Embryo outcomes were evaluated 3 days after oocyte retrieval， and clinical pregnancy rates were assessed 28 days after embryo transfer. The baseline data of three groups were observed. The TCM syndrome scores and serum CA125 levels before and after treatment were compared between the treatment and control groups. The baseline endocrine levels， Gn days， Gn dosage， hormone levels on the day of HCG administration， number of oocytes retrieved， number of 2 pronucleus （2PN） fertilizations， number of available embryos， high-quality embryo rate， and clinical pregnancy rate were also assessed in all three groups. Six patients from each group were selected for determination of the protein levels of JNK， c-Jun， and nuclear receptor subfamily 4 group A member 2 （NR4A2） in ovarian granulosa cells （GCs） on the day of oocyte retrieval by Western blot. Results（1） There were no statistically significant differences in the baseline data among three groups， indicating comparability. （2） Compared with the baseline within the same group， the treatment group showed a decrease in the syndrome score of kidney deficiency and blood stasis after treatment. After treatment， serum CA125 levels decreased in both groups （P<0.05）， with a more substantial reduction in the treatment group， resulting in a difference between the two groups （P<0.05）. （3） There were no significant differences among three groups in terms of baseline serum levels of follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， and progesterone （P）， as well as the duration and dosage of Gn administration and the serum levels of LH， E₂， and P on the day of HCG administration. （4） For embryo outcomes， the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rates in the treatment group and the blank group were higher than those in the control group （P<0.05）， and the treatment group and the blank group had similar 2PN fertilizations. （5） There were differences in clinical pregnancy rate among three groups （P<0.05）， and the treatment group had higher pregnancy rate than the control and blank groups. （6） The protein levels of JNK， c-Jun， and NR4A2 in the GCs of the treatment group were lower than those in the control group （P<0.01） and close to those in the blank group （P<0.01）. （7） No obvious adverse reactions were observed in any of the subjects during the clinical observation process. ConclusionZishen Quyu Jiedu formula can ameliorate the clinical symptoms of patients with EMs due to kidney deficiency and blood stasis， reduce the serum CA125 level， increase the number of oocytes retrieved， 2PN fertilizations， available embryos， and high-quality embryo rate， and improve pregnancy outcomes. The mechanism may involve downregulating the levels of JNK， c-Jun， and NR4A2 to reduce the apoptosis of ovarian GCs and improve the ovarian function in the patients.

Lung transplantation is the ultimate therapeutic option for end-stage pulmonary diseases such as interstitial pneumonia, chronic obstructive pulmonary disease and pneumoconiosis. Currently, the shortage of allogeneic lung donors significantly limits the opportunity for end-stage lung disease patients to receive lung transplantation. In recent years, with the rapid development of biomedical engineering technologies, especially the major breakthroughs in genetic modification and cloning, xenogeneic lung transplantation has shown important potential for clinical translation. Among them, genetically modified pigs have become the most promising xenogeneic lung source due to the close similarity of organ size and physiological characteristics to humans, and the ability to perform targeted gene knockouts (such as α-Gal antigen knockout) to reduce the occurrence of hyperacute rejection. This article focuses on the research progress of porcine xenogeneic lung transplantation, systematically reviews the latest achievements and challenges in animal experiments and human trials, and introduces the technical experience accumulated by Shenzhen Third People's Hospital in the porcine-to-monkey xenogeneic lung transplantation model, in the hope of providing practical references for future research in this field.

Objective To explore the potential mechanism of Xinnao Maikang in improving ApoE-/-atherosclerosis mice based on PPARγ/LXRα/ABCA1 pathway.Methods Totally 50 ApoE-/-mice were randomly divided into model group,atorvastatin group,Xinnao Maikang high-,medium-and low-dosage groups,and fed with high-fat diet for 12 weeks to establish atherosclerosis model.Another 10 C57BL/6J mice were selected as normal group,and atorvastatin group was given atorvastatin calcium suspension by intragastric administration,Xinnao Maikang high-,medium-and low-dosage groups were given Xinnao Maikang Decoction 56,28,14 g/kg by intragastric administration,the normal group and model group were given equal volume of normal saline by intragastric administration for 8 weeks.Liver index of mice was detected,serum lipid level of mice was detected by automatic biochemical analyzer,TC and TG contents in liver tissue were detected by biochemical kit,morphology of aortic intima and liver tissue were observed by HE staining,lipid deposition in liver tissue was observed by oil red O staining,the expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue were detected by Western blot.Results Compared with the normal group,the liver index in the model group significantly increased(P<0.05),the contents of serum TC,TG and LDL-C significantly increased(P<0.05),and the contents of HDL-C significantly decreased(P<0.05),the contents of TC and TG in liver tissue increased(P<0.05),the aortic wall was thickened,the number of subcutaneous foam cells increased,the arrangement of liver cells were disaffected,and a large number of fat vacuoles could be seen,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue significantly decreased(P<0.01).Compared with the model group,the liver index of Xinnao Maikang high-,medium-and low-dosage groups and atorvastatin group significantly decreased(P<0.05),the serum contents of TC,TG and LDL-C significantly decreased(P<0.05),and the HDL-C contents significantly increased(P<0.05),the contents of TC and TG in liver tissue significantly decreased(P<0.05),the aortic wall thickened and the subcutaneous foam cells decreased,the liver cells were arranged neatly,and fat degeneration was reduced to varying degrees,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue of Xinnao Maikang high-dosage group and atorvastatin group significantly increased(P<0.05,P<0.01).Conclusion Xinnao Maikang can decrease blood lipid level,reduce atherosclerotic plaque and reduce lipid deposition in liver of atherosclerotic mice,and its mechanism may be related to regulating PPARγ/LXRα/ABCA1 pathway,regulating lipid metabolism,promoting reverse cholesterol transport.

Objective To explore the potential mechanism of Xinnao Maikang in improving ApoE-/-atherosclerosis mice based on PPARγ/LXRα/ABCA1 pathway.Methods Totally 50 ApoE-/-mice were randomly divided into model group,atorvastatin group,Xinnao Maikang high-,medium-and low-dosage groups,and fed with high-fat diet for 12 weeks to establish atherosclerosis model.Another 10 C57BL/6J mice were selected as normal group,and atorvastatin group was given atorvastatin calcium suspension by intragastric administration,Xinnao Maikang high-,medium-and low-dosage groups were given Xinnao Maikang Decoction 56,28,14 g/kg by intragastric administration,the normal group and model group were given equal volume of normal saline by intragastric administration for 8 weeks.Liver index of mice was detected,serum lipid level of mice was detected by automatic biochemical analyzer,TC and TG contents in liver tissue were detected by biochemical kit,morphology of aortic intima and liver tissue were observed by HE staining,lipid deposition in liver tissue was observed by oil red O staining,the expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue were detected by Western blot.Results Compared with the normal group,the liver index in the model group significantly increased(P<0.05),the contents of serum TC,TG and LDL-C significantly increased(P<0.05),and the contents of HDL-C significantly decreased(P<0.05),the contents of TC and TG in liver tissue increased(P<0.05),the aortic wall was thickened,the number of subcutaneous foam cells increased,the arrangement of liver cells were disaffected,and a large number of fat vacuoles could be seen,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue significantly decreased(P<0.01).Compared with the model group,the liver index of Xinnao Maikang high-,medium-and low-dosage groups and atorvastatin group significantly decreased(P<0.05),the serum contents of TC,TG and LDL-C significantly decreased(P<0.05),and the HDL-C contents significantly increased(P<0.05),the contents of TC and TG in liver tissue significantly decreased(P<0.05),the aortic wall thickened and the subcutaneous foam cells decreased,the liver cells were arranged neatly,and fat degeneration was reduced to varying degrees,the protein expressions of PPARγ,LXRα,ABCA1,ABCG1 and SR-BⅠ in liver tissue of Xinnao Maikang high-dosage group and atorvastatin group significantly increased(P<0.05,P<0.01).Conclusion Xinnao Maikang can decrease blood lipid level,reduce atherosclerotic plaque and reduce lipid deposition in liver of atherosclerotic mice,and its mechanism may be related to regulating PPARγ/LXRα/ABCA1 pathway,regulating lipid metabolism,promoting reverse cholesterol transport.

Oromandibular dystonia (OMD) is a type of Meige syndrome, which is characterized by involuntary repeated abnormal postured contraction of bilateral masticatory muscles, orbicularis oris muscles and mimetic muscles. Involved nerves are buccal branch of facial nerve, mandibular marginal branch and/or mandibular branch of trigeminal nerve. At present, the pathogenesis of OMD is still unclear, and no specific treatment for OMD is noted. This article reviews the pathogenesis, clinical manifestations, classifications, diagnoses, differential diagnoses and treatments of oromandibular dystonia in order to strengthen the understanding of the disease.

The current organ allocation rules prioritize elderly and urgent patients on the lung transplantation (LT) waiting list. A steady increase in the threshold at which age is taken into consideration for LT has been observed. This retrospective cohort study recruited 166 lung transplant recipients aged ≽ 65 years between January 2016 and October 2020 in the largest LT center in China. In the cohort, subgroups of patients aged 65-70 years (111 recipients, group 65-70) and ≽ 70 years (55 recipients, group ≽ 70) were included. Group D restrictive lung disease was the main indication of a lung transplant in recipients over 65 years. A significantly higher percentage of coronary artery stenosis was observed in the group ≽ 70 (30.9% vs. 14.4% in group 65-70, P = 0.014). ECMO bridging to LT was performed in 5.4% (group 65-70) and 7.3% (group ≽ 70) of patients. Kaplan-Meier estimates showed that recipients with cardiac abnormalities had a significantly increased risk of mortality. After adjusting for potential confounders, cardiac abnormality was shown to be independently associated with the increased risk of post-LT mortality (HR 6.37, P = 0.0060). Our result showed that LT can be performed in candidates with an advanced age and can provide life-extending benefits.
Aged ; Humans ; East Asian People ; Heart Diseases/etiology* ; Lung Transplantation/adverse effects* ; Retrospective Studies

Hydroxytyrosol is an important fine chemical and is widely used in food and medicine as a natural antioxidant. Production of hydroxytyrosol through synthetic biology is of important significance. Here we cloned and functionally characterized a hydroxylase encoding gene HpaBC from Escherichia coli BL21, and both subunits of this enzyme can be successfully expressed to convert the tyrosol into hydroxytyrosol. A HpaBC gene integration expression cassette under the tac promoter was constructed, and integrated into the genome of a tyrosol hyper-producing E. coli YMG5A*R using CRISPR-Cas9 technology. Meanwhile, the pathway for production of acetic acid was deleted, resulting in a recombinant strain YMGRD1H1. Shake flask fermentation showed that strain YMGRD1H1 can directly use glucose to produce hydroxytyrosol, reaching a titer of 1.81 g/L, and nearly no by-products were detected. A titer of 2.95 g/L was achieved in a fed-batch fermentation conducted in a 5 L fermenter, which is the highest titer for the de novo synthesis of hydroxytyrosol from glucose reported to date. Production of hydroxytyrosol by engineered E. coli lays a foundation for further construction of hydroxytyrosol cell factories with industrial application potential, adding another example for microbial manufacturing of aromatic compounds.
Escherichia coli/genetics* ; Fermentation ; Glucose ; Metabolic Engineering ; Phenylethyl Alcohol/analogs & derivatives*

As one of the four major types of organ transplantation, lung transplantation has been developed rapidly in recent years. With the establishment of Quality Management and Control Center for Lung Transplantation of National Health Commission, the formulation of Technical Management Specifications for Lung Transplantation and Standard Procedures and Technical Specifications for Lung Transplantation and the implementation of a series of measures, the quality and quantity of lung transplantation have been steadily increased in China. It will provide a guarantee for further promoting the development of lung transplantation in China by the establishment and improvement of scientific quality control parameters for clinical application of lung transplantation technology, the formulation of standard procedures and technical specifications for lung transplantation, strengthening the management of standardized training bases for lung transplantation, building up a multidisciplinary lung transplantation team and constructing a complete lung transplantation database.

Objective:To compare the performance and surgical outcomes of disposable digital flexible ureteroscope with a reusable fiberoptic flexible ureteroscope in treatment of upper urinary stones.Methods:A prospective, multicenter, single-blind and randomized controlled study was performed from April 2018 to December 2018. Eligible patients were randomized, in a ratio of 1∶1, to either experimental group or control group. The inclusion criteria for the study were: aged 18-60 years, solitary upper urinary stone or multiple stones with stone size less than 2 cm, absence of urinary tract infection (UTI) or UTI was controlled, normal liver and renal function. Exclusion criteria included: patients with congenital anomalies, calyceal diverticular stone, IP angle less than 30°, renal insufficiency. pregnancy or lactation, cardiopulmonary function abnormality and coagulation abnormalities. Patients in experimental group received ureteroscopy through a disposable digital flexible ureteroscope (PU3022A, PUSEN), while patients in control group received ureteroscopy through a reusable fiberoptic flexible ureteroscope (Flex-X2, STORZ). The primary endpoint was the high-quality rate of images during the operation. The secondary endpoints included success rate of fragmentation and postoperative complication rates.Results:93 patients were recruited, and 90 of them were finally complete the study (i.e., 45 patients in each group). The demographic and preoperative parameters were comparable between the two groups except the stone size in patients with solitary stone. The high-quality rate of images was significantly higher in experiment group than that in control group (100.0% vs. 15.6%, P<0.001). There were no significant differences in terms of success rate of fragmentation(68.9% vs. 71.1%, P=0.818), hemoglobin dropped (3.91 g/L vs. 3.62 g/L, P=0.880), serum creatinine changed, and postoperative complication rates(6.7% vs.6.7%, P=1.000). Conclusions:Disposable digital flexible ureteroscope achieves similar surgical outcomes to the reusable fiberoptic flexible ureteroscope with a better quality of endoscopic images.