Clinical analysis of 226 cases of deviated nose with deviated nasal septum treated by endoscopic assisted functional rhinoplasty / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the method and effect of endoscopic assisted functional rhinoplasty for patients with deviated nose and deviated nasal septum, which achieve correction of nasal morphology and ventilation dysfunction. Methods: The clinical data of 226 patients with deviated nose and deviated nasal septum from June 2009 to February 2022 who were treated by endoscopic assisted functional rhinoplasty in the Affiliated Hospital of Qingdao University were analyzed retrospectively. There were 174 males and 52 females, with the age ranging from 7 to 67 years old. The effect was evaluated by subjective and objective evaluation methods. SPSS 27.0 software was used for statistical analysis. Results: All patients were followed up for 6 to 24 months, 174 cases were cured (174/226, 76.99%), 52 cases were effective (52/226, 23.01%), and the total effective rate was 100% (226/226). The difference between preoperative and postoperative facial appearance deviation was statistically significant ((6.84±2.25)mm vs (1.82±1.05)mm, t=38.94, P<0.001), and the nasal ventilation function of all patients was improved. Conclusions: Endoscopic assisted functional rhinoplasty for the patients with deviated nose combined with deviated nasal septum has the advantages of clear surgical field, fewer complications, and good result. It can achieve the purpose of simultaneous correction of nasal and ventilation dysfunction, which is recommended for popularizing in clinical application.

Inheritance, innovation and development of traditional Chinese medicine in new era call for scientific supervision / 中国中药杂志

Pharmaceutical products need to ensure the effectiveness, safety and quality controllability through scientific supervision, and as the broad masses of the people are full of new expectations for the supply of high-quality traditional Chinese medicine products, the reform and innovation of traditional Chinese medicine regulatory policies are also facing new opportunities and new challenges. National Medical Products Administration, National Administration of Traditional Chinese Medicine and other relevant departments have implemented the requirements of the Party Central Committee and the State Council, vigorously promoted the reform of the regulatory system in line with the characteristics of traditional Chinese medicine, introduced a series of innovative policies, and achieved phased results. Including the new registration classification standards in line with the characteristics of traditional Chinese medicine, encouraging the development of classical formulas and hospital preparations, encouraging the research and development of symptomatic Chinese medicines, and gra-dually improving the "three-combined " evidence system. However, in the face of the development problems of traditional Chinese medicine in the new era, it is still necessary to improve the scientific supervision system, further optimize the management measures for the registration of traditional Chinese medicines based on classical formulas, accelerate the improvement of the standard system for traditional Chinese medicine formula granules, and form management measures to encourage and support the secondary development of traditional Chinese medicines. In terms of scientific supervision of traditional Chinese medicine, it is necessary to follow the characteristics and development laws of traditional Chinese medicine itself, comprehensively consider the characteristics of epochal, scientific and systematic in regulatory policies, and serve the inheritance and innovative development of traditional Chinese medicine with scientific supervision.

Current status and thought of transcatheter mitral edge-to-edge repair in the treatment of hypertrophy cardiomyopathy / 中华外科杂志

Septal reduction therapies, which include septal myectomy and alcohol septal ablation and so on, are the current treatment strategies for patients with obstructive hypertrophic cardiomyopathy and drug-refractory symptoms. With the deepening of theoretical understanding and the rapid development of interventional therapies, some researchers have tried to perform transcatheter mitral valve edge-to-edge repair to treat high-risk patients with hypertrophic cardiomyopathy, including obstructive and non-obstructive. The reported results are relatively satisfactory, but many urgent problems need to be solved, such as the lack of data on animal experiments and large cohort studies, and the unknown medium- and long-term outcomes. However, transcatheter mitral valve edge-to-edge repair brings new ideas for the diagnosis and treatment of patients with hypertrophic cardiomyopathy. On one hand, it can be used as a monotherapy, on the other hand, it can be combined with novel molecular targeted drug therapy or emerging minimally invasive surgical procedures targeting hypertrophic ventricular septum, which deserves our further attention and exploratory research.

Chinese Guideline on the Management of Polypoidal Choroidal Vasculopathy (2022) / 中国医学科学杂志(英文版)

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

Tumoral calcinosis on thigh in a hemodialysis patient and literature review / 中华肾脏病杂志

The paper reported a patient under maintained hemodialysis for 11 years, with a large mass appeared in the right thigh after local injury. The mass was clinically considered as tumoral calcinosis combined with clinical, imaging and pathological findings. Several treatments such as enhancing dialysis adequacy, low calcium dialysate, calcimimetic agent, non-calcium- phosphorus binding agents, parathyroidectomy and intravenous infusion of sodium thiosulfate could not vanish the mass. Finally, the lump was surgically removed. The treatment of tumoral calcinosis in the hemodialysis patient can provide a instruction for similar situations in clinical practice.

The effect of percutaneous kyphoplasty on the vertebral height and Cobb angle in elderly patients with osteoporotic thoracolumbar compression fractures / 中国医师杂志

Objective:To investigate the effect of percutaneous kyphoplasty on the vertebral height and Cobb angle in elderly patients with osteoporotic thoracolumbar compression fractures.Methods:Seventy elderly patients with osteoporotic thoracolumbar compression fractures who were admitted to the Affiliated Hospital of Hubei University of Traditional Chinese Medicine from March 2019 to March 2020 were selected as the study objects. They were grouped according to the random number table method, with 35 patients in each group. The patients in the observation group were treated with multi-point balloon expansion percutaneous kyphoplasty, and the patients in the control group were treated with single balloon expansion percutaneous kyphoplasty. The Visual Analogue Scale (VAS) and Oswestry Dysfunction Index (ODI) score were compared between the two groups before and after treatment. The relative height of injured vertebrae, Cobb angle, bone cement diffusion volume ratio, operation time, radiation exposure time and bone cement injection volume were recorded.Results:There was no significant difference in VAS and ODI score between the two groups before operation (all P>0.05). At 12 months after operation, the VAS and ODI score of the two groups were lower than those before operation (all P<0.05), and the ODI score of the observation group was significantly lower than that of the control group ( P<0.05). At 12 months after operation, the relative height of injured vertebrae in the observation group was higher than that in the control group, and the local Cobb angle was significantly lower than that in the control group (all P<0.05). The total effective rate of the observation group was significantly higher than that of the control group (94.28% vs 82.86%, P<0.05). Compared with the control group, the observation group had higher proportion of grade Ⅱ in the diffusion volume ratio of bone cement and more bone cement injection, and longer operation time (all P<0.05), while there was no significant difference in the radiation exposure time between the two groups ( P>0.05). Conclusions:The treatment of percutaneous kyphoplasty with multi-point expansion of balloon under overextended posture can more effectively improve the relative height of injured vertebrae and improve local Cobb angle of elderly patients with osteoporotic thoracolumbar compression fractures, and does not increase the risk of bone cement leakage. It is worthy of clinical application and promotion.

Effect and Mechanism of Yishen Tongluo Prescription on miR-514a-5p/TNFSF15 Signaling Pathway in MN Rats / 中国实验方剂学杂志

ObjectiveTo explore the molecular mechanism of Yishen Tongluo prescription in inhibiting the apoptosis of glomerular podocytes in rats with membranous nephropathy （MN） based on the miR-514a-5p/tumor necrosis factor superfamily member 15 （TNFSF15） signaling pathway. MethodEighty SD rats were pre-immunized and injected with cationized bovine serum albumin （C-BSA） into the tail vein for inducing MN， and the successfully modeled MN rats were randomly divided into the model group， high-， middle-， and low-dose （26.44， 13.22， 6.61 g·kg-1） Yishen Tongluo prescription groups， and benazepril （10 mg·kg-1） group， with 10 rats in each group， and another 20 healthy rats were classified into the normal group. Rats in each group were gavaged with the corresponding drugs， once a day， for four successive weeks. After the administration， the 24-hour urine total protein （UTP） level， serum total cholesterol （TC）， triglyceride （TG）， albumin （ALB）， creatinine （SCr）， and urea nitrogen （BUN） levels were measured. The miR-514a-5p and TNFSF15 mRNA expression levels in the rat kidney tissue were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and the expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， Synaptopodin， TNFSF15， and podocyte apoptosis-related proteins B lymphocytoma-2 （Bcl-2）-related X protein （Bax）， Bcl-2-associated death promoter （BAD） protein， and B-cell lymphoma-extra large （Bcl-XL） by immunohistochemistry （IHC）. Western blot was used to detect the expression levels of TNFSF15， Bax， BAD， Bcl-2， and BCL-XL in the rat kidney tissue. The apoptosis rate of rat kidney tissue was measured using the in situ end labeling method （Tunnel）. ResultCompared with the normal group， the level of miR-514a-5p in the kidney tissue was significantly reduced （P<0.05）， and the TNFSF15 mRNA expression was significantly increased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， Podocalyxin， and Synaptopodin were down-regulated （P<0.05）. The protein expression levels of TNFSF15， Bax， and BAD were increased （P<0.05）， whereas the Bcl-2 and Bcl-XL protein expression levels were decreased （P<0.05）. The number of apoptotic cells diminished significantly （P<0.05）. Compared with the model group， the level of miR-514a-5p in the kidney tissue was significantly increased （P<0.05）， while the level of TNFSF15 mRNA was significantly decreased （P<0.05）. The expression levels of podocyte marker proteins Nephrin， Podocin， podocalyxin， and Synaptopodin were up-regulated （P<0.05）， whereas the TNFSF15， Bax， and BAD protein expression levels were down-regulated （P<0.05）. Bcl-2 and Bcl-XL protein expression levels rose （P<0.05）. The number of apoptotic cells significantly decreased （P<0.05）. ConclusionYishen Tongluo prescription reduces the apoptosis of rat kidney podocytes and alleviates the kidney injury of MN rats through the miR-514a-5p/TNFSF15 signaling pathway.

Jiangzhi Tongluo Soft Capsules Regulate SIRT1/FoxO3 Pathway to Affect Cell Apoptosis in Rats with Membranous Nephropathy / 中国实验方剂学杂志

ObjectiveTo observe the effect of Jiangzhi Tongluo soft capsule on the protein levels of silent mating-type information regulation 2 homolog 1 （SIRT1） and forkhead transcription factor FoxO3 and podocyte apoptosis in the renal tissue of rats with membranous nephropathy and to reveal the underlying molecular mechanisms for the treatment of MN. MethodSixty male SD rats were randomly assigned into 6 groups with 10 rats each. The six groups included a normal group， a model group， benazepril hydrochloride group， and Jiangzhi Tongluo soft capsule groups of low， medium and high doses （25， 50， 100 mg·kg-1， respectively）. The model rats were established by injection with cationized bovine serum albumin into the tail vein. After modeling， the rats were administrated with corresponding agents by gavage for 4 weeks. At the end of the 4th week， an electron microscope was used to observe the pathological changes in the kidney. Western blot was employed to detect the protein levels of SIRT1 and FoxO3 protein in rat kidney， and immunohistochemistry to detect the expression of B lymphocytoma-2 （Bcl-2）， Bcl-2-associated X protein （Bax）， Bcl-2-associated death promoter （Bad）， and podocyte split diaphragm proteins nephrin and podocin. ResultCompared with normal group， the expression of pro-apoptotic factors Bax， Bad， and FoxO3 in the kidney was up-regulated （P<0.05）， while that of anti-apoptotic factors Bcl-2， SIRT1， nephrin， and podocin was down-regulated （P<0.05） after modeling. Compared with the model group， the treatments down-regulated the expression of Bax， Bad， and FoxO3 （P<0.05） and up-regulated that of Bcl-2， SIRT1， nephrin， and podocin （P<0.05）. ConclusionJiangzhi Tongluo soft capsule may regulate the SIRT1/FoxO3 pathway to reduce podocyte apoptosis and maintain podocyte structure stability， thereby exerting the renal protection effect.

Network Meta-analysis of efficacy and safety of oral Chinese patent medicines combined with conventional western medicine in treatment of hypertension / 中国中药杂志

This study aims to systematically evaluate the effect of oral Chinese patent medicines on hypertension with network Meta-analysis. Randomized controlled trials on the treatment of hypertension with oral Chinese patent medicine combined with conventional western medicine were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library(from establishment of the database to August 2021). Two researchers independently screened the articles, extracted the data, and evaluated article quality. Then R 4.1.0 was employed for data analysis. Finally, 195 eligible articles were screened out, involving 22 546 patients and 18 oral Chinese patent medicines. The results of the network Meta-analysis are as follows. In terms of reducing systolic blood pressure(SBP) and diastolic blood pressure(DBP), Xuesaitong, Qiangli Dingxuan Tablets, Songling Xuemaikang Capsules combined with conventional western medicine are superior. In improving blood lipids, the overall effects of Xinmaitong Capsules, Compound Xueshuantong Capsules, Ginkgo Folium preparations, Yindan Xinnaotong Soft Capsules, and Naoxintong Capsules combined with conventional western medicine are outstanding. In terms of regulating endothelial function, Yindan Xinnaotong Soft Capsules, Xinmaitong Capsules, Zhenju Jiangya Tablets, Compound Danshen Dripping Pills, Xuesaitong with conventional western medicine have certain advantages. As for the safety, the incidence of adverse reactions of conventional western medicine combined with oral Chinese patent medicines is lower than that of conventional western medicine alone. In summary, compared with conventional western medicine alone, the 18 oral Chinese patent medicines combined with conventional western medicine in the treatment of hypertension show advantages in improving blood pressure, blood lipids, and endothelial function. Among them, Xuesaitong, Qiangli Dingxuan Tablets, and Songling Xuemaikang Capsules may be the best oral Chinese patent medicines for lowering blood pressure. The conclusion needs to be further verified by more high-quality studies.

The prosperity and challenge of ocular fundus imaging / 中华眼底病杂志

Ocular fundus imaging technology has developed rapidly in the past decade. The exsiting imaging technology is constantly updated and new imaging technology emerges one after another. The related research and development investment, equipment usage and paper publication are all growing rapidly. At the same time, it is developing towards the direction of multi-technology combination, integration of artificial intelligence and big data, as well as small-size and automation use of equipment. However, there are many challenges behind the prosperity of ocular fundus imaging, such as professionally remodeling of fundus diseases knowledge system standardization, balance and independence of scholarly communication, misunderstanding of "multimodal images", validation of the effectiveness and applicability of emerging technologies, clinical imaging research innovation, original technology innovation and technology reserve, fundus imaging data integration and analysis system for the future.

Effect of moxibustion on renal function and hypercoagulable state in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis / 中国针灸

OBJECTIVE@#To compare the effect of moxibustion combined with basic treatment and simple basic treatment on the clinical symptoms, renal function and hypercoagulable state in patients with idiopathic membranous nephropathy (IMN) of low to medium risk with spleen-kidney deficiency and blood stasis.@*METHODS@#A total of 60 patients with IMN of low to medium risk with spleen-kidney deficiency and blood stasis were randomized into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 1 case dropped off). In the control group, the conventional basic treatment of anti-hypertension, regulating blood lipid and anti-coagulation was adopted. On the basis of the control group, moxibustion was applied at Shenshu (BL 23), Pishu (BL 20), Guanyuan (CV 4), Zusanli (ST 36) and Sanyinjiao (SP 6) in the observation group, once a day, 5 days a week continuously with 2 day interval. The treatment of 6 months was required in the both groups. Before treatment and 3 and 6 months into treatment, the total TCM syndrome score, the renal function indexes (24-hour urinary protein quantity [UTP], albumin [ALB], urea nitrogen [BUN] and creatinine [Scr]), the blood coagulation indexes (fibrinogen [FIB], D-Dimer [D-D], p-selection and von Willebrand factor [vWF]), total cholesterol (TC) and triacylglycerol (TG) levels were observed, and the therapeutic efficacy was evaluated on 3 and 6 months into treatment in the two groups.@*RESULTS@#The effective rates of 3 and 6 months into treatment were 78.6% (22/28) and 89.3% (25/28) in the observation group, which were higher than 62.1% (18/29) and 75.9% (22/29) in the control group respectively (@*CONCLUSION@#Moxibustion combined with basic treatment can effectively improve the clinical symptoms, renal function and renal microcirculation in patients with idiopathic membranous nephropathy of low to medium risk with spleen-kidney deficiency and blood stasis, the therapeutic effect is superior to the simple basic treatment.

Prognostic factors of salvage radiotherapy after radical prostatectomy / 中华泌尿外科杂志

Objective:To investigate the prognosis after salvage radiotherapy with or without hormone therapy for prostate cancer.Methods:From May 2014 to December 2020, 248 patients undergoing salvage radiotherapy due to prostate-specific antigen (PSA)persistence or biochemical progression after radical prostatectomy at Sun Yat-sen University Cancer Center (n=157) and West China Hospital, Sichuan University (n=91) were analyzed. Median age was 66 (45-78) years old. Median PSA was 23.50 (0.18-845.00) ng/ml. The number of PSA persistence and biochemical progression were 143 (59%) and 105 (42%). The number of pT 2, pT 3a, pT 3b, pT 4, and unknown T stage was 99, 49, 78, 15 and 7 cases.The number of N 0, N 1 and unknown N stage was 153, 44 and 51 cases. 165 cases had positive surgical margin. Gleason score of 6, 7, 8, >8 score and unknown was in 12, 104, 34, 90 and 8 patients. Early and late salvage radiotherapy was performed in 117 and 131 patients, and 70 patients (28%) were CRPC. Hormone therapy was used combined with radiotherapy in 182 patients (73%). PSA decline after radiotherapy was compared with Chi-squre test. Kaplan-Meier method and log-rank test were used to compare progression free-survival (PFS)after radiotherapy. Univariate and multivariate analyses of PFS were performed using Cox proportional hazards model. Early salvage radiotherapy was defined as PSA≤0.5 ng/ml before radiotherapy, and late salvage radiotherapy was defined as PSA>0.5ng/ml. Results:PSA response (PSA decline ≥50%) rate was 94% (233/248), and 82% (203/248) patients had PSA decline ≥ 90%. Twelve (5%) patients had rising PSA after completing radiotherapy, but only 4 (2%) had real progression. The median PFS was 69 months (95% CI 68-70), and 3-year and 5-year PFS rate were 80% and 67%. PFS of PSA persistence and biochemical progression were similar ( HR =0.71, 95% CI 0.37-1.37, P=0.311). Compared with late salvage radiotherapy, early salvage radiotherapy had better PFS [69 (95% CI 68-70) vs. 59 (95% CI 44-74) months, P<0.001]. Compared with hormone sensitive, castration-resistant was associated with worse PFS (5-year PFS rate 74% vs. 51%, P<0.001). In multivariate analysis, Gleason score>8, castration-resistant and late salvage radiotherapy were unfavorable prognostic factors. Conclusions:In patients receiving salvage radiotherapy with or without hormone therapy for PSA persistence and biochemical progression after radical prostatectomy, high PSA level before radiotherapy and castration resistant is associated with poor prognosis.

Effect of Modified Shengjiangsan on Renal Fibrosis in Rats with Membranous Nephropathy Based on TLR4/NF-κB Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of modified Shengjiangsan on renal fibrosis in rats with membranous nephropathy （MN） and to explore the mechanism of its complications of renal fibrosis. Method:Rats were injected with cationized bovine serum albumin（C-BSA）in the tail vein to establish a rat model of membranous nephropathy. The normal group，model group，modified Shengjiangsan group （27.3 g·kg^-1）and benazepril group（10 mg·kg^-1）were established in this study. Each group was given corresponding dosage of the drug once a day for 4 weeks of continuous intervention. After the administration，we observed the pathological changes of rat kidneys by the technology of Masson staining， silverhexylamine iodate （PASM） staining， transmission electron microscopy （TEM）， immunofluorescence technology （IF） was used to detect immunoglobulin（Ig）G deposition in rat kidneys. The levels of interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， interleukin-6 （IL-6）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） in rat serum were detected by enzyme-linked immunosorbent assay （ELISA） method. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry （IHC） were used to detect the mRNA and protein expression levels of monocyte chemotactic protein 1 （MCP-1）， intercellular adhesion molecule 1 （ICAM-1）， nuclear factor kappa B （NF-<italic>κ</italic>B）， Toll-like receptor 4 （TLR4）， plasminogen activator inhibitor 1 （PAI-1）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， <italic>α</italic>-smooth muscle actin （<italic>α</italic>-SMΑ） and type Ⅳ Collagen （Collagen Ⅳ） in rat kidney tissues. Result:Compared with normal group， the kidney tissue of the model group was obviously fibrotic， the serum levels of IL-1<italic>β</italic>， IL-6， and TNF-<italic>α</italic> were significantly increased（<italic>P</italic><0.05）， and the expressions of MCP-1， ICAM-1， NF-<italic>κ</italic>B， TLR4， PAI-1， TGF-<italic>β</italic>₁， <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein in kidney tissue were significantly increased（<italic>P</italic><0.05）. Compared with model group， modified Shengjiangsan and benazepril significantly improved renal fibrosis in rats， reduced the levels of IL-1<italic>β</italic>， IL-6， and TNF-<italic>α</italic> in the serum of MN rats（<italic>P</italic><0.05）， down-regulated MCP-1， ICAM-1， NF-<italic>κ</italic>B， TLR4， PAI-1， TGF-<italic>β</italic>₁， <italic>α</italic>-SMA and Collagen Ⅳ mRNA and protein expression in kidney tissue（<italic>P</italic><0.05）. Conclusion:Modified Shengjiangsan can reduce the release and expression of inflammatory factors by down-regulating the TLR4/NF-<italic>κ</italic>B signaling pathway， inhibit renal fibrosis， and reduce renal damage in MN rats.

Yiqiyangyin Huoxuetongluo Prescription Reduces Renal Cell Apoptosis in Rats with Diabetic Nephropathy by Inhibiting JAK2/STAT3 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effect of Yiqiyangyin Huoxuetongluo prescription on janus kinase 2/signal transducer and activator of transcription 3 （JAK2/STAT3） signaling pathway and cell apoptosis in rats with diabetic nephropathy （DN）， and to explore the mechanism of its intervention in DN. Method:A total of 100 SD rats were randomly divided into an experimental group （<italic>n</italic>=80） and a normal group （<italic>n</italic>=20）. The DN model was induced by high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） in the experimental group， and confirmed by the pathological changes of kidney tissues in rats （three in each group） observed under light and electron microscopes. The model rats were randomly divided into a model group （normal saline， equal volume）， low-， medium-， and high-dose （5.775， 11.550， and 23.100 g·kg^-1） Yiqiyangyin Huoxuetongluo prescription groups， and an irbesartan group （irbesartan tablets， 0.016 g·kg^-1）. After drug intervention （<italic>i.g</italic>.， once a day for 16 consecutive weeks）， the 24-hour urine total protein （UTP）， serum total cholesterol （TC）， triglyceride （TG）， creatinine （SCr）， and blood urea nitrogen （BUN） levels of the rats were measured. Western blot was used to detect the protein expression of JAK2/STAT3 signaling pathway. Immunohistochemistry was used to determine the protein expression of B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， zonula occludens-1 （ZO-1）， and actinin-4 in rat kidney tissues. Result:Compared with the normal group， the model group exhibited elevated UTP， serum TC， TG， BUN， and SCr levels （<italic>P</italic><0.05）， severe pathological damage of rat kidney tissues， up-regulated expression of phospho-JAK2 （p-JAK2）， phospho-STAT3 （p-STAT3）， and Bax， increased renal cell apoptosis， and diminished expression of Bcl-2， ZO-1， and actinin-4 （<italic>P</italic><0.05）. Compared with the model group， the Yiqiyangyin Huoxuetongluo prescription group and the irbesartan group showed dwindled UTP， serum TC， TG， BUN， and SCr levels （<italic>P</italic><0.05）， relieved pathological damage of rat kidney tissues， down-regulated p-JAK2， p-STAT3， and Bax expression， and up-regulated expression of Bcl-2， ZO-1， and actinin-4 （<italic>P</italic><0.05）. Conclusion:Yiqiyangyin Huoxuetongluo prescription can reduce renal cell apoptosis and improve the prognosis of DN by inhibiting the activation of JAK2/STAT3 signaling pathway.

Renal Protection of Yishen Tongluo Prescription in Rats with Membranous Nephropathy and Its Influence on AMPK/mTOR/ULK1 Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effects of Yishen Tongluo prescription （YTP） on autophagy-related proteins in rats with membranous nephropathy （MN） and explore its possible molecular mechanism in protecting the kidney. Method:Twenty of 80 Sprague-Dawley （SD） rats were randomly selected as the normal control， and the rest rats were pre-immunized and injected with cationized bovine serum albumin （C-BSA） through the tail vein to induce MN. The SD rats that were successfully modeled were randomized into the model group， benazepril hydrochloride group （10 mg·kg^-1）， and low- （6.61g·kg^-1）， medium- （13.22 g·kg^-1）， and high-dose （26.44 g·kg^-1） YTP groups， and administered with the corresponding drugs by gavage， once a day， for four consecutive weeks. Then the changes in such quantitative indicators as plasma albumin （ALB）， triglyceride （TG）， total cholesterol （TC）， serum creatinine （SCr）， blood urea nitrogen （BUN）， and 24-hour urinary total protein （UTP） were detected， followed by hematoxylin and eosin （HE） staining， Masson's trichrome staining， and periodic Schiff-methenamine （PASM） staining for observing the pathological changes in kidney under the transmission electron microscope （TEM）. The deposition of immunoglobulin G （IgG） and complement 3 （C3） in the glomerulus was detected by fluorescence immunoassay. The expression levels of autophagy marker proteins Beclin-1， microtubule-associated protein light chain 3Ⅱ （LC3Ⅱ）， and p62 were measured by immunohistochemistry （IHC）， and those of related proteins in the adenosine monophosphate-activated protein kinase / mechanisic target of rapamycin/Unc-51-like kinase 1 （AMPK/mTOR/ULK1） signaling pathway were determined by Western blot assy. Result:Compared with the normal group， the model group exhibited significantly increased UTP （<italic>P</italic><0.01） and serum TG and TC （<italic>P</italic><0.01）， decreased ALB （<italic>P</italic><0.01）， disordered glomerular structure， enlarged volume， thickened basement membrane， vacuolated renal tubules， excessively deposited collagen fibers and fuchsinophilic proteins， extensively fused podocyte foot processes， and diffusely deposited IgG and C3 in glomerular capillary loops. Besides， the expression levels of Beclin-1， LC3II， and phosphorylated AMPK （p-AMPK） decreased （<italic>P</italic><0.01）， while those of p62， phosphorylated mTOR （p-mTOR）， and phosphorylated ULK1 （p-ULK1） increased （<italic>P</italic><0.01）. The comparison with the model group revealed that the TG， TC， and UTP levels in the low-， medium-， and high-dose YTP groups and the benazepril hydrochloride group were reduced to varying degrees （<italic>P</italic><0.05， <italic>P</italic><0.01）， whereas the ALB level was increased （<italic>P</italic><0.01）. There was no statistically significant difference in SCr or BUN level. The pathological damages were alleviated. The expression levels of Beclin-1， LC3Ⅱ， and p-AMPK were up-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）， while those of p62， p-mTOR， and p-ULK1 were down-regulated （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:YTP protects the kidney of rats with MN possibly by regulating related proteins in the AMPK/mTOR/ULK1 signaling pathway and activating the autophagy.

Clinical Observation of Yishen Tongluo Decoction in Treating Chronic Glomerulonephritis with Spleen and Kidney Qi Deficiency and Blood Stasis Syndrome / 中国实验方剂学杂志

Objective:To observe the clinical efficacy as well as anti-inflammatory and anti-fibrosis mechanism of Yishen Tongluo decoction in the treatment of chronic glomerulonephritis （CGN） with spleen and kidney Qi deficiency and blood stasis syndrome. Method:According to the random number table method， one hundred and twenty patients were divided into control group （60 cases） and observation group （60 cases）. The two groups were given oral valsartan capsules， 160 mg/time， 1 time/day， and dipyridamole tablets orally， 50 mg/time， 3 times/day. Patients in control group additionally took Wubi Shanyao pills orally， 9 g/time， 2 times/day， while patients in observation group additionally took Yishen Tongluo decoction orally， 1 dose/day. Both groups were treated continuously for four months. Before and after treatment， 24 h urine total protein （24 h UTP）， creatinine （SCr）， urea nitrogen （BUN）， serum cystatin C （CysC）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>）， interleukin-6 （IL-6）， IL-17， interferon-<italic>γ</italic> （IFN-<italic>γ</italic>）， transforming growth factor-<italic>β</italic>₁ （TGF-<italic>β</italic>₁）， connective tissue growth factor （CTGF）， matrix metalloproteinase-9 （MMP-9）， tissue inhibitor of metalloproteinases （TMP-1） and hypoxia inducible factor-1<italic>α </italic>（HIF-1<italic>α</italic>） levels were detected in both groups. The scores of spleen and kidney Qi deficiency and blood stasis syndrome were graded. Urine protein， and urine red blood cells （urinary RBC） were monitored. Result:The 24 h UTP， SCr， BUN and CysC levels of the observation group were lower than those of the control group （<italic>P</italic><0.01）. The score of spleen and kidney Qi deficiency and blood stasis syndrome in the observation group was lower than that in the control group （<italic>P</italic><0.01）. The levels of TNF-<italic>α</italic>， IL-6， IL-17 and IFN-<italic>γ </italic>in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The levels of TGF-<italic>β</italic>₁， CTGF， TMP-1 and HIF-1<italic>α</italic> in the observation group were lower than those in the control group （<italic>P</italic><0.01）. While MMP-9 level was higher than that in control group （<italic>P</italic><0.01）. The clinical effective rate was 88.33% （53/60） in the observation group， higher than 73.33% （44/60） in the control group （<inline-formula><alternatives><mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msup><mml:mrow><mml:mi>χ</mml:mi></mml:mrow><mml:mrow><mml:mn mathvariant="normal">2</mml:mn></mml:mrow></mml:msup></mml:math><graphic specific-use="big" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/155A9E27-C0C9-44b4-96FF-AF947372054E-M002.jpg"><?fx-imagestate width="3.30200005" height="3.64066648"?></graphic><graphic specific-use="small" xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="alternativeImage/155A9E27-C0C9-44b4-96FF-AF947372054E-M002c.jpg"><?fx-imagestate width="3.30200005" height="3.64066648"?></graphic></alternatives></inline-formula>=4.356， <italic>P</italic><0.05）. Conclusion:On the basis of conventional Western medicine treatment， Yishen Tongluo decoction in the treatment of CGN patients with spleen and kidney Qi deficiency and blood stasis syndrome can reduce proteinuria， and improve traditional Chinese medicine （TCM） syndromes， with anti-inflammatory and anti-kidney fibrosis effects. Thereby， it plays a role in protecting renal function and delaying the malignant progression of renal function， with high clinical efficacy and value of clinical use.

Effect of Modified Shengjiangsan on Oxidative Stress and Apoptosis in MN Rats via Regulating HIF-1α/NOX4 Signaling Pathway / 中国实验方剂学杂志

Objective:To investigate the intervention effect of modified Shengjiangsan on hypoxia-inducible factor-1<italic>α </italic>（HIF-1<italic>α</italic>）/nicotinamide adenine dinucleotide phosphate oxidase 4 （NOX4） signaling pathway in membranous nephropathy （MN） rats and to explore its mechanism to reduce oxidative stress and apoptosis in renal tissues. Method:Cationized bovine serum albumin （C-BSA） was injected into the tail vein of rats to replicate the MN model. Rats were randomly divided into a model group， a modified Shengjiangsan group， and a benazepril group after modeling， and administered by gavage once a day accordingly. At the end of the 4^th week， the 24-h urine total protein （UTP）， urea nitrogen （BUN）， and serum creatinine （SCr） levels of each group were detected. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and reactive oxygen species （ROS） in renal tissues of rats. In situ end labeling（TUNEL） staining was used to detect the cell apoptosis rate. The mRNA and protein expression levels of HIF-1<italic>α</italic> and NOX4 were detected by real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR）and Western blot， respectively. The immunohistochemistry method was used to detect the protein expression levels of B-cell lymphomas -2 （Bcl-2）， B-cell lymphomas xl （Bcl-xl）， Bcl-2 associated X protein （Bax）， Bcl-2 cell death regulator antibody （Bim）. Result:Compared with the normal group， the model group showed increased UTP （<italic>P</italic><0.05）， decreased SOD， elevated MDA and ROS （<italic>P</italic><0.05）， up-regulated mRNA and protein expression of HIF-1<italic>α</italic> and NOX4 （<italic>P</italic><0.05）， enhanced protein expression of Bax and Bim， declining protein expression of Bcl-xl and Bcl-2 （<italic>P</italic><0.05）， and increased cell apoptosis in renal tissues. Compared with the model group， the modified Shengjiangsan group and the benazepril group displayed declining UTP （<italic>P</italic><0.05）， up-regulated SOD， decreased MDA and ROS （<italic>P</italic><0.05）， down-regulated mRNA and protein expression of HIF-1<italic>α</italic> and NOX4 （<italic>P</italic><0.05）， diminished protein expression of Bax and Bim， elevated protein expression of Bcl-xl and Bcl-2 （<italic>P</italic><0.05）， and reduced cell apoptosis in renal tissues （<italic>P</italic><0.05）. Conclusion:The protective effect of modified Shengjiangsan on the kidney is presumedly achieved by reducing the oxidative stress and apoptosis in renal tissues of MN rats via inhibiting the HIF-1<italic>α</italic>/NOX4 signaling pathway.

Effect of Modified Shengjiangsan on Notch Signal Pathway and Podocyte Apoptosis in MN Rats / 中国实验方剂学杂志

Objective:The purpose of this article was to observe the effect of modified Shengjiangsan on podocyte apoptosis in membranous nephropathy （MN） rats， to explore the molecular mechanism of its treatment of MN and to provide experimental basis for its clinical application. Method:The MN rat model was established by injection of cationic bovine serum albumin into the tail vein of rats. The successfully modeled rats were then randomly divided into model group （equal volume of normal saline）， modified Shengjiangsan group （27.3 g·kg^-1） and benazepril group （10 mg·kg^-1）， with corresponding drug dosage once a day for 4 weeks of continuous intervention. After drug administration， the 24-hour urine protein （UTP） was detected. Real time fluorescent quantitative polymerase chain reaction （Real-time PCR） and immunohistochemical （IHC） methods were used to detect Podocalyxin， Nephrin， Podocin， Synaptopodin mRNA and protein expression levels in rat kidney tissue. terninal-deoxynucleoitidyl transferase medsated nick and labeling （TUNEL） method was used to detect cell apoptosis rate in rat kidney tissue， and Western blot was used to detect Notch1， Hes1， B lymphoblastoma-2 （Bcl-2） associated X protein （Bax）， and Bcl-2 protein expression levels in rat kidney tissue. Result:Compared with the normal group， UTP in the model group increased significantly， renal tissue cell apoptosis increased significantly， podocyte marker proteins podocalyxin， Nephrin， Podocin， Synaptopodin mRNA and protein expression levels decreased significantly， and Notch1， Hes1， Bax protein expression increased significantly， and Bcl-2 protein expression was significantly reduced（<italic>P</italic><0.05）. Compared with the model group， UTP levels in MN rats were significantly reduced in modified Shengjiangsan and benazepril groups， with reduced rate of renal cell apoptosis， increased mRNA and protein expression levels of podocalyxin， Nephrin， Podocin， and Synaptopodin in renal tissue， decreased Notch1， Hes1， Bax protein expression， and increased Bcl-2 protein expression（<italic>P</italic><0.05）. Conclusion:Modified Shengjiangsan can inhibit the Notch signaling pathway， reduce the apoptosis of rat kidney tissue podocytes， and reduce the kidney injury of MN rats.

Multiple fundus imaging diagnosis: knowing the principles well for a rational application / 中华实验眼科杂志

Multimodal fundus imaging techniques, based on lights and shadows, appear to have a rapidly great progress in recent years.Fundus imaging techniques are divided into anatomical approaches and functional approaches according to the working characteristics and principle of different instruments.Nowadays, fundus imaging techniques are developing toward a wide field, microview, multimodal, quantitative, and intelligent way.However, to our knowledge, the fundus is very broad with many unexplored territories and unsolved mysteries until now.The road of clinical industrialization of emerging imaging techniques is still long, and there is also a potential challenge in the application of artificial intelligence deep learning in ophthalmology.Multimodal fundus imaging techniques are beneficial for us to accurately diagnose and dynamically monitor eye diseases, but with so many examination methods, how to choose a highly sensitive and specific way to avoid the waste of medical resources and reduce unnecessary financial burden of patients is the responsibility of ophthalmologists.

Effect of TRIM31 Gene Silencing on the Proliferation and Apoptosis of U266 Cells and Its Mechanism / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of the tripartite motif containing 31 (TRIM31) gene silencing on the proliferation and apoptosis of multiple myeloma cells and its possible mechanism.@*METHODS@#The normal bone marrow plasma cells (nPCs) were selected as control, and the mRNA and protein expression levels of TRIM31 in human multiple myeloma cell lines (U266, RPMI-8226, NCI-H929 and KMS-11) were detected by RT-qPCR and Western blot. Recombinant lentivirol vector containing shRNA-TRIM31 and its negative control were used to infect U266 cells respectively, and the mRNA expression level of TRIM31 in infected cells was detected by RT-qPCR. Then cell proliferation, colony forming and apoptosis were analyzed by CCK-8, soft agar assay, and flow cytometry, respectively. The protein expression levels of TRIM31, cleaved-caspase-3, BCL-2, Bax, p-Akt (Ser473), Akt and PI3K (p110α) were evaluated by Western blot. In addition, the PI3K/Akt signaling pathway-specific inhibitor LY294002 and TRIM31-shRNA lentivirus were used to interfere with U266 cells, and the cell proliferation, apoptosis, and protein expression of p-Akt (Ser473) and Akt were detected by CCK-8, flow cytometry and Western blot, respectively.@*RESULTS@#Compared with nPCs, the expression levels of TRIM31 mRNA and protein in U266, RPMI-8226, NCI-H929 and KMS-11 cells were significantly increased (P<0.001), especially in U266 cells. After lentivirus infection, the levels of TRIM31 mRNA and protein in U266 cells were significantly decreased (P<0.001). TRIM31 silencing significantly inhibited the proliferation of U266 cells (P<0.05), attenuated the ability of cell cloning, improved cell apoptosis, up-regulated the protein expressions of cleaved-caspase-3 and Bas as well as down-regulated expressions of BCL-2, p-Akt (Ser473) and PI3K (p110α). There was no significant effect on Akt protein. Intervention of LY294002 significantly enhanced the inhibition on cell proliferation and the promotion on apoptosis mediated by TRIM31 gene silencing in U266 cells.@*CONCLUSION@#TRIM31 gene silencing can inhibit U266 cell proliferation and promote its apoptosis, which may be closely related to inhibition of PI3K/Akt signaling pathway.