1.Apoptosis Regulation by Buzhong Yiqitang via PERK/eIF2α/ATF4/CHOP Pathway to Enhance Pulmonary Surfactant-associated Protein C Expression and Ameliorate Lung Injury in CIH Mice
Luyao ZHANG ; Yangjing WANG ; Bingbing LIU ; Jieru LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):19-27
ObjectiveTo investigate the effects of Buzhong Yiqitang on the abnormal expression of pulmonary surfactant-associated protein C (SFTPC) and lung injury induced by chronic intermittent hypoxia (CIH) and the mechanism of action. MethodsForty healthy adult male SPF-grade C57BL/6 mice were randomly allocated into five experimental groups: a normoxia group, a CIH group, and low-, medium-, and high-dose Buzhong Yiqitang groups, with eight mice in each group. During the modeling, mice in the normoxia group were housed under standard oxygen concentrations, while the CIH and all Buzhong Yiqitang groups were placed in a hypoxic chamber for 8 h daily over 35 d. Prior to each chamber session, mice in the low-, medium-, and high-dose Buzhong Yiqitang groups were administered decoctions by gavage at corresponding doses (8.1, 16.2, 32.4 g·kg-1·d-1 of crude drug, respectively), while those in normoxia and CIH groups received an equivalent volume of saline by gavage. The general conditions of the mice were recorded before and after the experiment. Pulmonary function was assessed using a non-invasive detection system. Serum SFTPC levels were measured using enzyme-linked immunosorbent assay (ELISA). Histopathological changes in lung tissue were evaluated using hematoxylin-eosin (HE) staining. Apoptosis in lung tissue was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). Protein expression of SFTPC, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), protein kinase R-like endoplasmic reticulum kinase (PERK), phosphorylated PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), activating transcript factor 4 (ATF4), and CCAAT/enhancer-binding protein homologous protein (CHOP) in lung tissue was analyzed by Western blot. Immunofluorescence staining was employed to assess the expression of SFTPC and CHOP proteins in lung tissue. ResultsCompared to those in the normoxia group, mice in the CIH group showed significantly impaired pulmonary function and increased histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels increased, while SFTPC expression in lung tissue was reduced (P<0.05, P<0.01). The rate of apoptotic cells in lung tissue increased, and the expression of endoplasmic reticulum stress markers p-PERK, p-eIF2α, ATF4, and CHOP was upregulated (P<0.05, P<0.01). Compared with the CIH group, Buzhong Yiqitang intervention improved pulmonary function indicators and decreased the histopathological lung injury scores (P<0.05, P<0.01). Serum SFTPC levels were decreased, and lung tissue SFTPC expression was recovered (P<0.05, P<0.01). The apoptotic rate of lung tissue cells was significantly reduced, with downregulation of pro-apoptotic Bax and upregulation of anti-apoptotic Bcl-2 expression (P<0.05, P<0.01). Activation and expression of p-PERK, p-eIF2α, ATF4, and CHOP were also decreased (P<0.05, P<0.01). ConclusionBuzhong Yiqitang can alleviate lung injury and improve pulmonary function by reducing lung cell apoptosis and enhancing alveolar surfactant secretion, which may be related to the modulation of the PERK/eIF2α/ATF4/CHOP signaling pathway.
2.Analysis of syphilis epidemiological characteristics among the resident population in Ruian City, 2014‒2023
Wansheng HONG ; Jiangmin CHEN ; Limin ZHOU ; Yunlei HU ; Chunnan CHEN ; Liangchai CHEN ; Jun LI ; Jieru HUANG ; Zumu ZHOU
Shanghai Journal of Preventive Medicine 2024;36(11):1026-1030
ObjectiveTo understand the epidemiological characteristics of syphilis in Ruian City, so as to provide a scientific basis for developing syphilis prevention and control strategies. MethodsDescriptive epidemiological methods were used to investigate the infection status of syphilis cases reported among the permanent resident population in Ruian City from 2014 to 2023, and its epidemiological characteristics were analyzed. ResultsA total of 5 482 syphilis cases were reported in Ruian from 2014 to 2023, with a male-female ratio of 1∶1.47. The average annual incidence rate from 2014 to 2023 was 37.51/100 000, with a declining trend in the incidence rate among females (APC=-4.78%, P<0.05). The incidence of primary and secondary syphilis decreased, while the proportion of latent syphilis cases increased. No cases of congenital syphilis were reported from 2017 to 2023. The majority of cases (60.29%) were reported among individuals aged 20‒<50 years. In terms of occupation, the highest proportion was found among housekeepers and the unemployed, constituting 42.70% the total cases. Dermatology departments reported the most cases in medical institutions, accounting for 33.38% of the total cases. The most likely route of infection was heterosexual transmission, accounting for 85.84%. ConclusionThe incidence of syphilis among females in Ruian City shows a declining trend, but the overall situation remains concerning. Prevention and control efforts should be intensified among key groups and high-risk populations, along with an enhancement on health education to curb the spread of syphilis.
3.Effect of urine mixing degree on 24-hour urinary total protein in patients with chronic kidney disease based on generalized estimating equation
Shanfang QIU ; Weiwei WU ; Yang LI ; Yi FANG ; Xiaoyan JIAO ; Wenqi SHAO ; Shuan ZHAO ; Jie TENG ; Jieru CAI ; Xiaoqiang DING
Chinese Journal of Clinical Medicine 2024;31(3):428-432
Objective To explore the effect of urine mixing degree on 24-hour urinary total protein(24 h UTP)in patients with chronic kidney disease(CKD).Methods From October 1,2023 to December 31,2023,30 hospitalized patients who needed to complete 24 h UTP testing in Zhongshan Hospital,Fudan University were selected.A 5 L unified container was used to collect urine for 24 hours.After collection and one hour's standing,the urine sample was divided into upper,middle,and lower equal parts according to volume,which was defined as direct-sampling group.Then,the urine samples were fully mixed with a magnetic stirrer and sampled again according to the above-mentioned three-equal sampling method,which was defined as mixed-sampling group.The generalized estimating equation was used to compare the urinary protein concentration before and after mixing and at different sampling location.Results The results of generalized estimating equation showed that after controlling the variable"sampling position",there was no significant difference in urinary protein concentration between the direct-sampling group and the mixed-sampling group.After controlling the variable"mixing method",there was still no significant difference in urinary protein concentration at different sampling positions.After adjusting the covariates such as age,gender,and estimated glomerular filtration rate(eGFR),the results were consistent.Conclusions With standard protocol,the entire 24-hour urine sample is a relatively even-distributed solution.After the total urine collection is completed,the temporary sample can be directly extracted from any level of the original urine within 1 hour,and the urine protein concentration of the sample multiplied by the urine volume can reflect the 24 h UTR.
4.Buzhong Yiqitang Reduces CIH-induced Pulmonary Inflammatory Injury by ACE2-Ang(1-7)-Mas Axis
Qi CHEN ; Jixian SONG ; Yi TANG ; Jianchao SI ; Xinyue YANG ; Ensheng JI ; Jieru LI
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(17):18-25
ObjectiveTo investigate the intervention effect of Buzhong Yiqitang (BZYQT) on pulmonary inflammation in mice induced by chronic intermittent hypoxia (CIH) and preliminarily elucidate its mechanism. MethodForty healthy male C57BL/6 mice aged 6-8 weeks were randomly divided into the following groups: normoxia group, model group (exposed to CIH), and low-, medium-, and high-dose BZYQT groups. The normoxia group was exposed to a normoxic environment, while the model group and the low-, medium-, and high-dose BZYQT groups were exposed to intermittent hypoxia. In the BZYQT groups, the BZYQT (8.1, 16.2, 32.4 g·kg-1·d-1) was administered orally 30 min before placing the mice in the hypoxic chamber, while the model group and the normoxia group received an equivalent volume of normal saline. After five weeks of modeling, pulmonary function of the mice was measured using an EMKA animal lung function analyzer, and lung tissue samples were collected after the pulmonary function tests. Hematoxylin-eosin (HE) staining was performed to observe the histopathological changes in the lung tissue of each group. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) in the serum, as well as angiotensin Ⅱ (Ang Ⅱ) and angiotensin-(1-7) [Ang(1-7)] in lung tissue. Western blot and immunohistochemistry were used to detect the protein expression of IL-6, IL-8, TNF-α, angiotensin-converting enzyme 2 (ACE2), and mitochondrial assembly receptor (Mas). ResultCompared with the normoxia group, the model group showed significant abnormalities in lung function (P<0.05, P<0.01), lung tissue changes, such as thickening of alveolar walls and inflammatory cell infiltration, increased levels of IL-6, IL-8, TNF-α in the serum and Ang Ⅱ in lung tissue (P<0.01), decreased level of Ang(1-7) (P<0.01), increased protein expression of IL-6, IL-8, and TNF-α, and decreased protein expression of ACE2 and Mas (P<0.05, P<0.01). Compared with the model group, the BZYQT groups showed improvement in lung function (P<0.05, P<0.01), and HE staining of lung tissue showed approximately normal alveolar wall thickness and reduced inflammatory cell infiltration. Immunohistochemistry and Western blot analysis showed a significant decrease in the expression of inflammatory-related proteins (P<0.05, P<0.01), and a significant increase in ACE2 and Mas protein expression (P<0.05, P<0.01). ConclusionBZYQT can improve lung injury in mice exposed to CIH by regulating the ACE2-Ang(1-7)-Mas axis to inhibit inflammatory responses.
5.A novel and low-toxic peptide DR3penA alleviates pulmonary fibrosis by regulating the MAPK/miR-23b-5p/AQP5 signaling axis.
Dan WANG ; Bochuan DENG ; Lu CHENG ; Jieru LI ; Jiao ZHANG ; Xiang ZHANG ; Xiaomin GUO ; Tiantian YAN ; Xin YUE ; Yingying AN ; Bangzhi ZHANG ; Wenle YANG ; Junqiu XIE ; Rui WANG
Acta Pharmaceutica Sinica B 2023;13(2):722-738
Pulmonary fibrosis (PF) is a pathological change caused by repeated injuries and repair dysfunction of the alveolar epithelium. Our previous study revealed that the residues Asn3 and Asn4 of peptide DR8 (DHNNPQIR-NH2) could be modified to improve stability and antifibrotic activity, and the unnatural hydrophobic amino acids α-(4-pentenyl)-Ala and d-Ala were considered in this study. DR3penA (DHα-(4-pentenyl)-ANPQIR-NH2) was verified to have a longer half-life in serum and to significantly inhibit oxidative damage, epithelial-mesenchymal transition (EMT) and fibrogenesis in vitro and in vivo. Moreover, DR3penA has a dosage advantage over pirfenidone through the conversion of drug bioavailability under different routes of administration. A mechanistic study revealed that DR3penA increased the expression of aquaporin 5 (AQP5) by inhibiting the upregulation of miR-23b-5p and the mitogen-activated protein kinase (MAPK) pathway, indicating that DR3penA may alleviate PF by regulating MAPK/miR-23b-5p/AQP5. Safety evaluation showed that DR3penA is a peptide drug without obvious toxicity or acute side effects and has significantly improved safety compared to DR8. Thus, our findings suggest that DR3penA, as a novel and low-toxic peptide, has the potential to be a leading compound for PF therapy, which provides a foundation for the development of peptide drugs for fibrosis-related diseases.
6.Prescription audit led rational drug use management in medical institutions by GAPS method
Juan LI ; Xiulan LIU ; Wei LI ; Min GUO ; Lu ZENG ; Yan HE ; Jieru GUO ; Guangjie WU ; Dong LIU
Chinese Journal of Hospital Administration 2021;37(10):831-837
Based on the GAPS(goal, analyze, problem, solution) management model, the authors analyzed the problems existing in the practice of prescription audit and the strategies of continuous optimization. Multi-disciplinary team(MDT) and evidence-based practice were applied to help the continuous optimization of prescription audit practice and promote the rational drug use management of medical institutions. Through the establishment of accurate control process, the personalized management of prescription dosage of chronic diseases, perioperative drugs, special grade antibiotics and auxiliary drugs was realized. The practice of prescription audit based on the GAPS management model, on the one hand, could improve the quality and efficiency of prescription audit, gradually improve the qualified rate of prescription, strengthen clinical use intervention and promote rational drug use; On the other hand, it could reflect the value of pharmacists′ professional technicians, provide patients with more high-quality pharmaceutical care, and gradually realize the prescription audit mode of " improving quality, controlling cost and increasing efficiency" .
7.Evaluation of interference factors in creatinine measurement by using new guideline CLSI EP7-A3
Wen SHI ; Jieru HUANG ; Dongdong LIU ; Min HE ; Chuhong ZHENG ; Qian XIAO ; Li LIN ; Yile HUANG ; Lin LI ; Jianhua XU
Chinese Journal of Laboratory Medicine 2020;43(3):307-311
Objective:To investigate the interfering factors in the determination of creatinine(Cr) using the American Clinical Laboratory Standards Association (CLSI) EP7-A3 document.Methods:According to the CLSI EP7-A3 document, fresh serum (no hemolysis, lipemia, and jaundice) was used on the day of the experiment and confirmed the interfering substances through the pairing difference experiment and the point-to-point analysis method was used in the dose effect experiment to clarify the difference of interfering substances.Results:Triglyceride (16.94 mmol/L), dobutamine hydrochloride (4.01 μmol/L), ascorbic acid (298 μmol/L) did not interfere with the determination of Cr. Free bilirubin (684 μmol/L), conjugated bilirubin (684 μmol/L), calcium hydroxybenzene sulfonate (144 μmol/L) and hemoglobin (10 g/L) were used as the maximum concentrations of interferences for the dose effect test, the results showed that the above interferences had negative interference on the determination of Cr.Conclusion:According to EP7-A3, it is valuable to evaluate the interference factors of creatinine determination.
8.Pharmacologic Therapy Updates of Chinese and American Authoritative Guidelines in Type 2 Diabetes Mellitus
Herald of Medicine 2018;37(11):1299-1302
Type 2 Diabetes mellitus is one of the most important chronic non-communicable diseases that threaten human health around the world,and its pharmacologic therapy has always been the focus of research. Chinese Diabetes Society (CDS) and American Diabetes Association (ADA) published the new guidelines in type 2 diabetes mellitus in 2017 and 2018, updated the recommendations for diagnosis and treatment of type 2 diabetes mellitus.This article reviews the update points of the treatment route and the therapeutic drugs.
9.Comparison of the Clinical Outcomes of Fresh Embryo Transfer with GnRH Agonist Long Protocol Versus GnRH Antagonist Protocol in Different Age Groups and Different Responders
Jieru ZHU ; Jianping OU ; Weijie XING ; Xin TAO ; Liuhong CAI ; Tao LI ; Li SUN ; Hui LIN
Journal of Sun Yat-sen University(Medical Sciences) 2017;38(5):738-745
[Objective]To compare the clinical outcomes of fresh embryo transfer of the in vitro fertilization/intracytoplasmic sperm injection and embryo transfer(IVF/ICSI-ET)in different age groups as well as in different responders using gonadotropin-re-leasing hormone agonist(GnRH-a)long protocol or GnRH antagonist(GnRH-ant)protocol.[Methods]A retrospective analysis was performed on 737 IVF/ICSI cycles,including 386 cycles of GnRH-a long protocol(group A)and 351 cycles of GnRH-ant protocol (group B),from August 28,2015 to December 31,2016. Then all the cycles were divided into sub-groups by ages and retrieved oo-cyte numbers:group a1(<38 years),group a2(≥38 years);group b1(n≤5),group b2(6≤n≤15),group b3(n>15). The basic information of patients and clinical outcomes were compared.[Results](1)Comparable results were obtained from group A and group B in these following variables such as fertilization rate,normal fertilization rate,biochemical pregnancy rate and miscarriage rage. But the stimulation period,the total gonadotropin(Gn)dosage,estradiol(E2)level and endometrial thickness on the day of human chorionic gonadotropin(hCG)administration,number of oocytes retrieved and mature oocytes,ovarian hyperstimulation syn-drome(OHSS)rate,implantation rate and clinical pregnancy rate were significantly higher in group A than group B(P<0.05),and significantly higher cancellation rate of fresh embryo transfer was observed in group B(P<0.001).(2)When divided by ages,no mat-ter in sub-group a1 or sub-group a2,the implantation rate was slightly lower in GnRH-ant protocol than in GnRH-a long protocol, although they failed to reach significant difference(sub-group a1:32.6%vs 39.8%,P=0.067;sub-group a2:9.7%vs 17.9%,P=0.066). The clinical pregnancy rate was comparable using these two protocols in sub-group a1(54.8%vs 50.4%,P=0.429),but it was significantly lower by using GnRH-ant protocol than GnRH-a long protocol in sub-group a2(19.6%vs 39.1%,P=0.021).(3) When divided by numbers of oocytes retrieved,the implantation rate was significantly lower when using GnRH-ant protocol in sub-group b1(13.1%vs 26.0%,P=0.026),but we failed to observe significant differences in other two sub-groups. The clinical preg-nancy rates were comparable in all sub-groups ,whereas differed considerably in sub-group b1 (36.6% vs 19.3%,P = 0.056).[Conclusion]Overall,the implantation rate and clinical pregnancy rate were higher in GnRH-a long protocol than those in GnRH-ant protocol. Nevertheless,GnRH-ant protocol could reduce the dosage of Gn,shorten the treatment duration,and effectively reduce the occurrence of OHSS. There were similar pregnancy outcomes in two protocols for normal responders and high responders ,while for advanced patients or other poor responders,the implantation rate and clinical pregnancy rate were higher in GnRH-a protocol.
10. The study of using cordyceps-astragalus-salvia miltiorrhiza to treat acute lung injury induced by paraquat poisoning in rats
Qilu LI ; Jiling LIU ; Jieru WANG ; Xiangdong JIAN ; Baotian KAN ; Zhongchen ZHANG
Chinese Journal of Industrial Hygiene and Occupational Diseases 2017;35(4):251-256
Objective:
To study the therapy of cordyceps-astragalus-salvia miltiorrhiza in treating acute lung injury and pulmonary interstitial fibrosis induced by paraquat poisoning.
Methods:
All 120 adult Wister male rats were randomly assigned to three groups, the paraquat poisoning group (rats were intragastric administration paraquat 50 mg/kg body weight once at the beginning) , the cordyceps-astragalus-salvia miltiorrhiza therapy group (rats were given cordyceps-astragalus-salvia miltiorrhiza 90 mg/kg body weight intragastric administration half an hour after paraquat was given, then the same dose was given once a day) ; control group (rats were intragastric administration with physiological saline) . At 7th, 14th, 21st, and 28th day rats were sacrificed postanesthetic respectively after paraquat exposure, sample of lung tissue, bronchoalveolar lavage (BAL) , and venous blood were collected. GSH, SOD, TNF-α, TGF-β1, and HYP in plasma, bronchoalveolar lavage (BAL) , and the lung homogenates were determined. Optical microscope was performed to examine pathological changes in lung.
Results:
Each experimental time point paraquat group and the treatment group rats serum SOD content significantly lower than the control group (

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