1.The Effect of Mitochondrial Damage in Chondrocytes on Osteoarthritis
Zhen-Wei LI ; Jing-Yu HOU ; Yu-Ze LIN ; Zhi-Qi ZHANG ; Shang-Yi LIU ; Xiao-Wen LIU ; Kang-Quan SHOU
Progress in Biochemistry and Biophysics 2024;51(7):1576-1588
The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.
2.Bioequivalence study of glipizide tablets in Chinese healthy subjects
Fei-Lang ZHENG ; Lin-Zhong CHENG ; Hai-Ju LI ; Lu YANG ; Ze-Yuan LIU ; Su-Ling WANG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1628-1632
Objective To study the bioequivalence of two glipizide tablets in healthy Chinese subjects.Methods Randomized,open,single-administration,two-period,self-cross-over trial design was used in the study.There were 28 Chinese healthy subjects in the fasted state and 28 in the fed state,complete repeat cross single dose oral glipizide tablets test preparation or reference preparation 5 mg.The plasma concentration of glipizide was determined by liquid chromatography/tandem mass spectrometry at different time points after administration.The non-compartmental model was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two formulations.Results The main pharmacokinetic parameters of glipizide in the fasted state were as follows:Cmax were(551.60±91.26)and(518.10±105.10)ng·mL-1;AUC0-t were(3 074.33±861.91)and(3 026.77±934.25)h·ng·mL-1;AUC0-∞ were(3 204.85±990.78)and(3 166.35±1 107.36)h ng·mL-1.The parameters of glipizide in the fed state were as follows:Cmax were(517.30±98.97)and(472.80±114.48)ng·mL-1;AUC0-t were(3 001.12±830.87)and(2 932.79±736.35)h·ng·mL-1;AUC0-∞ were(3 067.00±918.84)and(2 997.44±819.14)h·ng·mL-1.The 90%confidence interval of the Cmax,AUC0-t and AUC0-∞ of the test formulation and the reference formulation were from 80.00%to 125.00%.The incidence of adverse events in fasted group and fed group was no serious adverse events.Conclusion The two glipizide tablets were bioequivalent under fasted and fed conditions,and good security.
3.Effects of ginsenoside Rf on endometriosis model rats
Lin ZHANG ; Jing-He CAO ; Xiao-Hui ZHANG ; Ze-Wu LI ; Xiao-Li CHEN
The Chinese Journal of Clinical Pharmacology 2024;40(19):2869-2874
Objective To investigate the ameliorative effect of ginsenoside Rf on endometriosis(EMS)and its mechanism.Methods In animal experiments,Wistar female rats were randomly divided into sham group(laparotomy without other treatment),model group(EMS construction),low dose group(1.0 mg·kg-1 ginsenoside Rf),middle dose group(2.0 mg·kg-1 ginsenoside Rf),high dose group(3.0 mg·kg-1 ginsenoside Rf),positive group(0.25 mg·kg-1 pregnrienone capsule).The volume of ectopic lesions and the number of painful twisting were detected;the apoptosis rate in tissues was detected by TdT mediated dUDP nick end labeling(Tunel)assay;the expression of related proteins in each group was detected by Western blot assay.Cell experiment:The isolated primary rat endometrial cells were randomly divided into control group(normal tissue isolation),EMS group(EMS cells),Rf group(20 μmol·L-1 ginsenoside Rf treated EMS cells),combined group(20 μmol·L-1 ginsenoside Rf and 50 μmol·L-1 autophagy inhibitor 3-MA treated EMS cells).Western blot assay was used to detect the expression of related proteins;flow cytometry was used to detect apoptosis.Results Animal experiment:The times of body twisting in sham group,model group,high dose group and positive group were 0,37.10±4.64,14.70±1.90 and 20.20±1.78,respectively;the ectopic lesion volumes were 0,(118.91±19.51),(50.11±9.69)and(37.64±3.56)mm,respectively;the apoptosis rates were(3.43±0.33)%,(3.22±0.27)%,(20.42±1.82)%and(22.92±2.67)%,respectively;Beclin 1 protein expression were 0.32±0.03,0.36±0.04,0.79±0.12,0.35±0.07,respectively;glutathione peroxidase 4(GPX4)protein expression were 1.10±0.07,0.94±0.11,0.53±0.03,0.96±0.16,respectively.The above indexes of the model group were compared with those of the sham group,and the above indexes of the high dose group were compared with those of the model group,and the differences were significant(all P<0.05).Cell experiment:Beclin1 protein expression in control group,EMS group,Rf group and combined group were 0.22±0.05,0.31±0.03,0.52±0.07 and 0.19±0.03,respectively;GPX4 protein expression were 0.97±0.07,0.81±0.09,0.63±0.05 and 1.05±0.09,respectively;the apoptosis rates were(3.48±0.04)%,(3.42±0.23)%,(21.66±2.95)%and(12.51±1.15)%,respectively;the above indexes in Rf group were compared with those in EMS group,and the above indexes in combined group were compared with those in Rf group,and the differences were significant(all P<0.05).Conclusion Ginsenoside Rf can improve endometrial lesion,pain sensitivity and apoptosis in EMS rats,which may be related to the regulation of autophagy dependent ferroptosis.
4.Bioequivalence study of rasagiline mesylate tablets in Chinese healthy subjects
Gang CHEN ; Xiao-Lin WANG ; Si-Qi ZANG ; Ze-Juan WANG ; Xiao-Na LIU ; Ai-Hua DU ; Min LI ; Ya-Nan ZHANG ; Dan ZHANG ; Li-Na ZHANG ; Jin WANG
The Chinese Journal of Clinical Pharmacology 2024;40(19):2885-2890
Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90%confidence interval(CI)of the geometric mean ratio(GMR)were 94.11%-118.06%,99.22%-107.74%and 99.16%-107.44%for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00%-125.00%.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90%CI of GMR were 96.99%-101.19%and 97.17%-101.41%for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00%-125.00%.The 95%upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00%-125.00%.The incidence of adverse events in fasting and fed studies was 22.86%and 22.92%,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.
5.Integration of the concept of"a community of common health for mankind"into medical humanities education:appearance context,content construction,and practical path
Lin TAN ; Chengjie LI ; Ze FAN
Chinese Medical Ethics 2024;37(6):732-737
At present,there are some shortcomings in China's medical humanities education,such as inadequate adaptation to the needs of the development of philosophy and social sciences with Chinese characteristics,and insufficient early warning of crises brought about by emerging medical technologies.The concept of"a community of common health for mankind"had been established in the appearance context of medical humanities education,which also gave medical humanities education a richer contemporary significance and development opportunities.Taking the courses of medical ethics and health law as examples,the concept of"a community of common health for mankind"fits well with the core of medical humanities education in terms of value significance,logical mechanisms,and content elements,which is more conducive to highlighting the localized results of medical humanities research.Therefore,the existing theoretical frameworks should be integrated with the concept of"a community of common health for mankind",to create a medical humanities education system with Chinese characteristics and universal significance,as well as to enhance the quality and effects of humanities education by integrating the disciplinary systems,education modes,education chains,and other paths.
6.Comparison of the performance of different nutritional screening tools for preoperative patients with Crohn's disease
Ze-Hua ZHAO ; Chu-Lin CHEN ; Xiang-Hong YE ; Yi LI
Parenteral & Enteral Nutrition 2024;31(2):114-117,123
Objective:To explore the application value of different nutritional screening tools in the evaluation of preoperative malnutrition assessment of Crohn's patients. Methods:Using the convenient sampling method, a retrospective analysis was conducted on CD patients who underwent elective surgery at the general surgery department of General Hospital of Eastern Theater Command from January 2021 to March 2022. The preoperative nutritional status of the patients was understood. Taking the consensus on malnutrition assessment diagnosis standards (GLIM) as the gold standard. The correlation, difference and diagnostic efficacy of 3 nutritional risk screening tools were compared. Results:A total of 212 patients were included. Using GLIM as the diagnostic standard, 131 patients (61.79%) had malnutrition. The incidence of malnutrition risk was 66.03%, 85.38% and 55.66% using NRS 2002 score, NS IBD score and PNI score, respectively. The sensitivities of the above three scores in the preoperative nutritional screening of IBD patients were 81.46%, 85.48%, 79.63%, respectively; the specificity were 62.36%, 54.71%, 57.12%, respectively; and the areas under the curve were 0.749, 0.763, 0.831, respectively. In the evaluation of diagnostic efficacy, NS IBD score had the highest sensitivity, and NRS 2002 had the best specificity. Conclusion:For patients with Crohn's disease undergoing elective surgery, the three nutritional risk screening tools can provide a basis for malnutrition risk screening. The items of PNI score are objective, concise, and convenient. As for the evaluation of diagnostic efficacy, the NS IBD score has the highest sensitivity and the NRS 2002 has the best specificity.
7.Summary of best evidence for case management of home enteral nutrition patients
Chun-Yan LIU ; Hong-Lin YAO ; Jia-Qi LI ; Shuo SHEN ; Ze-Hua ZHAO ; Xiang-Hong YE
Parenteral & Enteral Nutrition 2024;31(5):306-311
Objective:To summarize the best evidence on case management of patients with home enteral nutrition.Methods:Relevant evidence on the case management of home enteral nutrition patients was retrieved by literature search,and the evidence was extracted and summarized for the literature that met the quality requirements.Result:A total of 10 literatures were included,including 1 guideline,3 expert consensus,2 industry standards,1 systematic review and 3 randomized controlled trials.By establishment of archives,policy management,establishment of multidisciplinary teams,overall evaluation of home enteral nutrition,as well as implementation management,a total of 33 home enteral nutrition case management was summarized from 6 aspects including health education and follow-up,etc.Conclusion:All the summarized relevant evidence about case filing and management of home enteral nutrition patients can be applied in clinical practice to promote the standardized management of home enteral nutrition.
8.Clinical Observation of Self-formulated Shenqi Buwei Decoction in the Treatment of Stable Chronic Obstructive Pulmonary Disease with Lung-Spleen Qi Deficiency Syndrome
Meng-Meng ZHANG ; Qiao LI ; Qing-Yong XIONG ; Jia-Yao LI ; Lin-Na XIE ; Jia-Sheng LU ; Ze-Geng LI
Journal of Guangzhou University of Traditional Chinese Medicine 2024;41(8):1994-2000
Objective To observe the clinical efficacy of self-formulated Shenqi Buwei Decoction(derived from Huangqi Renshen Decoction)in treating patients with stable chronic obstructive pulmonary disease(COPD)differentiated as lung-spleen qi deficiency syndrome.Methods A total of 110 patients with stable COPD differentiated as lung-spleen qi deficiency syndrome were randomly divided into a control group and an observation group,with 55 patients in each group.The control group was given Tiotropium Bromide Inhalation Powder for the inhalation treatment,and the observation group was given Shenqi Buwei Decoction on the basis of treatment for the control group,and the course of treatment covered 3 months.The changes of pulmonary function indicators of forced expiratory volume in one second(FEV1),forced vital capacity(FVC),and one-second rate of FEV1/FVC,modified Medical Research Council index(mMRC)dyspnea scores,6-minute walk test(6MWT),COPD Assessment Test(CAT)scores,and traditional Chinese medicine(TCM)syndrome scores in the two groups were observed before and after treatment.After treatment,the clinical efficacy and safety of the two groups were evaluated.Results(1)During the trial,one patient was excluded and two patients fell off from the observation group,and three patients fell off from the control group.Eventually,52 patients in each of the two groups were included in the efficacy statistics.(2)After 3 months of treatment,the total effective rate of the observation group was 80.77%(42/52)and that of the control group was 67.31%(35/52).The intergroup comparison(tested by chi-square test)showed that the therapeutic effect of the observation group was slightly superior to that of the control group,but the difference was not statistically significant(P>0.05).(3)In terms of indexes,After treatment,the levels of pulmonary function indicators of FEV1,FEV1/FVC in the control group and FEV1,FVC,FEV1/FVC in the observation group were significantly improved compared with those before treatment(P<0.05),and the improvement of FEV1,FVC,FEV1/FVC in the observation group was significantly superior to that in the control group(P<0.05).(4)After treatment,the 6MWT,mMRC and CAT scores of the two groups were significantly improved compared with those before treatment(P<0.05),and the improvement in the observation group was significantly superior to that in the control group(P<0.05).(5)After treatment,the TCM syndrome scores of the two groups of patients were significantly decreased in comparison with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.05).(6)During the treatment process,no obvious adverse reactions occurred in the two groups of patients,there were no abnormal changes in the safety indicators,either.Conclusion On the basis of conventional western medicine treatment,the combined use of Shenqi Buwei Decoction exerts certain efficacy in the treatment of patients with stable COPD differentiated as lung-spleen qi deficiency syndrome.The combined therapy can effectively improve the ventilation function,relieve the clinical symptoms,improve the quality of life and delay the decline of lung function of the patients.
9.Cerebral oxygen metabolism and brain electrical activity of healthy full-term neonates in high-altitude areas:a multicenter clinical research protocol
Bi ZE ; Jin GAO ; Xiao-Fen ZHAO ; Yang-Fang LI ; Tie-Song ZHANG ; Xiao-Mei LIU ; Hui MAO ; Ming-Cai QIN ; Yi ZHANG ; Yong-Li YANG ; Chun-Ye HE ; Yan ZHAO ; Kun DU ; Lin LIU ; Wen-Hao ZHOU ; Chinese High Altitude Neonatal Medicine Alliance
Chinese Journal of Contemporary Pediatrics 2024;26(4):403-409
Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]
10.Sexual Dimorphism in Mechanical Hypersensitivity Induced by Subcutaneous Injection of M-CSF
Xiang-ge PENG ; Zhen-jia LIN ; Hui ZHANG ; Shi-ze LENG ; Yuan TANG ; Yu-fan ZHENG ; Zhi TAN ; Li-jun ZHOU
Journal of Sun Yat-sen University(Medical Sciences) 2023;44(3):395-402
ObjectiveTo investigate whether there exists gender differences in mechanical pain hypersensitivity induced by the subcutaneous injection of macrophage colony-stimulating factor (M-CSF) in normal mice and to explore the preliminary mechanism. MethodsThirty 10-week-old C57BL/6J mice were randomly divided into three groups, (n = 10 mice/group, half male and half female). The albumin control group (BSA, 0.3 μg), low dose M-CSF group (L M-CSF, 0.075 μg) and high dose M-CSF group (H M-CSF, 0.3 μg) received 50 μL BSA or M-CSF injected subcutaneously into the left medial thigh once daily for 3 consecutive days. Before and after drug administration, von-Frey mechanical sensitivity test was used to detect the mechanical paw withdrawal threshold (PWT) in each group. Immunofluorescence was performed to examine the expression changes of Ionized calcium-binding adaptor molecule 1 (Iba1) in skin, calcitonin gene-related peptide (CGRP) and phosphorylated ERK1/2 (p-ERK) in L5-L6 DRG and lumbar spinal dorsal horn. ResultsIn female mice, only high dose of M-CSF caused mechanical allodynia, whereas in male mice both doses produced marked allodynia. Mechanically, high-dose M-CSF induced massive aggregation of subcutaneous macrophages (marked by Iba1) in male and female mice, but more dramatic dependence in female mice. Similar gender differences were also found in the increase of p-ERK and CGRP expression in dorsal root ganglion (DRGs). Notably, CGRP expression was especially elevated in the fibers of DRG in male mice. Correspondingly, the expressions of p-ERK and CGRP+ terminals in the superficial spinal dorsal horn of male mice were significantly higher than those of female mice after M-CSF treatment. ConclusionSubcutaneous injection of M-CSF triggers sexual dimorphism in mechanical pain hypersensitivity, which is related with differential changes in peripheral macrophage expansion and sensitization of the nociceptive pathway.

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