ObjectiveTo explore the impact of Gegen Qinliantang（GQT） on the fecal short-chain fatty acids（SCFAs） metabolism in antibiotic-associated diarrhea（AAD） through targeted metabolomics. MethodA total of 240 SD rats were randomly divided into six groups（n=40， half male and half female）， including blank group， model group， bifidobiogen group（0.15 g·kg^-1）， and GQT high-， medium-， and low-dose groups（10.08， 5.04， 2.52 g·kg^-1）， except for the blank group， clindamycin（250 mg·kg^-1） was given to all groups by gavage for modeling every day for 7 d. After successful modeling， each administered group was gavaged with the corresponding dose of the drug， and the blank and model groups were gavaged with an equal volume of normal saline solution， 1 time/d， for 14 d. At 0， 3， 7， 14 d after the drug intervention， eight rats were randomly selected from each group， respectively. Gas chromatography-time-of-flight mass spectrometry（GC-TOF-MS） was used to perform targeted metabolomic analysis of SCFAs in the feces of rats， and partial least squares-discriminant analysis（PLS-DA） was applied to compare the differences in metabolic profiles between groups at different treatment times， and to compare the changes in the contents of SCFAs in rat feces between groups. ResultPLS-DA results showed that the blank group could be clearly distinguishable from the model group， with GQT exhibiting a closer proximity to the blank group after 7 d of treatment. After further analyzing the composition of SCFAs， it was found that the proportion of acetic acid increased and the proportions of butyric acid， valeric acid， hexanoic acid and isovaleric acid decreased in the model group compared with the blank group. After the treatment with GQT， the proportions of butyric acid， isobutyric acid， valeric acid， and isovaleric acid increased， and the proportions of acetic acid， propionic acid and caproic acid decreased. Subsequent differential analysis revealed that GQT could significantly improve the content of butyric acid， and had a certain retrogressive effect on the contents of valeric acid and hexanoic acid. ConclusionThe medium dose group of GQT can improve the contents of SCFAs in AAD feces after 7 days of treatment， which may be related to the improvement of the composition ratio of SCFAs and the contents of butyric acid， valeric acid and caproic acid.

Objective:To evaluate the effect of the impaction of posterior wall on the prognosis following open reduction and internal fixation for fractures of acetabular posterior wall.Methods:A retrospective study was conducted to analyze the data from the 83 patients with fracture of acetabular posterior wall who had been consecutively treated by open reduction and internal fixation at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital from January 2017 to December 2020. The patients were divided into 2 groups based on involvement of posterior wall impaction. In the impaction group of 33 cases, there were 26 males and 7 females with an age of (47.4±11.6) years; in the non-impaction group of 50 cases, there were 43 males and 7 females with an age of (41.3±12.0) years. The quality of postoperative fracture reduction, the function of the affected hip at the last follow-up, and the complication rate during follow-up were compared between the 2 groups. Multifactorial binary logistic regression and age subgroups were used to analyze the effects of posterior wall impaction on functional outcomes.Results:The age, rate of associated injuries in other body parts, and rate of posterior wall comminution in the impaction group were significantly higher than those in the non-impaction group ( P<0.05), but there was no statistically significant difference in other general data of patients between the 2 groups ( P>0.05). All patients were followed up for (44.5±13.3) months after surgery. The rate of anatomical reduction in the non-impaction group (96.0%, 48/50) was significantly higher than that in the impaction group (57.6%, 19/33) ( P<0.05), and the good and excellent rate by the modified Merle d'Aubigné & Postel scale at the last follow-up in the non-impaction group (84.0%, 42/50) was significantly higher than that in the impaction group (51.5%, 17/33) ( P<0.05). There was no significant difference in the incidence of complications between the 2 groups ( P>0.05). After adjusting for age and gender, the difference in hip function was still significantly different between the 2 groups ( OR=0.23, 95% CI: 0.06 to 0.79, P=0.020). The effect of posterior wall impaction on functional outcomes was statistically significant in patients aged ≥50 years ( P=0.008), whereas the difference was not statistically significant in patients aged <50 years ( P=0.194). Conclusions:Compared with non-impaction ones, acetabular fractures of posterior wall impaction tend to lead to poorer quality of reduction, which in turn affects the postoperative recovery of hip joint function. The impact of impaction fractures on functional recovery is more significant in patients aged 50 years and above.

Objective To investigate the expression and clinical significance of serum long non-coding RNA small nucleolar RNA host gene 16(lncRNA SNHG16)and mothers against decapentaplegic homolog 4(SMAD4)in elderly patients with chronic obstructive pulmonary disease(COPD)and pulmonary infection(PI).Methods A total of 237 elderly COPD patients admitted to the hospital from January 2021 to January 2023 were enrolled in the study.Among them,117 patients with concomitant PI were classified as the concur-rent group,and 120 patients without concomitant PI were classified as the COPD group.Real-time fluores-cence quantitative polymerase chain reaction(qRT-PCR)was applied to detect the expression level of serum lncRNA SNHG16 in two groups.Enzyme linked immunosorbent assay(ELISA)was applied to detect the lev-el of SMAD4 in patients'serum.Simplified clinical pulmonary infection scale(sCPIS)was used to evaluate the degree of PI of patients in the concurrent group.Multivariate Logistic regression was applied to analyze the in-fluencing factors of PI in elderly COPD patients.Correlation between serum lncRNA SNHG16,SMAD4 levels and sCPIS in elderly COPD patients with PI was analyzed by using Spearman correlation analysis.Receiver op-erating characteristic(ROC)curve was applied to analyze the diagnostic value of serum lncRNA SNHG16 and SMAD4 levels in elderly COPD patients with PI.Results The serum relative expression level of lncRNA SNHG16 in the concurrent group was higher than that in the COPD group,but the serum SMAD4 level was lower than that in the COPD group(P<0.05).In addition,the proportions of patients with age≥70 years,smoking history,complicated with diabetes and COPD course≥5 years and the levels of tumor necrosis fac-tor-α(TNF-α),interferon-γ(INF-γ)in the concurrent group were higher than those in the COPD group,and FEV1/FVC and the level of interleukin-10(IL-10)in concurrent group were lower than those in COPD group(P<0.05).Multivariate Logistic analysis showed that age≥70 years old,complicated with diabetes,COPD course≥5 years,high levels of TNF-α,INF-γ and lncRNA SNHG16 were risk factors for elderly patients with COPD complicated with PI(P<0.05),but high FEV1/FVC and high levels of SMAD4 and IL-10 were protective factors(P<0.05).Spearman correlation analysis showed that serum relative expression level of ln-cRNA SNHG16 was positively correlated with sCPIS in COPD patients with PI(r=0.505,P<0.001),while SMAD4 level was negatively correlated with sCPIS(r=-0.550,P<0.001).The area under the curve(AUC)of the combined diagnosis of serum lncRNA SNHG16 and SMAD4 for PI in elderly COPD patients was higher than those of individual diagnosis(Z=2.416,P=0.016;Z=2.375,P=0.018).Conclusion The serum relative expression level of lncRNA SNHG16 increases and SMAD4 level decreases in elderly COPD pa-tients with PI,both are influencing factors for elderly COPD patients complicated with PI,and both are related to the degree of PI in patients,and both have diagnostic value for elderly COPD patients complicated with PI,and the diagnostic efficacy of combined detection is better.

Objective: To evaluate the anti-fatigue effects of different extracts from Cistanche tubulosa (Schenk) Wight (C. tubulosa, Rou Cong Rong), focusing on central and exercise-induced fatigue in mice. This study investigated the pharmacological effects of the total oligosaccharides, polysaccharides, and phenylethanoid glycosides (CPhGs) extracted from C. tubulosa. Methods: Models of sleep deprivation and forced swimming fatigue were established to simulate central and exercise-induced fatigue. The mice were treated with different extracts of C. tubulosa, and their effects were assessed using behavioral tests to measure exercise capacity, learning, and memory function. Biochemical analyses were performed to evaluate the changes in serum and brain neurotransmitter levels, liver and muscle glycogen storage, and various fatigue-related biomarkers. Results: This study found that treatment with C. tubulosa extract improved exercise capacity, learning, and memory in mice. Total oligosaccharides from C. tubulosa enhanced adrenocorticotropic hormone, cholinesterase, and thyroid-stimulating hormone levels, reduced cortisol levels in central fatigue models, and ameliorated biochemical markers of exercise-induced fatigue, including lowering lactic acid, blood urea nitrogen, and malondialdehyde levels. Among the tested extracts, the total oligosaccharides showed the most comprehensive anti-fatigue effects. Conclusion The anti-fatigue effects of C. tubulosa, particularly those of its total oligosaccharides, are pronounced in both central and exercise-induced fatigue. These effects are mediated by the regulation of neurotransmitter levels, enhancement of glycogen storage, and improvement of antioxidant enzyme activity, suggesting potential therapeutic benefits in fatigue-related conditions.

Objective:To explore the correlation between hip muscle factors measured with CT imaging and recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures.Methods:A prospective cohort study was conducted on the clinical data of 680 elderly patients with hip fractures admitted to Beijing Jishuitan Hospital of Capital Medical University from November 2018 to December 2019. The patients were assigned to dependent group and assistant group according to whether they regained pre-injury independent mobility within 1 year after surgery. Gender, age, body mass index, personal history, living habits, past diseases, Charlson comorbidity index, laboratory test indicators, fracture types, anesthesia types, surgical methods, rehabilitation training, time from injury to surgery, and hip muscle parameters in both groups were recorded. OsiriX software was employed in the measurement of the hip muscles to measure the muscle area and density of the gluteus maximus and gluteus medius/minimus on CT images, and the average values were calculated as hip muscle area and density. Then the variables of hip muscle area and density were converted seperately to gender-normalized Z-scores, and were divided into high-area group ( Z≥0) and low-area group ( Z<0), and high-density group ( Z≥0) and low-density group ( Z<0) respectively. Observable variables were primarily analyzed using univariate analysis between the independent group and assistant group. Those variables with statistically significant differences in the univariate analysis or would potentially affect mobility recovery according to previous researches although there were no statistical significance were included in a multivariate Logistic regression analysis. Three Logistic regression models were designed (Model 1 uncorrected, Model 2 corrected for gender, age and body mass index, Model 3 corrected for variables in Model 2 and other variables included after above-mentioned analysis) to analyze whether muscle parameters were risk factors for recovery of independent mobility. Additionally, generalized estimating equations were used for repeated measurement to analyze the correlation between hip muscle area and recovery of independent mobility after surgery. Results:Compared to the assistant group, the independent group were younger in age, with lower rate of living alone, being housebound, cognitive impairment, and Charlson comorbidity index, lower level of hemoglobin and albumin, higher rate of femoral neck fractures, lower rate of internal fixation, shorter time from injury to surgery, larger hip muscle area, and higher hip muscle density ( P<0.05 or 0.01). Multivariate Logistic regression analysis showed that, in the fully corrected Model 3, only hip muscle area remained significantly correlated with recovery of independent mobility ( P<0.05), while no significant difference was found between the high-density group and low-density group ( P>0.05). In the repeated measurement, patients in the high-area group were 1.84 times more likely to restore independent mobility than those in the low-area group ( OR=1.84, 95% CI 1.33, 2.53, P<0.01). Conclusions:Hip muscle area measured with CT imaging is closely correlated to the recovery of independent mobility within 1 year after surgery in elderly patients with hip fractures. Moreover, larger hip muscle area indicates a larger likelihood of recovery of independent mobility.

Objective To summarize the occurrence of complications in renal graft biopsy,and to analyze the indications for puncture and types of pathological diagnosis.Methods The data of 703 samples of ultrasound-guided renal graft biopsy from 644 kidney transplant recipients from January 1,2017,to December 31,2022 was retrospectively analyzed.The puncture qualification rate,complications,indicative biopsy indications and pathological diagnosis types were analyzed.The application of surveillance biopsy and pathological diagnosis were also analyzed.Results The qualification rate of renal tissue puncture biopsy was 99.9％,and the complications of puncture bleeding included one sample of perinephric hematoma and one sample of hematuria.Increased serum creatinine(76.8％)and proteinuria(13.8％)were the main indications for puncture,and 48 samples(6.8％)were surveillance biopsy for the assessment of therapeutic effects.A total of 399 samples of pathological diagnosis of rejection,including 293 samples of cellular rejection reaction,60 samples of antibody rejection reaction,and 46 samples of mixed rejection reaction.One hundred and ninety-five samples of recurrence or new-onset kidney disease,mainly including 144 samples of IgA nephropathy and 42 samples of focal segmental glomerulosclerosis.Fifty-seven samples of infection related kidney disease,including 56 samples of BK virus-associated nephropathy(BKVAN).Thirty-one samples of calcineurin inhibitor(CN1)nephrotoxicity injury,including 15 samples of acute CNI nephrotoxicity injury and 16 samples of chronic CNI nephrotoxicity injury.Forty-five samples for other diagnoses.Conclusions The success rate and safety of renal graft biopsy are high,and at present,cellular rejection reaction is still the main pathological diagnosis of indicative biopsy for renal graft.

Objective:To explore the attitude of kidney transplant (KT) recipients towards xenotransplantation and explore its related influencing factors to provide auxiliary references for the clinical research of xenotransplantation in China.Methods:The questionnaire data of "Attitude survey of KT recipients towards xenotransplantation" were collected from 194 KT recipients followed up at Organ Transplant Center of Affiliated Tongji Hospital. Nonparametric tests were utilized for comparing score differences and χ2 tests for comparing responses to specific questions. Variables with statistical significance in non-parametric test were included into multifactor linear regression analysis for exploring the influencing factors of recipients' attitudes towards xenotransplantation. Results:KT recipients had a higher score (75 points) on attitude scale of xenotransplantation. "Cognitive preference" dimension scored the highest (85 points); "Fear of risk" dimension scored lowest (50 points). The results of univariate analysis indicated that gender ( P=0.020), medical background ( P=0.006) and knowledge of clinical trial cases ( P<0.001) were the influencing factors of score of cognitive preference. Educational background ( P=0.029) was the factor affecting the score of "risk concern" dimension. Age ( P=0.028) and knowledge of clinical trial cases ( P=0.001) were the factors influencing the score of "psychosocial" dimension. Whether medical background ( P=0.018) and knowledge of clinical trial cases ( P=0.008) were the factors influencing the score of "efficacy expectation" dimension; Gender ( P=0.010), medical background ( P=0.018) and knowledge of clinical trial cases ( P=0.008) were the factors influencing total score. The results of multi-factor analysis revealed that gender ( B=-0.821, 95% CI: -1.419~0.223, P=0.007), medical background ( B=0.938, 95% CI: 0.097~1.779, P=0.029) and knowledge of clinical trials of xenotransplantation in the United States ( B=1.498, 95% CI: 0.887~2.110, P<0.001) was the influencing factor of cognitive preference. Educational background (B=-0.693, 95% CI: -1.353~-0.034, P=0.040) was the influencing factor of score on "risk concern" dimension. Knowledge of clinical trials of xenotransplantation in the United States ( B=1.075, 95% CI: 0.418~1.731, P=0.001) was an influencing factor of score on "social psychological" dimension; Knowledge of clinical trials of xenotransplantation in the United States ( B=0.710, 95% CI: 0.063~1.358, P=0.032) was an influencing factor of score on "efficacy expectation" dimension; Gender ( B=-2.259, 95% CI: -4.094~-0.423, P=0.016), medical background ( B=2.799, 95% CI: 0.219~5.378, P=0.034) and knowledge of clinical trials of xenotransplantation in the United States ( B=3.237, 95% CI: 1.360~5.114, P=0.001) were the influencing factors of total score. Conclusions:KT recipients have a higher awareness rate of xenotransplantation and a better acceptance of xenotransplantation in general. Those males with medical background and knowing clinical cases of xenotransplantation demonstrate a better attitude towards xenotransplantation. More concerned about the risk of infection, respondents expect heterologous pig kidneys to achieve the same long-term survival as allogeneic kidneys.

Objective:To explore the efficacy and safety of daratumumab in late antibody-mediated rejection (late AMR) after kidney transplantation (KT).Methods:From December 2020 to December 2021, the relevant clinical data were reviewed for 8 patients with late AMR after receiving daratumumab at Affiliated Tongji Hospital. In intensive phase, the combination of plasma exchange (PP)/intravenous immunoglobulin (IVIG) and daratumumab were dosed once a week; in maintenance phase, once every 2 to 4 weeks. The levels of donor-specific antibody (DSA) and renal function were compared pre-treatment and Month 3/12 post-treatment. The treatment-related toxicities were observed. Independent sample T test was utilized for inter-group comparison.Results:The median treatment course during intensive period was 9(4-17) sessions. Maintenance treatment lasted for 5 to 19 months and 2 cases withdrew after 5 to 6 treatments for achieving antibody clearance. A total of 11 DSAs were detected in 8 recipients. At Month 3/12, mean fluorescent intensity (MFI) of DSA was 6 016±4 775 and 6 438±3 668. Both were significantly lower than 11 944±5 237 pre-treatment and the difference was statistically significant ( P=0.012, 0.004). Seven recipients achieved stable renal function during treatment and one recipient resumed hemodialysis at Month 18 due to acute rejection. Glomerular filtration rate of 7 recipients was (40.6±20.1), (53.6±20.9) and (49.0±17.2) ml·min -1· (1.73 m 2) -1 pre-treatment and Month 3/12 and no significant differences existed among different timepoints. During follow-ups, 2 cases developed mild nasal congestion during an early stage of daratumumab infusion while the remainders had no obvious discomfort during infusion and tolerance was decent. Conclusion:Early combination of daratumumab with PP/IVIG, followed by a course of daratumumab has demonstrated an excellent antibody reduction effect on late AMR. During treatment, renal function remains generally stable.

This study aimed to explore the effects and mechanisms of total flavones of Abelmoschus manihot(TFA), the extracts from traditional Chinese medicine indicated for kidney diseases, on insulin resistance(IR) and podocyte epithelial-mesenchymal transition(EMT) in diabetic kidney disease(DKD), and further to reveal the scientific connotation. Thirty-two rats were randomly divided into a normal group, a model group, a TFA group, and a rosiglitazone(ROS) group. The modified DKD model was induced in rats by methods including high-fat diet feeding, unilateral nephrectomy, and streptozotocin(STZ) intraperitoneal injection. After modeling, the rats in the four groups were given double-distilled water, TFA suspension, and ROS suspension correspondingly by gavage every day. At the end of the 8th week of drug administration, all rats were sacrificed, and the samples of urine, blood, and kidney tissues were collected. The parameters and indicators related to IR and podocyte EMT in the DKD model rats were examined and observed, including the general condition, body weight(BW) and kidney weight(KW), the biochemical parameters and IR indicators, the protein expression levels of the key signaling molecules and structural molecules of slit diaphragm in the renal insulin receptor substrate(IRS) 1/phosphatidylinositol 3-kinase(PI3K)/serine-threonine kinase(Akt) pathway, foot process form and glomerular basement membrane(GBM) thickness, the expression of the marked molecules and structural molecules of slit diaphragm in podocyte EMT, and glomerular histomorphological characteristics. The results showed that for the DKD model rats, both TFA and ROS could improve the general condition, some biochemical parameters, renal appearance, and KW. The ameliorative effects of TFA and ROS were equivalent on BW, urinary albumin(UAlb)/urinary creatinine(UCr), serum creatinine(Scr), triglyceride(TG), and KW. Secondly, they could both improve IR indicators, and ROS was superior to TFA in improving fast insulin(FIN) and homeostasis model assessment of insulin resistance(HOMA-IR). Thirdly, they could both improve the protein expression levels of the key signaling molecules in the IRS1/PI3K/Akt pathway and glomerulosclerosis in varying degrees, and their ameliorative effects were similar. Finally, both could improve podocyte injury and EMT, and TFA was superior to ROS. In conclusion, this study suggested that podocyte EMT and glomerulosclerosis could be induced by IR and the decreased activation of the IRS1/PI3K/Akt pathway in the kidney in DKD. Similar to ROS, the effects of TFA in inhibiting podocyte EMT in DKD were related to inducing the activation of the IRS1/PI3K/Akt pathway and improving IR, which could be one of the scientific connotations of TFA against DKD. This study provides preliminary pharmacological evidence for the development and application of TFA in the field of diabetic complications.
Rats ; Animals ; Diabetic Nephropathies/drug therapy* ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Abelmoschus/chemistry* ; Podocytes ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition ; Flavones/pharmacology* ; Insulin Resistance ; Reactive Oxygen Species ; Diabetes Mellitus

Renal tubular injury in patients with diabetic kidney disease(DKD) may be accompanied by glomerular and microvascular diseases. It plays a critical role in the progression of renal damage in DKD, and is now known as diabetic tubulopathy(DT). To explore the multi-targeted therapeutic effects and pharmacological mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese medicine for treating kidney disease, in attenuating DT, the authors randomly divided all rats into four groups: a normal control group(normal group), a DT model group(model group), a DT model+TFA-treated group(TFA group) and a DT model+rosiglitazone(ROS)-treated group(ROS group). The DT rat model was established based on the DKD rat model by means of integrated measures. After successful modeling, the rats in the four groups were continuously given double-distilled water, TFA suspension, and ROS suspension, respectively by gavage every day. After 6 weeks of treatment, all rats were sacrificed, and the samples of their urine, blood, and kidneys were collected. The effects of TFA and ROS on various indicators related to urine and blood biochemistry, renal tubular injury, renal tubular epithelial cell apoptosis and endoplasmic reticulum stress(ERS), as well as the activation of the protein kinase R-like endoplasmic reticulum kinase(PERK)-eukaryotic translation initiation factor 2α(eIF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP) signaling pathway in the kidney of the DT model rats were investigated. The results indicated that hypertrophy of renal tubular epithelial cells, renal tubular hyperplasia and occlusion, as well as interstitial extracellular matrix and collagen deposition occurred in the DT model rats. Moreover, significant changes were found in the expression degree and the protein expression level of renal tubular injury markers. In addition, there was an abnormal increase in tubular urine proteins. After TFA or ROS treatment, urine protein, the characteristics of renal tubular injury, renal tubular epithelial cell apoptosis and ERS, as well as the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney of the DT model rats were improved to varying degrees. Therein, TFA was superior to ROS in affecting the pathological changes in renal tubule/interstitium. In short, with the DT model rats, this study demonstrated that TFA could attenuate DT by multiple targets through inhibiting renal tubular ERS-induced cell apoptosis in vivo, and its effect and mechanism were related to suppressing the activation of the PERK-eIF2α-ATF4-CHOP signaling pathway in the kidney. These findings provided preliminary pharmacological evidence for the application of TFA in the clinical treatment of DT.
Rats ; Animals ; Abelmoschus ; Reactive Oxygen Species/metabolism* ; Flavones/pharmacology* ; Endoplasmic Reticulum Stress ; Diabetic Nephropathies/drug therapy* ; Apoptosis ; Diabetes Mellitus