Objective To investigate the value of repeat renal biopsy in the treatment and prognosis of nephrotic syndrome(NS)and acute kidney injury(AKI)following immunosuppressive therapy in patients with lupus nephritis(LN). Methods A retrospective analysis was conducted for the clinicopathological data and follow-up records of LN patients undergoing repeat renal biopsy at Peking Union Medical College Hospital from January 1,2009 to December 31,2021. Results A total of 76 patients(55 females,72.4%)were included in this study,with the mean age at the first biopsy being(29.0±10.4)years,the median inter-biopsy interval of 4.0(2.0,7.0) years,and the median total follow-up duration of 7.5(5.0,13.8)years.Pathological transformation occurred in 46(60.5%)patients,and 2 patients had comorbid diabetic nephropathy.At repeat renal biopsy,50(65.8%) patients presented NS.These patients demonstrated lower estimated glomerular filtration rate(eGFR)(P<0.001),higher chronicity index(CI)(P=0.029),and higher complement C3(P<0.001)and C4(P<0.001)levels than those with NS at the first renal biopsy(n=50).Among the 28(36.8%) patients with AKI at repeat renal biopsy,8(28.6%)experienced acute exacerbation of chronic renal insufficiency.These patients exhibited higher serum creatinine level(P=0.002),C4 level(P=0.033),CI(P=0.042),and prevalence of thrombotic microangiopathy(P=0.046)than the patients showing AKI at the first renal biopsy(n=16),while the activity index(AI)showed no significant difference(P=0.051).Over 50% of NS and AKI patients underwent treatment modifications post-repeat renal biopsy,with clinical remission rates comparable to those after the first renal biopsy(both P>0.05).Elevated CI(≥5,P=0.001)and serum creatinine(≥140 μmol/L,P<0.001)at repeat renal biopsy were identified as independent risk factors for poor prognosis.The patients with AKI at repeat renal biopsy had higher incidence of endpoint events than the non-AKI patients(P=0.015).Neither AKI at the first renal biopsy nor NS at both biopsies had significant associations with prognosis. Conclusions Repeat renal biopsy reveals not only sustained high disease activity but also accelerates chronic progression in LN patients,which underscore its critical role in guiding the therapy for severe LN post-immunosuppression.AKI,CI≥5,and serum creatinine ≥140 μmol/L at repeat renal biopsy are strongly associated with poor prognosis.
Humans ; Lupus Nephritis/drug therapy* ; Female ; Retrospective Studies ; Adult ; Male ; Prognosis ; Biopsy ; Kidney/pathology* ; Acute Kidney Injury/pathology* ; Nephrotic Syndrome/pathology* ; Glomerular Filtration Rate ; Young Adult ; Immunosuppressive Agents/therapeutic use* ; Middle Aged

Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration.Despite extensive studies on mineralized parenchymal tissue rebuilding,regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet.Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage.But to date,the absence of promising therapeutic biomaterials/scaffolds remains.The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds.To address these issues,in this study,we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds.Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses.A feasible scaffold,polylactic acid electrospinning membrane(PLA),was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center,meanwhile supporting proper osteointegration with defect bony edges.Especially,transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered.This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing,offering clinicians potential choices for regenerating such complicated injuries.

OBJECTIVE To study the effects of methimazole on the urinary metabolomics of hyperthyroidism rats， and to preliminarily investigate its possible mechanism. METHODS Thirty SD rats were randomly divided into control group， model group and methimazole group， with 10 rats in each group. Except for the control group， the rats in the other two groups were given Levothyroxine sodium tablets 160 mg/kg by intragastric administration for 15 days； at the same time， methimazole group was additionally given methimazole 3.6 mg/kg daily by intragastric administration every day. The basic condition of the rats was observed， and the body weight and anal temperature were measured. After the last medication， the serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， free triiodothyronine （FT3）， free tetraiodothyronine （FT4）， and thyroid stimulating hormone （TSH） were determined； 24-hour urine was collected on the 15th day after administration. UPLC-TOF-MS was used to analyze the urine metabolomics of rats. Principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen out related differential metabolites， and potential metabolic pathways were analyzed by using HMDB and KEGG. RESULTS Compared with the control group， the rectal temperature， serum levels of T3， T4， FT3 and FT4， the expressions of differential metabolites sebacic acid， cholic acid 3-O-glucuronic acid and N6， N6， N6-trimethyl-L-lysine in urine were significantly up-regulated， while body weight， serum level of TSH， the expressions of deoxycytidine and 2-oxo-4-methylthiobutanoic acid in urine were significantly down-regulated （P＜0.01）. Compared with model group， above indexes of rats were reversed significantly in methimazole group （P＜0.01 or P＜0.05）. Above five differential metabolites were mainly involved in four signaling pathways: pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism. CONCLUSIONS Methimazole might improve hyperthyroidism by modulating the four pathways of pentose and glucuronate interaction， lysine degradation， cysteine and methionine metabolism， and pyrimidine metabolism.

Objective:To compare the efficacy and safety of red light and daylight photodynamic therapy in the treatment of facial common acne.Methods:From March 2019 to November 2019, 52 patients with facial common acne who received 5-aminolevulinic acid photodynamic therapy in the Department of Dermatology, Chongqing Hospital of Traditional Chinese Medicine were enrolled, including 34 males and 18 females, aged 18-35 years, with an average age of 23.2 years. A 5% concentration of 5-aminolevulinic acid was applied to the entire face, with the right side of the face being exposed to red light for 20 minutes and the left side to daylight for 2 hours. The treatment was administered once a week for a total of 4 sessions. After the treatment, the acne remission, adverse reactions, and patient satisfaction on both sides of the face were compared.Results:Compared with before treatment, the number of inflammatory and non-inflammatory lesions on both sides of the face in the enrolled patients decreased, and there was no significant difference in the clearance rate of skin lesions between the two sides [53.7% (28/52) vs 59.1% (31/52), χ 2=0.89, P>0.05]. The overall effective rate on the red light side was 88.5% (46/52), and 82.7% (43/52) on the daylight side, with no significant difference between the two (χ 2=0.38, P>0.05). In terms of adverse reactions, mild erythema was common, and it was less on the daylight side than on the red light side [34.6% (18/52) vs 19.2% (10/52), χ 2=5.98, P<0.05]. During the treatment period, the pain score on the daylight side decreased compared to the red light side [(7.6±2.3) vs (4.1±1.3), t=13.10, P<0.001]. Overall satisfaction with the daylight side was reported in 49 cases (94.2%), and with the red light side in 37 cases (71.2%), with the daylight side being higher than the red light side, and the difference was statistically significant (χ 2=9.60, P<0.05). Conclusion:Daylight photodynamic therapy is as effective as red light photodynamic therapy for common acne, but it produces fewer adverse reactions and higher patient satisfaction.

Vascular calcification is a highly regulated process of ectopic calcification in cardiovascular system while no effective intervention can be clinically performed up to date.As vascular calcification undergoes a common regulatory mechanism within bone formation,bone morphogenetic protein 7(BMP-7)main-tains contractile phenotype of vascular smooth muscle cells and further inhibits vascular calcification via promoting the process of osteoblast differentiation,reducing ectopic calcification pressure by increasing bone formation and reducing bone resorption.This work systematically reviews the role of BMP-7 in vascular calcifi-cation and the possible mechanism,and their current clinical application as well.The current proceedings may help develope early diagnostic strategy and therapeutic treatment with BMP-7 as a new molecular marker and potential drug target.The expec-tation could achieve early prevention and intervention of vascular calcification and improve poor prognosis on patients.

A liquid chromatography-tandem mass spectrometry method was established and validated for determining the concentrations of costunolide(CO), piperine(PI), agarotetrol(AG), glycyrrhizic acid(GL), vanillic acid(VA), and glycyrrhetinic acid(GA) in rat plasma. This method was then applied to the toxicokinetic study of these six compounds in rats with chronic cerebral ischemia(CCI) following multiple oral doses of Zhachong Shisanwei Pills. Finally, the effects of continuous multiple-dose administration of Zhachong Shisanwei Pills on the liver of CCI rats were investigated. The results showed that after oral administration of different doses of Zhachong Shisanwei Pills, the in vivo exposure of AG, VA, and GA was relatively high, with AUC_(0-∞) values ranging from 604.0-2 494.2, 1 305.4-4 634.5, and 2 177.5-4 045.7 h·ng·mL~(-1), respectively, while the exposure of CO, PI, and GL was relatively low, with AUC_(0-∞) values ranging from 37.8-238.2, 2.4-17.0, and 146.9-408.5 h·ng·mL~(-1), respectively. The C_(max) and AUC_(0-∞) of the six compounds were positively correlated with the administered dose. The T_(max) of PI and AG ranged from 0.3 to 2.0 h, their T_(1/2) ranged from 0.8 to 2.9 h, and their mean residence time(MRT) ranged from 1.0 to 3.7 h. The T_(max) of GL and VA was shorter(0.4-1.9 h), while their T_(1/2)(2.6-5.9 h) and MRT(2.5-8.5 h) were longer. Both CO and GA exhibited a bimodal phenomenon, with T_(max) ranging from 1.6 to 6.6 h, T_(1/2) ranging from 2.8 to 7.7 h, and MRT ranging from 4.1 to 12.9 h. Liver histopathology after 28 days of continuous multiple-dose administration of Zhachong Shisanwei Pills showed that the liver tissue remained normal at a low dose(crude drug 0.8 g·kg~(-1), approximately 5 times the clinical equivalent dose). However, as the dose increased(crude drug 1.1-3.0 g·kg~(-1), 6.9-18.8 times the clinical equivalent dose), varying degrees of liver damage were observed. Blood biochemical tests revealed no significant changes in the serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP), and total bile acid(TBA) in CCI rats from administration groups 1 to 3(crude drug 0.8, 1.1, 1.5 g·kg~(-1)). However, ALT, AST, ALP, and TBA levels in groups 4 and 5(crude drug 2.1, 3.0 g·kg~(-1)) showed significant increases. This study preliminarily elucidated the toxicokinetic characteristics of the six compounds in Zhachong Shisanwei Pills and their effects on liver tissue in CCI rats, providing data as a reference for clinical use.
Animals ; Tandem Mass Spectrometry/methods* ; Rats ; Drugs, Chinese Herbal/toxicity* ; Male ; Rats, Sprague-Dawley ; Brain Ischemia/blood* ; Chromatography, Liquid/methods* ; Polyunsaturated Alkamides/blood* ; Piperidines/toxicity* ; Benzodioxoles/toxicity* ; Alkaloids/blood* ; Liquid Chromatography-Mass Spectrometry

Rapid turnover of the intestinal epithelium is a critical strategy to balance the uptake of nutrients and defend against environmental insults, whereas inappropriate death promotes the spread of inflammation. PPARα is highly expressed in the small intestine and regulates the absorption of dietary lipids. However, as a key mediator of inflammation, the impact of intestinal PPARα signaling on cell death pathways is unknown. Here, we show that Pparα deficiency of intestinal epithelium up-regulates necroptosis signals, disrupts the gut vascular barrier, and promotes LPS translocation into the liver. Intestinal Pparα deficiency drives age-related hepatic steatosis and aggravates hepatic fibrosis induced by a high-fat plus high-sucrose diet (HFHS). PPARα levels correlate with TRIM38 and MLKL in the human ileum. Inhibition of PPARα up-regulates necroptosis signals in the intestinal organoids triggered by TNF-α and LPS stimuli via TRIM38/TRIF and CREB3L3/MLKL pathways. Butyric acid ameliorates hepatic steatosis induced by intestinal Pparα deficiency through the inhibition of necroptosis. Our data suggest that intestinal PPARα is essential for the maintenance of microenvironmental homeostasis and the spread of inflammation via the gut-liver axis.

Objective To establish the GC characteristic choromatogram of Huanglian Shangqing tablets(pills and granules),and to investigate the quality of the medicinal materials(Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae)containing volatile oil in Huanglian Shangqing tablets(pills and granules).Methods Agilient HP-5 capillary column(30 m×0.32 mm,0.25 μm)was used with temperature programming,the split ratio was 5∶1,the split flow was 5 mL·min-1,the injection volume was 1 μL,and the inlet temperature was 250℃.A hydrogen flame ionization detector was used,with the detector temperature of 260℃,and the column flow was 1 mL·min-1.The quality of samples from different manufacturers was evaluated by using the GC characteristic choromatogram of volatile oil and the identification of characteristic peaks,combined with similarity analysis and principal component analysis.Results The characteristic chromatograms of 192 batches of samples from 56 manufacturers were established.The peaks of Weeping Forsythia,Mentha Hyplocalyx and Herba Schizonepetae were identified as α-pinene and β-pinene,menthol and menthone,and pulegone respectively.The GC choromatogram of volatile oil components in Huanglian Shangqing tablets(pills)from different manufacturers were quite different,and some peaks of indicator components in the products from a few manufacturers have missing.Conclusion The established GC characteristic chromatograms can reflect the product quality status and can be used for the quality evaluation and product quality control of Huanglian Shangqing tablets(pills and capsules).Huanglian Shangqing tablets(pills and capsules)from some manufacturers are insufficient in the active ingredients of volatile oil,therefore,the product quality needs to be improved.

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q₁, Q₃) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q₁, Q₃) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans ; Male ; Middle Aged ; Young Adult ; Adult ; COVID-19/epidemiology* ; Incidence ; SARS-CoV-2 ; Logistic Models

Objective: To evaluate the secondary attack rates of the SARS-CoV-2 Omicron variant and the associated factors. Methods: A total of 328 primary cases and 40 146 close contacts of the SARS-CoV-2 Omicron variant routinely detected in local areas of Jiangsu Province from February to April 2022 were selected in this study, and those with positive nucleic acid test results during 7 days of centralized isolation medical observation were defined as secondary cases. The demographic information and clinical characteristics were collected, and the secondary attack rate (SAR) and the associated factors were analyzed by using a multivariate logistic regression model. Results: A total of 1 285 secondary cases of close contacts were reported from 328 primary cases, with a SAR of 3.2% (95%CI: 3.0%-3.4%). Among the 328 primary cases, males accounted for 61.9% (203 cases), with the median age (Q₁, Q₃) of 38.5 (27, 51) years old. Among the 1 285 secondary cases, males accounted for 59.1% (759 cases), with the median age (Q₁, Q₃) of 34 (17, 52) years old. The multivariate logistic regression model showed that the higher SAR was observed in the primary male cases (OR=1.632, 95%CI: 1.418-1.877), younger than 20 years old (OR=1.766, 95%CI: 1.506-2.072),≥60 years old (OR=1.869, 95%CI: 1.476-2.365), infected with the BA.2 strain branch (OR=2.906, 95%CI: 2.388-3.537), the confirmed common cases (OR=2.572, 95%CI: 2.036-3.249), and confirmed mild cases (OR=1.717, 95%CI: 1.486-1.985). Meanwhile, the higher SAR was observed in the close contacts younger than 20 years old (OR=2.604, 95%CI: 2.250-3.015),≥60 years old (OR=1.287, 95%CI: 1.052-1.573) and exposure for co-residence (OR=27.854, 95%CI: 23.470-33.057). Conclusion: The sex and age of the primary case of the Omicron variant, the branch of the infected strain, case severity of the primary case, as well as the age and contact mode of close contacts are the associated factors of SAR.
Humans ; Male ; Middle Aged ; Young Adult ; Adult ; COVID-19/epidemiology* ; Incidence ; SARS-CoV-2 ; Logistic Models