Objective:To investigate the clinicopathological features and the prognosis of IgA nephropathy (IgAN) in children with massive proteinuria.Methods:It was a retrospective cohort study. Clinical data of IgAN children with massive proteinuria admitted to the Department of Nephrology, Children's Hospital Affiliated to Capital Institute of Pediatrics from January 2008 to December 2021 were retrospectively analyzed. Patients were divided into effective group and ineffective group according to whether urine protein turned negative after 6 months of initial treatment. The follow-up endpoint event was defined as a reduction in proteinuria of less than 50% or end-stage renal disease (ESRD) achievement. MedCalc software was used to perform Kaplan-Meier survival analysis, and Log-rank test was used to compare the difference of renal survival between the two groups.Results:A total of 127 patients were diagnosed as primary IgAN by renal biopsy, of whom 57 patients with IgAN showed massive proteinuria. These 57 IgAN patients with macroproteinuria accounted for 44.9% of the total IgAN patients and were enrolled in the study. Among the 57 cases, 33 cases (57.9%) were Lee's grade Ⅲ, 11 cases (19.3%) were below Lee's grade Ⅲ, and 13 cases (22.8%) were above Lee's grade Ⅲ. The follow-up time was 4.0 (3.0,5.8) years. In the initial treatment, among 57 patients, 46 (80.7%) were effective (effective group) and 11 (19.3%) were ineffective (ineffective group). Compared with the effective group, the ineffective group had a higher proportion of concurrent AKI at the onset of disease and longer recovery time of renal function, with significant difference (7/11 vs. 13/46, χ2=4.878, P=0.027). Compared with the effective group, the proportion of Lee grade Ⅲ or above was higher in the ineffective group, and the difference was statistically significant (5/11 vs. 8/46, χ2=3.971, P=0.046). There were significant differences in endocapillary hypercellularity (E1), segmental glomerulosclerosis or adhesion (S1) and cellular/fibrocellular crescents (C2) of Oxford classification between IgAN children with Lee grade Ⅲ or below and those over Lee grade Ⅲ (11/13 vs. 20/44, χ2=6.204, P=0.013; 12/13 vs. 17/44, χ2=11.566, P=0.001; 9/13 vs. 7/44, χ2=14.131, P=0.001). Among 57 patients, endpoint events occurred in 2 patients who both were urinary protein unmitigated, and none of the children progressed to ESRD. There was no significant difference in cumulative renal survival between the two groups by Kaplan-Meier survival analysis and Log-rank test ( χ2=0.537, P=0.460) after addition of calcineurin inhibitors (CNIs) to the initial treatment ineffective group. Conclusions:Macroproteinuria is the prominent manifestation of IgAN in children. The pathological type is mainly Lee grade Ⅲ. Children with macroproteinuria have a good prognosis in the short and medium term after active treatment. For IgAN with macroproteinuria that does not respond well to initial treatment, AKI is more common at onset, and renal function recovery time is longer. The application of CNIs may have a certain effect on improving the renal outcome of IgAN with massive proteinuria.

Bartter syndrome (BS, OMIM #601678) is a rare inherited salt-losing tubulopathy characterized by hypokalemia metabolic alkalosis with secondary renin-angiotensin-aldosterone system activation. As reported, BS type 1 is generally presented prenatal and neonatal period, and symptoms usually appear before and after birth or in infancy, accompanied by severe salt loss, whilst kidney function remains mostly normal. In this study, we report a case of BS type 1 with childhood onset and proteinuria and renal impairment. The child was born preterm due to hyperamniotic fluid, but there were no apparent symptoms after birth until the age of 3 when the child began to present with polydipsia, polyuria and increased nocturnal uria. At the age of 5, she had elevated serum creatinine level and proteinuria. After admission, she was diagnosed with chronic tubulointerstitial disease and stage 2 chronic kidney disease(CKD). According to the chloride clearance test, the abnormal function of medullary thick ascending limb Henle′s loop, was confirmed and BS type 1 was diagnosed by gene sequencing. After active management of complications, kidney function of the child improved. In the long-term follow-up, the urinary protein amount of the child still increased, eGFR slowly decreased, and the child was currently in the CKD2 stage. Children with prenatal BS may not present typical clinical manifestations immediately after birth until the onset of relevant clinical symptoms in childhood. BS type 1 patients may have renal impairment, which needs to be identified in time. Clinical differentiation diagnosis between BS and Gitelman syndrome can be made by chloride clearance tests. Early diagnosis and treatment are critical to improve prognosis.

The purpose of this study was to enrich the genomic information and provide a basis for further development and utilization of Polygonatum kingianum. The fresh rhizome of P. kingianum was used as the experimental material, and the full-length transcriptome was sequenced by PacBio Sequel platform. The final measured polymerase reads were 1 120 485, with a total of 77.73 GB of data. In NR database, 41 864 homologous sequence alignments were aligned to 5 species; 40 506 were annotated in the KOG database and classified into 26 categories based on their functionality; 69 060 GO annotated 32 functional groups divided into 3 categories: cellular components, molecular functions, and biological processes; 45 779 annotations were added to 145 metabolic pathways in the KEGG database. Among them, there are 127 identified transcripts related to polysaccharide synthesis in the glycolysis/gluconeogenesis metabolic pathway, 144 in the starch and sucrose metabolic pathway, 85 in the amino acid sugar and nucleotide sugar metabolic pathway, and 69 in the fructose and mannose metabolic pathway. In addition, 1 781 transcription factors were detected, distributed in 37 transcription factor families; 180 293 SSR loci were detected, among which single base repeats accounted for the most, accounting for 30.48% of all base repeats, and at least five base repeats, accounting for only 0.14% of single base repeats. The results of this study provide important data supporting for enriching the genomic information of P. kingianum and exploring its effective biosynthetic pathway.

Objective To evaluate the effect of acupuncture at Yin Wei point on postoperative nausea and vomiting(PONV)in female patients undergoing abdominal surgery.The clinical efficacy of postoperative nausea and vomiting(PONV)and its impact on gut microbiota.Methods This study included 184 patients who underwent gynecological laparoscopic surgery in Jinhua Central Hospital from January 2021 to April 2024.They were randomly divided into control group(n=93)and acupuncture group(n=91)using a random number method.At the completion of surgery,the control group received intravenous injection of 5mg of tropisetron hydrochloride.In acupuncture group,on the basis of control group,intervention was performed by needling the palmar Yin Wei points of both forearms for 30 minutes before surgery.The incidence and severity of PONV were compared between two groups of patients.In addition,fecal samples were collected from two groups of patients before and after surgery,and differential analysis of gut microbiota community structure was performed using 16S amplicon absolute quantitative sequencing technology.Results In the 0-24 hours after surgery,40 cases of the acupuncture group and 56 cases of control group experienced PONV.The acupuncture group's PONV incidence was lower than control group's(P＜0.05).The nausea severity of acupuncture group after surgery was significantly lower than that of control groups.The proportion of patients taking antiemetic drugs after surgery in acupuncture group was also significantly lower than that in control group(P＜0.05).Before surgery,the two groups have no significant difference regarding Chao1,ACE,Shannon,and Simpson indices(P＞0.05).After surgery,the acupuncture group's Chao1,ACE,and Shannon indices were significantly higher than control group's(P＜0.05).The Simpson scores of two groups of patients were compared after surgery,and no significant difference was found(P＞0.05).The Observed,Chao1,ACE,and Shannon indices were significantly higher in the acupuncture group after surgery than before(P＜0.05).The incidence of adverse reactions in acupuncture group and control group were 8.8％and 8.6％,respectively,and there was no statistical significance(P＞0.05).Conclusion Acupuncture at Yin Wei point combined with intravenous injection of tropisetron can reduce the incidence of PONV in patients undergoing gynecological laparoscopic surgery.

Exosomes are a kind of extracellular vesicles,which directly stimulate target cells through receptor-mediated interaction,or exert their biological functions by transferring various bioactive molecules to target cells,playing a key role in intercellular communi-cation between cells and their microenvironment.From the perspective of tissue engineering,pulp regeneration refers to the combination of scaffolds,stem cells,and signaling factors implanted into a properly treated pulp cavity.Under the action of scaffolds and signaling factors,stem cells proliferate and differentiate to form pulp dentin-like complexes,restoring pulp function.In recent years,studies have found that p38MAPK,TGF-β/SMAD,Wnt/β-Catenin signaling pathway and some other signaling pathways are important for the se-cretion in regulating pulp regeneration,and play a key role in pulp regeneration.Therefore,this article reviews the mechanism and re-search progress of signaling pathways related to the regulation of pulp regeneration by exosomes.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To investigate the incidence and risk factors for acute kidney injury(AKI)in children with primary nephrotic syndrome(PNS),as well as the role of neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)in the early identification of AKI in these children.Methods A prospective collection of clinical data from children hospitalized with PNS at the Children's Hospital of the Capital Institute of Pediatrics from January 2021 to October 2022 was conducted.The children were divided into two groups based on the presence of AKI:the AKI group(47 cases)and the non-AKI group(169 cases).The risk factors for AKI in children with PNS were identified by multivariate logistic regression analysis.Urinary KIM-1 and NGAL levels were compared between the AKI and non-AKI groups,as well as among the different stages of AKI.Results The incidence of AKI in children with PNS was 21.8%.Multivariate logistic regression analysis revealed that steroid-resistant nephrotic syndrome,gastrointestinal infections,and heavy proteinuria were independent risk factors for AKI in these children with PNS(P<0.05).Urinary KIM-1 and NGAL levels were higher in the AKI group compared to the non-AKI group(P<0.05),and the urinary NGAL and KIM-1 levels in the AKI stage 2 and stage 3 subgroups were higher than those in the AKI stage 1 subgroup(P<0.017).Conclusions KIM-1 and NGAL can serve as biomarkers for the early diagnosis of AKI in children with PNS.Identifying high-risk populations for AKI in children with PNS and strengthening the monitoring of related risk factors is of significant importance.

Objective To investigate the correlation between tongue and pulse indicators and the out-come of live birth in patients undergoing frozen-thawed embryo transfer(FET),as well as the association between these indicators and patients'endocrine parameters. Methods This study was conducted at Reproductive Medicine Center,Shuguang Hospital Af-filiated to Shanghai University of Traditional Chinese Medicine,Shanghai,China,from March 8,2021 to January 5,2022.Patients undergoing FET were divided into live birth and non-live birth groups according to their live birth outcome.The differences between the endocrine pa-rameters[basic follicle stimulating hormone(b FSH),basic luteinizing hormone(b LH),basic estradiol(b E2),basic progesterone(b P),basal endometrial thickness,follicle stimulating hormone(FSH)on endometrial transition day,luteinizing hormone(LH)on endometrial transition day,estradiol(E2)on endometrial transition day,progesterone(P)on endometrial transition day,and endometrial thickness on endometrial transition day]and the tongue and pulse indicators[tongue body(TB)-L,TB-a,TB-b,tongue coating(TC)-L,TC-a,TC-b,perAll,perPart,h1,h4,h5,t1,h1/t1,and h4/h1]of patients in the two groups were analyzed,with the correlation between these variables analyzed as well using Spearman's correlation coefficient.Multivariate logistic regression was employed to identify the influential factors in the live birth prediction models across various datasets,including Model 1 consisting of endocrine indica-tors only,Model 2 solely consisting of tongue and pulse indicators,and Model 3 consisting of both tongue,pulse,and endocrine indicators,as well as to evaluate efficacy of the models de-rived from different datasets. Results This study included 78 patients in live birth group and 144 patients in non-live birth group.Compared with non-live birth group,live birth group exhibited higher levels of TB-L(P=0.01)and TB-a(P=0.04),while demonstrated lower levels of b FSH(P=0.01),perAll(P=0.04),and h4/h1(P=0.03).The Spearman's correlation coefficient analysis revealed statisti-cally significant correlation(P<0.05)between TB-L,TB-b,TC-L,TC-b,perAll,perPart,h4,h5,t1,h1/t1 and b FSH,b LH,basal endometrial thickness,LH on endometrial transition day,E2 on endometrial transition day,P on endometrial transition day,and endometrial thickness on endometrial transition day in live birth group.The multivariate logistic regression analysis showed that the prediction Model 3 for live birth outcome[area under the curve(AUC):0.917,95%confidence interval(CI):0.863-0.971,P<0.001]surpassed the Model 1(AUC:0.698,95%CI:0.593-0.803,P=0.001),or the Model 2(AUC:0.790,95%CI:0.699-0.880,P<0.001).The regression equations for the live birth outcomes,integrating tongue and pulse indicators with endocrine parameters,included the following measures:FSH on endometrial transition day[odds ratio(OR):0.523,P=0.025],LH on endometrial transition day(OR:1.277,P=0.029),TB-L(OR:2.401,P=0.001),perPart(OR:1.018,P=0.013),h1(OR:0.065,P=0.021),t1(OR:4.354,P=0.024),and h4/h1(OR:0.018,P=0.016). Conclusion In infertility patients undergoing FET,there exists a correlation between tongue and pulse indicators and endocrine parameters.The corporation of tongue and pulse indica-tors significantly improved the predictive capability of the model for live birth outcomes.Specifically,tongue and pulse indicators such as TB-L,perPart,h1,t1,and h4/h1 exhibited a discernible correlation with the ultimate live birth outcomes.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

This study investigated the mechanism of Gegen Qinlian Decoction(GQD) in improving glucose metabolism in vitro and in vivo by alleviating endoplasmic reticulum stress(ERS). Molecular docking was used to predict the binding affinity between the main effective plasma components of GQD and ERS-related targets. Liver tissue samples were obtained from normal rats, high-fat-induced diabetic rats, rats treated with metformin, and rats treated with GQD. RNA and protein were extracted. qPCR was used to measure the mRNA expression of ERS marker glucose-regulated protein 78(GRP78), and unfolded protein response(UPR) genes inositol requiring enzyme 1(Ire1), activating transcription factor 6(Atf6), Atf4, C/EBP-homologous protein(Chop), and caspase-12. Western blot was used to detect the protein expression of GRP78, IRE1, protein kinase R-like ER kinase(PERK), ATF6, X-box binding protein 1(XBP1), ATF4, CHOP, caspase-12, caspase-9, and caspase-3. The calcium ion content in liver tissues was determined by the colorimetric assay. The ERS-HepG2 cell model was established in vitro by inducing with tunicamycin for 6 hours, and 2.5%, 5%, and 10% GQD-containing serum were administered for 9 hours. The glucose oxidase method was used to measure extracellular glucose levels, flow cytometry to detect cell apoptosis, glycogen staining to measure cellular glycogen content, and immunofluorescence to detect the expression of GRP78. The intracellular calcium ion content was measured by the colorimetric assay. Whereas Western blot was used to detect GRP78 and ERS-induced IRE1, PERK, ATF6, and eukaryotic translation initiation factor 2α(eIF2α) phosphorylation. Additionally, the phosphorylation levels of insulin receptor substrate 1(IRS1), phosphatidylinositol 3-kinase regulatory subunit p85(PI3Kp85), and protein kinase B(Akt), which were involved in the insulin signaling pathway, were also measured. In addition, the phosphorylation levels of c-Jun N-terminal kinases(JNKs), which were involved in both the ERS and insulin signaling pathways, were measured by Western blot. Molecular docking results showed that GRP78, IRE1, PERK, ATF4, and various compounds such as baicalein, berberine, daidzein, jateorhizine, liquiritin, palmatine, puerarin and wogonoside had strong binding affinities, indicating that GQD might interfere with ERS-induced UPR. In vivo results showed that GQD down-regulated the mRNA transcription of Ire1, Atf6, Atf4, Grp78, caspase-12, and Chop in diabetic rats, and down-regulated GRP78, IRE1, PERK, as well as ERS-induced apoptotic factors ATF4 and CHOP, caspase-12, caspase-9, and caspase-3, while up-regulating XBP1 to enhance adaptive UPR. In addition, GQD increased the calcium ion content in liver tissues, which facilitated correct protein folding. In vitro results showed that GQD increased glucose consumption in ERS-induced HepG2 cells without significantly affecting cell viability, increased liver glycogen synthesis, down-regulated ATF6 and p-eIF2α(Ser51), and down-regulated IRE1, PERK, and GRP78, as well as p-IRS1(Ser312) and p-JNKs(Thr183/Tyr185), while up-regulating p-PI3Kp85(Tyr607) and p-Akt(Ser473). These findings suggested that GQD alleviates excessive ERS in the liver, reduces insulin resistance, and improves hepatic glucose metabolism in vivo and in vitro.
Rats ; Animals ; Proto-Oncogene Proteins c-akt ; Endoplasmic Reticulum Chaperone BiP ; Caspase 3 ; Caspase 9 ; Diabetes Mellitus, Experimental ; Caspase 12 ; Calcium/pharmacology* ; Molecular Docking Simulation ; Endoplasmic Reticulum Stress ; Protein Serine-Threonine Kinases/genetics* ; Liver ; Apoptosis ; Insulin ; Glucose ; Glycogen/pharmacology* ; RNA, Messenger