Objective To elucidate the molecular mechanism of sirtuin-3 (SIRT3) in regulating mitochondrial biogenesis in human renal tubular epithelial cells. Methods Cells were stimulated with different concentrations of H₂O₂ and divided into four groups: control (NC), 50 μmol/L H₂O₂, 110 μmol/L H₂O₂ and 150 μmol/L H₂O₂. SIRT3 protein expression was then measured. SIRT3 was knocked down with siRNA, and cells were further assigned to five groups: control (NC), negative-control siRNA (NCsi), SIRT3-siRNA (siSIRT3), NCsi+H₂O₂, and siSIRT3+H₂O₂. After 24 h, cellular adenosine triphosphate (ATP) and mitochondrial superoxide anion (O₂•⁻) levels were determined, together with mitochondrial expression of SIRT3, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), superoxide dismutase 2 (SOD2), acetylated-SOD2 and adenosine monophosphate activated protein kinase α1 (AMPKα1). Results The 110 and 150 μmol/L H₂O₂ decreased SIRT3 protein (both P<0.05). ATP and mitochondrial O₂•⁻ did not differ between NC and NCsi groups (both P>0.05). Compared to the NCsi group, the siSIRT3 group exhibited elevated O₂•⁻ level, decreased SIRT3 protein and increased expression levels of SOD2 and acetylated SOD2 protein (all P<0.05). Compared to the NCsi group, the NCsi+H₂O₂ group exhibited decreased cellular ATP levels, elevated mitochondrial O₂•⁻ levels, and reduced protein expression levels of SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 (all P<0.05). Compared with the siSIRT3 group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, SOD2, TFAM, AMPKα1, PGC-1α and NRF1 protein expression levels and a decrease in acetylated SOD2 protein expression levels (all P<0.05). Compared with the NCsi+H₂O₂ group, the siSIRT3+H₂O₂ group showed a decrease in cellular ATP levels, an increase in mitochondrial O₂•⁻ levels, a decrease in SIRT3, AMPKα1, PGC-1α and NRF1, TFAM protein expression levels, and an increase in SOD2 and acetylated SOD2 protein expression levels (all P<0.05). Conclusions SIRT3 promotes mitochondrial biogenesis in tubular epithelial cells via the AMPK/PGC-1α/NRF1/TFAM axis, representing a key mechanism through which SIRT3 ameliorates oxidative stress-induced mitochondrial dysfunction.

[Objective] To explore the predictive value of HALP score for prognosis in patients with multiple myeloma (MM). [Methods] A retrospective analysis was conducted on laboratory indicators and related clinical data of newly diagnosed multiple myeloma (NDMM) patients, treated at the Affiliated Hospital of North Sichuan Medical College from January 2016 to October 2023, prior to their first treatment. The HALP score was calculated, and the optimal cutoff value for HALP was determined using X-tile software. Survival analysis was performed using Kaplan-Meier curves for high HALP and low HALP groups. Univariate and multivariate analyses were conducted using the Cox regression model, and a forest plot was generated using Graphpad Prism to illustrate factors that may impact patient prognosis. The predictive ability of HALP score combined with β2-microglobulin and ECOG score for prognosis in MM patients was evaluated using receiver operating characteristic curve (ROC) analysis. [Results] A total of 203 MM patients were included, with the optimal cutoff value for HALP score being 29.15 (P<0.05). Among them, 101 patients were in the low HALP score group, and 102 patients were in the high HALP score group. The results of univariate and multivariate analysis using the Cox regression model showed that a HALP score <29.15 was an independent risk factor for progression-free survival (PFS) and overall survival (OS) (P<0.05). ROC curve analysis indicated that the combination of HALP score with β2-microglobulin and ECOG score had a higher predictive value for prognosis in MM patients compared to using HALP score alone. [Conclusion] The HALP score is closely related to the prognosis of patients with NDMM. A low HALP score indicates a poorer prognosis, while the combination of HALP score with β2-microglobulin and ECOG score provides a higher predictive value when assessed together.

Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

Objective:To optimize the ethanol reflux extraction process of total saponins in total saponins of Trillium tschonoskii Rhizome. Methods:On the basis of single factor tests, making the total extraction rate of three main compounds [paris saponin Ⅵ, paris saponin Ⅶ and pennogenin-3- O-α-L-rhamnopyranosyl-(1→4)-[O-α-L-rhamnopyranosyl (1→2)]- O-β-D-glucopyranoside (PRRG)] as the indicator, the optimal extraction parameter was selected with the main influencing factors: the ethanol concentration, solid-liquid ratio, and extraction time by the central composite design-response surface method.Results:The optimal extraction parameter for the ethanol extract of total saponins of Trillium tschonoskii Rhizome was as follows: ethanol concentration 69%, extraction time 1.9 h, and solid liquid ratio 1∶9.7. The binomial fitting complex correlation coefficient r = 0.966 1, and the deviation between the extracted predicted value and the actual value is 4.68%. Conclusion:The central composite design-response surface method is simple and reliable for the optimization of extraction process of total saponins of Trillium tschonoskii Rhizome.

Objective:To analyze the characteristics, diagnosis and prognosis of acute fatty liver of pregnancy (AFLP), and to guide the management of AFLP patients.Methods:The clinical data of 34 AFLP patients admitted to Beijing Obstetrics and Gynecology Hospital, Capital Medical University from January 2009 to December 2019 were retrospectively analyzed. The general situation, diagnostic characteristics, treatment and maternal and neonatal prognosis of the AFLP patients were collected and analyzed.Results:The incidence of AFLP in our hospital was 0.022% (34/152 383). The age of onset was (30.6±4.9) years old, and the gestational age was (35.3±2.4) weeks. Most of the first symptom was gastrointestinal symptoms of unknown cause in the third trimester of pregnancy (53%, 18/34), accompanied by different degrees of elevated liver enzymes. Cesarean section was performed in 97% (33/34) of patients for termination of pregnancy. Only one pregnant woman was diagnosed prenatal and delivered vaginally, and the prognosis of both mother and infant was good. Five cases were transferred to intensive care unit, including 2 cases of acute renal failure, 1 case of gastrointestinal bleeding and 2 cases of disseminated intravascular coagulation. There was no maternal death. Severe asphyxia occurred in 2 neonates.Conclusions:Attention should be paid to the digestive tract symptoms during the third trimester of pregnancy and the diversity of clinical manifestations of AFLP for early detection. Once AFLP is diagnosed, pregnancy should be terminated as soon as possible to improve maternal and infant outcomes.

Objective:Select a suitable macroporous resin for the purification technic of total saponins from Panacis Japonici Rhizoma and determine the parameter of purification technic. Methods:Made the content of total saponins as the index, used static adsorption test and combined the adsorption kinetic parameters to select the type of macroporous resin. By using dynamic adsorption experiment to investigate the technical parameters of the purified macroporous resin extracted from Panacis Japonici Rhizoma. Then the preparation technic of the total saponins of Panacis Japonici Rhizoma was determined. Results:The D101 macroporous resin could absorpt and desorpt total saponins of Panacis Japonici Rhizoma effectively. The optimal purification parameters were as follow: the loading mass concentration was 0.1 g/ml (based on crude drug), and the loading volume was 100 ml (which means the loading volume of resin per ml was equivalent to 3.3 grams of crude drug). During the elution process, distilled water (3 BV) and 20% ethanol (3 BV) were used to remove impurity, and then 70% ethanol elution (6 BV) was used to enrich the total saponins. The flow rate of loading and elution was 0.5 ml/min. The transfer rate of total saponins could reache 85.6%. Conclusion:The D101 macroporous resin can effectively enrich and purify the total saponins of Panacis Japonici Rhizoma, which provides the scientific basis for the development and utilization of Panacis Japonici Rhizoma.

Objective:To summarize the phenotype and genotype of X-linked adrenoleukodystrophy (X-ALD) patients, and compare the phenotype and genotype characteristics between children and adult patients.Methods:The comprehensive clinical data of 30 patients with X-ALD admitted to Beijing Jingdu Children′s Hospital and the First Medical Center of People′s Liberation Army General Hospital from August 2012 to December 2019 were analyzed, including their clinical manifestations and the results of gene test, biochemical test and magnetic resonance imaging examination, etc.Results:Among the 30 patients, 15 (50.0%) were childhood cerebraI ALD (CCALD, onset age 5－10 yeas, mean 7 years), 13 (43.3%) were adrenomyeloneuropathy (AMN, onset age 21－41 yeas, mean 29 years). One (3.3%) was adult cerebral ALD (onset age 29 yeas), one (3.3%) was pure Addison disease (onset age 3.5 yeas). Most common clinical phenotype in children was CCALD and the first symptoms were inattention, learning ability decline, vision and hearing impairment. Otherwise the most common type in adult was AMN and the first symptoms were mainly progressive weakness of the lower limbs, muscle spasm, and abnormal gait. These patients came from 29 different families, among whom, 25 patients conducted gene test and 22 different types of ABCD1 gene mutations were found. Missense mutation was the main gene mutation type. Patients with different clinical types had no specificity in gene mutation types.Conclusions:In China, the most common clinical classification of X-ALD in children is CCALD, and AMN in adults. No clear correlation has been found between genotype and phenotype.

The 30th International Symposium on Amyotrophic Lateral Sclerosis-Motor Neuron Disease was held in Perth, Australia from December 4 to 6, 2019. This article mainly introduces the clinical research of this meeting, including epidemiology, non-motor symptoms, auxiliary examinations and biomarkers, etc., while the basic research includes genomics and genetics, protein metabolism abnormalities, neuroimmunity and inflammation, synapse pathology and preclinical treatment strategies,

BACKGROUND: Chronic urticaria (CU) is a common skin disease, which has a negative effect on quality of life. Current treatments do not fully control the symptoms of urticaria for many CU patients, thus effective and safe treatments for CU are still needed. OBJECTIVE: This review aims to evaluate the effectiveness and safety of cupping therapy in patients with CU. SEARCH STRATEGY: The search strategy looked for the presence of related keywords, such as "chronic urticaria" and "cupping therapy," in the title and abstract of research articles indexed in major databases. Randomized controlled trials (RCTs) were selected after querying nine electronic databases from their inception to May 2019 with the above search terms. INCLUSION CRITERIA: RCTs were included if they recruited patients with CU who were intervened with dry or wet cupping. Publications could be written in Chinese or English. DATA EXTRACTION AND ANALYSIS: Data were extracted, and the studies were assessed for the quality of their methodological design and risk of bias. Meta-analyses of the RCT data were conducted to assess the total effective rate of the treatment as the primary outcome. Skin disease quality of life index score, recurrence rate, and adverse events were assessed as secondary outcomes. Subgroup analyses were conducted based on different interventions. RESULTS: Thirteen comparisons from 12 RCTs involving 842 participants were included. There were no significant differences between wet cupping and medications in total effective rate (n = 372; risk ratio [RR] = 1.10, 95% confidence interval [CI] 0.97 to 1.25; P = 0.14) or recurrence rate (n = 240; RR = 0.56, 95% CI 0.23 to 1.36; P = 0.20). Cupping therapy, in combination with antihistamine treatment was more efficacious than antihistamines alone, with a greater total effective rate (n = 342; RR = 1.18, 95% CI 1.01 to 1.39; P = 0.03) and lower recurrence rate (n = 342; RR = 0.52, 95% CI 0.32 to 0.84; P = 0.007). Cupping therapy combined with acupuncture was more effective than acupuncture alone (n = 156; RR = 1.25, 95% CI 1.07 to 1.46; P = 0.006). No serious adverse events were reported. CONCLUSION: Wet cupping may be as effective as treatment with antihistamines. When cupping therapy is used as an adjuvant therapy to antihistamines or acupuncture, it may enhance the efficacy. Results drawn from these studies should be interpreted with caution and applied with care to clinical practice, because of the poor quality among the studies that were reviewed. SYSTEMATIC REVIEW REGISTRATION PROSPERO, CRD42019137451.

Objective: To explore the molecular basis for an individual with ABO subtype. Methods: The ABO phenotype of the proband was determined by convention serological testing. Exons 6 and 7 of the ABO gene were subjected to PCR amplification and bi-directional Sanger sequencing. Haplotypes for exons 6 and 7 of the proband was determined using an ABO haplotype-specific amplification and sequencing technique. Results: Red blood cells of the proband showed a 4+ agglutination strength with anti-A or anti-H, no agglutination reaction with anti-A1, and a 3+ agglutination strength with anti-B. His serum had no reaction with standard A cells, O cells or self cells, but was weakly reactive with B cells at 4℃. The proband was assigned as an ABO subtype based on his serological features. Bi-directional sequencing of the ABO gene revealed heterozygosity of 261 G/del, 297AG, 526CG, 657CT, 703GA, 803GC and 930GA, and homozygosity of 796CC in the proband. Haplotype-specific amplification and sequencing showed that one of his alleles was ABO*O.01.01, and another contained a c. 796A>C variation compared with the ABO*B.01 allele, which led to replacement of methionine by leucine at position 266. Searching the ABO allele database of International Society of Blood Transfusion suggested the variation to be a novel one. Conclusion The c. 796A>C variation in the ABO*B.01 allele probably underlies the CisAB subtype. Accurate identification of the ABO subtype requires combined use of serological method and genetic testing.