Advances in the Diagnosis and Treatment of Cushing′s Syndrome / 罕见病研究

Cushing′s syndrome (CS), an endocrine disorder resulting from excessive glucocorticoid secretion by the adrenal cortex, poses significant challenges to both diagnosis and treatment. The diagnostic process involves comprehensive evaluation, combining laboratory tests and imaging studies for screening, qualification, and localization. Surgical intervention remains the primary treatment approach, although pharmacological therapy also plays a crucial role. With an increasing understanding of the pathogenesis of CS, more potential targets for orphan drug development have been discovered. This article summarizes the current status of diagnosis and treatment for CS and provides an outlook on future research directions.

Efficacy of Wuling capsules combined with low-dose quetiapine in the treatment of oldest-old patients with insomnia accompanied by anxiety and depression / 中国药房

OBJECTIVE To investigate the efficacy and safety of Wuling capsules combined with low-dose quetiapine in the treatment of oldest-old patients with insomnia accompanied by anxiety and depression. METHODS The clinical data of 96 oldest- old patients （aged≥80 years） with insomnia accompanied by anxiety and depression who were attending outpatient clinics or hospitalized in our hospital from June 2020 to December 2022 were retrospectively analyzed. According to the different drug treatments， the patients were divided into Wuling capsules group （0.99 g， tid， 34 cases）， quetiapine group （25-50 mg， qn， 30 cases） and combination group （using Wuling capsules and quetiapine simultaneously， same as the single drug groups， 32 cases）. Before and after 8 weeks of treatment， the patients of three groups were compared in terms of photoplethysmography sleep monitoring indexes （total sleep duration， sleep efficiency， sleep latency， and the number of awakening）， Pittsburgh sleep quality index （PSQI） score， 14-item Hamilton anxiety scale （HAMA-14） score， 17-item Hamilton depression scale （HAMD-17） score， mini-mental state examination （MMSE） score， and serum levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）； the therapeutic effects and adverse drug reactions of the three groups were observed and compared. RESULTS Compared with before treatment， the total sleep time， sleep efficiency and MMSE scores of the three groups were significantly longer or higher after treatment （P＜0.05）， while the sleep latency， number of awakening， PSQI score， HAMA-14 score， HAMD-17 score， serum IL-1β and TNF-α levels were significantly shorter or lower after treatment （P＜0.05）. Sleep latency， number of awakening， HAMA-14 score， HAMD-17 score and serum TNF-α level in quetiapine group were significantly shorter or lower than Wuling capsules group after treatment （P＜0.05）. Moreover， the above indexes in the combination group were significantly better than quetiapine group and Wuling capsules group （P＜0.05）. The total effective rate of treatment in the combination 1731786794@qq.com group was significantly higher than the other two groups （P＜0.05）. There was no significant difference in the incidence of mail：2408797210@qq.com adverse drug reactions among the three groups （P＞0.05）. CONCLUSIONS The therapeutic effect of Wuling capsules combined with low-dose quetiapine is better than that of individual drugs for oldest-old patients with insomnia accompanied with anxiety and depression， not increasing the risk of adverse reactions.

Short-term clinical efficacy observation of lesion removal, bone graft fusion, and external brace treatment for late-stage wrist tuberculosis / 中国骨伤

OBJECTIVE@#To observe the clinical efficacy of lesion removal, bone grafting, fusion, and external fixation in the treatment of late-stage wrist tuberculosis.@*METHODS@#From October 2015 to May 2019, 25 patients with late-stage wrist tuberculosis were treated using lesion removal, bone grafting, fusion, and external fixation. Among these patients, there were 14 males and 11 females, aged from 40 to 74 years old, with an average age of (60.72±8.45) years old. The duration of the disease ranged from 5 to 24 months, with an average of (11.52±7.61) months. There were 11 cases of left wrist tuberculosis and 14 cases of right wrist tuberculosis, with 5 cases accompanied by sinus formation. Postoperative regular anti-tuberculosis treatment was continued. Visual analogue score (VAS), inflammatory indicators, Gartland-Werley wrist function score, and upper limb function score were observed before and after treatment.@*RESULTS@#All 25 patients were followed up for ranging from 12 to 36 months with an average of (19.7±6.3) months. At the latest follow-up, all wounds were healed satisfactorily, and there was no recurrence of tuberculosis or infection. VAS at one week before operation and three months after operation were (5.16±1.14) score and (1.68±0.80) score respectively. One week before operation and three months after operation, erythrocyte sedimentation rate (ESR) was (44.20±20.56) mm·h-1 and (14.44±1.14) mm·h-1, and C-reactive protein (CRP) was (12.37±7.95) mg·L-1 and (4.3±3.37) mg·L-1. The differences in all three data sets were statistically significant (P<0.01). According to Gartland-Werley wrist function scoring, the scores at one week before operation and one year after operation were (21.32±3.44) and (14.96±1.37) respectively, showed a statistically significant difference (P<0.01). According to the upper limb function score (disabilities of the arm, shoulder, and hand, DASH), the score was (70.52±7.95) at one week before operation and(28.84±2.30) at one year after operation. The difference was statistically significant (P<0.01). At the latest follow-up, no patient had a recurrence of tuberculosis.@*CONCLUSION@#The short-term clinical efficacy of treating wrist tuberculosis with lesion removal, bone grafting, fusion, and external fixation is satisfactory.

Research progress of chemotherapy-related diarrhea induced by molecularly targeted anti-tumor drugs / 中国药房

Diarrhea caused by chemotherapy is called chemotherapy-related diarrhea （CRD）. CRD can lead to reduced treatment effectiveness and compliance， affect the long-term outcome of tumor patients， and can be life-threatening in severe cases. In addition to conventional chemotherapy drugs， many molecularly targeted drugs are also associated with CRD， including small molecule epidermal growth factor receptor （EGFR） inhibitors， anti-EGFR monoclonal antibodies， phosphoinositide 3-kinase inhibitors， small molecule inhibitors of vascular endothelial growth factor receptor， BCR-ABL1 and KIT inhibitors， human epidermal growth factor receptor 2 target inhibitors， cyclin-dependent protein kinase inhibitors， antibody-drug conjugates and other molecularly targeted drugs. The occurrence mechanism may be related to the intestinal mucosal injury or enteritis caused by molecularly targeted drugs. The clinical manifestations are increased stool frequency and/or loose imposition， and patients are often associated with excess hyperproduction and/or colic. The incidence of CRD varies with different drugs. Great importance should be attached to collecting medical history and differential diagnosis， actively intervening and conducting dynamic evaluation， strengthening patient education， and timely detecting and preventing the occurrence of intestinal toxicity.

A rare case of bilateral frontal lobe lesions due to thyroid storm

SUMMARY Thyroid storm is a rare but well-known life-threatening complication that occurs due to acute exacerbation of thyrotoxicosis with the increased levels of circulating thyroid hormones. Reports of metabolic encephalopathy associated with thyroid storm are scarce. We describe the case of a 23-year-old male patient with no previous history of abnormal thyroid function who had consumed excessive amounts of alcohol before disease onset. The patient was found unconscious and febrile on a roadside by a passerby and was admitted to our hospital's emergency department. His primary clinical presentation included hyperthermia (40.8 °C), nodal tachycardia (180 beats/min), seizures, coma, and hypoglycemia (2.18 mmol/L). The hypoglycemia was quickly corrected after admission, but his level of consciousness showed no improvement. With aggressive screening, the patient was found to have severe thyroid dysfunction (T3 = 6.67 nmol/L, T4 = 252.00 nmol/L, free T3 = 29.20 pmol/L, free T4 = 65.30 pmol/L, and TSH = 0.001 μIU/mL). After medical treatment, plasmapheresis, hemofiltration, and hemoperfusion, the patient showed substantial improvement in thyroid hormone levels and stabilization of vital signs, but the impaired consciousness and seizures persisted. Multiple computed tomography scans revealed brain abnormalities. Magnetic resonance imaging performed after tracheal extubation revealed bilateral frontal lobe lesions. We reported a case of metabolic encephalopathy in a patient with life-threatening thyroid storm and bilateral frontal lobe lesions. Hypoglycemia may have been involved in the development of encephalopathy in our patient. Health care providers should consider thyroid storm in the differential diagnosis of hyperthermia, seizures, and coma. Early plasmapheresis, hemofiltration, and hemoperfusion can lower T4 levels and improve prognosis in patients with thyroid storm and encephalopathy.

Analysis of related factors of plasma antibody titer in convalescent patients with COVID-19 / 中国输血杂志

【Objective】 To study the relationship between the plasma IgG, IgM, neutralizing antibody titer and sex, age, collection interval in convalescent patients with COVID-19, so as to guide the plasma collection of convalescent patients with COVID-19. 【Methods】 COVID-19 convalescent plasma was collected to determine the antibody titer, and the difference and correlation of data in each group were analyzed by SPSS statistical analysis software. 【Results】 The median titers (AU/mL)of IgG, IgM and neutralizing antibodies in males and females were 484.24 vs 516.04, 2.13 vs 1.73, and 1 124.74 vs 1 143.99, respectively, and there was no significant difference(P>0.05) . Age had weak positive correlation with IgG and neutralizing antibody, and the Spearman correlation coefficient was 0.188 (P<0.05). The median titers (AU/mL) of IgG, IgM and neutralizing antibody at first donation of 30 repeated donors were 522.3, 2.64 and 1 174.6, respectively, but at second donation were 332.08, 0.63 and 708.96, showing significant difference (P<0.05). 【Conclusion】 There was no significant difference in the plasma IgG, IgM and neutralizing antibody titers in convalescent COVID-19 patients of different ages and genders, and the titers met the requirements of clinical treatment guidelines. Although the plasma antibody level of repeated donors has decreased, it still has clinical value.

Study on the extensibility of platelet donor gene database in Shaanxi / 中国输血杂志

【Objective】 To analyze the commonality and characteristics between voluntary blood donors and hematopoietic stem cell donors in this region, and explore the potential for integration and development between China Marrow Donors Program (CMDP) and voluntary blood donors, especially platelet donor databases, so as to improve recruitment success rate and inventory rate. 【Methods】 The database modeling and comparison methods were used to screen and stratify the matching and integration degree between the voluntary blood donors in recent 10 years and the marrow donors in the Shaanxi Branch of CMDP. The frequencies of HLA-A,-B alleles, HPA alleles and haplotypes were calculated with Arlequin 3. 5. 2. 2 software, and the matching probability of different platelet donor reserve pools was conducted according to the phenotypic frequencies. 【Results】 Among the voluntary donors with known HLA genotypes in this region, according to their blood donation behavior,the active blood donors excavated were divided into the first, second, third and fourth echelons of platelet donor reserve pools, with 696, 2 752, 9 092 and 12 028 donors, respectively. The first echelon had the highest proportion of 10-50 times of platelet donations and 10-20 times of whole blood donations, with 13.65% and 26.01%, respectively. The second echelon had 10-20 times of whole blood donations and 10-50 times of platelet donations, accounted for 15.04% and 1.38%, respectively, which were significantly different from other echelons' blood donation characteristics (P<0.05). With a database size of the existing platelet donor bank adding the first and second echelons (n=4 955), there was a 69.02% probability of matching at least one donor with matching HLA-A-B phenotype. When considering the matching ABO and HPA phenotypes, the probability of finding at least one donor with fully matching HLA, HPA and ABO isotype (type B as an example) was 48. 73%. 【Conclusion】 The three groups of whole blood donation, apheresis platelet donation and marrow donation in Xi'an area have a large cross-distribution. Compared with expanding the storage capacity from scratch, the active blood donors in CMDP database are the largest back-up force of platelet donors. While expanding the effective storage capacity, it can minimize the cost of building platelet donor bank and the demand for resources.

Efficacy of decitabine combined with low dose chemotherapy on children with acute myeloid leukemia / 中华儿科杂志

Objective: To evaluate the efficacy of decitabine combined with low dose chemotherapy (LDC) in the treatment of high-risk, refractory and relapsed pediatric acute myeloid leukemia (AML). Methods: Clinical data of 19 AML children treated with decitabine combined with LDC in the Department of Hematology, Children's Hospital of Soochow University from April 2017 to November 2019 were analyzed retrospectively. The therapeutic response, adverse effects and survival status were analyzed,and the outcomes of patients were followed up. Results: Among 19 AML cases, there were 10 males and 9 females. Five cases were high-risk AML, 7 cases were refractory AML, and 7 cases were relapsed AML. After one course of decitabine+LDC treatment, 15 cases achieved complete remission, 3 cases got partial remission, and only 1 case didn't get remission. All patients received allogeneic hematopoietic stem cell transplantation as consolidation therapy. The follow-up time of all cases was 46 (37, 58) months, 14 children had survived. The cumulative three-year overall survival rate was (79±9) %, events free survival rates was (68±11) %, and recurrence free survival rate was (81±10) %. The most common adverse effects related to the induction treatment were cytopenia (19 cases) and infection (16 cases).There were no treatment-related death during the therapy. Conclusion: Decitabine combined with LDC is a safe and effective option for high-risk, refractory and relapsed AML children, which provides an opportunity for HSCT.

Lysosomal membrane protein Sidt2 knockout induces apoptosis of human hepatocytes in vitro independent of the autophagy-lysosomal pathway / 南方医科大学学报

OBJECTIVE@#To explore the regulatory mechanism of human hepatocyte apoptosis induced by lysosomal membrane protein Sidt2 knockout.@*METHODS@#The Sidt2 knockout (Sidt2-/-) cell model was constructed in human hepatocyte HL7702 cells using Crispr-Cas9 technology.The protein levels of Sidt2 and key autophagy proteins LC3-II/I and P62 in the cell model were detected using Western blotting, and the formation of autophagosomes was observed with MDC staining.EdU incorporation assay and flow cytometry were performed to observe the effect of Sidt2 knockout on cell proliferation and apoptosis.The effect of chloroquine at the saturating concentration on autophagic flux, proliferation and apoptosis of Sidt2 knockout cells were observed.@*RESULTS@#Sidt2-/- HL7702 cells were successfully constructed.Sidt2 knockout significantly inhibited the proliferation and increased apoptosis of the cells, causing also increased protein expressions of LC3-II/I and P62(P < 0.05) and increased number of autophagosomes.Autophagy of the cells reached a saturated state following treatment with 50 μmol/L chloroquine, and at this concentration, chloroquine significantly increased the expressions of LC3B and P62 in Sidt2-/- HL7702 cells.@*CONCLUSION@#Sidt2 gene knockout causes dysregulation of the autophagy pathway and induces apoptosis of HL7702 cells, and the latter effect is not mediated by inhibiting the autophagy-lysosomal pathway.

Efficacy of intravascular ultrasound versus coronary angiographic guided drug-eluting stent implantation in the treatment of left main coronary artery disease: a meta-analysis / 中华心血管病杂志

Objective: To compare the efficacy of intravascular ultrasound (IVUS) and coronary angiography guided drug eluting stent (DES) implantation for the treatment of left main coronary artery (LMCA) lesions. Methods: Randomized controlled trials (RCT) and observational studies, which compared IVUS with coronary angiography guided DES implantation for the treatment of LMCA lesions published before August 2021 were searched in PubMed, Embase and Cochrane Library databases. Baseline data, interventional procedures and endpoint events of each study were collected. The primary endpoint was major cardiovascular adverse events (MACE), and the secondary endpoints were all-cause death, cardiac death, myocardial infarction (MI), target lesion revascularization (TLR) and target vessel revascularization (TVR). The Newcastle-Ottawa Scale (NOS) and the Cochrane Collaboration Risk of Bias tool were used to evaluate the quality of the included studies. Results: Nine studies were included, including 3 RCT and 6 observational studies, with a total of 5 527 cases of LMCA. All the 6 observational studies had NOS scores≥6, and the 3 RCT had a low risk of overall bias. The results of meta-analysis showed that compared with coronary angiography guided group, MACE rate (OR=0.55, 95%CI 0.47-0.66, P<0.001), all-cause death (OR=0.56, 95%CI 0.43-0.74, P<0.001), cardiac death (OR=0.43, 95%CI 0.30-0.61, P<0.001), MI (OR=0.64, 95%CI 0.52-0.79, P<0.001), TLR (OR=0.49, 95%CI 0.28-0.86, P=0.013) and TVR (OR=0.77, 95%CI 0.60-0.98, P=0.037) were all significantly lower in the IVUS guided group. Conclusions: Compared with angiography guided, IVUS guided PCI with DES implantation in LMCA lesions could significantly reduce the risk of MACE, death, MI, TLR and TVR. IVUS is thus superior to coronary angiography for guiding PCI treatment among patients with LMCA.

Safety of butylphthalide and edaravone in patients with ischemic stroke: a multicenter real-world study / 老年心脏病学杂志（英文版）

BACKGROUND@#Butylphthalide (NBP) and edaravone (EDV) injection are common acute ischemic stroke medications in China, but there is a lack of large real-world safety studies on them. This study aimed to determine the incidence of adverse events, detect relevant safety signals, and assess the risk factors associated with these medications in real-world populations.@*METHODS@#In this study, data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021. Baseline confounders were eliminated using propensity score matching. The drugs' safety was estimated by comparing the results of 24 laboratory tests standards on liver function, kidney function, lipid level, and coagulation function. The drugs' relative risk was estimated by logistic regression. A third group with patients who did not receive NBP or EDV was constructed as a reference. Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV, respectively.@*RESULTS@#81,292 patients were included in this study. After propensity score matching, the NBP, EDV, and third groups with 727 patients in each group. Among the 15 test items, the incidence of adverse events was lower in the NBP group than in the EDV group, and the differences were statistically significant. The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results, whereas EDV had statistically significant effects on aspartate transaminase, low-density lipoprotein cholesterol and total cholesterol. Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count. EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase, alanine aminotransferase, aspartate aminotransferase, prothrombin time, and platelet count.@*CONCLUSIONS@#In a large real-world population, NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Research progress on cardiovascular effects of traffic-related air pollution and noise: Evidence from population-based and mechanism studies / 环境与职业医学

Traffic-related air pollution and noise are becoming increasingly prominent issues in the context of urbanization, both of which are modifiable environmental risk factors for cardiovascular diseases. Those two kinds of traffic-related pollution may have combined effects on the cardiovascular system of human beings, but the biological mechanisms by which they may interact have not been elucidated yet. Thus, we reviewed the research progress based on published population-based and mechanism studies from five aspects, including oxidative stress, inflammatory response, nervous system activation and stress hormones, coagulation dysfunction, and endothelial dysfunction, providing indications for possible common biological pathways. Future studies can construct co-exposure scenarios for traffic-related air pollution and noise to explore their common biological mechanisms in the cardiovascular system by examining the reviewed pathways to provide a scientific basis for the protection of susceptible populations. In addition, the effect modification by individual characteristics and underlying diseases may merit further exploration.

Efficacy and safety of intravitreal ranibizumab alone and combined laser therapy for the treatment of DME: a meta-analysis / 中华实验眼科杂志

Objective:To evaluate the efficacy and safety of intravitreal ranibizumab combined with laser (IVR+ Laser) and the intravitreal ranibizumab (IVR) monotherapy for the treatment of diabetic macular edema (DME).Methods:A meta-analysis was conducted on randomized controlled trial (RCT) literature related to IVR+ Laser therapy and IVR alone for DME.Databases including Cochrane Library, PubMed, EMbase, Web of Science, SinoMed, CNKI, VIP and WanFang Data were searched from their inception to April 2022.Literature screening, data extraction, quality evaluation and cross-checking were conducted independently by two researchers according to inclusion and exclusion criteria.Then a meta-analysis was conducted using RevMan 5.4.1 software.The two therapies were compared in terms of best corrected visual acuity (BCVA), central macular thickness (CMT), mean number of injections and adverse events.Results:Twelve RCTs involving 1 695 eyes were included in the study.Meta-analysis showed that at the end of follow-up, IVR+ Laser demonstrated better improvement in BCVA and CMT than IVR alone, and there were significant differences in the changes in BCVA and CMT between the two groups (weighted mean difference[WMD]=-0.66, 95% confidence interval[ CI]: -1.11--0.21, P<0.01; WMD=-5.05, 95% CI: -9.21--0.89, P=0.02).IVR+ Laser required significantly fewer injections than IVR alone (WMD=-1.16, 95% CI: -2.07--0.25, P=0.01).There were no significant differences in the adverse events incidence between the two therapies (all at P>0.05). Conclusions:The safety of IVR+ Laser is comparable to IVR alone, and it requires fewer injections for the treatment of DME.

Advances in the study of methods for evaluating patient adherence to drug therapy / 中华老年医学杂志

In this article, methods of measuring and evaluating treatment adherence, based on whether they are objective and subjective, are reviewed upon literature examination, and the advantages and disadvantages of each method for different population segments are also discussed.It is intended to provide medical professionals and researchers with a general framework about adherence assessment methods.During treatment and research, medical professionals and researchers should select the most appropriate methods for their purposes and provide effective and personalized evaluation methods to ultimately evaluate and improve patients' medication adherence.

CXCL1 as a potential therapeutic target for diabetic nephropathy / 中华内分泌代谢杂志

Objective:To screen highly expressed inflammatory factors in diabetic nephropathy models using protein microarray, analyze differential genes and their regulatory networks, and predict potential therapeutic small molecular compounds.Methods:The inflammatory factor microarray was used to screen the inflammatory factors with the same tendency in the cell model and animal model of diabetic nephropathy. The differential genes screened by R language were enriched and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG). STRING builds a protein interaction network online, Cytoscape software analyzes the core subnetwork, and Connectivity Map searches for and predicts small molecule compounds.Results:Diabetic nephropathy model was established using 16-week-old db/db mice and mesangial cells stimulated with high glucose, and the expression of C-X-C motif chemokine ligand 1(CXCL1) was elevated in both models. Multiple GEO datasets indicated a strong association between the high expression of CXCL1 and diabetic nephropathy. Specifically, GSE30122 showed an upregulation of 30 genes and a downregulation of 23 genes. GO enrichment analysis focused on biological processes such as humoral immunity and lipopolysaccharide response; While KEGG enrichment was mainly in pertussis and coagulation cascade pathways. CytoHubba identified 10 hub genes, such as ALB, LUM, and CXCL1. In addition, 10 small molecule compounds were predicted as potential therapeutic drugs using Connectivity Map.Conclusions:CXCL1 may serve as a key gene in the occurrence and development of diabetic nephropathy. ALB, LUM, CXCL1, MMP7, TGFBI, CCL2, S100A4, SOX9, VCAN, and CLU may participate in the regulatory network centered around CXCL1. There are 10 small molecular compounds demenestrating the potential to be therapeutic agents.

A preliminary study on the effect of arsenic exposure on necroptosis of mouse myocardial cells / 中华地方病学杂志

Objective:To study the effects of arsenic exposure on necroptosis pathway and inflammatory response of mouse myocardial cells.Methods:Sixty male C57BL/6J mice were randomly divided into control group (group C) and low, medium, and high dose arsenic exposure groups (groups L, M, H) based on body weight using a random number table method. Each group had 15 mice, and they drank 0.00, 0.15, 1.50, and 15.00 mg/L arsenic trioxide (As 2O 3) solution prepared with deionized water. The exposure period was 12 weeks. Hematoxylin-eosin (HE) staining and Masson trichrome staining of paraffin-embedded heart tissues were used to observe the histopathology changes of the heart. Transmission electron microscopy (TEM) was used to evaluate the ultrastructural changes of myocardial cells. The quantitative real-time PCR (qRT-PCR) was used to detect the mRNA expression of inflammatory genes [tumor necrosis factor (TNF)-α and interleukin(IL)-6] and the genes involved in necroptosis pathway [receptor-interacting protein (RIP) 1, RIP3 and mixed-lineage kinase domain-like protein (MLKL)]. Protein expressions of RIP1 and RIP3 in the heart were assessed by western blotting. Results:Histopathological examination results showed there were myocardial necrosis, inflammatory cells infiltration and fibroblasts hyperplasia and other changes in groups M and H. TEM analysis revealed marked ultrastructural changes in groups M and H, including fractured myofibril, fractured Z lines of sarcomere, and swollen mitochondria with fractured cristae. Compared with group C (1.00 ± 0.00), the mRNA expression of RIP1 in group H was significantly up-regulated (1.41 ± 0.06, P < 0.05); the mRNA expressions of RIP3 (1.29 ± 0.14, 1.56 ± 0.08), MLKL (1.23 ± 0.05, 1.36 ± 0.07), TNF-α (2.20 ± 0.10, 2.23 ± 0.18) and IL-6 (1.87 ± 0.16, 1.63 ± 0.15) were significantly up-regulated in groups M and H ( P < 0.05). The protein expressions of RIP1 (0.43 ± 0.04, 0.50 ± 0.04) and RIP3 (0.68 ± 0.02, 0.84 ± 0.05) in groups M and H were higher than those in group C (0.25 ± 0.01, 0.45 ± 0.04, P < 0.05). Conclusion:Subchronic arsenic exposure induces histopathological changes such as myocardial necrosis and fibrosis in mice, inducing necroptosis and inflammatory reactions in myocardial cells.

Effect of self-help cognitive behavioral therapy for insomnia combined with trazodone hydrochloride on elderly patients with depression and insomnia / 中国医师杂志

Objective:To observe the efficacy of self-help cognitive behavioral therapy for insomnia (CBTI), trazodone hydrochloride and their combination in the treatment of depression and insomnia comorbidity in the elderly.Methods:90 elderly patients with insomnia and depression admitted to the 901th Hospital of the Joint Logistic Support Force from October 2019 to October 2021 were selected as the study subjects. They were divided into trazodone group, CBTI group and trazodone combined with CBTI group(combination group), with 30 cases in each group. Trazodone group was treated with oral trazodone hydrochloride, CBTI group was treated with self-help CBTI, and the combination group was treated with oral trazodone hydrochloride combined with self-help CBTI. All three groups were treated for 4 weeks. The sleep latency, total sleep time and sleep efficiency of each group were compared at the time of admission and after 4 weeks of treatment. Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) were used for sleep assessment before and after treatment, and Self-Rating Depression Scale (SDS) was used for depression assessment.Results:Before treatment, there was no significant difference among the three groups in terms of sleep latency, total sleep time, sleep efficiency, PSQI, ESS and SDS (all P>0.05). After treatment, the sleep latency of the three groups was shorter than that before treatment, and the total sleep time was longer than that before treatment (all P<0.05). The sleep efficiency of the trazodone group and the combination group was higher than that before treatment, with statistically significant difference (both P<0.05). The indexes of the combined group were better than those of the trazodone group and the CBTI group (all P<0.05). The sleep latency of the trazodone group was shorter than that of the CBTI group, and the total sleep time was longer than that of the CBTI group (all P<0.05), with statistically significant difference (all P<0.05). After treatment, the PSQI, except for the SDS of CBTI group, the ESS and SDS of the three groups were lower than those before treatment (all P<0.05). The PSQI, ESS and SDS of the combined group were lower than those of the trazodone group and the CBTI group, and the ESS and SDS of the trazodone group were lower than those of the CBTI group, with statistically significant difference (all P<0.05). Conclusions:For the elderly patients with depression and insomnia, the combination of self-help CBTI and trazodone can not only improve insomnia but also relieve depression symptoms, and the effect is better than that of trazodone and self -help CBTI alone.

Comparison of different stone scoring systems in predicting the stone-free rate after RIRS for upper urinary tract lithiasis / 中华泌尿外科杂志

Objective:To compare the accuracy of different stone scoring systems for predicting the stone-free rate (SFR) after retrograde intrarenal surgery (RIRS).Methods:The clinical data of 227 patients with lithiasis undergoing RIRS from June 2017 to December 2020 in Affiliated Benq Hospital of Nanjing Medical University and Qingdao Fuwai Hospital were retrospectively analyzed. There were 152 males and 75 females. The average age was (53.0±10.4) years old. The average body mass index was (26.9±2.1)kg/m 2. The maximum diameter of the stone was (22.7±12.8)mm. The stone is located in left side in 133 cases and in right side in 94 cases. The stones of 44 cases were located in upper ureter, upper calyceal or renal pelvis, that of 23 cases were in medium calyceal, 157 cases in lower calyceal, and 3 cases in calyceal diverticulum.The average CT value of stone was (778.3±350.4)HU. American Society of Anesthesiology (ASA)scores: 86 cases of grade Ⅰ, 129 cases of grade Ⅱ, 12 cases of grade Ⅲ. Preoperative non-contrast CT was conducted and three-dimensional data were constructed. A single observer reviewed and entered the modified S.T.O.N.E., RUSS, modified S-ReSC, R. I.R.S., SHA.LIN, Ito nomogram, S. O.L.V.E., stone free index (SFI) scores. Logistic analysis were performed between every score and SFR. Receiver operating characteristic (ROC) curve was drawn to detect sensitivity and specificity of every score in predicting the SFR. The predictive accuracies of all scores were compared. Results:The SFR was 83.0%(189/227). There were statistically significant differences in modified S. T.O.N.E.(10.5±1.9 vs. 12.7±1.8), RUSS[1(0, 4) vs. 3(0, 6)], modified S-ReSC (8.2±5.6 vs. 11.8±6.0), R.I.R.S.(6.2±1.4 vs. 8.1±1.2), SHA.LIN (9.9±2.4 vs. 13.0±2.1), Ito nomogram (12.1±5.8 vs. 4.3±3.3), S. O.L.V.E. (6.8±1.6 vs. 8.7±1.2), SFI score (7.9±1.1 vs. 6.3±0.9) between the stone-free group and the stone remaining group ( P <0.05). Logistic regression revealed that modified S.T.O.N.E., RUSS, modified S-ReSC, R. I.R.S., SHA.LIN, Ito nomogram, S. O.L.V.E. and SFI score were significantly associated with SFR( P<0.05). There were no significant differences in the area under the curve (AUC) between the modified S. T.O.N.E., RUSS, R. I.R.S., SHA.LIN, Ito nomogram, S. O.L.V.E. and SFI score( P>0.05), but there were significant differences in the AUC between modified S-ReSC score and other score ( P<0.05). When the cutoff of SHA.LIN, SFI and R. I.R.S. score was determined as 10, 6 and 6 scores, the specificity of SHA.LIN, SFI and R. I.R.S. score was 94.7%, 92.6% and 89.5%, respectively. Conclusions:All score could predict the postoperative SFR of RIRS, while the SHA.LIN, SFI and R.I.R.S. score were more accurate than the other scores. The accuracy of the modified S-ReSC in predicting SFR after RIRS was slightly worse than other scores.

Cellular senescence and type 2 diabetes / 中华内分泌代谢杂志

Cellular senescence is a state in which cells enter permanent cell cycle arrest, which is characterized by senescence-associated secretory phenotype secretion, macromolecular damage, metabolic dysregulation and so on. Recent studies have shown a close relationship between cellular senescence and type 2 diabetes. On the one hand, the glycolipotoxic microenvironment of type 2 diabetes can accelerate cell senescence and accumulation. On the other hand, cellular senescence can promote the development of type 2 diabetes. For example, senescence of pancreatic β-cells leads to β-cell dysfunction and adipocytes senescence results in the secretion of pro-inflammatory cytokines, causing disturbances in lipid metabolism and exacerbating insulin resistance. Moreover, senescence of endothelial cells, retinal endothelial cells, and other cell types contributes to the occurrence of chronic complications in diabetes. Cellular senescence is not only an important factor in the onset of type 2 diabetes but also a consequence of its progression. Targeting cellular senescence holds promise as a new strategy for the treatment of type 2 diabetes.

Diagnosis status and genetic characteristics analysis of Fanconi anemia in China / 中华儿科杂志

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.