Aim To explore the ameliorative effects of berberine(BBR)on diabetic nephropathy(DN)in mice and investigate its potential mechanisms through transcriptomic analysis.Methods 8-week-old db/db mice were randomly assigned into four groups:model group(DN group),BBR 50 mg·kg-1 group(BBR-L group),BBR 100 mg·kg-1 group(BBR-H group),and empagliflozin 10 mg·kg-1 group(EMPA group).Age-matched db/m mice were used as the control group(NC group),with eight mice in each group.Each group received intragastric administration once daily for eight weeks.After the treatment,serum,u-rine,and kidney samples were collected to evaluate re-nal function indicators and observe renal pathological changes.Differentially expressed genes(DEGs)in kidney tissue were identified through transcriptomic a-nalysis,followed by KEGG and GO enrichment analy-sis.Potential targets were further validated using mo-lecular docking,molecular dynamics simulations,West-ern blot,and immunohistochemistry.Results Both BBR and EMPA significantly reduced fasting blood glu-cose levels in DN mice,improved renal function,and alleviated renal injury and fibrosis.Compared to the NC group,855 DEGs were identified in the DN group,while 194 DEGs were identified in the BBR-H group compared to the DN group.KEGG enrichment analysis indicated that the mechanisms underlying BBR's effects on DN were primarily related to type 1 diabetes and bile secretion pathways.Molecular docking results demonstrated a strong binding affinity between BBR and FXR and a moderate binding affinity with SHP.Molecular dynamics simulations corroborated the doc-king results.FXR and SHP protein expression signifi-cantly decreased in the DN group compared to the NC group.At the same time,BBR treatment significantly increased the expression of these proteins compared to the DN group.Conclusion BBR may mitigate DN-in-duced renal injury by modulating bile acid and lipid homeostasis through the FXR-SHP pathway.

Objective:To construct an evaluation index system for the perioperative medical service efficiency.Methods:From September to November 2023, this study conducted literature search and research group discussions to select initial indicators for evaluating the efficiency of perioperative medical services guided by value-based healthcare; 2-round Delphi methods were used to construct an evaluation index system for perioperative medical service efficiency, and the weights of the indicators were determined using the analytic hierarchy process.Results:The expert motivation for both rounds of Delphi method was 100.00%, the expert authority coefficient was 0.94, and the Kendall coordination scores were 0.56 and 0.75, respectively. The final established evaluation index system for perioperative medical service efficiency included 2 primary indexes, 9 secondary indexes, and 41 tertiary indexes. The first level indexes included medical quality and medical cost, with relative weights of 66.67% and 33.33%, respectively. Among them, medical quality included 7 secondary indexes: medical management, medical safety, service mode, information construction, patient outcomes, service efficiency, and satisfaction; Medical costs include 2 secondary indiexes: patient costs and medical institution costs.Conclusions:The evaluation index system for the efficiency of perioperative medical services reflected the connotation of value-based healthcare and could comprehensively and objectively evaluate the efficiency of perioperative medical services.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveTemporal heterogeneity in lung cancer presents as fluctuations in the biological characteristics, genomic mutations, proliferation rates, and chemotherapeutic responses of tumor cells over time, posing a significant barrier to effective treatment. The complexity of this temporal variance, coupled with the spatial diversity of lung cancer, presents formidable challenges for research. This article will pave the way for new avenues in lung cancer research, aiding in a deeper understanding of the temporal heterogeneity of lung cancer, thereby enhancing the cure rate for lung cancer. MethodsRaman spectroscopy emerges as a powerful tool for real-time surveillance of biomolecular composition changes in lung cancer at the cellular scale, thus shedding light on the disease’s temporal heterogeneity. In our investigation, we harnessed Raman spectroscopic microscopy alongside multivariate statistical analysis to scrutinize the biomolecular alterations in human lung epithelial cells across various timeframes after benzo(a)pyrene exposure. ResultsOur findings indicated a temporal reduction in nucleic acids, lipids, proteins, and carotenoids, coinciding with a rise in glucose concentration. These patterns suggest that benzo(a)pyrene induces structural damage to the genetic material, accelerates lipid peroxidation, disrupts protein metabolism, curtails carotenoid production, and alters glucose metabolic pathways. Employing Raman spectroscopy enabled us to monitor the biomolecular dynamics within lung cancer cells in a real-time, non-invasive, and non-destructive manner, facilitating the elucidation of pivotal molecular features. ConclusionThis research enhances the comprehension of lung cancer progression and supports the development of personalized therapeutic approaches, which may improve the clinical outcomes for patients.

[Objective] To investigate the influencing factors of immune-related thyroid dysfunction (irTD) treated with programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors and their impact on overall survival (OS) of cancer. [Methods] We enrolled 211 cancer patients treated with PD-1/PD-L1 inhibitors. Clinical differences between irTD groups were compared, and subgroup analysis was performed. Multifactor Logistic regression analysis was used to identify influencing factors of irTD, while survival analysis was used to explore the relationship between the occurrence of irTD and OS, and the log-rank test was used for comparison between groups. The multi-model COX regression analysis was used to evaluate the impact of irTD on OS. [Results] The incidence rate of irTD was 26.1%, with 13.3%, 10.0% and 2.8%, respectively for grade 1, grade 2, and grades 3-4, and the median time of occurrence was at week 9 (IQR: 5-25 weeks). Significant differences were observed between the irTD and non-irTD groups in terms of gender, smoking history, targeted therapy history, and baseline thyroid antibody status (P<0.05). In irTD patients, thyroglobulin antibody (TGAb) levels began to increase from week 3, remained above the baseline from week 6 to week 30, and then gradually declined to the baseline level after week 30. The change in thyroid microsomal antibody (TMAb) levels was less pronounced than that of TGAb. Subgroup analysis showed that patients with hyperthyroidism were younger at the time of initial immunotherapy than those with hypothyroidism (P<0.05) and had lower baseline TSH levels (P<0.05). Multifactor Logistic regression analysis revealed that patients with positive baseline thyroid antibodies had a 4.595-fold higher risk of developing irTD compared to those with negative antibodies (95% CI: 2.286-9.239, P<0.001). Survival analysis revealed that patients with irTD had a longer OS and the multi-model COX regression analysis revealed that after adjusting for factors such as age, gender, chemotherapy, tumor type and tumor metastasis status, patients with irTD had a significantly longer OS (HR=0.228, 95% CI: 0.079-0.656, P=0.006). [Conclusion] The severity of irTD was predominantly grades 1-2, with grades 3-4 being rare. Positive baseline thyroid antibodies were an independent risk factor for the development of irTD. Patients who develop irTD have a longer OS, which may be due to their stronger immune response.

AIM: To investigate the effect of Nd:YAG laser peripheral iridotomy(LPI)on macular retinal thickness in patients with primary angle-closure glaucoma(PACG).METHODS: Prospective study. A total of 30 patients(30 eyes)with PACG in our hospital from October 2019 to October 2021 were selected as the PACG group, and 20 healthy people(20 eyes)were selected as the control group(randomly selected one eye)during the same period. The PACG group received LPI treatment and was followed up for 1mo after surgery. Best corrected visual acuity(BCVA), intraocular pressure, corneal endothelial cells, anterior chamber depth(ACD)and axial length(AL)measured by IOL Master 500 optical measuring instrument and macular retinal thickness measured by spectral-domain optical coherence tomography(SD-OCT)in both groups were collected. The ACD, intraocular pressure, AL and macular retinal thickness were compared between the two groups and the PACG group before and after LPI, and the correlation was analyzed.RESULTS: The ACD in the PACG group at 1wk and 1mo after surgery was deeper than that before surgery(all P<0.05). There was no significant difference in intraocular pressure and AL in the PACG group before and after surgery(all P>0.05). The retinal thickness at central fovea of macula, the superior side, temporal side, inferior side, and nasal side of the inner and outer central macular rings were 243.50±13.24, 324.50±13.46, 308.83±15.94, 310.00±14.24, 314.50±16.29, 300.67±19.95, 290.17±12.58, 302.40±16.37 and 307.33±14.84μm in the PACG group, respectively, and were 266.14±16.16, 342.67±15.86, 327.95±16.41, 337.85±13.03, 341.24±15.58, 313.76±17.59, 290.24±16.29, 303.81±13.91, 323.01±14.80μm in the control group, respectively. The differences at central fovea of macula, the superior side, temporal side, inferior side, and nasal side of the inner central macular rings were statistically significant between the two groups(all P<0.05). In the PACG group, the retinal thickness at 9 areas of macular in 1wk after operation were higher than those before operation, and they were close to the preoperative level at 1mo after operation, but the differences of each area in the overall comparison were not statistically significant(all P>0.05).CONCLUSIONS: The macular retinal thickness of patients with PACG is thinner than that of normal people, and it can become thicker in the early stage after LPI.

AIM: To identify the pathogenic gene in a family with primary open angle glaucoma(POAG)from Nantong, Jiang Province, and to analyze its clinical phenotype and pathogenic mechanism.METHOD: A POAG pedigree was reviewed and recruited from January 2020 to December 2020, which spans 5 generations, with 33 people in total. A total of 13 family members were enrolled in our study, of whom 4 members were diagnosed with POAG, 1 with ocular hypertension(OHT), and the other 8 members were unaffected. Detailed medical history was collected and a comprehensive ophthalmic examination was performed. High throughput sequencing was used to screen for possible pathogenic gene, and Sanger sequencing was used to verify candidate pathogenic gene.RESULT: All patients in this family were found to have elevated intraocular pressure(IOP)and diagnosed with glaucoma at a young age, requiring surgical treatments to control the IOP. The highest IOP of proband was up to 55mmHg. A heterozygous mutation(c.1197C>A, p.Phe399Leu)of LTBP2 gene was found in the proband genome by whole exon sequencing(WES). Sanger sequencing verified that the mutation was not isolated from the family disease.CONCLUSION: LTBP2 (c.1197C>A)mutation was not the pathogenic gene of POAG in this family. However, the pathogenic potential of LTBP2 gene in POAG cases is worth studying.

Objective:To investigate the diagnostic method and value of echocardiography in screening right patent ductus arteriosus(PDA) of infants.Methods:This was a prospective study.Thirty-one infants with right PDA diagnosed by ultrasound and confirmed by prenatal ultrasonography, electronic computed tomography angiography, angiocardiography and/or surgery in Hebei Children′s Hospital from April 2014 to May 2022 were collected as research subjects, and the association of right ductus arteriosus with aortic arch anomalies and complex cardiac malformations were summarized. The diagnostic method and value of ultrasonic screening were summed up.Results:Of the 31 cases, 30 cases were correctly diagnosed by ultrasound and 1 case was misdiagnosed, who was a left aortic arch descending to the right, a crossover variation of the right and left pulmonary arteries, and a rightward displacement of the ductus arteriosus. Among these cases diagnosed correctly, 27 cases (including 24 cases with right aortic arch and 3 cases with left aortic arch) presented that ductus arteriosus was open and its ostium of pulmonary artery end was located in the proximal right pulmonary artery in views of parasternal short-axis view of great vessels at cardiac base with the combination of two dimensions and color Doppler flow imaging. Other 3 cases of right aortic arch were all single ventricle with transposition of the great artery. Due to the parallel relationship of the two great arteries, the standard parasternal short-axis view of great vessels could not be obtained, and the right ductus arteriosus was found in the high parasternal views.In all of the 27 cases with right aortic arch and right ductus arteriosus, high parasternal views showed that one end of the ductus arteriosus was connected to the right aortic arch isthmus and the other end was connected to the right pulmonary artery. In all of the 3 cases with left aortic arch and right ductus arteriosus, the high parasternal views showed that one end of the ductus arteriosus was connected to the right subclavian artery and the other end was connected to the right pulmonary artery. Among the 27 cases with right aortic arch, 16 cases were accompanied with mirror image branches, 9 cases of which had complex cardiac malformations; 10 cases were associated with aberrant left subclavian artery, 1 case of which had complex cardiac malformations; 1 case was with isolated left subclavian artery, and without complex cardiac malformations. All 3 cases of left aortic arch were accompanied with isolated right subclavian artery and none of them were associated with complex cardiac malformations. Clinical outcomes of 30 cases with right PDA: 14 cases underwent ductus arteriosus ligation due to thick ductus or other heart malformations. In other 16 cases, 4 cases were closed spontaneously, 9 cases had persistent small ductus arteriosus, and 3 cases were lost to follow-up.Conclusions:Right ductus arteriosus is mostly related to the right aortic arch, and those with mirror image branches are prone to complex cardiac malformations; cases of left aortic arch with right ductus arteriosus are tend to accompany isolated right subclavian artery. Ultrasound has an important application in the screening and diagnosis of right PDA.

Objective: This study’s objective is to assess the efficacy and safety of Pulsed Magnetic Therapy System (PMTS) in improving insomnia disorder. Methods: Participants with insomnia disorder were randomly assigned to receive either PMTS or sham treatment for four weeks (n= 153; PMTS: 76, sham: 77). Primary outcomes are the Insomnia Severity Index (ISI) scores at week 0 (baseline), 1, 2, 3, 4 (treatment), and 5 (follow-up). Secondary outcomes are the Pittsburgh Sleep Quality Index at baseline and week 4, and weekly sleep diary-derived values for sleep latency, sleep efficiency, real sleep time, waking after sleep onset, and sleep duration. Results: The ISI scores of the PMTS group and the sham group were 7.13±0.50, 11.07±0.51 at week 4, respectively. There was a significant group×time interaction for ISI (F3.214, 485.271=24.25, p<0.001, ηp 2=0.138). Only the PMTS group experienced continuous improvement throughout the study; in contrast, the sham group only experienced a modest improvement after the first week of therapy. At the end of the treatment and one week after it, the response of the PMTS group were 69.7% (95% confidence interval [CI]: 58.6%–79.0%), 75.0% (95% CI: 64.1%–83.4%), respectively, which were higher than the response of the sham group (p<0.001). For each of the secondary outcomes, similar group×time interactions were discovered. The effects of the treatment persisted for at least a week. Conclusion PMTS is safe and effective in improving insomnia disorders.

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.
Male ; Humans ; Child ; Disorders of Sex Development/pathology* ; Hypospadias/complications* ; Cryptorchidism/complications* ; Retrospective Studies ; Adrenal Hyperplasia, Congenital ; Steroid 21-Hydroxylase