ObjectiveTo explore the potential mechanism of moxibustion at Guanyuan （CV 4） in delaying skin photoaging. MethodsThirty-two male Wistar rats were randomly divided into four groups， namely blank group， model group， vitamin E group， and moxibustion group， with 8 rats in each group. Except for the blank group， dorsal skin of rats were exposed to ultraviolet （UV） radiation to establish a skin photoaging model. One week after modeling， the moxibustion group received moxibustion at "Guanyuan （CV 4）" once a day， five days per week； the vitamin E group received vitamin E （25 mg/kg·d） once a day by gavage， five days per week； the blank group， model group， and moxibustion group received an equivalent volume of normal saline via gavage； the intervention lasted for 7 weeks. After 7 weeks， dorsal skin tissues were collected to analyze the following indicators， such as skin tissue moisture content， histomorphological changes using hematoxylin-eosin （HE） staining， Collagen Ⅰ and collagen Ⅲ content using ELISA. Malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， superoxide dismutase （SOD）， hydrogen peroxide （H₂O₂）， and catalase （CAT） activity in skin tissue were dectected. Western Blot was used to determin autophagy-related proteins， including microtubule-associated protein 1A/1B-light chain 3 （LC3）， polyubiquitin-binding protein （p62）， and autophagy-specific gene （Beclin-1）； LC3， p62， and Beclin-1 mRNA expression was detected via qRT-PCR， and autophagosome formation was observed using transmission electron microscopy （TEM）. ResultsHE staining showed that the epidermal structure in the blank group was orderly and evenly thick， while the model group exhibited uneven epidermal thickness. In the moxibustion group， the epidermis was well-structured， smooth， and uniform， with densely arranged dermal layers； the epidermis in the vitamin E group was thicker than that in the model group. Compared with the blank group， the model group exhibited decreased skin moisture content and reduced level of Collagen Ⅰ and collagen Ⅲ， reduced SOD， CAT， and GSH-Px activity in skin tissue， increased H₂O₂ and MDA activity， elevated p62 protein and mRNA expression， reduced LC3 and Beclin-1 protein and mRNA expression （P＜0.05 or P＜0.01）. Compared with the model group， the moxibustion group showed significant improvement in all these indicators （P＜0.05 or P＜0.01）； whereas the vitamin E group did not show a statistically significant difference in Collagen Ⅰ and collagen Ⅲ levels （P＞0.05）. TEM results showed that， compared with the blank group， the model group had atrophic skin cells， extensive mitochondrial vacuolization， and degraded cellular structures； the moxibustion group exhibited crescent- or cup-shaped autophagosomes with a significantly increased number of autophagosomes per unit area， whereas the vitamin E group showed less improvement than the moxibustion group. ConclusionMoxibustion at "Guanyuan （CV 4）" may alleviate skin photoaging by regulating oxidative stress imba-lance， modulating cellular autophagy， and promoting collagen synthesis， thereby slowing the aging process of the skin.

Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.

Objective To investigate the ameliorative effect of Lentinan (LNT) on sodium arsenite (SA)-induced hepatic lipid deposition in mice. Methods C57BL/6 mice were used as the experimental subjects, which were divided into control group, SA-exposed group, LNT + SA-exposed group and LNT control group. Blood and liver tissue samples were collected at the end of the experiment, and serum glutathione transaminase (ALT) and glutathione aminotransferase (AST) levels were detected by enzyme-linked immunosorbent assay (ELISA). A part of liver tissues was stained with hematoxylin-eosin (HE) or oil red O to observe the characteristics of liver pathological damage and lipid deposition, and another part of liver tissues was used to detect triglyceride (TG) and Adiponectin (APN) levels by ELISA. Results Compared with control group or LNT control group, SA-exposed group showed the increased levels of AST and ALT, showing the characteristics of liver histopathological damage and lipid deposition, and the APN level decreased while the TG level increased (P<0.05). Compared with SA-exposed group, the levels of AST and ALT decreased in LNT + SA-exposed group, showing the reduced degree of liver tissue damage and lipid deposition, and APN level upregulated while TG level downregulated (P<0.05). Conclusion Chronic SA exposure induces liver function damage, APN downregulation and lipid deposition in C57BL/6 mice, while LNT intervention leads to the significantly improvement of hepatic damage and lipid deposition, which may be related to the elevated APN level in liver.

Objective To explore the clinical effects of hypoglycemic drugs on depression degree in patients with type 2 diabetes mellitus(T2DM).Methods A total of 160 newly diagnosed T2DM patients or T2DM patients who have not used hypoglycemic drugs in the past 3 months with mild to moderate depressive episodes and visited our outpatient department were enrolled in this study from January to December 2022.All the participants HbA1c were ranged from 7%to 9%.They were randomly divided into four groups:Metformin treatment group(Met,n=40),Met combined with sulfonylurea treatment group(Met+SUs,n=40),Met combined with DPP-4i treatment group(Met+DPP-4i,n=40),and Met combined with GLP-1 receptor agonist treatment group(Met+GLP-1RA,n=40).All the patients were scored with the Hamilton Depression Rating Scale(HAMD)and the Hamilton Anxiety Rating Scale(HAMA)in each group.Results The Met+DPP-4i and Met+GLP-1RA groups showed the most significant decrease in HAMD and HAMA scores after treatment(P<0.05),while the proportion of moderate depression and significant anxiety in HAMD decreased(P<0.05).Pearson correlation analysis showed that?HAMD,?HAMA were positively correlated with ?HbA1c in the Met+GLP-1RA group(P<0.05).Conclusion The combination of Met with DPP-4i and GLP-1RA has the most significant effect on improving the degree of depression in patients with T2DM and depression.

Objective:To summarize the clinical characteristics and pathogenic mutation of gene NUDT2 in the child with intellectual disability with or without peripheral neuropathy (IDDPN). Methods:The clinical characteristics and development of one child attending the Department of Rehabilitation of Tianjin Children's Hospital were evaluated retrospectively,and the relationship between the clinical phenotype and gene mutation profile of NUDT2 was analyzed. Results:The child had global developmental delay, special appearance, low muscle tone of the limbs, accompanied by peripheral nerve damage in the limbs, and whole exome sequencing found that the child carried a homozygous mutation of NUDT2 gene, c.34C>T (p.R12X), which was a nonsense mutation. Sanger verified that both parents were carriers of c.34C>T heterozygous mutations. In the inclusion of 10 registered IDDPN patients, it was found that all of them were homozygous mutations, and the clinical phenotypes all had different degrees of cognitive impairment and movement disorders, among which only 3 cases were complicated by peripheral nerve damage. Conclusions:The child in this case had low birth weight/length, weak sucking ability in infancy, cognitive impairment, peripheral nerve damage, and genetic testing showed homozygous nonsense mutation of NUDT2 gene, which provided evidence support for the clinical understanding of the disease.

Objective To investigate the clinical value of fat attenuation index (FAI) on coronary CT angiography (CCTA) in evaluating the degree of coronary artery stenosis and the diagnostic value of plaque vulnerability. Methods A total of 80 patients treated for coronary artery diseases from January 2021 to November 2023 were retrospectively included. All patients were diagnosed with non-calcified plaque (NCP) by CCTA examination. Patients were divided according to the severity of luminal stenosis (39 with mild stenosis, 24 with moderate stenosis, and 17 with severe stenosis). According to plaque vulnerability, the patients were divided into a vulnerable plaque group (27 cases) and a non-vulnerable plaque group (53 cases). A Spearman correlation analysis was used to evaluate the correlation between FAI and stenosis severity in patients with NCP, and a multivariate logistic regression analysis was used to explore the factors influencing vulnerable plaques. Results FAI was significantly lower in the severe stenosis group (−76.95 ± 7.91 HU) than in the mild stenosis group (−66.73 ± 7.69 HU) and the moderate stenosis group (−71.58 ± 8.65 HU), and FAI was significantly lower in the moderate stenosis group than in the mild stenosis group (t = 4.534, 2.190, 4.534, P < 0.05). The correlation analysis showed that FAI was negatively correlated with the severity of coronary artery stenosis (r = −0.726, P < 0.05). There were significant differences between vulnerable and non-vulnerable plaque groups in hypertension [23 (85.19%) vs. 30 (56.60%)], smoking history [8 (29.63%) vs. 4 (7.55)], and FAI (−67.64 ± 8.32 HU vs. −75.69 ± 7.88 HU) (t = 6.535, 6.841, 4.164, P < 0.05). The multivariate logistic regression analysis showed that FAI was a risk factor for vulnerable plaque (odds ratio = 1.439, P < 0.05). Conclusion FAI can be used to effectively assess the risk stratification of NCP and is of great significance in guiding the clinical management of patients.

Objective To investigate the clinical value of fat attenuation index (FAI) on coronary CT angiography (CCTA) in evaluating the degree of coronary artery stenosis and the diagnostic value of plaque vulnerability. Methods A total of 80 patients treated for coronary artery diseases from January 2021 to November 2023 were retrospectively included. All patients were diagnosed with non-calcified plaque (NCP) by CCTA examination. Patients were divided according to the severity of luminal stenosis (39 with mild stenosis, 24 with moderate stenosis, and 17 with severe stenosis). According to plaque vulnerability, the patients were divided into a vulnerable plaque group (27 cases) and a non-vulnerable plaque group (53 cases). A Spearman correlation analysis was used to evaluate the correlation between FAI and stenosis severity in patients with NCP, and a multivariate logistic regression analysis was used to explore the factors influencing vulnerable plaques. Results FAI was significantly lower in the severe stenosis group (−76.95 ± 7.91 HU) than in the mild stenosis group (−66.73 ± 7.69 HU) and the moderate stenosis group (−71.58 ± 8.65 HU), and FAI was significantly lower in the moderate stenosis group than in the mild stenosis group (t = 4.534, 2.190, 4.534, P < 0.05). The correlation analysis showed that FAI was negatively correlated with the severity of coronary artery stenosis (r = −0.726, P < 0.05). There were significant differences between vulnerable and non-vulnerable plaque groups in hypertension [23 (85.19%) vs. 30 (56.60%)], smoking history [8 (29.63%) vs. 4 (7.55)], and FAI (−67.64 ± 8.32 HU vs. −75.69 ± 7.88 HU) (t = 6.535, 6.841, 4.164, P < 0.05). The multivariate logistic regression analysis showed that FAI was a risk factor for vulnerable plaque (odds ratio = 1.439, P < 0.05). Conclusion FAI can be used to effectively assess the risk stratification of NCP and is of great significance in guiding the clinical management of patients.

Objective:To explore the interrelationship among three simplified hand and wrist bone age assessment methods and to establish corresponding bone ages for each substage in male children.Methods:This retrospective case series study included 169 left hand and wrist X-rays from 152 male children who underwent bone age assessments at the Pediatric Orthopedics and Pediatrics Departments,Beijing Jishuitan Hospital,Capital Medical University from January 2019 to December 2023. The age at the time of X-ray was (13.7±2.0) years (range:9.1 to 17.9 years). Reasons for bone age assessment included evaluating the progress of adolescent idiopathic scoliosis in 36 cases, predicting limb length discrepancies in 28 cases, and predicting the height of healthy adolescents in 88 cases. Bone age was first graded using the Chinese hand-wrist bone age assessment method. Three simplified hand and wrist bone age assessment methods were then applied:Sanders simplified skeletal maturity staging system(Sanders stage), the distal radius and ulna classification (DRU), and e thumb ossification composite index (TOCI). Somers′delta correlation test was used to analyze the relationship among the results of the three simplified methods. The bone age and standard deviation for each sub-stage were calculated, and gender differences in bone age for the same sub-stage were compared with previous study.Results:The DRU, TOCI and Sanders stages showed a strong correlation when assessing bone age in male children, with Somers′delta correlation coefficients ranging from 0.881 to 0.876 (all P<0.01). The sub-stages with the smallest standard deviations (shorter duration) in each of the three classifications can serve as a quick reference for determining precise bone age, included proximal thumb epiphysis covered, without sesamoid (12.0 years);proximal thumb epiphysis covered with sesamoid or distal radial covered (13.0 years), early capping of the thumb epiphysis, radial epiphysis medial side capping(13.5 years), all phalangeal epiphyses capping (14.0 years), distal phalangeal physes beginning to close (14.5 years), all distal phalangeal physes closed (15.0 years), middle or proximal phalangeal physes beginning to close (15.5 years), all digital epiphyses closed (16.5 years), and nearly complete distal radius fusion with a notch (17.5 years). On average, the bone ages of males were 2 years behind those of females in the same substage. Conclusions:The DRU, TOCI, and Sanders stages can be applied to male children, and it is showed good correlation between them. The subtypes with shorter duration can be used as a quick assessment method to determine the bone age.

Objective To analyze the potential distribution and quality zoning of Gentiana farreri Balf.f.;To provide a theoretical basis for the conservation,sustainable utilization,and domestication of this Tibetan medicine resource.Methods The MaxEnt model and geographic information system software ArcGIS 10.2 were used to conduct ecological suitability zoning of Gentiana farreri Balf.f.in China through searching online specimen libraries and field investigations.SPSS25.0 software was used to construct a relationship model between indicator components and ecological factors,combined with ArcGIS software spatial analysis technology,to form a quality zoning of Gentiana farreri Balf.f.medicinal material.Results The primary environmental factors influencing the ecological suitability of Gentiana farreri Balf.f.were altitude,precipitation in May,April and December,and the mean monthly diurnal temperature range.The most suitable growth areas for Gentiana farreri Balf.f.were predominantly found at the junction of Gansu,Sichuan and Qinghai provinces,certain parts of Tibet,and selected regions of Sichuan.The southern part of Tibet and the southwestern part of Sichuan were identified as having higher comprehensive quality of Gentiana farreri Balf.f.medicinal materials.Conclusion The findings of this study can serve as a reference for the production planning and quality assessment of Gentiana farreri Balf.f.

Background and purpose:Epidermal growth factor receptor exon 20 T790M(EGFR T790M)mutation is one of the acquired resistance mechanisms in non-small cell lung cancer(NSCLC)against first-/second-generation EGFR tyrosine kinase inhibitors(EGFR TKIs).Additionally,EGFR T790M mutation can also be observed in NSCLC patients who have not undergone EGFR TKIs treatment.This study aimed to compare the clinical pathological characteristics and prognostic differences between NSCLC patients with de novo and acquired EGFR T790M mutation,and further explore the immune microenvironment features of acquired T790M mutation in NSCLC.Methods:This study retrospectively included 3 762 cases of NSCLC diagnosed at Fudan University Shanghai Cancer Center from April 2020 to September 2022.Among them,2 070 cases(55.02%)exhibited EGFR mutations,and 556 cases(14.77%)received EGFR TKIs treatment.Specifically,there were 119 cases(3.16%)of NSCLC with EGFR T790M mutation,including 51 cases(1.35%)of de novo T790M mutation and 68 cases(1.81%)of acquired EGFR T790M mutation.Clinical data of the patients were collected for comparative analysis between NSCLC patients with de novo and acquired T790M mutation.Multiple immunofluorescence histochemistry(mIHC)was employed to explore the immune microenvironment characteristics of NSCLC patients with acquired T790M mutation.Results:The proportion of de novo and acquired T790M mutations was higher in female patients compared to males.Patients with de novo T790M mutation tended to be younger.Both de novo and acquired T790M mutations were more commonly found in poorly differentiated carcinomas.Among NSCLC patients with de novo T790M mutation,there was a higher rate of programmed death ligand-1(PD-L1)expression(60.00%).In contrast,among NSCLC patients with acquired T790M mutation,the rate of PD-L1 expression was lower(22.39%).Acquired T790M mutation in NSCLC was often accompanied by TP53 alterations(39.7%).Cox regression analysis results indicated that mesenchymal to epithelial transition(MET)factor alteration was a risk factor for the occurrence of acquired T790M mutation(P=0.000 5).The average overall survival(OS)showed no significant difference between de novo and acquired T790M mutations(35.4 and 37.3 months respectively).However,patients with acquired T790M mutation exhibited a higher proportion of recurrence and metastasis.In acquired T790M mutation,there was a higher presence of immune cell infiltration within the stromal compartment,such as CD20+B cells,CD23+B cells,CD8+T cells,CD8+PD-1-/+cells,CD20+PD-1-/+cells and CD23+PD-1-/+cells.Additionally,the study found that when EGFR was accompanied by tumor suppressor gene(TSG)alterations,the average distance between tumor cells and CD8+T cells,CD20+B cells,CD8+PD-1+cells,CD20+PD-1+cells and CD23+PD-1+cells was closer compared to cases with only EGFR mutations.Conclusion:In comparison to patients with de novo T790M mutation,patients with acquired T790M mutation exhibit a lower rate of PD-L1 positivity.Acquired T790M mutation often accompanies TP53 alterations,and MET alteration is identified as a risk factor triggering acquired T790M mutation.Although patients with acquired T790M mutation face higher risk of recurrence and metastasis,their average OS does not significantly differ from those with de novo T790M mutation.In cases of acquired T790M mutation,the presence of TSG mutations can alter the spatial distribution of immune cells,potentially leading to benefits from immunotherapy.