ObjectiveTo construct and evaluate a mouse model that simulates the pathological progression of immune checkpoint inhibitor-associated pneumonitis (CIP), in order to address the critical issue of the lack of standardized animal models in this research field. MethodsThirty-five SPF-grade 6-week-old male C57BL/6J mice were randomly assigned to a control group (n=5), a bleomycin (BLM) group (n=15), and a BLM+programmed death-1 (PD-1) monoclonal antibody (BLM+PD-1) group (n=15). Corresponding drugs were administered via intraperitoneal injection for intervention. The general condition, body weight changes, survival rate, and pulmonary histopathological alterations were systematically monitored. ResultsCompared with the BLM group, the BLM+PD-1 group exhibited significantly more severe pulmonary fibrosis, characterized by progressive body weight loss and more severe deterioration of general conditions. Histopathological examination showed that pulmonary inflammation was alleviated 4 weeks post-modeling in the BLM group. In contrast, pulmonary lesions continued to worsen in the BLM+PD-1 group, with no evidence of resolution of inflammation 28 days post-modeling. Quantitative immunohistochemical analysis revealed that the positive expression rate of interleukin-17A (IL-17A) in lung tissues reached 34.28% in the BLM+PD-1 group 14 days post-modeling, which was markedly higher than that in the BLM group (24.02%, P < 0.000 1). The positive expression rate of α-smooth muscle actin (α-SMA) was 12.40% in the BLM+PD-1 group 14 days post-modeling, nearly twice the level in the BLM group (5.87%). 28 days post-modeling, the positive expression rate of α-SMA remained at 7.72% in the BLM+PD-1 group, while it declined to 3.38% in the BLM group. ConclusionThe addition of a PD-1 inhibitor to bleomycin treatment accelerates the progression of pulmonary interstitial fibrosis and effectively recapitulates the pathological process of lung injury and fibrosis driven by aberrant immune activation during clinical immunotherapy. Accordingly, this study successfully establishes a dynamic CIP animal model recapitulating the progression from early inflammatory response to pulmonary fibrosis. This model addresses the critical shortage of animal models for this condition and offers an experimental platform for further mechanistic studies and the development of therapeutic strategies.

Objective To investigate the correlation between levels of low-density lipoprotein cholesterol(LDL-C)and atrial fibrillation in a hypertensive population.Methods Hypertension screening was performed in the Wuyuan County of Jiangxi Province from June to August 2022.Data were collected using face-to-face questionnaire surveys,physical measurements,and biochemical tests.Logistic regres-sion analysis was used to analyze the effect of LDL-C on atrial fibrillation.The restricted cubic spline method was used to fit the correlation curve.Results A total of 14 314 patients with hypertension were included in the analysis,with an average age of 65.7±9.2 years.There were 570 patients detected with atrial fibrillation(the rate of atrial fibrillation was 4.0％).The rates of atrial fibrillation for LDL-C＜1.80 mmol/L,1.80-＜2.60 mmol/L,2.60-＜3.40 mmol/L and≥3.40 mmol/L were 10.2％(67/654),5.7％(216/3 807),3.3％(189/5 805),and 2.4％(98/4 048),respectively.Logistic regression analysis showed that,compared with LDL-C＜1.80 mmol/L group,LDL-C 1.80-＜2.60 mmol/L group,2.60-＜3.40 mmol/L group,and ≥ 3.40 mmol/L group had a lower risk of atrial fibrillation(OR=0.53,95％CI:0.39-0.72,P＜0.001;OR=0.32,95％CI:0.23-0.45,P＜0.001;OR=0.22,95％CI:0.16-0.32,P＜0.001).Curve-fitting results showed that LDL-C levels were negatively associated with the risk of atrial fibrillation.Subgroup analysis showed that LDL-C level was negatively associated with the risk of atrial fibrillation in patients without a history of stroke(OR=0.51,95％CI:0.44-0.58,P＜0.001),while the association was not statistically significant in patients with a history of stroke(OR=0.80,95％CI:0.54-1.19,P=0.273).Conclusion In hyperten-sive patients without a history of stroke,LDL-C levels negatively correlated with the risk of atrial fibrillation.

Objective To investigate the correlation between levels of low-density lipoprotein cholesterol(LDL-C)and atrial fibrillation in a hypertensive population.Methods Hypertension screening was performed in the Wuyuan County of Jiangxi Province from June to August 2022.Data were collected using face-to-face questionnaire surveys,physical measurements,and biochemical tests.Logistic regres-sion analysis was used to analyze the effect of LDL-C on atrial fibrillation.The restricted cubic spline method was used to fit the correlation curve.Results A total of 14 314 patients with hypertension were included in the analysis,with an average age of 65.7±9.2 years.There were 570 patients detected with atrial fibrillation(the rate of atrial fibrillation was 4.0％).The rates of atrial fibrillation for LDL-C＜1.80 mmol/L,1.80-＜2.60 mmol/L,2.60-＜3.40 mmol/L and≥3.40 mmol/L were 10.2％(67/654),5.7％(216/3 807),3.3％(189/5 805),and 2.4％(98/4 048),respectively.Logistic regression analysis showed that,compared with LDL-C＜1.80 mmol/L group,LDL-C 1.80-＜2.60 mmol/L group,2.60-＜3.40 mmol/L group,and ≥ 3.40 mmol/L group had a lower risk of atrial fibrillation(OR=0.53,95％CI:0.39-0.72,P＜0.001;OR=0.32,95％CI:0.23-0.45,P＜0.001;OR=0.22,95％CI:0.16-0.32,P＜0.001).Curve-fitting results showed that LDL-C levels were negatively associated with the risk of atrial fibrillation.Subgroup analysis showed that LDL-C level was negatively associated with the risk of atrial fibrillation in patients without a history of stroke(OR=0.51,95％CI:0.44-0.58,P＜0.001),while the association was not statistically significant in patients with a history of stroke(OR=0.80,95％CI:0.54-1.19,P=0.273).Conclusion In hyperten-sive patients without a history of stroke,LDL-C levels negatively correlated with the risk of atrial fibrillation.

Objective:To explore the characteristics of natural foci of hemorrhagic fever with renal syndrome (HFRS) in Gansu Province.Methods:The information of HFRS case data and rodent density monitoring data from 2012 to 2022 in Gansu Province were collected and epidemiological methods were used to analyze and investigate the characteristics of the epidemic focus.Results:A total of 869 cases of HFRS were reported, and four patients died from 2012 to 2022. The annual incidence rate is between 0.05 per 100 000 and 1.21 per 100 000. The cases were mainly distributed in the eastern, southeast, southern, and south of the central region of Gansu Province. Most cases were distributed between age 20-60, and the sex ratio was 1.85∶1 (564∶305). Most cases were farmers (61.80%, 537/869), herdsmen (19.79%,172/869) and students (6.33%, 55/869). In a wild rat-type epidemic focus,the incidence peak was from November to January of the following year. The natural rodent hosts of HFRS were Rattus norvegicus, Apodemus agrarius, and Mus musculus. The hantaan virus carriage rates were 2.79% (21/754), 0.42% (5/1 179) and 0.31% (2/643),respectively. Three epidemic foci were defined: two derived from the Pingliang and Gannan prefecture new outbreaks epidemic foci, respectively, while the other was the residue of the Dingxi epidemic focus. Conclusions:The southern, south of the central region and eastern part of Gansu Province are current key HFRS epidemic foci dominated by Rattus norvegicus, Apodemus agrarius, and Mus musculus, respectively. The virus genotype is hantaan virus. Case reporting areas should strengthen epidemic monitoring; the key epidemic areas should strengthen and implement various prevention and control measures to reduce the harm caused by HFRS.

Objective:To conduct whole-genome sequencing of two serum samples from imported dengue fever (DF) cases in Gansu province in 2023, analyze the molecular biological characteristics of the dengue virus (DENV) strains, accumulate baseline data for DF research in Gansu province, and provide a scientific basis for the prevention and control of imported epidemics.Methods:Two serum samples that tested positive for DENV nucleic acid were sequenced for their entire genome using a third-generation sequencing platform. The obtained sequences were subjected to phylogenetic analysis, sequence homology analysis, amino acid sequence similarity analysis, and analysis of differences in mutation sites.Results:Two complete DENV genomes were obtained through third-generation sequencing, with sequence lengths of 10 715 bp and 10 714 bp respectively. The nucleotide similarity between them was 99.11%, and the amino acid similarity was 99.59%. Homology and phylogenetic analyses indicated that both sequences belonged to DENV type 1 genotype Ⅲ and were highly homologous to isolates from Singapore, India, Nepal, and the Guangzhou city of China. The nucleotide similarity is greater than 96.91%, and the amino acid similarity is greater than 98.70%. Analysis of amino acid site differences showed that DENV-2023-GS001 and DENV-2023-GS002 had 10 and 14 mutation sites in the E protein, respectively, but the main sites related to virulence remained unchanged.Conclusions:In 2023, two cases of imported DF in Gansu province were identified as genotype Ⅲ of DENV type 1. In terms of genetic evolutionary relationships, these viruses are most closely related to those from countries such as Singapore, India, and Nepal. This indicates that there remains a risk of DENV importation and transmission in Gansu province.

Objective:To explore the feasibility of gel-clot method for bacterial endotoxin test of denosumab injec-tion.Methods:Referring to general chapter 1143 in ChP 2020.Vol Ⅲ and Technical Report No.82 on Low Endotoxin Recovery published by PDA,bacterial endotoxin was detected by turbidimetric kinetic method and the endotoxin recovery of denosumab injection with different dilutions was calculated.Then based on the recovery,it was judged whether there was a LER issue and it was predicted how well the samples interfered the reaction between TAL reagent and bacterial endotoxin.Pre-experiment of gel-clot interference test was performed with TAL reagents of different sensitivity.The gel-clot interference test was performed for three batches of samples and the bacterial endotoxin was tested with TAL reagents from different manufacturers separately.Results:Denosumab injection had no LER issue,and whose high concentration had the interference on the reaction between TAL reagent and bacterial endotoxin.The interference of gel-clot TAL reagent having a sensitivity of not less than 0.25 EU·mL-1,was elim-inated by diluting the samples to 6 mg·mL-1 with BET water.Conclusion:The gel-clot method for the detection of bacterial endotoxin in denosumab injection is feasible and can be used as a routine quality control method.

Objective:To explore the feasibility of gel-clot method for bacterial endotoxin test of denosumab injec-tion.Methods:Referring to general chapter 1143 in ChP 2020.Vol Ⅲ and Technical Report No.82 on Low Endotoxin Recovery published by PDA,bacterial endotoxin was detected by turbidimetric kinetic method and the endotoxin recovery of denosumab injection with different dilutions was calculated.Then based on the recovery,it was judged whether there was a LER issue and it was predicted how well the samples interfered the reaction between TAL reagent and bacterial endotoxin.Pre-experiment of gel-clot interference test was performed with TAL reagents of different sensitivity.The gel-clot interference test was performed for three batches of samples and the bacterial endotoxin was tested with TAL reagents from different manufacturers separately.Results:Denosumab injection had no LER issue,and whose high concentration had the interference on the reaction between TAL reagent and bacterial endotoxin.The interference of gel-clot TAL reagent having a sensitivity of not less than 0.25 EU·mL-1,was elim-inated by diluting the samples to 6 mg·mL-1 with BET water.Conclusion:The gel-clot method for the detection of bacterial endotoxin in denosumab injection is feasible and can be used as a routine quality control method.

Objective:To conduct whole-genome sequencing of two serum samples from imported dengue fever (DF) cases in Gansu province in 2023, analyze the molecular biological characteristics of the dengue virus (DENV) strains, accumulate baseline data for DF research in Gansu province, and provide a scientific basis for the prevention and control of imported epidemics.Methods:Two serum samples that tested positive for DENV nucleic acid were sequenced for their entire genome using a third-generation sequencing platform. The obtained sequences were subjected to phylogenetic analysis, sequence homology analysis, amino acid sequence similarity analysis, and analysis of differences in mutation sites.Results:Two complete DENV genomes were obtained through third-generation sequencing, with sequence lengths of 10 715 bp and 10 714 bp respectively. The nucleotide similarity between them was 99.11%, and the amino acid similarity was 99.59%. Homology and phylogenetic analyses indicated that both sequences belonged to DENV type 1 genotype Ⅲ and were highly homologous to isolates from Singapore, India, Nepal, and the Guangzhou city of China. The nucleotide similarity is greater than 96.91%, and the amino acid similarity is greater than 98.70%. Analysis of amino acid site differences showed that DENV-2023-GS001 and DENV-2023-GS002 had 10 and 14 mutation sites in the E protein, respectively, but the main sites related to virulence remained unchanged.Conclusions:In 2023, two cases of imported DF in Gansu province were identified as genotype Ⅲ of DENV type 1. In terms of genetic evolutionary relationships, these viruses are most closely related to those from countries such as Singapore, India, and Nepal. This indicates that there remains a risk of DENV importation and transmission in Gansu province.

Objective:To investigate the therapeutic effect of skull drilling and/or grinding combined with artificial dermis and vacuum sealing drainage in repairing scalp defects with skull exposure.Methods:From October 2014 to May 2018, 18 patients with scalp defect and skull exposure were treated in the Department of Burn and Plastic Surgery, the Second Clinical College of North Sichuan Medical College, including 10 males and 8 females, with an average age of 64 years (range, 34-86 years). The patients were divided into two groups: group A (by drilling skull or/and grinding combined with artificial dermis cover and vacuum sealing drainage plus two split thickness skin graft repair) and group B (by drilling skull or/andgrinding combined with artificial dermis cover plus two covering leather grinding stage split thickness skin graft repair), 9 cases in each group. The head wound granulation tissue, postoperative complications, skin graft survival rate and wound healing time were compared between the two groups. Vancouver scar assessment scale (VSS) was used to evaluate the wound healing in the two groups.Results:The time of granulation cultivation in group A and group B was (16.44±1.42) days and (29.11±13.32) days, the difference was statistically significant ( P<0.05); The wound healing time of group A and group B was (26.00±3.32) days and (40.67±14.37) days, the difference was statistically significant ( P<0.05); The postoperative complications of group A and group B were 1 case and 5 cases respectively, the difference was statistically significant ( P<0.05). The skin graft survival rates of group A and group B were (97.11±3.44)% and (95.00±4.74)%, the difference was not statistically significant ( P>0.05); The wound scar VSS scores of group A and group B were (7.67±1.32) points and (8.78±1.99) points, the difference was not statistically significant ( P>0.05). Conclusions:By drilling skull and/or grinding combined with artificial dermis cover and vacuum sealing drainage and two stage split thickness skin graft for repairing scalp defect with skull exposure wound can not only better scalp defect with skull exposure wounds, and reduce the postoperative complications, and significantly accelerate wound healing, but also can effectively improve the quality of wound healing, which is worthy of clinical application.

Objective:To observe the analgesic effect of local anesthesia combined with nerve block anesthesia on golden microneedles for improving facial aging.Methods:Between December 2018 and December 2019 in Burn and Plastic Surgery of Nanchong Central Hospital, sixty female patients (between 30 and 58 years old, with an average of 45.2 years old) with natural facial skin aging were randomly divided into two groups: Group A: surface anesthesia group (30 cases); Group B: local anesthesia combined with nerve block anesthesia (30 cases). Intraoperative and postoperative pain scores, length of operation, and incidence of adverse reactions were compared between groups A and B.Results:Pain score during surgery was (6.90±0.96) points in Group A, (3.63±0.72) points in Group B. The difference between the two groups was statistically significant ( t=14.93, P<0.05); Pain score at 30 minutes after operation was (2.03±0.62) in Group A, (0.77±0.73) in Group B, the difference between the two groups was statistically significant ( t=7.28, P<0.05). There was no statistically significant difference between the two groups in the pain score at 24 hours after operation ( P>0.05); The operation process in group B was simplified, and the treatment time was significantly shortened. The difference between the two groups was statistically significant ( t=17.93, P<0.05). Conclusions:The method of local anesthesia combined with nerve block anesthesia is used in the treatment of gold microneedles to improve the analgesic effect in facial aging, which significantly shortens the treatment time and has fewer adverse reactions. This method is worth popularizing.