ObjectiveTo observe the effects of Hedysari Radix polysaccharide on the apoptosis of gastric sinus smooth muscle cells and explore the underlying mechanism via the insulin-like growth factor-1 （IGF-1）/phosphatidylinositol 3-kinase （PI3K）/serine-threonine kinase （Akt） pathway in the rat model of diabetic gastroparesis （DGP）. MethodSixty-two Wistar male rats were randomized into a blank group （n=12） and a modelling group （n=50）. The rat model of DGP was established by small-dose multiple intraperitoneal injections of streptozotocin combined with an irregular high-fat and high-sugar diet for 4 weeks. The modeled rats were randomized into model group， mosapride citrate （1.35 mg·kg^-1）， and high-， medium-， and low-dose （200， 100， and 50 mg·kg^-1， respectively） Hedysari Radix polysaccharide groups. The rats were administrated with corresponding drugs by gavage， and those in the blank and model groups with equal volumes of pure water by gavage once a day for 8 consecutive weeks. The random blood glucose and body mass were measured every 2 weeks， and gastric emptying rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes of smooth muscle in gastric antrum， and terminal deoxynucleoitidyl transferase-mediated nick-end labeling （TUNEL） was employed to detect the apoptosis of smooth muscle cells in the gastric antrum. The expression of IGF-1， phosphorylated （p）-PI3K， and p-Akt in the smooth muscle of gastric sinus tissue was detected by immunohistochemistry. Western blot was employed to determine the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the smooth muscle of the gastric antrum. ResultCompared with the blank group， the model group showed elevated random blood glucose at all time points （P<0.01）， decreased body mass and gastric emptying rate （P<0.01）， increased apoptotic index of smooth muscle cells in the gastric antrum （P<0.01）， down-regulated protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and up-regulated protein level of Bax （P<0.01）. Compared with the model group， the 8 weeks of drug administration lowered the random blood glucose， increased the body mass and gastric emptying rate （P<0.05， P<0.01）， decreased the apoptotic index of smooth muscle cells in the gastric antrum （P<0.05， P<0.01）， up-regulated the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and down-regulated the protein level of Bax （P<0.05， P<0.01）. Compared with the mosapride citrate group，the administration of low-dose Hedysari Radix polysaccharide for 6 and 8 weeks lowered the random blood glucose and decreased the body mass （P<0.05， P<0.01），low and medium-dose Hedysari Radix polysaccharide decreased the gastric emptying rate and the apoptotic index of smooth muscle cells in the astragaloside low-dose group decreased （P<0.05）. The protein levels of IGF-1，p-PI3K/PI3K，p-Akt/Akt and Bcl-2（low dose）were down-regulated and the protein level of Bax was up-regulated by low doses of Hedysari Radix polysaccharide （P<0.05， P<0.01）. Compared with high-dose Hedysari Radix polysaccharide， low-dose Hedysari Radix polysaccharide elevated random blood glucose and reduced body mass after 6 and 8 weeks of administration （P<0.05， P<0.01）， and the low and medium doses decreased the gastric emptying rate， increased the apoptotic index of smooth muscle cells in the gastric antrum （P<0.05， P<0.01）， down-regulated the protein levels of IGF-1， p-PI3K/PI3K， p-Akt/Akt， and Bcl-2， and up-regulated the protein level of Bax （P<0.05， P<0.01）. Compared with the medium-dose group，the low-dose group of Hedysari Radix polysaccharide had lower body mass，lower gastric emptying rate in rats，higher apoptotic index of smooth muscle cells in gastric sinus tissue after 6 and 8 weeks of administration （P<0.05， P<0.01）， and lower protein expression of IGF-1，p-PI3K/PI3K，p-Akt/Akt. ConclusionHedysari Radix polysaccharide protects the smooth muscle cells in gastric antrum against apoptotic injury and promotes gastric motility by activating the IGF-1/PI3K/Akt signaling pathway， as manifested by the up-regulated expression of IGF-1， p-PI3K， p-Akt， and Bcl-2 and down-regulated expression of Bax.

Objective:To explore the prognostic value of epidermal growth factor receptor (EGFR) co-mutation status in patients with advanced lung adenocarcinoma.Methods:Clinical data of patients with stage ⅢB-Ⅳ lung adenocarcinoma who were first diagnosed in the Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Hebei North University from January 2019 to December 2022 were collected prospectively. Patients were divided into EGFR mutation group ( n=82) and EGFR co-mutation group ( n=74) according to whether EGFR was combined with other gene mutations. The level of circulating tumor DNA (ctDNA) in peripheral blood was measured by real time fluorescence quantitative PCR. Objective response rate (ORR), disease control rate (DCR), the levels of ctDNA in peripheral blood, and progression-free survival (PFS) were compared between two groups of patients before and after 1 month of treatment. The univariate and multivariate analyses were conducted by Cox proportional hazards regression model. Results:In the EGFR mutation group, there were 45 cases of EGFR19 deletion mutation and 37 cases of EGFR21 mutation. In the EGFR co-mutation group, there were 41 cases of EGFR19 deletion mutation, 33 cases of EGFR21 mutation, 46 cases of TP53 mutation, 16 cases of RB1 mutation, 6 cases of PTEN mutation, 2 cases of MET amplification, 1 case of ERBB2 mutation, 1 case of KRAS mutation, 1 case of RET rearrangement, and 1 case of ALK rearrangement. There were statistically significant differences between the EGFR mutation group and the EGFR co-mutation group in the maximum tumor diameter ( χ2=5.04, P=0.025) and stage ( χ2=3.92, P=0.048). The ORRs of the two groups were 64.63% (53/82) and 37.84% (28/74), respectively, with a statistically significant difference ( χ2=11.19, P<0.001). The DCRs were 96.34% (79/82) and 86.49% (64/74), respectively, with a statistically significant difference ( χ2=4.95, P=0.026). The ctDNA levels in the EGFR mutation group and EGFR co-mutation group after one month of treatment decreased compared to before treatment[2.63 (1.83, 3.30) ng/μl vs. 4.73 (3.92, 5.49) ng/μl, Z=-7.06, P<0.001; 4.26 (2.26, 6.07) ng/μl vs. 5.28 (4.37, 6.09) ng/μl, Z=-5.15, P<0.001], the ctDNA levels in the EGFR co-mutation group were higher than those in the EGFR mutation group before treatment and after 1 month of treatment ( Z=-2.47, P=0.013; Z=-4.29, P<0.001). In the EGFR co-mutation group, the ctDNA levels in peripheral blood of patients who were effectively treated with targeted therapy decreased after 1 month of treatment compared to before treatment [(2.03±0.63) ng/μl vs. (3.92±0.82) ng/μl, t=42.94, P<0.001], the levels of ctDNA in peripheral blood of ineffectively treated patients before and after 1 month of treatment were higher than those of effectively treated patients [(5.84±0.57) ng/μl vs. (3.92±0.82) ng/μl, t=-11.91, P<0.001; (5.87±1.64) ng/μl vs. (2.03±0.63) ng/μl, t=-14.43, P<0.001]. The median PFS of the EGFR mutation group and the EGFR co-mutation group of patients were 10.4 and 8.3 months, respectively, with a statistically significant difference ( χ2=22.28, P<0.001). Univariate analysis suggested that the maximum tumor diameter ( HR=0.10, 95% CI: 0.06-0.16, P<0.001), performance status (PS) score ( HR=0.09, 95% CI: 0.06-0.15, P<0.001), stage ( HR=0.09, 95% CI: 0.05-0.14, P<0.001), pre-treatment ctDNA level ( HR=12.04, 95% CI: 8.21-17.65, P<0.001), ctDNA level after 1 month of treatment ( HR=3.75, 95% CI: 3.10-4.54, P<0.001) and EGFR co-mutations ( HR=2.21, 95% CI: 1.57-3.12, P<0.001) were found to be significant factors affecting the PFS of stage ⅢB-Ⅳ lung adenocarcinoma patients receiving targeted therapy; Multivariate analysis demonstrated that PS score ( HR=0.25, 95% CI: 0.14-0.47, P<0.001), stage ( HR=0.49, 95% CI: 0.24-0.98, P=0.044), pre-treatment ctDNA level ( HR=4.73, 95% CI: 3.08-7.28, P<0.001), ctDNA level after 1 month of treatment ( HR=2.15, 95% CI: 1.65-2.80, P<0.001), and EGFR gene co-mutation ( HR=2.26, 95% CI: 1.40-3.64, P<0.001) were independent risk factors for PFS in stage ⅢB-Ⅳ lung adenocarcinoma patients receiving targeted therapy. Conclusion:Both the EGFR mutation group and EGFR co-mutation group show a decrease in ctDNA levels after targeted therapy for one month compared to before treatment. The median PFS of EGFR co-mutation patients is shorter than that of patients with a single EGFR mutation. PS score, stage, ctDNA levels before and after treatment, and EGFR gene co-mutation are all independent factors affecting PFS in stage ⅢB-Ⅳ lung adenocarcinoma patients after targeted therapy.

Objective To observe the clinical efficacy of autologous hair follicle stem cell transplantation for hair restoration in patients with alopecia. Methods Ten patients with alopecia, including five with androgenic alopecia and five with seborrheic alopecia, were selected from November 2022 to May 2023. They were treated with autologous hair follicle stem cell transplantation. Data before treatment were used as the control group, and data after treatment were used as the study group. Follow-up was conducted for 3 to 8 months. The FPF scoring system was designed to collect data and evaluate the treatment effect. Results Nine patients had an improvement score of ≥7 points, and one patient had an improvement score of 2 points, with a treatment excellence rate of 90% (9/10). Compared with the total score of (2.81±0.92) points in the control group, the total score of the study group was (9.00±2.21) points, and the difference was statistically significant (P < 0.001). Conclusion Autologous hair follicle stem cell transplantation for hair restoration is safe and effective, and has a broad range of indications.

Objective To explore the effect mechanism of lipophagy in diabetic nephropathy model rats based on intervention of Dangui Hongqi ultrafiltration in diabetic nephropathy model rats.Methods Fifty male Wistar rats of SPF grade were randomly selected 7 rats as the blank group,and the other 43 rats were given a one-time high-dose intraperitoneal injection of streptozotocin combined with high-fat and high-sugar diet to prepare diabetes nephropathy model.The modeling rats were randomly divided into model group,irbesartan group(17.9 mg/kg),and TCM low-,medium-,and high-dosage groups(1.5,3,6 g/kg).The rats were continuously gavaged by corresponding drugs for 12 weeks.Randomized blood glucose,body mass,and 24 h urine protein content were detected;biochemical tests were used for GSP,SCr,BUN,TG,TC,HDL-C,LDL-C,FFA content;HE staining was used to observe morphology changes in renal tissue,Masson staining was used to observe fibrosis changes in renal tissue,renal tissue microstructure changes were observed under transmisson electron microscopy,RT-qPCR was used to detect the mRNA expressions of mTOR and LC3B in renal tissue,and Western blot was used to detect the protein expressions of mTOR,TFEB,p-TFEB,and LC3B in renal tissue.Results Compared with the blank group,the model group rats showed a significant increase in randomized blood glucose(P<0.01),a significant decrease in body mass(P<0.01),a significant increase in 24 h urine protein content(P<0.01),a significant increase in GSP,SCr,BUN,TG,TC,LDL-C,FFA content(P<0.01),and a significant decrease in HDL-C content(P<0.01);renal tubular epithelial cells underwent vacuolar degeneration,cytoplasmic vacuolization,and extensive infiltration of inflammatory cells,collagen fibers increased and were distributed randomly,the number of lipid droplets increased,and autophagosomes decreased;the mTOR mRNA expressions in renal tissue significantly increased(P<0.01),the LC3B mRNA expressions significantly decreased(P<0.01),the mTOR and p-TFEB protein expressions significantly increased(P<0.01),the expression of TFEB,LC3BⅡ protein significantly decreased(P<0.01).Compared with the model group,the randomized blood glucose and 24 h urine protein content of rats in each treatment group were significantly reduced,the body mass significantly increased,and the contents of GSP,SCr,BUN,TG,TC,LDL-C,FFA decreased at 12 week of treatment,while the content of HDL-C increased;the inflammatory cell infiltration,fibrosis,and lipid droplet deposition in renal tissue alleviated to varying degrees;the expressions of mTOR mRNA decreased,the expressions of LC3B mRNA increased,the expressions of mTOR and p-TFEB protein decreased,while the expression of TFEB and LC3BⅡ protein increased.There was a statistically significant difference in the irbesartan group and TCM high-dosage group(P<0.01,P<0.05).Conclusion Dangui Hongqi ultrafiltration can improve the disorder of glucose and lipid metabolism,antagonize heterotopic lipid deposition in the kidney,promote lipid phagocytosis,and delay the process of diabetic nephropathy in model rats.The mechanism may be related to mTOR/TFEB signaling pathway.

Objective To explore the value of peripheral blood circulating DNA in predicting the efficacy and prognosis of immunotherapy for advanced non-small cell lung cancer.Method A retrospective study was conducted on 78 NSCLC patients who were admitted to the Respiratory and Critical Care Medicine Department of the First Affiliated Hospital of Hebei North University and were treated with tirelizumab for advanced driver gene negativity from January 2021 to December 2021.After 2 cycles of immunotherapy,the efficacy was evaluated according to the Solid Tumor Efficacy Evaluation Criteria(RECIST 1.1),including complete remission,partial remission,disease stability,and disease progression.CR and PR patients were defined as the experimental group(n=48)Other patients were defined as the control group(n=30),and the ctDNA levels in peripheral blood were measured before and after treatment in both groups.ROC curves were used to analyze the predictive value of periph-eral blood ctDNA levels for achieving objective remission after immunotherapy.All patients were followed up and their progression free survival were calcutated.Using univariate and multivariate regression analysis identified the factors affecting the prognosis of patients after immunotherapy.Using Spearman correlation coefficient analyzed the correlation between ctDNA levels and PFS.Kalplan Meier survival curve were used for survival analysis.Result The peripheral blood ctDNA levels before and after treatment in the experimental group were(4.47±1.21)ng/μL and(2.65±1.14)ng/μL,respectively(t=7.559,P<0.001),while those in the control group were(4.54±1.15)ng/mL and(4.29±1.57)ng/μL,respectively(t=0.699,P=0.487).There was no statistically significant difference in peripheral blood ctDNA levels between the two groups before treatment(t=-0.25,P=0.801).The peripheral blood ctDNA levels in the experimental group decreased compared to the control group after treatment(t=-5.35,P<0.001).The ROC curve analysis showed that the area under the curve for predicting objective remission after immunotherapy based on peripheral blood ctDNA levels was 0.819,with a sensitivity of 81.3%and specificity of 80%.Peripheral blood ctDNA levels were negatively correlated with progression free survival(r=-0.784,P=0.000).Single factor COX regression was used to analyze the clinical and pathological characteristics and ctDNA levels of enrolled patients,and the results showed that the maximum tumor diameter was greater than 5 cm(HR=0.501,95%CI:6.731～35.567)Tumor stage IV(HR=0.392,95%CI:0.227～0.677),treatment approach(HR=15.473,95%CI:6.731～35.567),and ctDNA levels(HR=4.657,95%CI:3.182～6.555)are all influencing factors for PFS in advanced NSCLC patients after immunotherapy.Multiple factor analysis was conducted on the appeal indicators with statistical differences,and the results showed that treatment approach(HR=2.981,95%CI:1.019～8.722)and peripheral blood ctDNA levels(HR=3.918,95%CI:2.619～5.861)It is an independent influencing factor of PFS in advanced NSCLC patients.The Kalplan Meier survival curve was used for analysis,and the results showed that the median PFS of the treatment effective group was 8.4 months,while the median PFS of the control group was 5.4 months.(χ2=49.277,P=0.000).Conclusion Immunotherapy combined with chemotherapy can enhance the ability to kill tumor cells,and peripheral blood ctDNA levels can evaluate the efficacy and prognosis of immunotherapy,which can be used to guide immunotherapy in advanced NSCLC patients.

Objective:To study the trinucleotide repeats of GCN (GCA, GCT, GCC, GCG) encoding Alanine in exon 3 of the PHOX2B gene among healthy individuals from southwest China and two patients with Congenital central hypoventilation syndrome (CCHS). Methods:The number and sequence of the GCN repeats of the PHOX2B gene were analyzed by capillary electrophoresis, Sanger sequencing and cloning sequencing of 518 healthy individuals and two newborns with CCHS, respectively. Results:Among the 1036 alleles of the 518 healthy individuals, five alleles were identified, including (GCN) 7, (GCN) 13, (GCN) 14, (GCN) 15 and (GCN) 20. The frequency of the (GCN) 20 allele was the highest (94.79%). And five genotypes were identified, which included (GCN) 7/(GCN) 20, (GCN) 13/(GCN) 20, (GCN) 14/(GCN) 20, (GCN) 15/(GCN) 20, (GCN) 20/(GCN) 20. The homozygous genotypes were all (GCN) 20/(GCN) 20, and the carrier rate was 89.58%. Four GCN sequences of the (GCN) 20 homozygous genotypes were identified among the 464 healthy individuals. The GCN repeat numbers in the exon 3 of the PHOX2B gene showed no significant difference between the expected and observed values, and had fulfilled the, Hardy-Weinberg equilibrium. The genotypes of the two CCHS patients were (GCN) 20/(GCN) 25 and (GCN) 20/(GCN) 30, respectively. Conclusion:It is important to determine the GCN repeats and genotypic data of the exon 3 of the PHOX2B gene among the healthy individuals. The number of GCN repeats in 518 healthy individuals was all below 20. The selection of appropriate methods can accurately detect the polyalanine repeat mutations (PARMs) of the PHOX2B gene, which is conducive to the early diagnosis, intervention and treatment of CCHS.

Objective:To investigate the effect of failure mode and effect analysis (FMEA) based catheter information platform in preventing catheter-related bloodstream infection (CRBSI) in intensive care unit to improve the current status of CRBSI.Methods:In this study, a retrospective cohort study was conducted using the purposive sampling method, and 140 patients with indwelling central venous catheters admitted to the ICU of Peking University Shenzhen Hospital from August to December 2021 were set as the control group; the 140 patients with indwelling central venous catheters admitted to the ICU from January to May 2022 were set as the observation group. The control group used electronic forms to record and manage at the bedside after CRBSI cluster nursing measures were given, and the observation group used the catheter information platform based on FMEA to conduct information management on catheter evaluation and maintenance process after CRBSI cluster nursing measures were given. Compared the implementation rate (6 items), implementation time, qualification rate, and incidence of CRBSI in ICU patients between two groups of ICU nurses.Results:The implementation rate of CRBSI cluster nursing measures among ICU nurses in the observation group: strict hand hygiene by nurses was 87%(122/140), maximum aseptic barrier during puncture was 97%(136/140), aseptic operation during catheter maintenance was 91%(128/140), 75% alcohol disinfection of connectors was 84%(118/140), 24-hour change of infusion lines was 95%(133/140), and timely change of patches/dressings was 89%(125/140), they were greater than those in the control group 70%(98/140), 87%(122/140), 71%(100/140), 61%(86/140), 71%(99/140), 69%(96/140), the differences were statistically significant ( χ2 values were 9.67 to 29.07, all P<0.05); the execution time and qualification rate among ICU nurses in the observation group were (9.11 ± 2.83) minutes and 91.4% (128/140), the control group were (10.00 ± 2.84) minutes and 60.7% (85/140), with statistically significant differences ( t value was -2.64, χ2 values was 36.28, all P<0.05). Conclusions:The FMEA-based catheterization information platform can help enhance the efficiency of the implementation of CRBSI clustering nursing measures by ICU nurses, improve the quality of care, and thus reduce the occurrence of CRBSI, and the feasibility of clinical promotion is high.

Objective:To study the epidemic and etiologic characteristics of influenza virus(Flu)and respiratory syncytial virus (RSV) infections in outpatient influenza-like illness(ILI)cases of children under 10 years of age in Gansu province in 2018 And to provide evidences for diagnosis, treatment, control and prevention of Flu and RSV infections in Gansu province.Methods:A total of 8 559 pharyngeal swab samples of ILI outpatients cases were tested with real-time fluorescent PCR to detect Flu, 3 436 of which were detected by RT-PCR for RSV.Results:Of the 8559 specimens, 934 (10.91%) samples were positive for Flu. Among them, 431 were positive for H1N1, 70 were positive for H3N2, 428 were positive for Flu B, 5 were mixed; 320 of the 3436 (9.31%, ) samples were positive for RSV. There were significant differences in the positive rates of Flu and RSV among 14 cities and prefectures ( χ2=56.99, χ2=263.34, Р< 0.01). Influenza reached its peak in January 2018 with a positive rate of 50.70%. Flu B/Yamagata strain (53.53%) and A H1N1 (39.93%) were prevalent simultaneously. The peak of RSV epidemic was from February to April, the positive rate was 13.98%. The RSV positive rate of children under 5 years of age was 10.11%, higher than that of children over 5 years of age was 6.94%. There was statistical significance ( χ2=7.67, Р<0.01). Conclusions:RSV and influenza viruses are the main pathogens in ILI cases of children under 10 years of age. There are epidemic peaks in winter and spring every year. It is suggested that the monitoring of RSV and the development and application of vaccine should be strengthened.

As most patients of central serous retinopathy (CSC),the symptoms of acute onset will alleviate by oneself after 4-6 months.About 30％-50％ of patients with CSC experience chronic or recurrent cases.Resulting in persistent neurosensory detachments and subretinal fluid,causing significant vision loss.Mineralocorticoid receptor (MR) is a kind of nuclear hormone receptors,plays a role in theregulation of water and electrolyte balance.Excessive MR signaling is associated with many diseases.Study found that MR antagonists decreased the thickness of the retina and improved in vision,there was no serious adverse reactions during the period of treatment.Initial dose of MR antagonists was 25 mg per day,1 week later,dosage was increased to 50 mg per day,and treatment for about 3 months.There is no conclusive effective treatment and the dosage are still unknown.MR antagonists may be a safe and effective way to treat CSC,though evidence is scant.Prospective,multicenter,large-scale trials is required.

In recent years,it has been found high myopia is significantly related with primary open-angle glaucoma.Myopic retinopathy is high risk factors of primary open-angle glaucoma,and the retinal degeneration of high myopia is similar to the feature of primary open-angle glaucoma,which cause difficult to early diagnosis.How to identify early-stage glaucoma from high myopia patients,and give early intervention treatment has become a difficult problem.This article reviews research literature about the relationship between high myopia and between primary open-angle glaucoma.