Objective:To investigate the relationship between the neutrophil- to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP), and the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).Methods:The clinical data of 47 patients with NSCLC who received immunotherapy at The First Affiliated Hospital of Anhui University of Science and Technology from December 2021 to May 2023 were retrospectively analyzed. Based on the duration of immunotherapy, patients with a duration of more than 1 year were classified as having a good immune response, while those with a duration of less than 1 year were classified as having a poor immune response. The clinical pathological characteristics of patients with good and poor immune responses were compared. The cutoff values for NLR, LMR, and CRP were calculated using receiver operating characteristic curves, and patients were grouped based on these cutoff values. The predictive probabilities of different combinations were compared. Univariate and multivariate Cox analyses were performed to identify factors affecting patient survival.Results:Significant differences were observed in the distribution of therapy lines (1 st-line vs. 2 nd-line treatment), NLR, LMR, and CRP levels between patients with good immune response and those with poor immune responses (all P < 0.05). The area under the curve (AUC) for NLR was 0.763 [95% CI: (0.608, 0.918)], the AUC for LMR was 0.715 [95% CI: (0.544, 0.875)], and the AUC for CRP was 0.697 [95% CI: (0.540, 0.853)]. To assess the diagnostic value of combined indicators in predicting the efficacy of immunotherapy in NSCLC, different indicators were combined, resulting in the variables NLR + LMR, NLR + CRP, LMR + CRP, and NLR + LMR + CRP. Receiver Operating Characteristic curves were plotted based on the probabilities. The combination of NLR + LMR + CRP showed the best predictive performance, with an AUC of 0.897 [95% CI: (0.806, 0.988)]. Univariate and multivariate Cox analyses indicated that LMR [ HR: 0.428; 95% CI: (0.213, 0.858), P = 0.017] and the distribution of treatment lines [ HR: 1.815; 95% CI: (1.005, 3.642), P = 0.033] were important independent prognostic factors for progression-free survival. Conclusions:NLR, LMR, and CRP are correlated with immunotherapy efficacy in patients with NSCLC and provide predictive value. LMR and treatment line are independent prognostic factors for progression-free survival.

Objective To investigate the predictive value of uric acid for cardiovascular events in the elderly patients with ACS.Methods An observational follow-up study was conducted on 3440 ACS inpatients and outpatients admitted in the Heart Center of Beijing Chaoyang Hospital and the First Medical Center of Chinese PLA General Hospital from June 2017 to October 2022.According to the occurrence of cardiovascular events,they were divided into a cardiovascular event group(529 patients)and a non-cardiovascular event group(2911 patients).Their clinical data were collected for Cox risk proportional regression analysis.Results The cardiovascular event group had significantly uric acid when compared with the non-cardiovascular event group(P＜0.01).Af-ter adjusting the traditional risk factors and plasma biomarkers,uric acid was still a significant predictor for clinical endpoints(HR=2.634,95％CI:1.870-3.744,P＜0.01)and for cardiovascu-lar events(HR=1.508,95％CI:1.357-1.660,P＜0.01).Furthermore,uric acid was significantly correlated with acute heart failure,cardiovascular death and all-cause death(P＜0.01).Conclusion Uric acid is a risk predictor for cardiovascular events in elderly ACS patients,and can provide ear-ly warning information and diagnostic value for acute cardiovascular events.

Objective To establish a technical system for allogeneic kidney transplantation surgery in pigs using the Banna miniature pig inbred strain,and to evaluate it through routine blood tests,liver and kidney function tests,thus providing reference data for the preparation of allogeneic kidney transplantation models.Methods A total of 4 cases of allogeneic kidney transplantation surgeries were performed,including 1 case of single kidney transplantation in a healthy pig,2 cases of kidney transplantation after unilateral nephrectomy,and 1 case of kidney transplantation after bilateral nephrectomy.Before kidney transplantation,cross-matching and complement-dependent cytotoxicity(CDC)tests were used for matching between donor and recipient pigs.After kidney transplantation,peripheral blood samples were regularly collected from pigs for routine blood tests,liver function tests,and kidney function tests,and color Doppler ultrasound technology was used to detect blood supply to the transplanted kidneys.After reaching the experimental endpoint,both kidneys of pig DR1 and the left kidney of pig DR3 were collected and hematoxylin-eosin(HE)staining was performed to evaluate pathological changes in the transplanted kidneys.Results Recipient pigs DR1 and DR3 died at 17 days and 30 days after surgery respectively,while recipient pigs R and DR2 remained in good condition during the 30-day observation period.The results of liver and kidney function test showed that in pig DR1,alanine aminotransferase(ALT)levels increased on postoperative day 1(＞1 000 U/L),peaked on postoperative day 7(1 300 U/L),and aspartate aminotransferase(AST)levels peaked on postoperative day 1(＞3 000 U/L).On postoperative day 17,ALT and AST levels remained high(ALT,500 U/L;AST,700 U/L).In pigs R,DR2,and DR3,ALT and AST levels returned to normal around day 17.Serum creatinine(Crea)levels in pig R remained stable without postoperative increase.Crea levels in pigs DR1 and DR2 showed transient elevation on postoperative day 1,then gradually returned to normal(＜100 μmol/L).Crea levels in pig DR3 remained below 500 μmol/L from postoperative days 2-10,but increased between days 11-28,reaching up to 1 500 μmol/L,indicating gradual loss of kidney function.Ultrasound results showed that the preoperative resistive index(RI)of recipient pig R was 0.91.On postoperative day 24,renal cortex and medulla showed abundant blood flow signals with RI value of 0.88,which was close to the pre-transplantation RI value.For pig DR2,the RI value on postoperative day 17 was 0.89,with poor renal cortex blood flow and relatively good renal medulla blood flow.In pig DR1 on postoperative day 17,no blood flow signals were detected in the transplanted kidney.HE staining results showed that the non-transplanted healthy right kidney of pig DR1 had normal structure,while the transplanted left kidney showed blurred glomerular structure and nuclear dissolution,indicating that the left kidney had lost function before removal.In the transplanted left kidney of pig DR3,large numbers of red blood cells and lymphocyte infiltration were observed in glomeruli and renal tubules,indicating possible coagulation dysfunction and rejection reactions after kidney transplantation.Conclusion Banna miniature pig inbred strain is used as experimental animals to perform four cases of allogeneic pig-to-pig kidney transplantation.The physiological parameters of the recipient pig and the function of the transplanted kidney are monitored after surgery using routine blood tests,liver and kidney function tests,color Doppler ultrasound,and pathological examinations.The allogeneic pig-to-pig kidney transplantation technical system established in the study can provide a foundation for clinicians to conduct kidney transplantation surgeries.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective:To investigate the relationship between the neutrophil- to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), C-reactive protein (CRP), and the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).Methods:The clinical data of 47 patients with NSCLC who received immunotherapy at The First Affiliated Hospital of Anhui University of Science and Technology from December 2021 to May 2023 were retrospectively analyzed. Based on the duration of immunotherapy, patients with a duration of more than 1 year were classified as having a good immune response, while those with a duration of less than 1 year were classified as having a poor immune response. The clinical pathological characteristics of patients with good and poor immune responses were compared. The cutoff values for NLR, LMR, and CRP were calculated using receiver operating characteristic curves, and patients were grouped based on these cutoff values. The predictive probabilities of different combinations were compared. Univariate and multivariate Cox analyses were performed to identify factors affecting patient survival.Results:Significant differences were observed in the distribution of therapy lines (1 st-line vs. 2 nd-line treatment), NLR, LMR, and CRP levels between patients with good immune response and those with poor immune responses (all P < 0.05). The area under the curve (AUC) for NLR was 0.763 [95% CI: (0.608, 0.918)], the AUC for LMR was 0.715 [95% CI: (0.544, 0.875)], and the AUC for CRP was 0.697 [95% CI: (0.540, 0.853)]. To assess the diagnostic value of combined indicators in predicting the efficacy of immunotherapy in NSCLC, different indicators were combined, resulting in the variables NLR + LMR, NLR + CRP, LMR + CRP, and NLR + LMR + CRP. Receiver Operating Characteristic curves were plotted based on the probabilities. The combination of NLR + LMR + CRP showed the best predictive performance, with an AUC of 0.897 [95% CI: (0.806, 0.988)]. Univariate and multivariate Cox analyses indicated that LMR [ HR: 0.428; 95% CI: (0.213, 0.858), P = 0.017] and the distribution of treatment lines [ HR: 1.815; 95% CI: (1.005, 3.642), P = 0.033] were important independent prognostic factors for progression-free survival. Conclusions:NLR, LMR, and CRP are correlated with immunotherapy efficacy in patients with NSCLC and provide predictive value. LMR and treatment line are independent prognostic factors for progression-free survival.

Objective To establish a technical system for allogeneic kidney transplantation surgery in pigs using the Banna miniature pig inbred strain,and to evaluate it through routine blood tests,liver and kidney function tests,thus providing reference data for the preparation of allogeneic kidney transplantation models.Methods A total of 4 cases of allogeneic kidney transplantation surgeries were performed,including 1 case of single kidney transplantation in a healthy pig,2 cases of kidney transplantation after unilateral nephrectomy,and 1 case of kidney transplantation after bilateral nephrectomy.Before kidney transplantation,cross-matching and complement-dependent cytotoxicity(CDC)tests were used for matching between donor and recipient pigs.After kidney transplantation,peripheral blood samples were regularly collected from pigs for routine blood tests,liver function tests,and kidney function tests,and color Doppler ultrasound technology was used to detect blood supply to the transplanted kidneys.After reaching the experimental endpoint,both kidneys of pig DR1 and the left kidney of pig DR3 were collected and hematoxylin-eosin(HE)staining was performed to evaluate pathological changes in the transplanted kidneys.Results Recipient pigs DR1 and DR3 died at 17 days and 30 days after surgery respectively,while recipient pigs R and DR2 remained in good condition during the 30-day observation period.The results of liver and kidney function test showed that in pig DR1,alanine aminotransferase(ALT)levels increased on postoperative day 1(＞1 000 U/L),peaked on postoperative day 7(1 300 U/L),and aspartate aminotransferase(AST)levels peaked on postoperative day 1(＞3 000 U/L).On postoperative day 17,ALT and AST levels remained high(ALT,500 U/L;AST,700 U/L).In pigs R,DR2,and DR3,ALT and AST levels returned to normal around day 17.Serum creatinine(Crea)levels in pig R remained stable without postoperative increase.Crea levels in pigs DR1 and DR2 showed transient elevation on postoperative day 1,then gradually returned to normal(＜100 μmol/L).Crea levels in pig DR3 remained below 500 μmol/L from postoperative days 2-10,but increased between days 11-28,reaching up to 1 500 μmol/L,indicating gradual loss of kidney function.Ultrasound results showed that the preoperative resistive index(RI)of recipient pig R was 0.91.On postoperative day 24,renal cortex and medulla showed abundant blood flow signals with RI value of 0.88,which was close to the pre-transplantation RI value.For pig DR2,the RI value on postoperative day 17 was 0.89,with poor renal cortex blood flow and relatively good renal medulla blood flow.In pig DR1 on postoperative day 17,no blood flow signals were detected in the transplanted kidney.HE staining results showed that the non-transplanted healthy right kidney of pig DR1 had normal structure,while the transplanted left kidney showed blurred glomerular structure and nuclear dissolution,indicating that the left kidney had lost function before removal.In the transplanted left kidney of pig DR3,large numbers of red blood cells and lymphocyte infiltration were observed in glomeruli and renal tubules,indicating possible coagulation dysfunction and rejection reactions after kidney transplantation.Conclusion Banna miniature pig inbred strain is used as experimental animals to perform four cases of allogeneic pig-to-pig kidney transplantation.The physiological parameters of the recipient pig and the function of the transplanted kidney are monitored after surgery using routine blood tests,liver and kidney function tests,color Doppler ultrasound,and pathological examinations.The allogeneic pig-to-pig kidney transplantation technical system established in the study can provide a foundation for clinicians to conduct kidney transplantation surgeries.

Objective We aimed to evaluate the efficacy and safety of Shengxuebao Mixture in the treatment of cancer-related anemia(CRA)presenting with syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood.Methods A randomized,double-blind,placebo-controlled,multicenter clinical trial was conducted.Eligible patients with malignant tumors meeting the inclusion and exclusion criteria were enrolled from 26 hospitals,including Dongzhimen Hospital,Beijing University of Chinese Medicine,Xiaogan Central Hospital,and Yangzhou Hospital of Traditional Chinese Medicine,from June 1,2022,to September 30,2024.Patients were allocated 1:1 to either the experimental group receiving Shengxuebao Mixture or the control group receiving its simulator(placebo)using a block randomization method under double-blind conditions.Both groups received 15 mL orally three times daily for 28 consecutive days.The primary efficacy indicators included the hemoglobin(Hb)improvement rate(RHb)and the traditional Chinese medicine(TCM)syndrome improvement rate(RTCM)at week 4 of treatment.The secondary efficacy indicators encompassed Hb and red blood cell(RBC)count,Karnofsky Performance Status(KPS)score,TCM syndrome score,individual TCM symptom scores,and changes in each of these indicators compared to the baseline period at weeks 2,4,and 6 of treatment.Safety evaluations were conducted at week 4 of treatment.Results A total of 239 patients were enrolled,with 225 cases included in the Full Analysis Set(FAS)(109 in the experimental group vs.116 control group),163 in the Per Protocol Set(PPS)(77 vs.86),and 225 in the Safety Set(SS)(109 vs.116).Baseline characteristics between groups showed no significant differences.Significant differences were observed between the experimental and control groups in RHb at week 4(FAS:49.51%vs.35.24%,P<0.05;PPS:53.25%vs.36.05%,P<0.05)and RTCM at week 4(FAS:61.54%vs.39.62%,P<0.01;PPS:64.94%vs.40.70%,P<0.01).At weeks 2,4,and 6,the experimental group showed greater improvements in Hb and RBC counts than the control group.Additionally,the TCM syndrome scores were lower in the experimental group than in the control group at these time points.Except for week 2 in PPS,the KPS improvement was better in the experimental group than in the control group(P<0.05).The experimental group also demonstrated a greater reduction in scores for individual TCM symptoms such as spiritlessness and weakness,poor appetite and reduced food intake at weeks 4 and 6 compared to the control group(P<0.05,P<0.01).Furthermore,the reduction in vertigo score was more pronounced in the experimental group at week 6(P<0.01).For the score of pale and lusterless complexion,only in the PPS was the reduction from baseline more significant in the experimental group than in the control group at weeks 4 and 6(P<0.05).No significant differences were observed between the experimental and control groups in the incidence of all adverse events or drug-related adverse reactions.Conclusion Shengxuebao Mixture demonstrates significant efficacy in patients with CRA presenting syndrome of deficiency of liver and kidney combined with syndrome of deficiency of both qi and blood,effectively increasing Hb levels,ameliorating TCM syndromes,alleviating clinical symptoms,and enhancing functional status,with no significant difference in adverse drug reactions compared to the placebo.

Objective To study the objective changes and effects of speech characteristics in patients with nasal endoscopic surgery,and to analyze the relationship between surgery and changes in vocal tract structure.Methods A prospective study was conducted on 45 patients who underwent nasal endoscopic surgery from June 2023 to December 2023.Among them,13 patients underwent nasal septum deviation correction surgery and/or nasal polypectomy and/or turbinate shaping surgery group(G1 group),11 patients underwent simple sinus opening surgery group(G2 group),and 21 patients underwent nasal sinus opening+nasal septum deviation correction surgery and/or nasal polypectomy and/or nasal turbinate shaping surgery group(G3 group).Spectrogram detection was completed before and 1 month after surgery.Nasal resistance(Refft value),acoustic indicators resonance peak frequency(F1-F4),bandwidth(B1-B4),difference between F1 amplitude and nasal murmur resonance peak amplitude(A1-P0),and difference between F1 and nasal murmur resonance peak amplitude(A1-P1)under different sound tasks(oral vowels,nasal vowels,and phrases and short sentences containing nasal vowels)were analyzed.Results After surgery,there was no significant change in the acoustic indicators in any of the groups,and the Refft value significantly decreased.The change in the resonance peak of oral vowels was not significant,but the bandwidth significantly decreased.A1-P1 in each group showed an upward trend after surgery,while A1-P0 showed a downward trend after surgery.Among them,A1-P1 in G1 group showed a significant increase compared to preoperative levels in/ma/,/na/,/mi/,and/ni/,and A1-P0 showed a significant decrease in/ma/and/na/compared to preoperative levels.There were statisti-cally significant differences in A1-P0 between G2 group and preoperative group in both/ma/and/na/.The A1-P1 levels in G3 group showed significant differences compared to preoperative levels in/mi/and/ni/,and A1-P0 showed significant differences compared to preoperative levels in/ma/and/na/.Conclusion Nasal endoscopic surgery may have a measurable impact on the patient's speech.The spectrogram can be used to evaluate the postoperative pronuncia-tion characteristics of nasal endoscopy,with A1-P1 being a better measurement indicator for high vowels/i/and A1-P0 being a better measurement indicator for non high vowels/a/.

Objective To investigate the predictive value of uric acid for cardiovascular events in the elderly patients with ACS.Methods An observational follow-up study was conducted on 3440 ACS inpatients and outpatients admitted in the Heart Center of Beijing Chaoyang Hospital and the First Medical Center of Chinese PLA General Hospital from June 2017 to October 2022.According to the occurrence of cardiovascular events,they were divided into a cardiovascular event group(529 patients)and a non-cardiovascular event group(2911 patients).Their clinical data were collected for Cox risk proportional regression analysis.Results The cardiovascular event group had significantly uric acid when compared with the non-cardiovascular event group(P＜0.01).Af-ter adjusting the traditional risk factors and plasma biomarkers,uric acid was still a significant predictor for clinical endpoints(HR=2.634,95％CI:1.870-3.744,P＜0.01)and for cardiovascu-lar events(HR=1.508,95％CI:1.357-1.660,P＜0.01).Furthermore,uric acid was significantly correlated with acute heart failure,cardiovascular death and all-cause death(P＜0.01).Conclusion Uric acid is a risk predictor for cardiovascular events in elderly ACS patients,and can provide ear-ly warning information and diagnostic value for acute cardiovascular events.

Objective To develop GTKO (α-1,3-galactosyltransferase gene-knockout, GTKO)/hCD55 (human CD55) gene-edited xenotransplant donor pigs and verify their function. Methods In this study, CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated nuclease 9), PiggyBac transposon technology and somatic cell nuclear transfer technology were used to construct GTKO/hCD55 gene-edited Diannan miniature pigs. The phenotype and function of GTKO/hCD55 pigs were analyzed by Sanger sequencing, real-time fluorescence quantitative PCR, flow cytometry, immunofluorescence, bisulfite sequencing, antigen-antibody binding assays, and complement-dependent cytotoxicity assays. Results After transfection of PX458 and PiggyBac gene editing vectors into wild-type fetal pig fibroblasts, 48 single-cell colonies were obtained through puromycin drug screening. Two single-cell colonies were selected for somatic cell nuclear transfer, resulting in two fetal pigs at 33 days of gestation. The GGTA1(α-1,3-galactosyltransferase) genotypes of fetal pig F01 were -17 bp and wild type (WT), while the GGTA1 genotypes of fetal pig F02 were -26 bp/+2 bp and -3 bp. The hCD55 mRNA expression levels of both fetal pigs were significantly higher than those of WT pigs (P＜0.01). The fetal pig F02 was selected as the donor cell source for recloning, 11 surviving piglets were obtained, all identified as GTKO/hCD55 gene-edited pigs. These pigs showed absence of α-Gal antigen expression, but weak or no expression of hCD55 was observed. Methylation analysis of the hCD55 gene's CpG island showed hypermethylation in kidney tissue lacking hCD55 expression, whereas it was not methylated or partially methylated in kidney tissue expressing hCD55. Moreover, codon optimization of the CpG island of the hCD55 gene to reduce CG content could achieve stable expression of the hCD55 gene. In addition, antigen-antibody binding experiment showed that the amount of human IgM binding to GTKO/hCD55 gene-edited pig fibroblasts was significantly lower than that of WT pigs (P＜0.01). Complement-dependent cytotoxicity experiment showed that the survival rate of fibroblasts in GTKO/hCD55 pigs was significantly higher than that in WT pigs (P＜0.01). Conclusion This study demonstrates the successful generation of GTKO/hCD55 gene-edited xenotransplant donor pigs. Methylation-induced gene silencing of the hCD55 gene can be effectively avoided by reducing the CG content of the CpG island through codon optimization. This study provides a reference for the development of xenotransplant donor pigs and guides subsequent research on xenotransplantation.