ObjectiveTo explore the dose-effect relationship and safety of high， medium， and low doses of raw Astragali Radix in the modified Huangqi Chifengtang （MHCD） for treating proteinuria in immunoglobulin A （IgA） nephropathy， and to provide scientific evidence for the clinical use of high-dose Astragali Radix in the treatment of proteinuria in IgA nephropathy. MethodsA total of 120 patients with IgA nephropathy， diagnosed with Qi deficiency and blood stasis combined with wind pathogen and heat toxicity， were randomly divided into a control group and three treatment groups. The control group received telmisartan combined with a Chinese medicine placebo， while the treatment groups were given telmisartan combined with MHCD containing different doses of raw Astragali Radix （60， 30， 15 g）. Each group contained 30 patients， and the treatment period was 12 weeks. Changes in 24-hour urinary protein （24 hUTP）， traditional Chinese medicine （TCM） syndrome scores， effective rate， and renal function were observed before and after treatment. Safety was assessed by monitoring liver function and blood routine. ResultsAfter 12 weeks of treatment， 24 hUTP significantly decreased in the high， medium， and low-dose groups， as well as the control group （P<0.05， P<0.01）. The TCM syndrome scores in the high， medium， and low-dose groups also significantly decreased （P<0.01）. Comparisons between groups showed that the 24 hUTP in the high-dose group was significantly lower than in the medium， low-dose， and control groups （P<0.05， P<0.01）， and the 24 hUTP in the medium-dose group was significantly lower than in the control group （P<0.05）. The TCM syndrome scores in the high and medium-dose groups were significantly lower than in the low-dose and control groups （P<0.05， P<0.01）. The total effective rates for proteinuria in the high， medium， low-dose， and control groups were 92.59% （25/27）， 85.19% （23/27）， 60.71% （17/28）， and 57.14% （16/28）， respectively. The effective rates in the high and medium-dose groups were significantly higher than in the low-dose and control groups （χ²=13.185， P<0.05， P<0.01）. The effective rates for TCM syndrome scores in the high， medium， low-dose， and control groups were 88.89% （24/27）， 81.48% （22/27）， 71.43% （20/28）， and 46.43% （13/28）， respectively. The efficacy of TCM syndrome scores in the high and medium-dose groups was significantly higher than in the control group （χ²=14.053， P<0.01）. Compared with pre-treatment values， there was no statistically significant difference in eGFR and serum creatinine in the high and medium-dose groups. However， eGFR significantly decreased in the low-dose and control groups after treatment （P<0.05）， and serum creatinine levels increased significantly in the control group （P<0.05）. No statistically significant differences were observed in urea nitrogen， uric acid， albumin， total cholesterol， triglycerides， liver function， and blood routine before and after treatment in any group. ConclusionThere is a dose-effect relationship in the treatment of IgA nephropathy with high， medium， and low doses of raw Astragali Radix in MHCD. The high-dose group exhibited the best therapeutic effect and good safety profile.

Objective To explore the effectiveness and safety of percutaneous coronary artery shock wave balloon angioplasty(IVL)under the guidance of intravascular ultrasound(IVUS)for the treatment of severe calcification lesions in the left main artery(LM).Methods A total of 26 patients with severe LM(mouth,body,bifurcation)calcification admitted to Jiangnan University Affiliated Hospital from October 2022 to April 2024 were included,with an average age of 72.0(61.8,75.4)years.Under the guidance of IVUS,IVL was used for pre-treatment of calcified lesions,followed by percutaneous coronary intervention(PCI)with stent/drug balloon implantation.All patients were evaluated using IVUS before and after the use of IVL and after PCI.And compare the IVUS intracavity related data before and after treatment[plaque burden(PB)、minimum lumen area(MLA)、minimum lumen diameter(MLD)]and calcification fracture number,minimum stent area(MSA),stent expansion coefficient(expansion,EXP),etc.Results There were 26 patients(2 with opening lesions,7 with body lesions,and 17 with bifurcation lesions at the end of the main trunk),including 7 with stable angina pectoris(SAP),10 with unstable angina(UA),4 with acute ST-segment elevation myocardial infarction(STEMI),and 5 with non ST-segment elevation myocardial infarction(NSTEMI).The PB at the most severe site of calcification decreased by 79.50(76.00,83.75)％compared to 80.00(76.00,83.75)％after IVL(P=0.001),MLA increased by 3.39(3.14,3.68)mm2 compared to 3.38(3.14,3.67)mm2 after IVL(P=0.039),MLD increased by 3.21(3.07,3.30)mm compared to 3.20(3.07,3.30)mm after IVL(P=0.024),and there was 100％calcification rupture(1/2 cases,2/9 cases,≥3/15 cases).The stent/drug ball was successfully implanted 100％,with EXP of(89.15±4.42)％and an MSA of 7.20(6.46,7.45)mm2.No adverse events such as death,angina or recurrent myocardial infarction occurred during the 3 months follow-up after surgery.Conclusions After evaluation by IVUS and pre-treatment with IVL,PCI was successfully completed for severe calcification lesions in LM,and IVL can be used as an option for the treatment of severe calcification in LM.

Objective:To evaluate the feasibility of using the Chinese version of Addenbrooke's cognitive examination ver-sion Ⅲ(ACE-Ⅲ)on cognitive assessment in patients with cerebellar infarction. Method:Forty patients with isolated cerebellar infarction were collected in the department of neurology,Bei-jing Tiantan Hospital,along with 40 healthy controls were recruited matched by age and education.The clini-cal demographics was collected and the severity of ataxia and balance dysfunction was assessed.ACE-Ⅲ was used to evaluate cognitive function.The Cronbach's alpha and receiver operating characteristic(ROC)curve were used to assess the reliability and validity of ACE-Ⅲ respectively.Furthermore,the correlation of ACE-Ⅲtotal score with age and education was examined by spearman analysis. Result:The total score of ACE-Ⅲ in patients'group and healthy controls was 88.3±6.0 and 93.1±3.0 respec-tively,showing a significant different(P＜0.001).Compared with healthy group,patients with cerebellar infarc-tion had lower performance in attention(P＜0.001),language fluency(P＜0.001)and visuo-spatial function(P=0.001).The overall Cronbach's alpha of ACE-Ⅲ was 0.58,and the area under curve was 0.79±0.05(95％con-fidence interval:0.69-0.89).According to Youden index,the optimal cut-off for ACE-Ⅲ was 88.Further-more,spearman analysis showed cognitive function was significant negative associated with age in patients'group(r=-0.52,P＜0.0001)and healthy controls(r=-0.67,P＜0.001),and was significant positive associated with education in patients'group(r=0.74,P＜0.01)and healthy controls(r=0.72,P＜0.0001) Conclusion:ACE-Ⅲ scale is a good tool to detect cognitive dysfunction in patients with isolated cerebellar in-farction.The total score of ACE-Ⅲ is associated with age and educational attainment.

Objective:To explore the application effect of the modified presentation assimilation discussion combined with heuristic clinical medicine teaching in training of extracorporeal membrane oxygenation specialist nurses.Methods:The convenient sampling method was used to select 62 nurses who participated in training of extracorporeal membrane oxygenation specialist nurses in the Second Affiliated Hospital of Zhengzhou University from January to June 2023 as the research objects. A total of 30 nurses who participated in the 25th training session from January to March 2023 were selected as the control group, and 32 nurses who participated in the 26th training session from April to June 2023 were selected as the observation group. The control group received conventional training method, while the observation group received modified presentation assimilation discussion combined with heuristic clinical medicine teaching. The theoretical knowledge and operational skills of nurses, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction were compared between the two groups after training.Results:After training, the scores of theoretical knowledge and operational skills, core competence of extracorporeal membrane oxygenation specialist nurses and training satisfaction in observation group were higher than those in control group, and the differences were statistically significant ( P<0.05) . Conclusions:The modified presentation assimilation discussion combined with heuristic clinical medicine teaching can improve the theoretical knowledge and operational skills of extracorporeal membrane oxygenation specialist nurses, and the nurses' training satisfaction is higher.

Objective:To investigate the efficacy and prognosis of chemotherapy regimen containing Bruton's tyrosine kinase(BTK)inhibitor in the treatment of relapsed/refractory mantle cell lymphoma(R/R MCL).Methods:The clinical data of 134 patients with R/R MCL were collected and analyzed retrospectively.The clinical characteristics of patients and effect of chemotherapy regimen on efficacy,overall survival(OS)and progression-free survival(PFS)were observed.Results:The median age of the patients was 58(56-61)years old,and male to female ratio was about 2.9∶1.Patients with Ann Arbor stage Ⅲ-Ⅳ accounted for 77.6％,extranodal involvement＞2 for 43.3％,bone marrow involvement for 60.4％,gastrointestinal involvement for 24.6％,and hepatosplenomegaly for 38.1％.The median follow-up time was 30(2-103)months,overall response rate(ORR)was 41.8％,3-year PFS was not reached,and 3-year and 5-year OS rate was 62.7％and 53.8％,respectively.The ORR of BTK inhibitor group was 56.9％,which was higher than 32.5％of non-BTK inhibitor group(P=0.006).The difference was statistically significant in PFS between the two groups(P=0.002),but was not in OS(P＞0.05).The difference was statistically significant in OS between classical and special morphology(P＜0.001),but was not in PFS(P＞0.05).Ki-67 was an influencing factor for OS and PFS.Multivariate analysis showed that Ki-67,B symptoms,MIPI score,and Ann Arbor stage were independent prognostic factors affecting patients'OS.The second-line treatment regimen was an independent prognostic factor affecting patients'PFS.Conclusions:The chemotherapy regimen containing BTK inhibitors can effectively improve the efficacy and prolong the PFS of R/R MCL patients.Ki-67,B symptoms,MIPI score,and Ann Arbor stage are independent prognostic factors for R/R MCL patients.

Objective:To explore the role of NK cells in allogeneic hematopoietic stem cell micro-transplantation(MST)in the treatment of patients with acute myeloid leukemia(AML).Methods:Data from 93 AML patients treated with MST at our center from 2013-2018 were retrospectively analyzed.The induction regimen was anthracycline and cytarabine combined with peripheral blood stem cells transplantation mobilization by granulocyte colony stimulating factor(GPBSC),followed by 2-4 courses of intensive treatment with medium to high doses of cytarabine combined with GPBSC after achieving complete remission(CR).The therapeutic effects of one and two courses of MST induction therapy on 42 patients who did not reach CR before transplantation were evaluated.Cox proportional hazards regression analysis was used to analyze the impact of donor NK cell dose and KIR genotype,including KIR ligand mismatch,2DS1,haplotype,and HLA-Cw ligands on survival prognosis of patients.Results:Forty-two patients received MST induction therapy,and the CR rate was 57.1％after 1 course and 73.7％after 2 courses.Multivariate analysis showed that,medium and high doses of NK cells was significantly associated with improved disease-free survival(DFS)of patients(HR=0.27,P=0.005;HR=0.21,P=0.001),and high doses of NK cells was significantly associated with improved overall survival(OS)of patients(HR=0.15,P=0.000).Donor 2DS1 positive significantly increases OS of patients(HR=0.25,P=0.011).For high-risk patients under 60 years old,patients of the donor-recipient KIR ligand mismatch group had longer DFS compared to the nonmismatch group(P=0.036);donor 2DS1 positive significantly prolonged OS of patients(P=0.009).Conclusion:NK cell dose,KIR ligand mismatch and 2DS1 influence the therapeutic effect of MST,improve the survival of AML patients.

Objective: This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods: Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.

Objective:To investigate the application value of single-sperm sequencing in resolving the carrier status of preim-plantation genetic testing(PGT)for chromosomal structural rearrangements in Robertsonian translocations.Methods:Haplotypes were constructed by single-sperm isolation combined with single-sperm sequencing for a patient with 45,XY,der(13;14)(q10;q10).Twenty single-sperm samples were isolated by mechanical braking and subjected to whole-genome amplification(WGA),and then the Asian Screening Array(ASA)gene chip was used to detect the 183 708 single nucleotide polymorphisms(SNP)of the WGA products.The single sperm associated with the translocation that could be used as haplotype inference was detected by copy number variation(CNV)sequencing,and the chromosomal haplotypes with normal and Robertsonian translocations were inferred.Three biopsy samples of embryonic trophoblast cells were used as the objects.After whole-genome amplification,high-throughput sequencing was employed to determine the status of the translocation chromosome carried by the embryos.The available blastocysts were selected for transfer,and the amniotic fluid samples were taken at 18 weeks of gestation to confirm whether the fetus carried the pathogenic muta-tion.Results:A total of 6 037 SNP sites were screened by single-sperm sequencing,and 30 sites selected to distinguish normal and translocation haplotypes.Preimplantation haplotype analysis showed that all the three embryos were euploids without Robertsonian translocation chromosome.Genetic testing of amniotic fluid in the second trimester confirmed that the karyotype of the fetus was 46,XN,carrying no Robertsonian translocation chromosome.Conclusion:For male carriers of Robertsonian translocation,single sperm sequencing can be used to screen SNP sites to construct haplotypes for distinguishing normal and Robertsonian translocation em-bryos,and to provide a basis for embryo selection by preimplantation chromosomal structural genetic testing.

Objective:To observe the effects of moxibustion on the levels of glucose-6-phosphate dehydrogenase(G6PD)and reduced nicotinamide adenine dinucleotide phosphate(NADPH)in the plasma and spleen and the CD4+T-cell number in the spleen of rats with adjuvant arthritis,thus to explore the mechanism in rheumatoid arthritis(RA)treatment with moxibustion by regulating the CD4+T-cell proliferation through G6PD-mediated pentose phosphate pathway. Methods:Twenty-seven male Sprague-Dawley rats were randomly divided into a blank group,a model group,and a moxibustion group,with 9 rats in each group.Incomplete Freund's adjuvant was used to induce inflammation in the model group and the moxibustion group.The blank group and the model group were not intervened.In the moxibustion group,suspended moxibustion was performed at bilateral Zusanli(ST36),Guanyuan(CV4),and Ashi points for 30 min,once a day for 24 times in total.Hematoxylin-eosin staining was used to evaluate the histopathological changes of rat synovial tissue;the swelling degree of the rat toes was observed by measuring the toe volume;G6PD and NADPH in the spleen and plasma were detected by Western blotting and enzyme-linked immunosorbent assay.Flow cytometry was used to detect the CD4+T-cell number in the spleen. Results:Compared with the blank group,the levels of G6PD and NADPH in the plasma and spleen and the CD4+T-cell number in the spleen were significantly increased in the model group(P<0.01 or P<0.05).Compared with the model group,the NADPH level in the spleen and plasma and the CD4+T-cell number in the spleen in the moxibustion group decreased significantly(P<0.05 or P<0.01),and the G6PD level in the plasma decreased significantly(P<0.05),but there was no significant difference in the G6PD level in the spleen(P>0.05). Conclusion:Moxibustion can regulate immunity and improve joint synovial inflammation in RA.The mechanism may be that the G6PD-mediated pentose phosphate pathway reduces the production of metabolite NAPDH in CD4+T cells,thereby inhibiting the proliferation of naive CD4+T cells.

Objective: This study aimed to evaluate the effects of 2 endoscopic spine surgeries on the biomechanical properties of normal and osteoporotic spines. Methods: Based on computed tomography images of a healthy adult volunteer, 6 finite element models were created. After validating the normal intact model, a concentrated force of 400 N and a moment of 7.5 Nm were exerted on the upper surface of L3 to simulate 6 physiological activities of the spine. Five types of indices were used to assess the biomechanical properties of the 6 models, range of motion (ROM), maximum displacement value, intervertebral disc stress, maximum stress value, and articular protrusion stress, and by combining them with finite element stress cloud. Results: In normal and osteoporotic spines, there was no meaningful change in ROM or disc stress in the 2 surgical models for the 6 motion states. Model N1 (osteoporotic percutaneous transforaminal endoscopic discectomy model) showed a decrease in maximum displacement value of 20.28% in right lateral bending. Model M2 (unilateral biportal endoscopic model) increased maximum displacement values of 16.88% and 17.82% during left and right lateral bending, respectively. The maximum stress value of L4–5 increased by 11.72% for model M2 during left rotation. In addition, using the same surgical approach, ROM, maximum displacement values, disc stress, and maximum stress values were more significant in the osteoporotic model than in the normal model. Conclusion In both normal and osteoporotic spines, both surgical approaches were less disruptive to the physiologic structure of the spine. Furthermore, using the same endoscopic spine surgery, normal spine biomechanical properties are superior to osteoporotic spines.