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.

Schizophrenia has various obstacles in cognition， thinking， emotion， behavior and other aspects； it belongs to the category of “madness” in traditional Chinese medicine （TCM）. Once schizophrenia occurs， multiple factors are often intertwined， and a single therapy is difficult to be effective. At present， TCM compounds and active ingredients have significant effects in the clinical treatment of schizophrenia， which is an important direction for the development of new drugs for schizophrenia. This article summarizes the molecular mechanism of TCM compounds and active ingredients in the treatment of schizophrenia. It is found that Wendan decoction and Yudian decoction can inhibit the apoptosis of hippocampal cells by activating BDNF/TrKB/CREB signaling pathway； quercetin and icariin can promote neural development and regeneration by activating NMDA/ERK signaling pathway； Wendan decoction and icariin can maintain neural cell homeostasis by activating PI3K/AKT signaling pathway； Bushen zhuangyang capsule can enhance learning and memory abilities by activating CaMKⅡ signaling pathway； formulas such as Huatan huoxue tongzhi formula can enhance intercellular information transmission by inhibiting PKC signaling pathway； α-humulene and others can restore nerve cell function by inhibiting NRG1/ErbB4 signaling pathway. TCM compounds and active ingredients can improve schizophrenia by intervening in the above-mentioned signaling pathways.

Objective　To assess the diagnostic efficacy of the cell-free Mycobacterium tuberculosis DNA testing (CF-TB) in tuberculous pleurisy. Methods　A total of 71 patients diagnosed with tuberculous pleurisy and 35 patients with non-tuberculous pleurisy were selected from the Fifth People's Hospital of Wuxi between January to December 2022. The standard pleural puncture was conducted to collect pleural effusion, which was then utilized for Mycobacterium tuberculosis culture, GeneXpert Mycobacterium tuberculosis/rifampicin resistance (GeneXpert MTB/RIF), CF-TB, and adenosine deaminase (ADA) testing. Blood samples were subjected to tuberculosis infection T-cell spotting test (T-SPOT.TB) assay. The receiver operator characteristic curve (ROC) was applied to obtain the optimal cut-off value for pleural fluid CF-TB and to compare the diagnostic performance of CF-TB with other methods. Data analysis was conducted using SPSS 22.0 software, with statistical significance defined as P<0.05. Results　The ROC curve analysis determined that the optimal cycle threshold (Ct) value for diagnosing tuberculous pleurisy using CF-TB in pleural fluid was 38.489, with a sensitivity of 91.5% and specificity of 97.1%. In comparison, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T-SPOT.TB and pleural fluid ADA in diagnosing tuberculous pleurisy were 86.0%, 71.4%, 86.0%, 71.4%, 81.1%, and 55.0%, 91.4%, 92.9%, 50.8%, 67.0%, respectively, all of which were lower than the diagnostic efficiency of CF-TB. Furthermore, the specificity of pleural fluid CF-TB in diagnosing tuberculous pleurisy (97.1%) was not significantly different from GeneXpert MTB/RIF (100%) and Mycobacterium tuberculosis culture (100%), but its sensitivity (91.5%) was significantly higher than both GeneXpert MTB/RIF (19.7%) and Mycobacterium tuberculosis culture (28.2%), with a statistically significant difference (P<0.001). Conclusions　Compared to the conventional gold standard for diagnosing tuberculous pleurisy, CF-TB exhibits a higher sensitivity and its specificity is superior to that of tuberculosis immunological test. Consequently, CF-TB can serve as a valuable complement to other traditional detection methods in aiding the diagnosis of tuberculous pleurisy.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To compare the effect of modified postauricular transverse incision and traditional vertical incision for microvascular decompression in the treatment of hemifacial spasm.Methods:Prospective study method was used. A total of 116 patients with hemifacial spasm in Handan Central Hospital from January 1, 2019 to January 1, 2020 were selected, and divided into two groups according to the admission order. Both groups underwent microvascular decompression; control group (57 cases) received traditional vertical incision, while treatment group (59 cases) received modified postauricular transverse incision. The brainstem auditory evoked potential (BAEP), pain degree, surgical indicators, facial aesthetic satisfaction and complications were compared between two groups.Results:After treatment, the BAEP of latency, wave interval and wave amplitude in the two groups increased compared with that before treatment, and the BAEP of latency, wave interval and wave amplitude in the treatment group were higher than those in the control group: (1.89 ± 0.15) ms vs. (1.62 ± 0.21) ms, (7.89 ± 0.15) ms vs. (6.25 ± 0.41) ms, (1.79 ± 0.19) ms vs. (1.54 ± 0.11) ms ( P<0.05). After treatment, the visual analogue score (VAS) of patients in the two groups decreased compared with that before treatment, and the VAS of patients in the treatment group was lower than that in the control group: (1.15 ± 0.27) points vs. (2.18 ± 0.24) points ( P<0.05). The operation time, intraoperative bleeding volume and postoperative scar length of patients in the treatment group were less than those in the control group: (60.41 ± 3.81) h vs. (76.87 ± 3.87) h, (30.18 ± 4.19) ml vs. (56.87 ± 4.15) ml and (4.18 ± 1.07) cm vs. (6.87 ± 1.05) cm ( P<0.05). The satisfaction rate of patients in the treatment group was higher than that in the control group: 91.53% (54/59) vs. 71.93% (41/57) ( P<0.05). The complication rate of patients in the treatment group was lower than that in the control group: 5.08% (3/59) vs. 21.05% (12/57) ( P<0.05). Conclusions:Compared with traditional vertical incision, the modified transverse incision for microvascular decompression in the treatment of hemifacial spasm can reduce intraoperative blood loss and postoperative scar area, enhance brainstem auditory evoked potential, and improve facial aesthetics, which is worthy of recommendation.

Objective:To prepare 99Tc m-hydrazinonicotinamide(HYNIC)-αCD8/Fab ( 99Tc m-αCD8/Fab), and explore the predictive value of 99Tc m-αCD8/Fab SPECT/CT imaging for the efficacy of anti-programmed death-1 (PD-1) immunotherapy. Methods:The αCD8/Fab was modified with HYNIC- N-hydroxysuccinimide (NHS) and IRDye800-NHS to form HYNIC-αCD8/Fab and IRDye800-αCD8/Fab (Dye-αCD8/Fab), respectively. 99Tc m-αCD8/Fab was prepared in sodium bicarbonate buffer (pH=8.5), with SnCl 2 being used as the reducing agent. The labeling yield and radiochemical purity of 99Tc m-αCD8/Fab and its stability in PBS and fetal bovine serum (FBS) were tested in vitro. The mouse spleen and human peripheral blood lymphocytes were isolated for cell-specific binding and blocking experiments of 99Tc m-αCD8/Fab in vitro. SPECT/CT imaging was used to analyze the specific binding ability of the 99Tc m-αCD8/Fab probe in CT26 colon cancer mouse models (BALB/c). The near infrared fluorescence imaging and SPECT/CT imaging were performed to detect the intra-tumoral CD8 + T cell infiltration after anti-PD-1 therapy in tumor bearing mice, and the results were further verified by HE and immunofluorescence staining. CD8 + T cell depletion study was performed to determine the role of CD8 + T cells in the tumor responses to anti-PD-1 therapy. Two-way analysis of variance was used to compare the data difference. Results:The labeling yield of 99Tc m-αCD8/Fab was 90% with a high radiochemical purity (95%) and good stability in vitro (radiochemical purity still more than 80% after 720 min in PBS and FBS). 99Tc m-αCD8/Fab could specifically bind to mouse CD8 + T cells ((10.30±0.81) percent added radioactive dose (%AD)/10 6 cells), compared with the binding ability in human peripheral blood lymphocytes group and CD8 antibody blocking group ((1.78±0.61) and (1.59±0.25) %AD/10 6 cells; F=10.07, P<0.001). SPECT/CT imaging showed that 99Tc m-αCD8/Fab had markedly higher tumor uptake in the CT26 colon cancer mouse models. Near-infrared fluorescence imaging showed that the tumor uptake of 99Tc m-αCD8/Fab in the responsive group was significantly higher than in the nonresponsive group after anti-PD-1 treatment ((8.9±1.1)% vs (7.1±0.8)%; F=4.69, P=0.024), and SPECT/CT imaging found the similar result. HE and immunofluorescence staining of tumor and lymph nodes showed that the proportion of lymphocyte infiltration was higher in the responsive group. Furthermore, CD8 + T cell depletion significantly reversed the therapeutic effect of anti-PD-1 immunotherapy in tumor-bearing mice. Conclusions:In this study, 99Tc m-αCD8/Fab was successfully obtained. CD8-specific SPECT imaging could sensitively visualize the tumor-infiltrating CD8 + T cells, suggesting the potential application value to predict and evaluate the efficacy of immunotherapy in the clinical settings.

Objective:To explore the application effect of failure mode and effect analysis (FMEA) on reducing the unplanned extubation rates in patients with neurosurgical catheterization.Methods:FMEA theory was used to analyze the causes of unplanned extubation in neurosurgical patients with catheterization. The Risk Priority Number (RPN) was calculated and the failure modes with higher RPN were selected. The causes were analyzed, and the improvement measures were formulated to optimize the nursing plan. A total of 585 patients admitted to the Department of Neurosurgery of the Sixth Medical Center of PLA General Hospital from January 2018 to December 2019 were recruited as the FMEA group, the 631 patients admitted before FMEA application, from January 2016 to December 2017, were recruited as the control group. The control group was given routine nursing of Neurosurgery pipeline, and the FMEA group was given FMEA intervention on this basis. The difference of unplanned extubation rate between the two groups was compared.Results:The total incidence of unplanned extubation in FMEA group was 1.48% (21/1 417) , which was lower than 5.11% (72/1 408) in control group, with statistical significance ( P<0.001) . The unplanned extubation rates of gastric tube, urinary tube and operation related drainage tube in FMEA group were lower than in control group, and the differences were statistically significant ( P<0.05) . There was no significant difference in the incidence of unplanned extubation of endotracheal intubation and deep vein catheterization between the two groups ( P>0.05) . Conclusions:The FMEA model can be effective in reducing the rate of unplanned extubation for patients in neurosurgery, which is worthy of clinical application.

OBJECTIVE: To assess the value of BACs-on-Beads (BoBs) technique for the detection of chromosomal abnormalities in abortus tissues from recurrent pregnancy loss. METHODS: A total of 109 abortus samples were collected and analyzed with the BoBs technique. The incidence and types of chromosomal abnormalities for different age groups and gestational weeks were compared. RESULTS: The BoBs assay has succeeded in all cases, with an incidence for chromosomal abnormalities reaching 62.39% (68/109). The major findings included trisomy 16 (12/68), trisomy 22 (9/68), trisomy 13 (9/68) and trisomy 21 (8/68). The abnormal rate was significantly higher in those above 35-year-old compared with that of the <35-year-old group (P<0.05). More aberrations were found among abortus tissues derived from 42-70 days of pregnancy albeit with no statistical significance (P>0.05). The aberration rates were similar for samples derived from second, third and fourth time abortions (P>0.05). CONCLUSION BoBs technique can detect chromosomal aberrations in miscarriages and may be routinely used for the analysis of early spontaneous abortions.
Abortion, Habitual ; Abortion, Spontaneous ; Adult ; Chromosome Disorders ; Down Syndrome ; Female ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

Objective : To analyze the initial displacement of the upper central incisor and stress distribution of periodontal ligament under different torque values of upper incisors under the action of a four-curved auxiliary arch to provide a reliable basis for the safety of clinical application of four-curved auxiliary arches. Methods : A three-dimensional finite element model for torque control of upper anterior teeth with a homemade quadrilateral auxiliary arch was established. Four different states were analyzed: molar ligation without extraction space (group A), microimplant ligation without extraction space (group B), molar recovery with extraction space closure (group C) (the adductive traction force was set at 115 g) and microimplant recovery with extraction space closure (group D) (the adductive traction force was set at 115 g). When four types of torque (0.5 N, 1.0 N, 1.5 N, and 2.0 N) were applied. The initial displacement of upper central incisors and the stress distribution of periodontal ligament in 16 groups (A1-A4, B1-B4, C1-C4, D1-D4) were observed. Results : Under different conditions, as the strength of the four-curve auxiliary arch increases, the maxillary anterior teeth has crown labial inclination and a root lingual inclination. The displacement of the incisor tip increases with the increase in the loading force of the torque auxiliary arch, and the displacement of the incisor root apex increases as the force increases. The difference in incisor-apex displacement distance in A1-A4, B1-B4, C1-C4, D2 and D4 groups increased as the torque force increases, while the difference between the D3 group and D1 and D2 groups decreased slightly. The stress of the cervical periodontal ligament of the upper central incisor did not exceed the stress of the periodontal ligament in the following groups: A1, A2, B1, B2, B3, C1, C2, D1, and D2. The stress of the lip side of the upper central incisor did exceed the stress of the periodontal ligament in the following groups: A3, A4, B4, C3, C4, D3, and D4. In other words, when using the four-curved auxiliary arch as an implant anchorage, the force applied in the absence of extraction space should not exceed 1.5 N, and the force applied in the adduction of extraction space should not exceed 1.0 N. When using the nonimplant anchorage, the force applied in the absence of extraction space and the adduction of extraction space should not exceed 1.0 N. In addition, the range of force should not exceed the maximum stress of the periodontal ligament in the cervical region such that the effective and safe torque movement can be achieved. Under other stress conditions, the stress of the labial and cervical periodontal ligament of the upper central incisor exceeded the stress value (2.6 × 10-2MPa). The stress value of periodontal ligament was 2.6 × 10-2MPa in all groups. Conclusion A four-curved auxiliary arch has a significant effect on the upper anterior teeth, and the use of microimplants can better control root movement such that the crown of upper central incisors cannot be excessively lip inclined.

Objective: To investigate the roles of pattern recognition receptors (PRRs) including Toll-like receptors (TLRs), retinoic acid-inducible geneⅠ-like receptors (RLRs) and nucleotide binding oligomerization domain-like receptors (NLRs) in the pathogenesis of dengue fever (DF) and the induction of immune responses to dengue virus. Methods: Blood samples were collected from patients with DF at three different time points to isolate peripheral blood mononuclear cells (PBMCs) by density gradient centrifugation. Then PBMCs were used to extract ribonucleic acid (RNA). Expression of genes was detected by polymerase chain reaction (PCR) array. Results: Expression of genes relating to PRRs signaling pathways in DF patients increased significantly in the early stage of the disease as compared with those in healthy controls, but decreased gradually during the recovery period. Expression of genes encoding TLR7 and TLR8 was enhanced at the early stage of DF. No significant changes in the expression of TLR3 and TLR9 genes were observed during the course of the disease. The genes encoding RIG-Ⅰ, MDA5 and LGP2 of RLRs family as well as NOD2 and OAS2 of NLRs family were all up-regulated. Conclusion Signaling pathways mediated by PRRs including TLR7/8, RIG-Ⅰ, MDA5 and so on play an important role in the pathogenesis of DF and the induction of immune responses to dengue virus.