ObjectiveTo explore the clinical efficacy and mechanism of Bupi Qingfei prescription （BPQF） in treating stable bronchiectasis in the patients with syndromes of lung-spleen Qi deficiency and phlegm-heat accumulation in the lungs. MethodsA randomized， double-blind， placebo-controlled trial was conducted. Patients were randomized into BPQF and placebo control （PC） groups. On the basis of conventional Western medicine treatment， the BPQF granules and placebo were respectively administered at 10 g each time， twice a day， for a course of 24 weeks. The TCM symptom scores， Quality of Life Questionnaire for Bronchiectasis （QOL-B） scores， lung function indicators， T lymphocyte subsets， level of inflammatory factors in the sputum， level of neutrophil elastase （NE） in the sputum， and occurrence of adverse reactions were observed before and after treatment in the two groups. ResultsA total of 64 patients completed the study， encompassing 32 in the BPQF group and 32 in the PC group. After treatment， the BPQF group showed decreased TCM symptom scores （P<0.01）， increased QOL-B scores （P<0.01）， and declined levels of tumor necrosis factor （TNF）-α and NE （P<0.05， P<0.01）. The PC group showed decreased TCM symptom （except spleen deficiency） scores （P<0.01）， increased the QOL-B health cognition and respiratory symptom domain scores （P<0.05， P<0.01）， and a declined TNF-α level （P<0.01）. Moreover， the BPQF group had lower TCM symptom （except chest tightness） scores （P<0.05， P<0.01）， higher QOL-B （except treatment burden） scores （P<0.05， P<0.01）， and lower levels of interleukin-6 and TNF-α （P<0.05） than the PC group. Neither group showed serious adverse reactions during the treatment process. ConclusionBPQF can ameliorate the clinical symptoms of stable bronchiectasis patients who have lung-spleen Qi deficiency or phlegm-heat accumulation in the lungs by regulating the immune balance and inhibiting airway inflammatory responses.

Objective: To analyze the differences in bile acid profiles during different pregnancy durations of patients with intrahepatic cholestasis of pregnancy (ICP), so as to provide a reference for early prevention and treatment of ICP and optimization of maternal-infant health outcomes. Methods: Pregnant women who underwent routine prenatal examinations and delivered at Hangzhou Obstetrics and Gynecology Hospital from 2021 to 2023 were selected as study subjects. According to the ICP guidelines (2020), pregnant women were categorized into normal group, mild ICP group, and moderate/severe ICP group. Age, parity, and gravidity were collected through the obstetric electronic medical record system, liver function indicators and seven bile acid levels were collected through the hospital's laboratory information system. Differences in bile acid profiles across pregnancy durations among the three groups were compared. Results: A total of 238 pregnant women were enrolled, including 57 cases (23.95%) in the normal group, 136 cases (57.14%) in the mild ICP group, and 45 cases (18.91%) in the moderate/severe ICP group. There were statistically significant differences between the three groups in total bile acid (TBA), cholic acid (CA), chenodeoxycholic acid (CDCA), glycochenodeoxycholic acid (GCDCA), glycocholic acid (GCA), taurocholic acid (TCA) levels (all P<0.05). Compared with the normal group, CA, GCDCA and GCA, and TCA were higher in the mild and moderate/severe ICP groups; compared with the mild ICP group, GCA was higher in the moderate/severe ICP group (all P<0.05). Significant differences were observed in the levels of GCDCA, GCA, and TCA among three groups pregnant women in the early, mid, and late pregnancy (all P<0.05). Compared with the normal group, mild ICP group had higher GCDCA and GCA in the early and mid pregnancy; moderate/severe ICP group had higher TCA in the early pregnancy and higher GCDCA and GCA in the late pregnancy. Compared with the mild ICP group, mild ICP group had higher TCA in the early pregnancy and the moderate/severe ICP group had higher GCA in the late pregnancy. Conclusions GCDCA, GCA, and TCA levels remain higher in ICP patients than in normal pregnant women across all pregnancy durations. Personalized perinatal management plans can be developed based on bile acid profile dynamics to optimize maternal-fetal outcomes.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective:To evaluate the efficacy and safety of daratumumab in treating patients with monoclonal immunoglobulin deposition disease (MIDD) with renal injury.Methods:A case-series analysis study was conducted in MIDD patients with renal injury who received daratumumab treatment at the Department of Nephrology, Ruijin Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, from December 2021 to October 2023. The clinical data of patients at the time of diagnosis and during the follow-up period were collected. Hematological and renal responses were assessed and adverse reaction events were recorded.Results:Seven patients diagnosed with MIDD were included in this study, with a male-to-female ratio of 5∶2 and age of 46 (43, 52) years. One patient was light-heavy chain deposition disease, and the remaining 6 patients were light chain deposition disease. Among them, 5 patients had received prior treatment (1-2 lines of treatment with the regimen of cyclophosphamide, bortezomib and dexamethasone), while 2 patients were newly treated, one of whom had already started hemodialysis at diagnosis. Prior to receiving monoclonal antibody treatment, difference of serum free light chain (dFLC) among the 7 patients was 52 (7, 295) mg/L. Excluding 1 patient on dialysis, the remaining 6 patients had 24-hour urinary protein of 1.1 (0.2, 4.7) g, serum creatinine of 178.5 (157.8, 279.8) μmol/L and estimated glomerular filtration rate of 33.9 (24.2, 41.1) ml·min -1·（1.73 m 2） -1. The daratumumab treatment was 17 (10, 20) infusions, with treatment duration of 17 (9, 23) months and follow-up time of 24 (13, 32) months. After treatment, among 5 previously treated patients, hematological response evaluation showed that 1 patient with baseline dFLC <20 mg/L and minimal residual disease negativity upon re-examination, while the remaining 4 patients achieved hematological responses of complete response or better. Renal response evaluation revealed that, except for 1 patient with partial response, the other 4 patients achieved very good partial response (VGPR) or better. Among 2 newly diagnosed patients, both achieved hematological efficacy at least VGPR, with one achieving renal complete response, while the other one remaining dialysis- dependent. Overall, dFLC of 7 patients was 4.9 (2.1, 11.5) mg/L. Among 6 non-dialysis patients, 24-hour urinary protein was 0.19 (0.06, 0.42) g, serum creatinine was 153.0 (120.8, 188.0) μmol/L and estimated glomerular filtration rate was 40.4 (35.2, 57.3) ml·min -1·(1.73 m 2) -1. No severe adverse reactions were observed during daratumumab treatment. Conclusion:The application of daratumumab in the treatment of MIDD with renal injury is effective and well tolerated, achieving high-quality hematological responses, with high renal responses reaching or exceeding VGPR and improvement of renal function.

Objective:To investigate the value and significance of α-methylacyl-CoA racemase (AMACR), p63 and Ki-67 immunohistochemical detection in the pathological diagnosis of prostate cancer.Methods:A total of 156 archived prostate biopsy paraffin samples collected from Qidong Hospital of Traditional Chinese Medicine from June 2022 to August 2023 were selected as research materials. The expression of AMACR, p63 and Ki-67 in 48 cases of prostate cancer, 32 cases of high-grade prostatic intraepithelial neoplasia, 26 cases of low-grade prostatic intraepithelial neoplasia and 50 cases of prostatic hyperplasia were detected by immunohistochemistry. The correlation between the expression of AMACR, p63 and Ki-67 and the clinical and pathological features of prostate cancer patients, as well as their diagnostic efficacy for prostate cancer were analyzed.Results:There were statistically significant differences in the positive expression rates of AMACR, p63 and Ki-67 among the samples of different groups (all P<0.05). The positive expression rate of AMACR in the biopsy samples of prostate cancer group was 100%, and the high expression rate was 81.25%, which was significantly higher than that of the other three groups. The negative expression rate of p63 was 97.92%, which was significantly higher than the other three groups. The positive expression rate of Ki-67 was 81.25% and the high expression rate was 54.17%, which was significantly higher than the other three groups. The expression of AMACR was related to tumor length, TNM stage, differentiation degree and Gleason score of prostate cancer patients. The high expression rate of AMACR in patients with tumor size ≥1.5 cm, stage Ⅱ to Ⅲ, medium and highly differentiated tumors with Gleason score 8-10 was significantly higher than those with tumor size <1.5 cm, stage Ⅰ, low differentiation, and Gleason score 2-7 (all P<0.05). Ki-67 expression was correlated with tumor length, differentiation degree, lymph node metastasis and Gleason score in prostate cancer patients. The high expression rate of Ki-67 in patients with tumor size ≥1.5 cm, medium and highly differentiated tumors with lymph node metastasis and Gleason score 8-10 was significantly higher than that in patients with tumor size<1.5 cm, low differentiation, no lymph node metastasis and Gleason score 2-7 (all P<0.05). The expression of p63 was not correlated with the clinical and pathological features of patients with prostate cancer (all P>0.05). The sensitivity and negative predictive value of AMACR positive/p63 negative/Ki-67 positive combined diagnosis of prostate cancer were 100.00%, and the specificity was 81.82%. Conclusions:AMACR, p63 and Ki-67 in prostate biopsy samples can be used as good biomarkers for the diagnosis or exclusion of prostate cancer, and the combined detection can improve the diagnosis accuracy of prostate cancer.

Objective:To develop a staged exercise prescription for patients with Knee Osteoarthritis (KOA) based on internet information systems and evaluate its effectiveness, in order to provide a reference for exercise rehabilitation guidance for KOA patients.Methods:A systematic review of guidelines, expert consensus, systematic reviews, and evidence summaries on exercise prescriptions for osteoarthritis from January 1, 2012, to December 31, 2022, was conducted. After literature screening, semi-structured interviews, and expert consultations, a staged exercise prescription for KOA patients based on internet information systems was formulated. From April to October 2023, 90 KOA outpatients from Beijing Friendship Hospital, Capital Medical University, were selected using convenience sampling and randomly divided into the observation group and the control group, each with 45 cases. The control group received routine rehabilitation nursing, while the observation group implemented the staged exercise prescription based on the internet information system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Multidimensional Self-Efficacy for Exercise Scale (MSES) were used for evaluation before the intervention and at 4, 8, 16, and 24 weeks post-intervention. After the intervention, the Exercise Adherence Rating Scale (EARS) was used to assess exercise adherence in both groups.Results:A staged exercise prescription consisting of three phases and 27 items was successfully developed. At 8, 16, and 24 weeks after the intervention, the observation group had significantly lower scores in the pain, stiffness, and daily activity dimensions of the WOMAC compared to the control group, and the differences were statistically significant ( P<0.05). At the same time points, the observation group had significantly higher MSES scores than the control group, and the differences were statistically significant ( P<0.05). At 16 and 24 weeks post-intervention, the EARS scores of the observation group were also significantly higher than those of the control group, with statistically significant differences ( P<0.05) . Conclusions:The staged exercise prescription for KOA patients based on internet information systems is both scientifically valid and feasible. It can effectively alleviate knee joint symptoms, enhance exercise self-efficacy, and improve exercise adherence.

Objective:To develop a staged exercise prescription for patients with Knee Osteoarthritis (KOA) based on internet information systems and evaluate its effectiveness, in order to provide a reference for exercise rehabilitation guidance for KOA patients.Methods:A systematic review of guidelines, expert consensus, systematic reviews, and evidence summaries on exercise prescriptions for osteoarthritis from January 1, 2012, to December 31, 2022, was conducted. After literature screening, semi-structured interviews, and expert consultations, a staged exercise prescription for KOA patients based on internet information systems was formulated. From April to October 2023, 90 KOA outpatients from Beijing Friendship Hospital, Capital Medical University, were selected using convenience sampling and randomly divided into the observation group and the control group, each with 45 cases. The control group received routine rehabilitation nursing, while the observation group implemented the staged exercise prescription based on the internet information system. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Multidimensional Self-Efficacy for Exercise Scale (MSES) were used for evaluation before the intervention and at 4, 8, 16, and 24 weeks post-intervention. After the intervention, the Exercise Adherence Rating Scale (EARS) was used to assess exercise adherence in both groups.Results:A staged exercise prescription consisting of three phases and 27 items was successfully developed. At 8, 16, and 24 weeks after the intervention, the observation group had significantly lower scores in the pain, stiffness, and daily activity dimensions of the WOMAC compared to the control group, and the differences were statistically significant ( P<0.05). At the same time points, the observation group had significantly higher MSES scores than the control group, and the differences were statistically significant ( P<0.05). At 16 and 24 weeks post-intervention, the EARS scores of the observation group were also significantly higher than those of the control group, with statistically significant differences ( P<0.05) . Conclusions:The staged exercise prescription for KOA patients based on internet information systems is both scientifically valid and feasible. It can effectively alleviate knee joint symptoms, enhance exercise self-efficacy, and improve exercise adherence.

Objective:To explore the binding characteristics of N, N-diethyl-2-(2-(4-(2- 18F-fluoroethoxy)phenyl)-5, 7-dimethylpyrazolo[1, 5-a]pyrimidin-3-yl)acetamide ( 18F-DPA-714) and ( R)- N-sec-butyl- N-methyl-4-(3-( 18F-trifluoromethyl)phenyl)quinazoline-2-carboxamide ( 18F-TFQC) to the single nucleotide polymorphisms of the 18×10 3 translocator protein (TSPO), and to evaluate the imaging efficacy and feasibility of those 2 molecular probes in neuroinflammation rat models. Methods:To test the selectivity of 18F-DPA-714 and 18F-TFQC for TSPO polymorphisms, the wild-type (high-affinity binding, HAB) and mutant (low-affinity binding, LAB) sequences of the human TSPO gene were transfected into 293T cells respectively. A competitive inhibition assay was carried out with N-methyl- N-(1-methylpropyl)-1-(2-chlorophenyl)-3-isoquinoline carboxamide (PK11195) as an inhibitor to determine the binding affinities of 2 probes to TSPO polymorphisms. Rat neuroinflammation models ( n=6) were established using lipopolysaccharide. Three days after modeling, small animal PET/CT imaging was performed using 18F-DPA-714 and 18F-TFQC, respectively, to observe and compare the uptake of the tracers, and the ratio of SUV mean of the right striatum to SUV mean of the left striatum (SUVR) was calculated. After the imaging, the expression and distribution of microglia and TSPO were detected by tissue immunofluorescence. Repeated-measures analysis of variance was used to analyze the SUVR data of different groups. Results:The inhibition constants ( Ki) of 18F-TFQC on 293T-LAB and 293T-HAB cells were 23.51 and 14.60 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 1.61, indicating low sensitivity to TSPO single nucleotide polymorphisms. The Ki of 18F-DPA-714 for binding to 293T-LAB and 293T-HAB cells were 45.23 and 6.47 nmol/L, respectively, with a Ki LAB/ Ki HAB ratio of 6.99. Small animal PET/CT imaging demonstrated that specifically uptake of both probes could be found in neuroinflammatory lesions. The overall SUVR of 18F-DPA-714 in the lesions within 60minutes was slightly higher than that of 18F-TFQC, but no significant difference was observed ( F values: inter-group 0.40, time effect 0.30, cross-effect 0.03; all P>0.05). Conclusions:Compared with 18F-DPA-714, 18F-TFQC is less sensitive to TSPO gene polymorphisms, thus being more suitable for clinical application and promotion. It holds promise for the early identification of neuroinflammation and the efficacy monitoring of anti-inflammatory drug treatments.

Objective:To evaluate the efficacy and safety of daratumumab in treating patients with monoclonal immunoglobulin deposition disease (MIDD) with renal injury.Methods:A case-series analysis study was conducted in MIDD patients with renal injury who received daratumumab treatment at the Department of Nephrology, Ruijin Hospital, affiliated to Shanghai Jiao Tong University School of Medicine, from December 2021 to October 2023. The clinical data of patients at the time of diagnosis and during the follow-up period were collected. Hematological and renal responses were assessed and adverse reaction events were recorded.Results:Seven patients diagnosed with MIDD were included in this study, with a male-to-female ratio of 5∶2 and age of 46 (43, 52) years. One patient was light-heavy chain deposition disease, and the remaining 6 patients were light chain deposition disease. Among them, 5 patients had received prior treatment (1-2 lines of treatment with the regimen of cyclophosphamide, bortezomib and dexamethasone), while 2 patients were newly treated, one of whom had already started hemodialysis at diagnosis. Prior to receiving monoclonal antibody treatment, difference of serum free light chain (dFLC) among the 7 patients was 52 (7, 295) mg/L. Excluding 1 patient on dialysis, the remaining 6 patients had 24-hour urinary protein of 1.1 (0.2, 4.7) g, serum creatinine of 178.5 (157.8, 279.8) μmol/L and estimated glomerular filtration rate of 33.9 (24.2, 41.1) ml·min -1·（1.73 m 2） -1. The daratumumab treatment was 17 (10, 20) infusions, with treatment duration of 17 (9, 23) months and follow-up time of 24 (13, 32) months. After treatment, among 5 previously treated patients, hematological response evaluation showed that 1 patient with baseline dFLC <20 mg/L and minimal residual disease negativity upon re-examination, while the remaining 4 patients achieved hematological responses of complete response or better. Renal response evaluation revealed that, except for 1 patient with partial response, the other 4 patients achieved very good partial response (VGPR) or better. Among 2 newly diagnosed patients, both achieved hematological efficacy at least VGPR, with one achieving renal complete response, while the other one remaining dialysis- dependent. Overall, dFLC of 7 patients was 4.9 (2.1, 11.5) mg/L. Among 6 non-dialysis patients, 24-hour urinary protein was 0.19 (0.06, 0.42) g, serum creatinine was 153.0 (120.8, 188.0) μmol/L and estimated glomerular filtration rate was 40.4 (35.2, 57.3) ml·min -1·(1.73 m 2) -1. No severe adverse reactions were observed during daratumumab treatment. Conclusion:The application of daratumumab in the treatment of MIDD with renal injury is effective and well tolerated, achieving high-quality hematological responses, with high renal responses reaching or exceeding VGPR and improvement of renal function.

Objective:To investigate the value and significance of α-methylacyl-CoA racemase (AMACR), p63 and Ki-67 immunohistochemical detection in the pathological diagnosis of prostate cancer.Methods:A total of 156 archived prostate biopsy paraffin samples collected from Qidong Hospital of Traditional Chinese Medicine from June 2022 to August 2023 were selected as research materials. The expression of AMACR, p63 and Ki-67 in 48 cases of prostate cancer, 32 cases of high-grade prostatic intraepithelial neoplasia, 26 cases of low-grade prostatic intraepithelial neoplasia and 50 cases of prostatic hyperplasia were detected by immunohistochemistry. The correlation between the expression of AMACR, p63 and Ki-67 and the clinical and pathological features of prostate cancer patients, as well as their diagnostic efficacy for prostate cancer were analyzed.Results:There were statistically significant differences in the positive expression rates of AMACR, p63 and Ki-67 among the samples of different groups (all P<0.05). The positive expression rate of AMACR in the biopsy samples of prostate cancer group was 100%, and the high expression rate was 81.25%, which was significantly higher than that of the other three groups. The negative expression rate of p63 was 97.92%, which was significantly higher than the other three groups. The positive expression rate of Ki-67 was 81.25% and the high expression rate was 54.17%, which was significantly higher than the other three groups. The expression of AMACR was related to tumor length, TNM stage, differentiation degree and Gleason score of prostate cancer patients. The high expression rate of AMACR in patients with tumor size ≥1.5 cm, stage Ⅱ to Ⅲ, medium and highly differentiated tumors with Gleason score 8-10 was significantly higher than those with tumor size <1.5 cm, stage Ⅰ, low differentiation, and Gleason score 2-7 (all P<0.05). Ki-67 expression was correlated with tumor length, differentiation degree, lymph node metastasis and Gleason score in prostate cancer patients. The high expression rate of Ki-67 in patients with tumor size ≥1.5 cm, medium and highly differentiated tumors with lymph node metastasis and Gleason score 8-10 was significantly higher than that in patients with tumor size<1.5 cm, low differentiation, no lymph node metastasis and Gleason score 2-7 (all P<0.05). The expression of p63 was not correlated with the clinical and pathological features of patients with prostate cancer (all P>0.05). The sensitivity and negative predictive value of AMACR positive/p63 negative/Ki-67 positive combined diagnosis of prostate cancer were 100.00%, and the specificity was 81.82%. Conclusions:AMACR, p63 and Ki-67 in prostate biopsy samples can be used as good biomarkers for the diagnosis or exclusion of prostate cancer, and the combined detection can improve the diagnosis accuracy of prostate cancer.