Objective To explore the effects of Shenyuan Yiqi Huoxue Capsules on cardiopulmonary exercise function and quality of life in patients with ischemic cardiomyopathy.Methods Totally 66 patients with ischemic cardiomyopathy were divided into treatment group and control group using random number table method,with 33 cases in each group.Both groups received standardized Western medicine treatment,and the treatment group was additionally given Shenyuan Yiqi Huoxue Capsules,the control group was given Shenyuan Yiqi Huoxue Capsules simulator,three capsules per time,three times a day,orally.The observation period was 30 days.To evaluate the efficacy of TCM syndrome in two groups.The observation indicators included baseline data,TCM syndrome scores,cardiopulmonary exercise test detection indicators,MLHFQ score,SF-36 score,echocardiographic indicators,N-terminal pro-B-type natriuretic peptide(NT-pro BNP)and safety indicators.Results The total effective rate of the treatment group was 93.94%(31/33),while that of the control group was 78.79%(26/33).The treatment group was significantly better than the control group(P<0.05).Compared with before treatment,the TCM syndrome scores of the two groups of patients decreased(P<0.05),and after treatment,the TCM syndrome score of the treatment group was lower than that of the control group(P<0.05).Compared with before treatment,the peak oxygen uptake(peak VO2),anaerobic threshold(AT)and peak oxygen pulse(peak O2 pulse)of both groups of patients increased,while the carbon dioxide ventilation equivalent slope(VE/VCO2 slope)decreased(P<0.05).After treatment,the treatment group had higher peak VO2,AT and peak O2 pulse than the control group,while the VE/VCO2 slope was lower than the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in MLHFQ score and an increase in SF-36 score(P<0.05);after treatment,the MLHFQ score in the treatment group was lower than that in the control group,and the SF-36 score was higher than that in the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05);after treatment,the treatment group showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05).During the treatment period,no adverse reactions such as dizziness,nausea,vomiting or diarrhea were found in both groups of patients.Conclusion Shenyuan Yiqi Huoxue Capsules can significantly improve the clinical efficacy of ischemic cardiomyopathy patients,alleviate TCM symptoms,improve their cardiorespiratory function and quality of life.

Objective:To explore the expression changes of N6-methyladenosine (m6A)-related proteins in the hippocampus of mice with post traumatic stress disorder (PTSD)-like behavior and the therapeutic effects of sertraline hydrochloride.Methods:Male C57BL/6J mice aged 4-6 weeks were selected to establish a PTSD model using a single prolonged stress and foot shock stimulation. A total of 24 mice were randomly divided into the control group, model group, and sertraline group using a random number table, with 8 mice in each group. Mice in the sertraline group were intraperitoneally injected with sertraline hydrochloride (15 mg/kg, once daily) 24 h after PTSD modelling, continuing for 14 days. Mice in the control group and model group were injected with an equal volume of 0.9% NaCl solution (once daily, for 14 days). The anxiety, despair, and learning and memory functions of the mice were assessed using the open field test, Y-maze test, and forced swimming test. Western blot was performed to measure the protein expression levels of methyltransferase-like protein 3 (METTL3), fat mass and obesity-associated gene (FTO), ALKB homolog 5 (ALKBH5), Wilms tumour 1 associating protein (WTAP), and methyltransferase-like protein 14 (METTL14) in the hippocampus. Immunofluorescence was used to detect the expression levels of METTL3, FTO, and ALKBH5 in the hippocampus. Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 9.0.Comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way analysis of variance (ANOVA) or Kruskal-Wallis H test, followed by pairwise comparisons using LSD test. Results:(1) Behavioral results showed that the total distance travelled in the central area ( F=9.231, P<0.05) and the time spent in the central area ( H=8.045, P<0.05) showed statistically significant differences among the control, model, and sertraline groups. Mice in the control and sertraline groups travelled a greater distance((332.68±121.17)cm, (248.56±40.21)cm) and spent more time(24.98(23.08, 26.71)s, 22.52(18.86, 26.20)s) in the central area than those in the model group((131.66±84.90)cm, 9.14(6.56, 18.53)s) (all P<0.05). In the forced swimming test, the number of resting episodes ( F=16.882, P<0.05) and the duration of rest ( H=12.285, P<0.05) differed significantly among the three groups. Mice in the control group ((19.14±8.30) counts, 30.21 (18.98, 52.62) s) and the sertraline group ((17.63±8.14) counts, 25.90 (16.78, 37.56) s) had fewer resting episodes and shorter resting durations compared to those in the model group ((37.75±6.47) counts, 83.37 (64.62, 124.42) s) (all P<0.05). The percentage of alternations in the Y-maze experiment showed significant statistical differences among the three groups( F=6.844, P<0.05). Mice in the control group ((51.33±11.49)%) and the sertraline group ((48.24±3.10)%) exhibited a higher percentage of alternations than that in the model group ((36.70±8.15)%) ( P<0.05). (2) Western blot results showed that the protein expression levels of METTL3, FTO, and ALKBH5 in the hippocampal tissue of the three groups showed significant differences ( F=10.263, 9.010, 6.950, all P<0.05). The METTL3 and FTO protein expression levels in the hippocampus in the control group (0.85±0.07, 0.86±0.04) and the sertraline group (0.93±0.06, 0.95±0.13) were higher than those in the model group (0.74±0.02, 0.68±0.04) (all P<0.05). However, the ALKBH5 protein expression levels in the control group (0.93±0.08) and the sertraline group (0.87±0.13) were lower than that in the model group (1.13±0.04) (both P<0.05). (3) Immunofluorescence results showed that the expression levels of METTL3, FTO, and ALKBH5 proteins in the hippocampal tissue of the three groups showed significant statistical differences ( F=37.912, 62.659, 54.417, all P<0.05). The expression levels of METTL3 and FTO in the hippocampus in the control group (14.03±0.32, 13.85±0.28) and the sertraline group (17.94±0.29, 10.52±0.66) were higher than those in the model group (11.67±1.48, 8.70±0.68) (all P<0.05). The expression levels of ALKBH5 in the control group (12.94±0.38) and the sertraline group (13.30±0.93) were lower than that in the model group (19.24±1.03) (both P<0.05). Conclusion:The expression of m6A-related proteins in the hippocampus of PTSD-like mice is altered. Sertraline treatment can significantly regulate the expression of these proteins and improve anxiety, despair, and learning and memory impairments in the PTSD-like mice.

Objective:To explore the expression changes of N6-methyladenosine (m6A)-related proteins in the hippocampus of mice with post traumatic stress disorder (PTSD)-like behavior and the therapeutic effects of sertraline hydrochloride.Methods:Male C57BL/6J mice aged 4-6 weeks were selected to establish a PTSD model using a single prolonged stress and foot shock stimulation. A total of 24 mice were randomly divided into the control group, model group, and sertraline group using a random number table, with 8 mice in each group. Mice in the sertraline group were intraperitoneally injected with sertraline hydrochloride (15 mg/kg, once daily) 24 h after PTSD modelling, continuing for 14 days. Mice in the control group and model group were injected with an equal volume of 0.9% NaCl solution (once daily, for 14 days). The anxiety, despair, and learning and memory functions of the mice were assessed using the open field test, Y-maze test, and forced swimming test. Western blot was performed to measure the protein expression levels of methyltransferase-like protein 3 (METTL3), fat mass and obesity-associated gene (FTO), ALKB homolog 5 (ALKBH5), Wilms tumour 1 associating protein (WTAP), and methyltransferase-like protein 14 (METTL14) in the hippocampus. Immunofluorescence was used to detect the expression levels of METTL3, FTO, and ALKBH5 in the hippocampus. Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 9.0.Comparisons between two groups were conducted using independent samples t-test, while comparisons among three groups were performed using one-way analysis of variance (ANOVA) or Kruskal-Wallis H test, followed by pairwise comparisons using LSD test. Results:(1) Behavioral results showed that the total distance travelled in the central area ( F=9.231, P<0.05) and the time spent in the central area ( H=8.045, P<0.05) showed statistically significant differences among the control, model, and sertraline groups. Mice in the control and sertraline groups travelled a greater distance((332.68±121.17)cm, (248.56±40.21)cm) and spent more time(24.98(23.08, 26.71)s, 22.52(18.86, 26.20)s) in the central area than those in the model group((131.66±84.90)cm, 9.14(6.56, 18.53)s) (all P<0.05). In the forced swimming test, the number of resting episodes ( F=16.882, P<0.05) and the duration of rest ( H=12.285, P<0.05) differed significantly among the three groups. Mice in the control group ((19.14±8.30) counts, 30.21 (18.98, 52.62) s) and the sertraline group ((17.63±8.14) counts, 25.90 (16.78, 37.56) s) had fewer resting episodes and shorter resting durations compared to those in the model group ((37.75±6.47) counts, 83.37 (64.62, 124.42) s) (all P<0.05). The percentage of alternations in the Y-maze experiment showed significant statistical differences among the three groups( F=6.844, P<0.05). Mice in the control group ((51.33±11.49)%) and the sertraline group ((48.24±3.10)%) exhibited a higher percentage of alternations than that in the model group ((36.70±8.15)%) ( P<0.05). (2) Western blot results showed that the protein expression levels of METTL3, FTO, and ALKBH5 in the hippocampal tissue of the three groups showed significant differences ( F=10.263, 9.010, 6.950, all P<0.05). The METTL3 and FTO protein expression levels in the hippocampus in the control group (0.85±0.07, 0.86±0.04) and the sertraline group (0.93±0.06, 0.95±0.13) were higher than those in the model group (0.74±0.02, 0.68±0.04) (all P<0.05). However, the ALKBH5 protein expression levels in the control group (0.93±0.08) and the sertraline group (0.87±0.13) were lower than that in the model group (1.13±0.04) (both P<0.05). (3) Immunofluorescence results showed that the expression levels of METTL3, FTO, and ALKBH5 proteins in the hippocampal tissue of the three groups showed significant statistical differences ( F=37.912, 62.659, 54.417, all P<0.05). The expression levels of METTL3 and FTO in the hippocampus in the control group (14.03±0.32, 13.85±0.28) and the sertraline group (17.94±0.29, 10.52±0.66) were higher than those in the model group (11.67±1.48, 8.70±0.68) (all P<0.05). The expression levels of ALKBH5 in the control group (12.94±0.38) and the sertraline group (13.30±0.93) were lower than that in the model group (19.24±1.03) (both P<0.05). Conclusion:The expression of m6A-related proteins in the hippocampus of PTSD-like mice is altered. Sertraline treatment can significantly regulate the expression of these proteins and improve anxiety, despair, and learning and memory impairments in the PTSD-like mice.

Objective:To explore changes in brain activity in patients with post-traumatic stress disorder(PTSD).Methods:A total of 40 participants involved in car accidents were included,and functional magnetic reso-nance imaging(fMRI)scans were collected within one week.Anxiety,depression,and personality assessments were conducted with the Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),and Eysenck Person-ality Scale for Adult(EPQ).After two months,a second fMRI scan was conducted,and a PTSD diagnosis was made.Participants were divided into a trauma-exposed group(n=23)and a PTSD group(n=17)based on wheth-er they developed PTSD.Changes in brain functional activity between the trauma-exposed group and the PTSD group were compared using the percentage of amplitude fluctuation(perAF)method.Results:Compared to the trauma-exposed group,the PTSD group showed a decreased perAF value in the left hippocampus at 1 week,and de-creased perAF values in the right mid-cingulate gyrus and left postcentral gyrus at 2 months(P＜0.05).When comparing the PTSD group at different times,the perAF values in the left middle temporal gyrus and left medial su-perior frontal gyrus decreased at 2 months(P＜0.05).Correlation analysis revealed that PCL-5 scores were posi-tively correlated with EPQ Psychoticism(r=0.32,P=0.041),HAMA(r=0.35,P＜0.05),and HAMD(r=0.34,P＜0.05).Regression analysis found that higher scores of EPQ psychoticism(OR=11.79)and HAMA(OR=1.62)were risk factors for post-accident PTSD,while higher scores of EPQ extraversion(OR=0.32)were pro-tective factors.Conclusion:It suggests that patients with post-traumatic stress disorder may show decreased activity in the right middle cingulate cortex,left postcentral gyrus,left middle temporal gyrus,and left medial superior fron-tal gyrus within two months after the traumatic event.

Objective To explore the effects of Shenyuan Yiqi Huoxue Capsules on cardiopulmonary exercise function and quality of life in patients with ischemic cardiomyopathy.Methods Totally 66 patients with ischemic cardiomyopathy were divided into treatment group and control group using random number table method,with 33 cases in each group.Both groups received standardized Western medicine treatment,and the treatment group was additionally given Shenyuan Yiqi Huoxue Capsules,the control group was given Shenyuan Yiqi Huoxue Capsules simulator,three capsules per time,three times a day,orally.The observation period was 30 days.To evaluate the efficacy of TCM syndrome in two groups.The observation indicators included baseline data,TCM syndrome scores,cardiopulmonary exercise test detection indicators,MLHFQ score,SF-36 score,echocardiographic indicators,N-terminal pro-B-type natriuretic peptide(NT-pro BNP)and safety indicators.Results The total effective rate of the treatment group was 93.94%(31/33),while that of the control group was 78.79%(26/33).The treatment group was significantly better than the control group(P<0.05).Compared with before treatment,the TCM syndrome scores of the two groups of patients decreased(P<0.05),and after treatment,the TCM syndrome score of the treatment group was lower than that of the control group(P<0.05).Compared with before treatment,the peak oxygen uptake(peak VO2),anaerobic threshold(AT)and peak oxygen pulse(peak O2 pulse)of both groups of patients increased,while the carbon dioxide ventilation equivalent slope(VE/VCO2 slope)decreased(P<0.05).After treatment,the treatment group had higher peak VO2,AT and peak O2 pulse than the control group,while the VE/VCO2 slope was lower than the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in MLHFQ score and an increase in SF-36 score(P<0.05);after treatment,the MLHFQ score in the treatment group was lower than that in the control group,and the SF-36 score was higher than that in the control group(P<0.05).Compared with before treatment,both groups of patients showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05);after treatment,the treatment group showed a decrease in left ventricular end systolic diameter,left ventricular end diastolic diameter and NT-pro BNP levels,while myocardial motion index and left ventricular ejection fraction increased(P<0.05).During the treatment period,no adverse reactions such as dizziness,nausea,vomiting or diarrhea were found in both groups of patients.Conclusion Shenyuan Yiqi Huoxue Capsules can significantly improve the clinical efficacy of ischemic cardiomyopathy patients,alleviate TCM symptoms,improve their cardiorespiratory function and quality of life.

Objective:To explore changes in brain activity in patients with post-traumatic stress disorder(PTSD).Methods:A total of 40 participants involved in car accidents were included,and functional magnetic reso-nance imaging(fMRI)scans were collected within one week.Anxiety,depression,and personality assessments were conducted with the Hamilton Anxiety Scale(HAMA),Hamilton Depression Scale(HAMD),and Eysenck Person-ality Scale for Adult(EPQ).After two months,a second fMRI scan was conducted,and a PTSD diagnosis was made.Participants were divided into a trauma-exposed group(n=23)and a PTSD group(n=17)based on wheth-er they developed PTSD.Changes in brain functional activity between the trauma-exposed group and the PTSD group were compared using the percentage of amplitude fluctuation(perAF)method.Results:Compared to the trauma-exposed group,the PTSD group showed a decreased perAF value in the left hippocampus at 1 week,and de-creased perAF values in the right mid-cingulate gyrus and left postcentral gyrus at 2 months(P＜0.05).When comparing the PTSD group at different times,the perAF values in the left middle temporal gyrus and left medial su-perior frontal gyrus decreased at 2 months(P＜0.05).Correlation analysis revealed that PCL-5 scores were posi-tively correlated with EPQ Psychoticism(r=0.32,P=0.041),HAMA(r=0.35,P＜0.05),and HAMD(r=0.34,P＜0.05).Regression analysis found that higher scores of EPQ psychoticism(OR=11.79)and HAMA(OR=1.62)were risk factors for post-accident PTSD,while higher scores of EPQ extraversion(OR=0.32)were pro-tective factors.Conclusion:It suggests that patients with post-traumatic stress disorder may show decreased activity in the right middle cingulate cortex,left postcentral gyrus,left middle temporal gyrus,and left medial superior fron-tal gyrus within two months after the traumatic event.

Objective:To explore the expression of NLRP3 inflammatory vesicles in hippocampal tissue and prefron-tal cortex in a mouse model of posttraumatic stress disorder(PTSD).Methods:Male C57BL/6J mice were randomly divided into 2 groups:the control group and the PTSD group.The PTSD group used conditioned foot shock(CF)and single-sustained stress(SPS)to prepare an animal model of PTSD.Anxiety and depression responses of the mouse mod-el were detected by the open field experiment and elevated cross maze test.Memory and memory capacity tests were es-tablished by the darkness-avoidance experimental system.Morphological changes in the hippocampus and prefrontal cor-tex of mice were observed by hematoxylin-eosin staining(HE),and the expression of NLRP3 inflammatory vesicles was detected using Western Blot and immunohistochemical staining.Results:The PTSD mouse group showed decreased body mass,anxiety and depression-like behaviors,and decreased learning and memory abilities compared with the con-trol group(P＜0.05).HE staining showed tissue damage in the hippocampal CA1 region and prefrontal cortex in PTSD mice compared with the control group.Western Blot and immunohistochemical staining showed that after 3 d of PTSD stimulation,hippocampal and prefrontal cortical NLRP3 inflammatory vesicles were activated(P＜0.05).Conclusion:Increased expression of NLRP3 inflammatory vesicles in the hippocampus and prefrontal cortex of PTSD model mice.

Objective　To understand the impact of early and timely treatment and initial antiviral treatment regimen on mortality and attrition of antiretroviral therapy. Methods A retrospective cohort study was conducted using download data on antiretroviral therapy for HIV-infected patients in Liuzhou City, Guangxi Province, from the database of the Basic Information System for AIDS Control and Prevention (BISAC) from 2010 to 2020. The Cox proportional risk regression model was used to analyze the influencing factors of mortality and attrition. Results A total of 15 713 infected patients were included, including 53.4% aged 18-<50 years, 69.4% male, 61.0% farmer, 75.1% CD4 count <350 cells /μL before initial antiviral treatment, the overall mortality rate was 4.30/100 person-years, and the overall attrition was 2.42/100 person-years. The results of Cox regression analysis showed that the influencing factors of mortality were pretreatment CD4 counts of 350-<500 cells/μL(AHR=0.72, 95%CI: 0.63-0.81) and ≥500 cells/μL (AHR= 0.64, 95%CI: 0.55-0.76); duration from diagnosis to initial antiviral treatment 91-180 days (AHR=1.25, 95%CI: 1.08-1.45), 181-365 days (AHR=1.26, 95%CI: 1.08-1.47), and ≥365 days (AHR=1.26, 95%CI: 1.11-1.44); initial antiviral treatment regimens of D4T+3TC+EFV/NVP (AHR=1.47, 95%CI: 1.32-1.63) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.73, 95%CI: 1.50-1.99). Factors affecting attrition were pretreatment CD4 counts of 350-499 cells/μL (AHR=1.32, 95%CI: 1.16-1.50) and ≥500 cells/μL (AHR=1.28, 95%CI: 1.10-1.50); interval from HIV positivity confirmation to initial dosing ≥365 days (AHR=1.21, 95%CI: 1.04-1.40), initial antiviral treatment regimens of TDF+3TC+NVP (AHR=1.32, 95%CI: 1.13-1.55), AZT+3TC+EFV/NVP (AHR=1.43, 95%CI: 1.26-1.62) and AZT/D4T/TDF+3TC+LPV/r (AHR=1.33, 95CI%: 1.06-1.67). Conclusions　Early and timely treatment and the initial antiviral treatment regimen of TDF+3TC+EFV have good efficacy, but attention should be paid to the high risk of attrition of HIV-infected people with high CD4 count before treatment.

Background::Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods::Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses.Results::In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V 100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V 100% relative percentages of all scans was 99.60% ± 1.18%. The median V 29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion::UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR–based dosimetry analysis.Clinical trial registration::Chinese Clinical Trial Registry ChiCTR2000033382.

Background::Magnetic resonance (MR)-guided ultra-hypofractionated radiotherapy with whole-pelvic irradiation (UHF-WPRT) is a novel approach to radiotherapy for patients with high-risk (HR) and very high-risk (VHR) prostate cancer (PCa). However, the inherent complexity of adaptive UHF-WPRT might inevitably result in longer on-couch time. We aimed to estimate the delivered dose, study the feasibility and safety of adaptive UHF-WPRT on a 1.5-Tesla MR-Linac.Methods::Ten patients with clinical stage T3a-4N0-1M0-1c PCa, who consecutively received UHF-WPRT, were enrolled prospectively. The contours of the target and organ-at-risks on the position verification-MR (PV-MR), beam-on 3D-MR(Bn-MR), and post-MR (after radiotherapy delivery) were derived from the pre-MR data by deformable image registration. The physician then manually adjusted them, and dose recalculation was performed accordingly. GraphPad Prism 9 (GraphPad Prism Software Inc.) was utilized for conducting statistical analyses.Results::In total, we collected 188 MR scans (50 pre-MR, 50 PV-MR, 44 Bn-MR, and 44 post-MR scans). With median 59 min, the mean prostate clinical target volume (CTV)-V 100% was 98.59% ± 2.74%, and the mean pelvic CTVp-V 100% relative percentages of all scans was 99.60% ± 1.18%. The median V 29 Gy change in the rectal wall was -2% (-18% to 20%). With a median follow-up of 9 months, no patient had acute Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or more severe genitourinary (GU) or gastrointestinal (GI) toxicities (0%). Conclusion::UHF-RT to the prostate and the whole pelvis with concomitant boost to positive nodes using an Adapt-To-Shape (ATS) workflow was technically feasible for patients with HR and VHR PCa, presenting only mild GU and GI toxicities. The estimated target dose during the beam-on phase was clinically acceptable based on the 3D-MR–based dosimetry analysis.Clinical trial registration::Chinese Clinical Trial Registry ChiCTR2000033382.