BackgroundNegative symptoms of schizophrenia impose a substantial burden on society， and the current antipsychotic drugs have limited efficacy in treating these symptoms. Intermittent theta burst stimulation （iTBS）， as a novel neuromodulation technique， shows potential therapeutic promise. However， the evidence for its efficacy in treating negative symptoms of schizophrenia and its relationship with associated immuno-inflammatory changes remain to be further elucidated. ObjectiveTo investigate the efficacy of iTBS targeting the left dorsolateral prefrontal cortex （L-DLPFC） on persistent negative symptoms of schizophrenia， and to analyze its relationship with changes in peripheral blood inflammatory markers， so as to provide references for the clinical application of iTBS in treating persistent negative symptoms and to offer clues for further research into its potential biological mechanisms. MethodsA randomized， double-blind， sham-controlled clinical trial was conducted. A total of 60 patients with schizophrenia who were hospitalized at Xuzhou Oriental Peopple's Hospital from February 20， 2024 to May 10， 2025 were consecutively enrolled. All patients met the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5） and fulfilled the criteria for persistent negative symptoms. Participants were randomly assigned into the study group and the control group， with 30 patients in each group. The two groups respectively received 20 sessions of either active iTBS or sham stimulation over a 4-week period. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale （PANSS） at the baseline， the end of treatment， and 3 months after treatment. Peripheral blood inflammatory markers were measured at the baseline and at the end of treatment， including white blood cell count， platelet count， neutrophil count， lymphocyte count， and monocyte count， the neutrophil-to-lymphocyte ratio （NLR）， monocyte-to-lymphocyte ratio （MLR）， and platelet-to-lymphocyte ratio （PLR） were also calculated. A linear mixed model was used to compare PANSS scores between the two groups. Spearman correlation analysis was performed to examine the association between reductions in inflammatory markers at the end of treatment and reductions in PANSS negative symptom subscale scores， with body mass index （BMI） and chlorpromazine-equivalent dose as covariates. Results①The time-group interaction effect for the PANSS negative symptom subscale score was statistically significant （F=5.410， P<0.01）. At the end of treatment and 3 months after treatment， the study group had significantly lower scores on the PANSS negative symptom subscale than the control group （P<0.01）. ② At the end of treatment， group differences in reduction scores for neutrophil count， NLR， and PLR were significant （Z=-2.262， -2.048， -2.070， P<0.05）. However， after FDR correction， the between-group differences in reductions in peripheral blood inflammatory markers were no longer statistically significant （P>0.05）. ③ After adjusting for BMI and chlorpromazine equivalents， the reduction in PANSS negative symptom subscale scores was positively correlated with the reduction in neutrophil count in the study group （r_s=0.382， P=0.045）. ConclusioniTBS targeting the L-DLPFC may be beneficial in improving persistent negative symptoms of schizophrenia， and its clinical efficacy may be associated with changes in neutrophil count. ［Funded by National Natural Science Foundation of China （number， 82371510）； Social Development Project of Jiangsu Province （number， BE2023668）. www.chictr.org.cn number， ChiCTR2500101060］

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

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

The pathological process continues to evolve for a long time after acute phase of traumatic brain injury (TBI), often coupling with neurodegeneration and neurodegenerative complications. Microvascular dysfunction and blood-brain barrier (BBB) dysfunction caused by neurovascular unit (NVU) dysfunction are closely related to the pathological process of many neurodegenerative diseases. The study on the pathological mechanism of neurovascular unit dysfunction is a promising research field of TBI-related neurodegeneration, and also provides a new idea for the treatment of neurodegeneration after TBI. Therefore, this article mainly reviews these.

The pathological processes of neurodegeneration and neurodegenerative changes after traumatic brain injury (TBI) are closely related to microglia. The pathophysiological functions of microglia are closely correlated to their different cell subtypes. Disease-related microglia (DAM) are a special subtype of microglia, which recently discover on the lesions of degenerative diseases of the central nervous system. DAM are identified as important cells that induce neurodegeneration. The in-depth discussion of DAM role in pathological mechanism of neurodegeneration after TBI provides new clues for understanding and treating neurodegeneration after TBI; therefore, this article focuses on the above content and summarizes the research progress of DAM and neurodegeneration after TBI.

Objective: To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle. Methods: Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α(TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3. Results: Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05). Conclusions ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.

OBJECTIVE: To investigate the role of endoplasmic reticulum stress (ERS) in rats with acute respiratory distress syndrome (ARDS) related right ventricular dysfunction and the protective effect of sodium 4-phenylbutyrate (4-PBA) on right ventricle. METHODS: Sixty male Spragne-Dawley (SD) rats were randomly divided into control group (CON group), lipopolysaccharide (LPS) model group, 4-PBA prevention group and 4-PBA treatment group, with 15 rats in each group. ARDS rat model was established by intratracheal instillation of LPS 10 mg/kg after tracheotomy; CON group was given the same amount of saline. 4-PBA prevention group and 4-PBA treatment group were given 4-PBA 500 mg/kg intragastric administration 2 hours before and after LPS respectively. Echocardiography was performed 12 hours after treatment to evaluate the right ventricular function. Then, the rats were sacrificed by bloodletting, and the serum and right ventricular tissue were harvested. The histopathological changes of myocardial were observed by hematoxylin-eosin (HE) staining, the levels of tumor necrosis factor-α (TNF-α), interleukins (IL-1β and IL-6) in serum and myocardial were detected by enzyme linked immunosorbent assay (ELISA), and Western Blot was used to detect the expression of the marker proteins of ERS in myocardial, including glucose regulatory protein 78 (GRP78), C/EBP cyclic adenosine phosphate reaction primitive binding transcription factor homologous protein (CHOP), caspase-12 and caspase-3. RESULTS: Compared with the CON group, the echocardiography showed pulmonary artery maximum pressure gradient (PAmaxPG), pulmonary artery acceleration time (PAAT), tricuspid annular plane systolic excursion (TAPSE) in LPS model group were significantly decreased, and right ventricular end-diastolic excursion (RVDd) was significantly increased, and the levels of TNF-α, IL-1β and IL-6 in serum and myocardial, as well as the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly increased. Compared with LPS model group, TAPSE of 4-PBA preventive and treatment groups were significantly increased (mm: 3.08±0.65, 2.96±0.61 vs. 2.48±0.45), RVDd were significantly decreased (mm: 3.67±0.58, 3.60±0.61 vs. 4.18±0.71), the levels of TNF-α, IL-1β and IL-6 in serum and myocardial were significantly decreased [TNF-α (ng/L): 187.98±18.98, 176.08±17.98 vs. 332.00±19.90 in serum, 135.06±19.00, 132.78±17.00 vs. 155.00±20.00 in myocardial; IL-1β(ng/L): 12.07±2.98, 11.05±2.41 vs. 24.06±4.01 in serum, 19.89±2.80, 21.06±2.80 vs. 26.00±2.60 in myocardial; IL-6 (ng/L): 42.98±7.90, 34.05±6.09 vs. 89.80±10.07 in serum, 129.45±25.00, 127.08±26.06 vs. 145.77±23.00 in myocardial]; the expressions of GRP78, CHOP, caspase-12 and caspase-3 in myocardial were significantly decreased (GRP78/GAPDH: 0.090±0.070, 0.103±0.060 vs. 0.167±0.090, CHOP/GAPDH: 0.109±0.090, 0.090±0.080 vs. 0.186±0.090, caspase-12/GAPDH: 0.769±0.230, 0.799±0.210 vs. 1.040±0.350, caspase-3/GAPDH: 0.391±0.060, 0.401±0.054 vs. 0.603±0.340), with statistically significant differences (all P < 0.05). There were no significant differences in each indexes between 4-PBA prevention group and 4-PBA treatment group (all P > 0.05). CONCLUSIONS ERS is involved in ARDS-related right ventricular dysfunction. 4-PBA can protect the right ventricular function of ARDS rats by inhibiting ERS and alleviating inflammation, and the preventive and therapeutic effects of 4-PBA are similar.
Animals ; Antineoplastic Agents/therapeutic use* ; Endoplasmic Reticulum Stress ; Male ; Phenylbutyrates/therapeutic use* ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome ; Tumor Necrosis Factor-alpha ; Ventricular Dysfunction, Right

Objective To explore the effect of acute respiratory distress syndrome (ARDS) induced by endotoxin on the right ventricular function in rats. Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into normal saline (NS) control group and lipopolysaccharide (LPS) model group with 30 rats in each group. The rat model of ARDS was reproduced by intratracheal instillation of LPS 10 mg/kg after tracheotomy, and the rats in NS control group was intratracheally given the same volume of NS instead of LPS. The survival of rats in each group was observed. Right ventricular function was evaluated by echocardiography at 6 hours and 12 hours after instillation of LPS or NS respectively. Then the rats were sacrificed by bloodletting, and the right heart and lung tissue were harvested. The lung wet/dry weight (W/D) ratio was assessed. The pathological changes in cardiopulmonary tissue in rats were observed with hematoxylin and eosin (HE) strain, and the pathological score of lung injury was calculated. Results There was no animal death in NS control group. In LPS model group, there were 3 rats dead at 6 hours, and 4 dead at 12 hours. The pathological manifestations of lung injury were found at 6 hours after instillation of LPS, and the marked pathological changes of ARDS, such as atelectasis and hyaline membranes were observed at 12 hours. There was no obvious abnormality in the lung tissue of the NS control group. Compared with the NS control group, the 12-hour lung W/D ratio and the lung injury pathological score in the LPS model group were significantly increased (lung W/D ratio:7.69±1.02 vs. 4.14±0.48, lung injury pathological score: 8.26±2.12 vs. 1.32±0.94, both P < 0.01). Echocardiography showed that the right heart function of rats was significantly abnormal with the prolongation of LPS induction time, which showed that pulmonary arterial diameter (PAD) and right ventricular diastolic diameter (RVDd) were increased, maximum blood flow velocity of pulmonary artery (PAVmax), maximum pulmonary artery pressure gradient (PAmaxPG),pulmonary artery acceleration time (PAAT) and tricuspid annular plane systolic excursion (TAPSE) were decreased, with significant differences at 12 hours as compared with those of NS normal group [PAD (mm): 2.84±0.31 vs. 2.11±0.37, RVDd (mm): 4.18±0.71 vs. 3.17±0.40, PAVmax (mm/s): 704.00±145.13 vs. 809.59±120.48, PAmaxPG (mmHg, 1 mmHg = 0.133 kPa): 2.07±0.88 vs. 2.73±0.76, PAAT (ms): 23.80±4.87 vs. 30.01±3.02, TAPSE (mm): 2.48±0.45 vs. 3.56±0.40, all P < 0.01]. Pathological examination showed that the cardiac tissue in the LPS model group showed disorder of myocardial cells and scattered inflammatory cells at 6 hours, and cardiomyocyte degeneration, structural destruction and inflammatory cells were found at 12 hours. Conclusion ARDS induced by instillation of LPS at 12 hours causes right ventricular dysfunction in rats.

Objective: To explore therapeutic effect of modified constraint-induced movement therapy on rehabilitation in patients with stroke hemiplegia.Methods: A total of 136 patients with stroke hemiplegia were selected and divided into routine rehabilitation group and modified rehabilitation group.After 12 weeks, scores of Fugal-Meyer motor assessment (FMA), modified Barthel index (MBI) and Berg balance scale (BBS), 6min walking distance (6MWD), psychological state and quality of life (QOL) were compared between two groups.Results: After 12 weeks, there were significant rise in scores of FMA, MBI and BBS and 6MWD, and significant reductions in scores of self-rating anxiety scale (SAS) and self-rating depression scale (SDS) in two groups, P<0.05 all.Compared with routine rehabilitation group, there were significant rise in scores of FMA [(53.23±5.13) scores vs.(60.67±5.67) scores], MBI [(57.83±6.11) scores vs.(69.93±6.74) scores] and BBS [(41.45±4.12) scores vs.(50.53±4.56) scores] and 6MWD [(179.46±24.62)m vs.(211.34±26.71)m], and significant reductions in scores of SAS [(50.75±2.56) scores vs.(41.11±1.53) scores] and SDS [(51.34±3.35) scores vs.(40.78±2.11) scores] in modified rehabilitation group, P<0.05 all.Compared with before rehabilitation, there were significant rise in physiological, psychological, social and setting dimension scores in both groups after rehabilitation, and those of modified rehabilitation group were significantly higher than those of routine rehabilitation group, P<0.05 all.Conclusion:Modified constraint-induced movement therapy can significantly improve movement, balance function, and anxiety, depression and daily living capacities in patients with stroke hemiplegia.

Objective To investigate the clinical effects and complications of uterine artery embolization (UAE) therapy using different embolic agents in treating uterine adenomyosis. Methods During 2004—2011, a total of 45 female patients with uterine adenomyosis were admmitted to authors’ hospital to receive uterine artery embolization therapy. The embolic agents used in the procedures included domestic iodized oil, sodium alginate microspheres and Embosphere microspheres. The patients were randomly divided into group A (n=15, using domestic iodized oil as embolic agent), Group B (n=13, using sodium alginate microspheres as embolic agent) and group C (n = 17, using Embosphere microspheres as embolic agent). After the treatment, all the patients were followed up for over 2 years, focusing on the observation of the clinical symptoms such dysmenorrheal, changes of MRI signs and severe complications. The results were analyzed and compared among the three groups. Results After UAE, the clinical symptoms such as the degree of dysmenorrhea, menstrual quantity, etc. were improved in all patients. Six months after UAE, the obvious remission rate of dysmenorrheal in group A, B and C was 33.3% (5/15), 30.8% (4/13) and 41.1%(7/17) respectively. Twelve months after UAE, MRI scanning showed that the uterine sizes in group A, B and C were reduced to 49.19%, 48.25% and 50.05% respectively. Follow-up examination at 24 months after UAE showed that recurrence of dysmenorrheal in group A, B and C was seen in 2, 4 and 2 cases respectively, and amenorrhea was seen in 2 cases of group A and one case in group C. Conclusion The use of domestic iodized oil, sodium alginate microspheres or Embosphere microspheres as embolic agents in performing super-selective uterine artery embolization for adenomyosis can effectively relieve the degree of dysmenorrheal, decrease the uterine size. In addition to ovarian dysfunction, the uterine cavity adhesion may be also a possible cause of amenorrhea occurring after UAE may. In order to ensure a similar clinical efficacy, the use of granular solid embolic agent is preferred as its safety is possibly higher than the liquid embolic agents.