Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.

Objective:To investigate whether herb cake-insulated moxibustion affects the expression of cholesterol metabolism-related protein 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR)and inhibits the development of atherosclerosis by regulating the exosomal miR-223 expression.Methods:Thirty-six male New Zealand rabbits were randomly assigned to a normal group,a model group,and an herb cake-insulated moxibustion group,with 12 rabbits in each group.The model and the herb cake-insulated moxibustion groups were fed a high-fat diet for 8 weeks to induce an atherosclerosis model.Following successful modeling,the herb cake-insulated moxibustion group was subjected to bundling and herb cake-insulated moxibustion intervention,while the other two groups were subjected only to bundling without moxibustion.After 8 weeks of intervention,hematoxylin-eosin(HE)staining was used to observe aortic morphology;the serum levels of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-C)were detected using an automatic biochemical analyzer in each group.Exosome morphology was observed using the transmission electron microscope;Western blotting(WB)was used to detect the protein levels of serum exosomal CD63 and CD9 markers,as well as liver HMGR;additionally,real-time fluorescence quantitative polymerase chain reaction was used to quantify serum exosomal miR-223.Results:HE staining showed thickened aortic intima,lipid infiltration,foam cell aggregation,and structural damage to the arterial wall in the model group.Meanwhile,after modeling,the serum levels of LDL-C,TC,and TG increased significantly in the model and herb cake-insulated moxibustion groups compared to the normal group(P<0.05),suggesting successful atherosclerosis rabbit model preparation.The serum exosomes of rabbits in the model group exhibited a saucer-like or semi-concave spherical shape with diameters of 120-150 nm.WB detection results showed positive expression of the exosomal markers CD63 and CD9.After 8 weeks of intervention,the miR-223 level in the model group was significantly lower than that in the normal group(P<0.01).In contrast,the herb cake-insulated moxibustion group demonstrated significantly reduced serum levels of TC,TG,and LDL-C(P<0.05),increased miR-223 expression(P<0.01),and decreased relative liver HMGR protein expression(P<0.05)compared to the model group.Conclusion:Herb cake-insulated moxibustion may alleviate the progression of atherosclerosis by up-regulating exosomal miR-223 expression and down-regulating HMGR protein expression,thereby inhibiting cholesterol anabolic metabolism.

Objective:To investigate whether herb cake-insulated moxibustion affects the expression of cholesterol metabolism-related protein 3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGR)and inhibits the development of atherosclerosis by regulating the exosomal miR-223 expression.Methods:Thirty-six male New Zealand rabbits were randomly assigned to a normal group,a model group,and an herb cake-insulated moxibustion group,with 12 rabbits in each group.The model and the herb cake-insulated moxibustion groups were fed a high-fat diet for 8 weeks to induce an atherosclerosis model.Following successful modeling,the herb cake-insulated moxibustion group was subjected to bundling and herb cake-insulated moxibustion intervention,while the other two groups were subjected only to bundling without moxibustion.After 8 weeks of intervention,hematoxylin-eosin(HE)staining was used to observe aortic morphology;the serum levels of total cholesterol(TC),triglyceride(TG),and low-density lipoprotein cholesterol(LDL-C)were detected using an automatic biochemical analyzer in each group.Exosome morphology was observed using the transmission electron microscope;Western blotting(WB)was used to detect the protein levels of serum exosomal CD63 and CD9 markers,as well as liver HMGR;additionally,real-time fluorescence quantitative polymerase chain reaction was used to quantify serum exosomal miR-223.Results:HE staining showed thickened aortic intima,lipid infiltration,foam cell aggregation,and structural damage to the arterial wall in the model group.Meanwhile,after modeling,the serum levels of LDL-C,TC,and TG increased significantly in the model and herb cake-insulated moxibustion groups compared to the normal group(P<0.05),suggesting successful atherosclerosis rabbit model preparation.The serum exosomes of rabbits in the model group exhibited a saucer-like or semi-concave spherical shape with diameters of 120-150 nm.WB detection results showed positive expression of the exosomal markers CD63 and CD9.After 8 weeks of intervention,the miR-223 level in the model group was significantly lower than that in the normal group(P<0.01).In contrast,the herb cake-insulated moxibustion group demonstrated significantly reduced serum levels of TC,TG,and LDL-C(P<0.05),increased miR-223 expression(P<0.01),and decreased relative liver HMGR protein expression(P<0.05)compared to the model group.Conclusion:Herb cake-insulated moxibustion may alleviate the progression of atherosclerosis by up-regulating exosomal miR-223 expression and down-regulating HMGR protein expression,thereby inhibiting cholesterol anabolic metabolism.

Objective:To explore the efficacy and its related factors of rituximab (RTX) in the treatment of children with frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome (FRNS/SDNS).Methods:It was a single-center retrospective study. The clinical data of FRNS/SDNS children first treated with RTX in the First Affiliated Hospital of Sun Yat-sen University from November 1, 2016 to September 1, 2023 were collected. The number of relapse within 1 year before and after RTX treatment, the time to first relapse after RTX treatment, and the time to B-cell reconstitution were analyzed. At the first treatment, a single dose of RTX was given at 375 mg/m 2, with a maximum dose of 500 mg, once a week, for 1 to 4 doses. The count of CD19 + lymphocytes in the peripheral blood of the children was continuously monitored. If B-cell reconstruction was performed, the decision on whether to proceed to the next course of RTX treatment was made based on clinical manifestations. Kaplan-Meier method was used to analyze relapse-free survival rate after receiving RTX. Cox proportional hazards regression model was used to analyze the related factors of relapse after RTX treatment. Results:A total of 98 FRNS/SDNS children receiving RTX treatment were enrolled, including 75 males (76.5%). The age at onset was 4.0 (1.9, 7.1) years and age of receiving RTX was 11.3 (8.5, 13.5) years. There were 90 children (91.8%) achieving complete remission, while 8 patients (8.2%) did not respond to RTX treatment, and 3 patients (3.1%) progressed to end-stage kidney disease after receiving RTX. The relapse-free survival rates at 6 months and 1 year after RTX treatment were 83.3% (75/90) and 57.9% (22/38), respectively. The frequency of relapse 1 year after RTX treatment decreased compared to 1 year before RTX treatment ( Z=-7.398, P<0.001). Compared with children without relapse during the period of B-cell depletion, relapsed children had a higher number of relapse within one year after RTX treatment ( Z=5.246, P<0.001). The time to first relapse after RTX treatment was 8.3 (4.6, 13.9) months in 51 relapse patients. Compared with children receiving 1 dose of RTX in the first course, those receiving 2 or more doses had a longer time to the first relapse ( Z=2.983, P=0.003). There was no statistically significant difference in time to the first relapse between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). The reconstruction time of B cells after the first course of RTX was 6.9 (5.3, 9.0) months. Compared to children receiving one dose of RTX in the first course, those receiving two or more doses had a longer B-cell reconstitution time ( Z=2.739, P=0.006). There was no statistically significant difference in B-cell reconstitution time between children who received mycophenolate mofetil therapy after RTX treatment and those who didn't ( P>0.05). Univariate Cox regression analysis showed that recurrence after calcineurin inhibitor (CNI) treatment before RTX treatment and the number of recurrence in one year before RTX treatment were correlated factors of recurrence after RTX treatment (both P<0.05). Multivariate Cox regression analysis showed that recurrence after CNI treatment before RTX treatment was an independent correlated factor of relapse after RTX therapy ( HR=3.496, 95% CI 1.245-9.818, P=0.018). Infusion reactions occurred in 10 patients (10.2%) and infections were observed in 24 patients (24.5%) during B cell depletion. No serious adverse events occurred. Conclusions:RTX is well tolerated and effective in treating FRNS/SDNS. Recurrence after CNI treatment before RTX treatment may be an independent related factor of relapse after RTX treatment.

Objective: To investigate the effects of herbal cake-partitioned moxibustion on the plasma levels of trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and flavin-containing monooxygenase 3 (FMO3) in rabbits with atherosclerosis (AS), as well as to explore the possible mechanism of herbal cake-partitioned moxibustion in treating AS. Methods: After 1-week adaptive feeding, 28 male New Zealand rabbits were divided into a blank group, a model group, an antibiotic group, and a herbal cake-partitioned moxibustion group according to the random number table method, with 7 rabbits in each group. Rabbits were fed with a basic diet in the blank group, while with a basic diet plus 1％ choline in the remaining groups to prepare the AS model. Rabbits were given drinking water with broad-spectrum antibiotics in the antibiotic group, and herbal cake-partitioned moxibustion in the herbal cake-partitioned moxibustion group for 12 weeks. The atherosclerotic plaques by hematoxylin-eosin (HE) staining, the blood lipid levels, the plasma TMA and TMAO levels by liquid chromatography-mass spectrometry were detected for rabbits in each group at the end of interventions. Liver FMO3 protein expression was detected by Western blotting. Liver FMO3 mRNA expression was detected by real-time fluorescence quantitative polymerase chain reaction. Results: HE staining showed that the arterial wall was rough, the intima was significantly thickened, and more foam cells and lipid deposits were seen in rabbits of the model group. Arterial wall thickening was not obvious with a few foam cells and lipid deposits in the herbal cake-partitioned moxibustion group. Compared with the blank group, the serum levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) were increased (P<0.01), the plasma levels of TMA and TMAO were increased (P<0.05, P<0.01), and the expression levels of liver FMO3 protein and mRNA were all increased (P<0.05, P<0.01); while the serum high-density lipoprotein cholesterol (HDL-C) level was decreased in the model group (P<0.05). Compared with the model group, the LDL-C and TC levels were decreased (P<0.01 or P<0.05), the HDL-C levels were increased (P<0.01), the TMA and TMAO levels were decreased (P<0.05), while the protein and mRNA expression levels of FMO3 were decreased without statistical significance in the herbal cake-partitioned moxibustion group and the antibiotic group. Conclusion: Herbal cake-partitioned moxibustion can slow atherosclerotic plaque formation and regulate lipid levels in AS rabbits, and the mechanism may be related to the down-regulation of TMA and TMAO expression in the plasma.

Objective: To observe the efficacy of herbal cake-partitioned moxibustion for lumbar disc herniation (LDH) due to kidney deficiency and blood stasis and observe the influence of this method on lumbar functions and inflammatory factors in patients with this condition. Methods: A total of 120 LDH patients who met the inclusion criteria were randomly divided into three groups, including a herbal cake-partitioned moxibustion group, a flour cake-partitioned moxibustion group, and a Western medication group, with 40 patients in each group. The patients in the Western medication group were treated with diflunisal tablets, 0.5 g per dose, 2 doses a day. Those in the herbal cake-partitioned moxibustion group were treated with additional herbal cake-partitioned moxibustion group at Back-Shu Points and Jiaji (EX-B2) Points once a day. Those in the flour cake-partitioned moxibustion group were treated with the same methods as in the herbal cake-partitioned moxibustion group, except that the herbal cake was replaced by a flour cake. All the patients were treated for 10 d. After treatment, the scores of the visual analog scale (VAS) and Japanese Orthopaedic Association (JOA) and the changes of the interleukin (IL)-6, tumor necrosis factor (TNF)-α, and substance P (SP) levels were observed, and the efficacy was evaluated. Results: After treatment, the VAS score and the levels of IL-6, TNF-α, and SP were lower than those before treatment, and the JOA score was higher than that before treatment in the three groups, indicating intra-group statistical significance (P<0.05). The VAS score and the levels of IL-6, TNF-α, and SP of the herbal cake-partitioned moxibustion group were lower than those of the flour cake-partitioned moxibustion group and the Western medication group, while the JOA score of the herbal cake-partitioned moxibustion group was higher than that of the other two groups, indicating inter-group statistical significance (P<0.05). The total effective rate of the herbal cake-partitioned moxibustion group was 92.5％, higher than that of the flour cake-partitioned moxibustion group (80.0％) and the Western medication group (72.5％), indicating inter-group statistical significance (P<0.05). Conclusion: On the basis of Western oral medication, additional herbal cake-partitioned moxibustion can alleviate the pain and improve the lumbar functions in patients with LDH due to kidney deficiency and blood stasis. The efficacy of the integrated method is better than that of either flour cake-partitioned moxibustion or Western medication alone, which may be related to the reduction of serum inflammatory factors.

Objective:To observe the effect of electroacupuncture (EA) on the expression of erythropoie-tin-producing hepatocyte receptor B2 (EphB2) in the cortex around the infracted area of middle cerebral artery occlusion (MCAO) rats at different timing, and to reveal the possible mechanism of acupuncture in the treatment of cerebral ischemia.
Methods:A total of 180 male Sprague-Dawley (SD) rats were randomly divided into a sham operation group, a model group, an acupoint group and a non-acupoint group, with 45 rats in each group. Rats in each group were further divided into three subgroups: postoperative 3 d, postoperative 14 d and postoperative 21 d groups, with 15 rats in each subgroup. The MCAO model was made by the modified occlusion method. The neurological function score, 2,3,5-triphenyl tetrazolium chloride (TTC) staining, immunohistochemistry assay, immunofluorescence double labeling method and Western blot were used to detect the corresponding indicators.
Results:The neurological impairment of rats was most obvious at postoperative 3 d, and then gradually improved with time, which was more significant in the acupoint group (P<0.05). The change of infarcted volume was consistent with the neurological function impairment. The number of EphB2 positive cells (EphB2+) around the infarcted area was decreased significantly at postoperative 3 d, and then gradually improved with time, which returned to the same level as that in the sham operation group at postoperative 21 d. The increase was most significant in the acupoint group (P<0.05), and the positive cell number was higher than that in the sham operation group (P<0.01). Western blot and immunohistochemistry results were basically consistent. Immunofluorescence displayed that EphB2+ and postsynaptic density-95 positive (PSD-95+) were co-expressed, after the MCAO operation, in the cortical neuron around the infracted area, and the number of co-expressing cells was increased gradually with time, which was most significant in the acupoint group (P<0.05).
Conclusion:Electroacupuncture at Ganshu (BL 18) and Shenshu (BL 23) can significantly improve the neurological function and cerebral infarcted volume ratio of MCAO rats, which may be related to the activation of EphB2 expression in cortex around the infracted area and the promotion of synaptic remodeling.

Objective:To observe the clinical efficacy of warm needling moxibustion plus flash cupping for remission-stage peripheral facial paralysis (FP) due to wind-cold.
Methods:Fifty eligible patients were randomized into a warm needling moxibustion group and an acupuncture-cupping group, 25 cases in each group. The warm needling moxibustion group was intervened by acupuncture at Fengchi (GB 20), Yangbai (GB 14) towards Yuyao (EX-HN 4), Xiaguan (ST 7), Dicang (ST 4) towards Jiache (ST 6), Quanliao (SI 18), and Hegu (LI 4), plus warm needling moxibustion at Quanliao (SI 18); the acupuncture-cupping group received flash cupping on the affected side in addition to the intervention given to the warm needling moxibustion group. The two groups were both treated once a day, 10 times as a treatment course, for 3 courses in total. The House-Brackmann (H-B) facial nerve grading system was observed before and after the intervention to evaluate the facial nerve function in the two groups, and the therapeutic efficacies were also compared between the two groups.
Results:The two treatment protocols both can promote the recovery of facial nerve function. The total effective rate was 92.0% in the acupuncture-cupping group versus 72.0% in the warm needling moxibustion group, and the between-group difference was statistically significant (P<0.05).
Conclusion:Warm needling moxibustion plus flash cupping can produce a more significant efficacy than dry warm needling moxibustion in treating remission-stage peripheral FP due to wind-cold.

Objective: To investigate the protective effect of moxibustion in initiating the endogenous protection information on gastric mucosa, and its relationship with the pathway of common peroneal nerve.Methods: Forty-eight Sprague-Dawley (SD) rats were randomly divided into a normal group (group A), a model group (group B), a moxibustion model group (group C) and a moxibustion model plus surgery group (group D), 12 in each group. Except for group A, rats in the other groups were treated with dehydrated ethanol and aspirin to prepare gastric mucosal damage model. The rats in group B were not treated with any interventions; rats in group C received moxibustion at Zusanli (ST 36), twice a day for continuous 3 d. The rats in group D were subjected to preparing the gastric mucosal damage model after the common peroneal nerve transection, followed by moxibustion at Zusanli (ST 36). After a 3-day intervention, ulcer index (UI) in each group was observed, and the levels of gastric mucosa-related repair cytokines of tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4) and heat shock protein 70 (HSP70) were detected.Results: Compared with group A, the pathological changes and UI of group B were worse (P=0.000), but TNF-α in serum and tissue was changed significantly (P=0.000,P=0.002), IL-4 in serum and tissue was improved significantly (P=0.000, P=0.000). Compared with group B, TNF-α and IL-4 in group C and group D were significantly improved (TNF-α:P=0.003, P=0.016; IL-4:P=0.000,P=0.002). Compared with group C, the changes of UI in group B and group D were poor (both P=0.000); the levels of TNF-α and IL-4 in serum were significantly decreased (TNF-α:P=0.000,P=0.025; IL-4:P=0.000, P=0.034); and tissue HSP70 levels were decreased significantly (P=0.000,P=0.033).Conclusion: Zusanli (ST 36) can transmit information through the pathway of common peroneal nerve, regulate the release of gastric mucosal protective factors, and up-regulate the expression of cytothesis-related proteins, so as to achieve the effect in repairing gastric mucosa.

OBJECTIVETo compare the clinical efficacy differences among acupuncture combined with western medicine, acupuncture alone and western medicine alone for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

METHODSNinety patients were randomly assigned into a needle-medicine group, an acupuncture group and a western medicine group, 30 patients in each group. The patients in the needle-medicine group were treated with acupuncture combined with western medicine; the scalp points included Shenting (GV 24), Xinhui (GV 22), Qianding (GV 21), Baihui (GV 20), Chengguang (BL 6), Tongtian (BL 7), etc. The body points were Zhongji (CV 3), Guanyuan (CV 4), Pangguangshu (BL 28), Ciliao (BL 32), etc. The acupuncture was given 30 min per treatment, once a day. Besides, oral administration of 0.2g levofloxacin (twice per day) and 0.2 mg tamsulosin (once a day) was applied. The patients in the acupuncture group and western medicine group were treated by acupuncture and western medicine respectively. 12-d treatment was taken as one session, and totally 2 sessions were given. The clinical efficacy of the three groups after treatment was compared as well as the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) total score and pain score, self-rating anxiety scale (SAS) and self-rating depression scale (SDS) before and after treatment.

RESULTSDuring the trial two patients dropped out, as a result, 30 patients in the needle-medicine group, 29 patients in the acupuncture group and 29 patients in the western medicine group were included in the analysis. After treatment, 21 patients were cured, 6 patients were markedly effective, 2 patients were effective and 1 patient failed in the needle-medicine group;12 patients were cured, 10 patients were markedly effective, 5 patients were effective and 2 patients failed in the acupuncture group; 11 patients were cured, 12 patients were markedly effective, 4 patients were effective and 2 patients failed in the medicine group; the efficacy in the needle-medicine group was superior to those in the acupuncture group and medicine group (both<0.05). Each score was improved after treatment in each group (all<0.01); the total score of NIH-CPSI as well as SAS and SDS scores in the needle-medicine group were superior to those in the acupuncture group and medicine group (<0.05,<0.01); the pain scores of NIH-CPSI in needle-medicine group and acupuncture group were superior to that in the medicine group (<0.05,<0.01), but the difference between the needle-medicine group and acupuncture group was not significant (>0.05).

CONCLUSIONSThe efficacy of acupuncture combined with western medicine for CP/CPPS is superior to that of acupuncture alone and western medicine alone, which could improve the symptom of prostatitis as well as status of anxiety and depression.