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.

AIM: To compare the efficacy of intravitreal injection of ranibizumab(IVR)and intravitreal injection of conbercept(IVC)in children with retinopathy of prematurity(ROP).METHODS: Retrospective study. A total of 1 100 eyes with ROP treated with intravitreal anti-VEGF at our hospital from January 2015 to June 2023 were included. According to the different therapeutic drugs, the children were divided into two groups: IVR group and IVC group. According to the degree of ROP, the patients were divided into three groups: aggressive ROP(A-ROP), Zone Ⅰ type 1 ROP and Zone Ⅱ type 1 ROP. The reactivation and retreatment between the two groups were compared after propensity score matching(PSM)analysis, and they were followed-up for at least 3 mo after surgery.RESULTS: In Zone Ⅱ type 1 ROP, there was a statistically significant difference in the rates of reactivation and retreatment between the IVR and IVC groups(P<0.05); however, in A-ROP and Zone I type 1 ROP, there were no statistically significant differences in the rates of reactivation and retreatment between the two groups(P>0.05). The risk of reactivation and retreatment of Zone I type 1 ROP was higher than the Zone II type 1 ROP. Furthermore, the use of drugs and corrected gestational age of first treatment were influencing factors of lesion recurrence and retreatment.CONCLUSION: There is a significant difference in the initial cure effect between the two drugs in Zone II type 1 ROP, with the reactivation and retreatment rates of the IVC group being much lower than those of the IVR group.

Objective:To investigate the role and underlying mechanisms of methyltransferase (Mettl) 3 in the process of angiotensin Ⅱ (Ang Ⅱ)-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis.Methods:C57BL/6J mice were used, in cell experiments, mouse renal pericytes were isolated and cultured using magnetic bead sorting. These pericytes were then induced to transdifferentiate into myofibroblasts with 1×10 6 mmol/L Ang Ⅱ, which was the Ang Ⅱ group, while pericytes cultured in normal conditions served as the control group. Successful transdifferentiation was verified by immunofluorescence staining, Western blotting, and real-time reverse transcription PCR (RT-qPCR) for α-smooth muscle actin (α-SMA). The levels of m6A modifications and related enzymes (Mettl3, Mettl14), Wilms tumor 1-associated protein (WTAP), fat mass and obesity protein (FTO), ALKBH5, YTHDF1, YTHDF2, YTHDC1, YTHDC2, YTHDC3 were assessed by Dot blot, RT-qPCR and Western blot. Mettl3 expression was inhibited in cells using lentivirus-mediated Mettl3-shRNA transfection, creating sh-Mettl3 and Ang Ⅱ+sh-Mettl3 groups, while lentivirus empty vector transfection served as the negative control (Ang Ⅱ+sh-NC group). The impact of Ang Ⅱ on pericyte transdifferentiation was observed, and the expression of downstream phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway proteins, including PI3K, AKT, phosphorylated AKT at serine 473 (p-AKT (S473)), and phosphorylated AKT at threonine 308 (p-AKT (T308)), were examined. PI3K gene transcription was inhibited by co-culturing cells with actinomycin D, and the half-life of PI3K mRNA was calculated by measuring residual PI3K mRNA expression over different co-culture time. The reversibility of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was assessed by adding the AKT activator SC79 to the Ang Ⅱ+sh-Mettl3 group. In animal experiments, mice were divided into these groups: sham group (administered 0.9% sterile saline), Ang Ⅱ group (infused with Ang Ⅱ solution), sh-Mettl3 group (injected with Mettl3 shRNA lentivirus solution), Ang Ⅱ+sh-Mettl3 group (infused with Ang Ⅱ solution and injected with Mettl3 shRNA lentivirus solution), and Ang Ⅱ+sh-Mettl3+SC79 group (administered Ang Ⅱ solution and Mettl3 shRNA lentivirus, with an additional injection of SC79). Each group consisted of six subject mice. Blood pressure was measured using the tail-cuff method before and after surgery, and serum creatinine, urea, and urinary albumin levels were determined 4 weeks post-surgery. Kidney tissues were collected at 28 days and stained using hematoxylin-eosin (HE) and Masson′s trichrome to assess the extent of renal fibrosis. Results:Primary renal pericytes were successfully obtained by magnetic bead sorting, and intervened with 1×10 6 mmol/L Ang Ⅱ for 48 hours to induce pericyte-to-myofibroblast transdifferentiation. Dot blot results indicated higher m6A modification levels in the Ang Ⅱ group compared to the control group ( P<0.05). RT-qPCR and Western blot results showed upregulation of Mettl3 mRNA and protein levels in the Ang Ⅱ group compared to the control group (both P<0.05). In the Ang Ⅱ+sh-Mettl3 group, Mettl3 protein expression was lower than that in the Ang Ⅱ group, with reduced expression levels of α-SMA, vimentin, desmin, fibroblast agonist protein (FAPa) and type Ⅰ collagen (all P<0.05). Compared to the control group, PI3K mRNA expression level was elevated in the Ang Ⅱ group, along with increased p-AKT (S473) and p-AKT (T308) expressions. In the Ang Ⅱ+sh-Mettl3 group, PI3K mRNA expression and p-AKT (S473) and p-AKT (T308) levels were decreased (all P<0.05). The half-life of PI3K mRNA was shorter in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ+sh-NC group (2.34 h vs. 3.42 h). The ameliorative effect of Mettl3 inhibition on Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation was reversible by SC79. Animal experiments showed higher blood pressure, serum creatinine, urea, and 24-hour urinary protein levels, and a larger fibrosis area in the Ang Ⅱ group compared to the sham group (all P<0.05). The fibrosis area was smaller in the Ang Ⅱ+sh-Mettl3 group than that in the Ang Ⅱ group ( P<0.05), but increased again upon addition of SC79. Conclusion:Mettl3-mediated RNA m6A epigenetic regulation is involved in Ang Ⅱ-induced pericyte-to-myofibroblast transdifferentiation and renal fibrosis, potentially by affecting PI3K stability and regulating the PI3K/AKT signaling pathway.

BACKGROUND: Hyaluronan-methylcellulose hydrogel cannot only be conjugated with short peptide sequences and growth factors to achieve sustained release, but also has a role in blocking dural defects and reducing inflammation. It is an ideal biomaterial for the treatment of spinal cord injury. OBJECTIVE: To investigate the effect of neurotrophin-3 modified hyaluronan-methylcellulose (HAMC-NT-3) hydrogel on the recovery of neurological function in rats with spinal cord injury. METHODS: Fifty-four female Sprague-Dawley rats (provided by the Experimental Animal Center of the Academy of Military Medical Sciences in China) were randomly divided into three groups (n=18 per group) . The sham group only underwent T10 laminectomy. In the model group and the experimental group, an aneurysm clip was used to establish spinal cord injury models after T10 laminectomy. The experimental group was locally injected with HAMC-NT-3 hydrogel. The Basso Beattie Bresnahan function scoring was performed at 1 day, 1, 2, 3, 4, 5, 6, 7, and 8 weeks after surgery. The inclined plane test was performed at 4, 6 and 8 weeks after surgery to evaluate the recovery of hindlimb motor function. ELISA was used to detect the concentrations of inflammatory factors in the spinal cord at 1 week after surgery. Immunohistochemical staining was used to observe the area of syringomyelia, glial fibrillary acidic protein expression and nerve regeneration at 8 weeks after surgery. RESULTS AND CONCLUSION: (1) The Basso Beattie Bresnahan scores of the model group and the experimental group were lower than those of the sham group at various time points after surgery (P < 0.05) . The Basso Beattie Bresnahan scores of the experimental group were higher than those of the model group at 4-8 weeks after surgery (P < 0.05) . (2) In the inclined plane test, the maximum inclined angles of the model group and the experimental group at each time point after surgery were lower than that of the sham group (P < 0.05) . The maximum inclined angles of the experimental group at 6 and 8 weeks after surgery were higher than those of the sham group (P < 0.05) . (3) The concentrations of tumor necrosis factor-α, interleukin-1β, interleukin-6 and interleukin-10 in the experimental group and the model group were higher than those in the sham group (P < 0.05) . The concentrations of tumor necrosis factor-α, interleukin-1β and interleukin-6 in the experimental group were lower than those in the model group (P < 0.05) . The concentration of interleukin-10 in the experimental group was higher than that in the model group (P < 0.05) . (4) Immunohistochemical staining showed that the expression levels of glial fibrillary acidic protein in the experimental group and the model group were higher than those in the sham group, while the expression of glial fibrillary acidic protein in the experimental group was lower than that in the model group. The area of syringomyelia in the experimental group was smaller than that in the model group (P < 0.05) . These results indicate that local injection of HAMC-NT-3 hydrogel can effectively inhibit inflammation as well as astrocyte activation and proliferation, reduce fibrous scar formation, and promote the protection of nerve tissue and the recovery of hindlimb motor function after spinal cord injury.

Objective To explore the clinical effect of phalangeal fractures with self-made mini external fixator. Methods From June, 2014 to June, 2017, 16 cases of phalangeal fracture were treated with self-made mini external fixator. In the followed-up periods, the regulating rechecks of X-ray and measurement of interpha-langeal joint activity were determined. The total active movement (TAM), numerical pain ranting scale (NPRS) and morning stiffness was used to estimate the fracture healing and the hand function recovery. Results Pain and ab-normal movement around fracture was found 6 weeks after the operation in 1 case, which had been healed by re-moving the external fixation, open reduction and internal fixation with kirschner wire. The other 15 cases were fol-lowed-up of 48-72 (average, 58) weeks. The fracture has healed. And there was no osteomyelitis, no breakage and loosening of steel needles. The clinical healing time of the fracture was 14 to 16 weeks, with an average of 15.5 weeks. According to the TAM, NPRS and morning stiffness, there was excellent in 11 cases, and good in 4 cases. Conclusion The self-made mini external fixator can maintain the stability after fracture reduction, provide the tension required for the healing of collateral ligament and joint capsule, and meet the need of early functional exer-cise. It is an ideal treatment option for phalangeal fractures.

Objective To systematically evaluate the efficacy and safety of posterior short segment and long segment pedicle screw internal fixation in the treatment of thoracolumbar burst fracture. Methods By searching the database, including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, a comprehensive study was carried out to make a comparison between the posterior short segment and the long segment pedicle screws internal fixation in treatment of thoracolumbar burst fracture, and Meta analysis was performed. Results A total of 14 related studies and 658 patients were enrolled in the study, including 320 patients in short segment group and 338 cases in long segment group, and Meta analysis was performed. The results suggested that there was no significant difference between the short segment group and the long segment group in terms of the deformity angle of the injured vertebra measured after operation and at the last follow?up, and sagittal index at the last follow?up ( MD=-0. 22,95%CI -2. 73,2. 28,P=0. 86;MD=-0. 28,95%CI -2. 23,1. 67, P=0. 78;MD=0. 47, 95%CI -3. 45, 4. 39, P=0. 81 ) . Besides, both groups had no statistical difference in post?operative COBB angle,anterior vertebral height and compression rate of injured vertebrae ( MD=0. 21,95%CI -0. 65,1. 06,P=0. 64; MD=-0. 46,95%CI -1. 40,0. 49,P=0. 34; MD=0. 47,95%CI -2. 28, 3. 21, P= 0. 74 ) , while the differences in COBB angle, anterior vertebral height, compression rate, correction loss were statistically significant at the last follow?up (MD=5. 11,95%CI 2. 81,7. 40,P<0. 0001;MD=-11. 89,95%CI-15. 28,-8. 50,P<0. 00001;MD=6. 46,95%CI 3. 85,9. 07,P<0. 00001) . There was no significant difference in VAS scores and the ODI scores between the two groups at the last follow?up ( MD =0. 01,95%CI -0. 15,0. 17,P=0. 9; MD=-0. 47,95%CI -2. 68,1. 74,P=0. 86),while the two groups showed statistically significant difference in fixation failure ( RR = 0. 08, 95%CI 0. 01, 0. 15, P = 0. 02 ) . Conclusion Posterior long segment pedicle screw internal fixation is more effective in treating thoracolumbar burst fracture than short segment surgery. It can reduce the COBB angle,restore the anterior height of the injured vertebra,and decrease the anterior vertebral pressure.

Objective To investigate the present situation of retinopathy of the prematurity(ROP)in Guang-dong Province.Methods A total of 1 52 hospitals engaged in neonatal medical service were selected from 1 3 cities in Guangdong Province by stratified random sampling method.The questionnaires of present situation and influential factors for ROP in Guangdong Province were distributed to the hospital officers to survey the special equipment in the Neonato-logy Department,ROP specialists and their training collected,the collected related equipment and the present situation of the disease,et al.Eventually,1 22 questionnaires was collected,and the return rate was 80.26%.One hundred and twenty -two hospitals entered into the study,including 50 tertiary hospitals,72 secondary and primary hospitals.Statisti-cal analysis was done with SPSS 1 9.0.Results Tertiary hospitals were better than secondary and primary hospitals in terms of conducting the oxygen monitoring (χ2 =1 8.639,P <0.01 ),ROP screening (χ2 =40.054,P <0.01 )and ROP treatment(χ2 =8.262,P <0.05).The restriction factors in the present situation of ROP were lack of specialists,tech-nology and equipment,especially the first two factors.The difference in lack of specialists and technology between tertia-ry hospitals and the lower -level hospitals was significant(χ2 =4.520,P <0.05).There were 63 hospitals able to con-duct ROP screening,and 1 6 hospitals without equipment could carry out ROP screening through referral or inviting the experts from other hospitals.Fifty -nine hospitals which couldn′t carry out ROP screening had to refer patients to other hsopitals or invite the experts from other hospitals for consultation of high risk patients.Conclusions The present situation of ROP in the tertiary hospitals in Guangdong Province is generally satisfactory,while that in the secondary and primary hospitals stays behind.The constraints for present situation of ROP examination and treatment were lack of spe-cialists,technology and equipment.The hospitals that can′t implement ROP screening should establish regional co -operation by referral and resource sharing to improve the present situation of ROP in Guangdong Province.

Objective:To understand the influence of neoadjuvant chemotherapy combined with psychological and ethical intervention on mood and life quality of patients with cancer. Methods: The 120 patients with locally advanced breast cancer were randomly divided into control group ( neoadjuvant chemotherapy group) and interven-tion group ( neoadjuvant chemotherapy combined with psychological ethics intervention group) , Chemotherapy and after chemotherapy respectively adopt Zung Self -Rating Depression Scale ( SDS ) , Zung Self -Rating Anxiety Scale (SAS) and Quality of Life Core Scale (QLQ-C30) as an investigative tool, mood and quality of life of the patients were assessed. The patients' mood and life quality were investigated. Results: Emotional state intervention group patients more significantly than control group patients improved (P<0. 01) and improve life quality. Con-clusions:Neoadjuvant chemotherapy for localized breast cancer patients with psychological ethics intervention can effectively reduce the patient's anxiety and depression, and improve the life quality of patients.

Objective To develop experimental animal model of the brain stem myoclonus,which more closely replicate clinic features of mechanism, behavior, neuroelectrophysiology and pharmacodynamics.Methods L-5-HTP (the precursor of L-5-HT)was microinjected into the dorsal pons of young guinea pig to induce myoclonus (electromyogram burst of myoclonus≤400 ms by synchronous recording).Some animals were pretreated with anticonvulsant VPA,CZP or CBZ at effective dose 50 (EC_(50)).Myoclonus was induced when the drug level was within their effective anticonvulsion concentration.The neuroelectrophysiological characteristics of myoclonus including latency,time of reaching its peak,duration of seizure peak,the maximum seizure frequency and total duration were detected.EMG and ictal electroencephalogram(EEG)were recorded synchronously.The origin of myoclonus and its correlation with epileptic discharges were further confirmed by jerk-locked back averaging(JLA).Results (1)L-5-HTP induced pure myoclonus from the dorsal pons of guinea pig permanently(8/every site,the rate of producing myoclonus is 100%).(2)The myoclonus presented bilaterally or as general myoclonus,which was sensitive to tactile and sound sensation.(3)The EMG duration of the myoclonus wag longer((208.75 ± 81.42)ms),and ictal EEG showed scattered and irregular spikes and sharp waves without time-locked correlation with EMG activities.(4)The synchronous ictal EEG of the myoclonus showed spike and sharp waves,but there was no time-locked EEG activity in JLA.(5)In the animals treated with anticonvulsant at EC_(50) concentrations:VPA and CZP decreased the maximum seizure frequency(there are 28.13±3.79 per minutes in VPA group and 37.17±4.67 perminutes in CZP group)and shortened the duration of peak time ((55.00±14.14)minutes in VPA group and(50.00±11.73)minutes in CZP group respectively)and total time(VPA group was(124.17±40.04)minutes and CZP group was(156.88±30.71)minutes)of myoclonus(F value were between 23.41 and 35.44,P＜0.01 or P＜0.05).CBZ increased duration of peak time((98.75±13.86)minutes)and total time((257.50±14.79)minutes)of myoclonus(P＜0.05 and 0.01).Conclusions The new model generates pure myoclonus originating from brain stem and also has a shorter duration of muscle construction(≤400 ms)and more sensitivity to tactile and sound sensation.Therefore,the model presents characteristics closer to the brain stem myoclonus in the clinic phenotype in respect of seizure behavior,pharmacodynamics and neuroelectrophysiology.