The core pathogenesis of attention deficit hyperactivity disorder （ADHD） lies in deficiency， stasis and stagnation. Deficiency arises from kidney essence depletion and spleen dysfunction in transportation and transformation， leading to inadequate nourishment of the marrow sea. Stasis caused by qi deficiency leads to obstruction in channels and collaterals， resulting in obstructed marrow transport. Stagnation is associated with the excess of the five minds transforming into fire， which scorches the brain orifices and leads to loss of control over marrow utilisation. Based on this， a "supplementation-unblocking-regulation" therapeutic approach is proposed. For deficiency， the focus is on supplementing kidney and fortifying spleen， and replenishing the marrow sea. For stasis， the priority is to unblock and open the orifices， and clear the marrow channels. For stagnation， the core is to clear fire and contain the mind， regulate and restore vital activity. In clinical practice， it is necessary to identify the primary and secondary pathogenic mechanisms and apply dynamic， combined treatment， integrating Chinese herbal medicine， acupuncture， and guiding exercises throughout the process， aiming to provide a reference for the diagnosis and treatment of ADHD with traditional Chinese medical.

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

BACKGROUND:Intervertebral disc degeneration is the main pathological factor causing low back pain,which is closely related to macrophage-mediated immune inflammation.Tongdu Huoxue Decoction is a proven prescription for the treatment of intervertebral disc degeneration,but it is still unclear whether it can treat intervertebral disc degeneration by regulating the polarization phenotype of macrophages to inhibit inflammation in intervertebral disc tissue.OBJECTIVE:To investigate the regulatory effects of Tongdu Huoxue Decoction on the expression of macrophage-related inflammatory factors in intervertebral disc tissues of rats,as well as its mechanisms for the treatment of intervertebral disc degeneration.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into sham operation group,model group,and Tongdu Huoxue Decoction group,with eight rats in each group.An intervertebral disc degeneration model was established using the annulus fibrosus puncture method in the latter two groups.On the 1st postoperative day,10.8 g/kg Tongdu Huoxue Decoction was given by gavage in the Tongdu Huoxue Decoction group,and the same dose of saline was given by gavage in the sham operation group and the model group,once a day.After 4 weeks of intervention,histopathological changes in the intervertebral disc tissues were assessed using hematoxylin-eosin.Immunohistochemistry and quantitative real-time PCR were performed to detect the relative expression levels of CD68,CD206,interleukin 1β,interleukin 10,type II collagen,and matrix metalloproteinase 13 proteins or mRNA in the intervertebral disc tissues.RESULTS AND CONCLUSION:(1)Hematoxylin-eosin staining results revealed that the model group exhibited a significant decrease in intervertebral disc height,disorganized annulus fibrosus structure with fissures,and unclear demarcation between the nucleus pulposus and the annulus fibrosus.The Tongdu Huoxue Decoction group showed organized arrangement of the annulus fibrosus with pyknosis.(2)Immunohistochemical results demonstrated that,compared with the model group,the Tongdu Huoxue Decoction group had significantly lower expressions of CD68,interleukin 1β,and matrix metalloproteinase 13,and significantly higher expressions of CD206,type II collagen and interleukin 10(P<0.05 or P<0.01).(3)qPCR results showed that there were significant differences in the mRNA expression of CD68,CD206,interleukin 1β,matrix metalloproteinase 13,type II collagen,and interleukin 10 between the three groups(P<0.001).To conclude,Tongdu Huoxue Decoction can improve intervertebral disc degeneration in the rat model of intervertebral disc degeneration,and its mechanism is associated with the inhibition of macrophage-related inflammatory responses in the intervertebral discs.

BACKGROUND:Intervertebral disc degeneration is the main pathological factor causing low back pain,which is closely related to macrophage-mediated immune inflammation.Tongdu Huoxue Decoction is a proven prescription for the treatment of intervertebral disc degeneration,but it is still unclear whether it can treat intervertebral disc degeneration by regulating the polarization phenotype of macrophages to inhibit inflammation in intervertebral disc tissue.OBJECTIVE:To investigate the regulatory effects of Tongdu Huoxue Decoction on the expression of macrophage-related inflammatory factors in intervertebral disc tissues of rats,as well as its mechanisms for the treatment of intervertebral disc degeneration.METHODS:Twenty-four Sprague-Dawley rats were randomly divided into sham operation group,model group,and Tongdu Huoxue Decoction group,with eight rats in each group.An intervertebral disc degeneration model was established using the annulus fibrosus puncture method in the latter two groups.On the 1st postoperative day,10.8 g/kg Tongdu Huoxue Decoction was given by gavage in the Tongdu Huoxue Decoction group,and the same dose of saline was given by gavage in the sham operation group and the model group,once a day.After 4 weeks of intervention,histopathological changes in the intervertebral disc tissues were assessed using hematoxylin-eosin.Immunohistochemistry and quantitative real-time PCR were performed to detect the relative expression levels of CD68,CD206,interleukin 1β,interleukin 10,type II collagen,and matrix metalloproteinase 13 proteins or mRNA in the intervertebral disc tissues.RESULTS AND CONCLUSION:(1)Hematoxylin-eosin staining results revealed that the model group exhibited a significant decrease in intervertebral disc height,disorganized annulus fibrosus structure with fissures,and unclear demarcation between the nucleus pulposus and the annulus fibrosus.The Tongdu Huoxue Decoction group showed organized arrangement of the annulus fibrosus with pyknosis.(2)Immunohistochemical results demonstrated that,compared with the model group,the Tongdu Huoxue Decoction group had significantly lower expressions of CD68,interleukin 1β,and matrix metalloproteinase 13,and significantly higher expressions of CD206,type II collagen and interleukin 10(P<0.05 or P<0.01).(3)qPCR results showed that there were significant differences in the mRNA expression of CD68,CD206,interleukin 1β,matrix metalloproteinase 13,type II collagen,and interleukin 10 between the three groups(P<0.001).To conclude,Tongdu Huoxue Decoction can improve intervertebral disc degeneration in the rat model of intervertebral disc degeneration,and its mechanism is associated with the inhibition of macrophage-related inflammatory responses in the intervertebral discs.

Hemophagocytic syndrome (HPS), which is currently named as hemophagocytic lymphohistiocytosis (HLH), is a hyperinflammatory syndrome characterized by persistent fever, hepatosplenomegaly, pancytopenia and hemophagocytosis found in bone marrow, liver, spleen and lymph nodes due to excessive activation of macrophages and cytotoxic T cells. Macrophage activation syndrome (MAS) is a specific form of HLH induced by autoinflammatory/autoimmune disorders which can be life-threatening and requires multiple disciplines. In order to improve clinicians′ understanding of MAS and standardize the clinical diagnosis and treatment practice of MAS, the rheumatology branch of Chinese Rheumatology Association organized domestic experts to formulate the diagnosis and treatment standard, in order to improve the diagnosis and treatment level of MAS and improve the prognosis of patients.

Objective:To analyze epidemiological characteristics of leprosy in China from 2016 to 2020, and to provide a scientific basis for further elimination of leprosy.Methods:Data collation and statistical analysis were conducted on annual reports on leprosy epidemic surveillance in China (excluding Hong Kong, Macao, and Taiwan regions) from 2016 to 2020.Results:From 2016 to 2020, a total of 2 697 new cases of leprosy were reported in China, including 46 (1.71%) children, 894 (33.15%) females, 374 (13.87%) floating people, 2 443 (90.58%) multibacillary cases, and 546 (20.24%) cases of grade 2 disabilities. A total of 203 relapsed cases were reported in the meantime. By the end of 2020, there had been 1 893 registered leprosy cases in China, and the number of cases was 68.62% fewer than that in 2010 (6 032 cases) ; there were 36 (1.2%) counties or cities with a prevalence rate above 1 per 100 000, and 72 (17.73%) new cases suffered from grade 2 disabilities.Conclusion:From 2016 to 2020, the reported incidence and prevalence of leprosy in China steadily decreased year by year, and overall, leprosy was still lowly prevalent.

OBJECTIVE To study th e pharmacodynamics and pha rmacokinetics of Qinglian ningxin capsule in rats with ischemic arrhythmia. METHODS Totally 30 male SD rats were randomly divided into blank control group ，model control group ， Qinglian ningxin capsule group （4.00 g/kg），Artemisia annua group（1.43 g/kg），Coptis chinensis group（0.42 g/kg），with 6 rats in each group. Administration groups were given relevant medicine intragastrically ；model control group and blank control group were given normal saline intragastrically ，once a day ，for consecutive 7 days. After last medication ，except for blank control group，other groups were given Posterior pituitary injection via tail vein （1 u/kg） to induce ischemic arrhythmia model. electrocardiogram changes of rats in each group were recorded. Another 36 rats were randomly divided into Qinglian ningxin capsule model group and Qinglian ningxin capsule control group （4.00 g/kg），A. annua model group and A. annua control group （1.43 g/kg），C. chinensis model group and C. chinensis control group （0.42 g/kg）. After the rats in each model group were injected with Posterior pituitary injection （1 u/kg）via tail vein ，administration groups were given relevant drugs intragastrically ， and control groups were given constant volume of normal saline intragastrically. Blood was taken from the orbit at different time points（0，0.25，0.75，1，2，4，6，8，12 and 24 h）. The concentrations of berberine hydrochloride and artemisinin in plasma were determined by HPLC ，and the pharmacokinetic parameters were calculated by WinNonlin 7.0 software. RESULTS Compared with the model control groups ，Qinglian ningxin capsule could significantly improve the heart rate slowing of rats and redu ced the prolongation of PR interval and QT interval significantly ，and the effects were generally better than those of A. annua group and C. chinensis group（P＜0.05）. Compared with A. annua control group and C. chinensis control group ，cmax，AUC0－t and AUC 0－∞ of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule control group，while CL was decreased significantly ；t1/2z of artemisinin was prolonged significantly （P＜0.05）. Compared with Qinglian ningxin capsule control group ，cmax（except artemisinin ），AUC0－t，AUC0－∞，MRT0－t and MRT 0－∞（except artemisinin ）of berberine hydrochloride and artemisinin were increased significantly in Qinglian ningxin capsule model group ，while CL was decreased significantly（P＜0.05）. CONCLUSIONS Qinglian ningxin capsule could significantly improve ischemic arrhythmia better than A. annua and C. chinensis ，and can improve the absorption of berberine hydrochloride and artemisinin in model rats and slow down their elimination.

Objective:To explore the features and application value of MRI in the spectrum of fetal cloaca malformation.Methods:The clinical, MRI and ultrasound data of 6 fetuses with spectrum of cloaca malformation were retrospectively analyzed in Guangzhou Women and Children′s Medical Center Affiliated to Guangzhou Medical University from January 2017 to February 2021, and the MRI features of each subtype were analyzed.Results:Among the 6 fetuses of spectrum of the cloaca malformation, 5 were confirmed by postnatal imaging and surgery, and 1 was confirmed by induced labor autopsy, including 3 persistent cloaca, 1 posterior cloaca, 1 cloaca variant, and 1 urogenital sinus. The high signal on T 1WI of the rectal meconium disappeared or became weaker, and the signal on T 2WI of meconium of the dilated colon increased in the 3 cases of persistent cloaca and 1 case of posterior cloaca. All 6 cases showed colonic dilatation. All cases except 1 persistent cloaca showed vaginal and/or uterine effusion. Two cases of persistent cloaca, 1 case of posterior cloaca and 1 case of cloaca variant showed duplicated genital tract. Two cases of persistent cloaca showed only 1 perineal opening, which opened at the urethral orifice. One case of cloaca variant showed 2 openings, which opened at the urethral orifice and in front of the normal anus, respectively. Conclusion:Prenatal MRI can help to clarify the diagnosis of cloacal malformation spectrum and to determine its specific classification.

Objective:To compare the effect of intracorporeal anastamosis and extracorporeal anastamosis on abdominal infection associated with laparoscopic right hemicolectomy.Methods:The clinical data of 210 patients with colon cancer who underwent laparoscopic right hemicolectomy in Dalian Third Peoples′s Hospital, Liaoning Province from January 2015 to December 2019 were analyzed retrospectively.Among them, 79 patients underwent intracorporeal anastamosis (intracorporeal anastamosis group) and 131 patients underwent extracorporeal anastamosis (extracorporeal anastamosis group). The perioperative indexes and postoperative abdominal infection were compared between the two groups.Results:In intracorporeal anastamosis group, the intraoperative bleeding was (45.2±4.2) mL, the operative time was (161.3±22.4) min, the number of lymph node dissection was (30.8±9.6), the postoperative exhaust time was (3.3±1.2) d, and the postoperative hospital stay was (7.6±0.5) d. In extracorporeal anastamosis group was (42.1±5.0) mL, (167.3±26.7) min, (32.9±8.6), (3.4±1.0) d and (7.5±0.6) d, respectively, there were no significant difference between the two groups (t value were 0.417, 0.207, 0.829, 0.338 and 0.293, respectively; P value were 0.699, 0.845, 0.231, 0.734 and 0.802, respectively). In intracorporeal anastamosis group, the incidence of abdominal infection (with anastomotic fistula)was 13.9%(11/79), the incidence of abdominal infection (without anastomotic fistula)was 10.1%(8/79), and in extracorporeal anastamosis group was 1.5%(2/131)and 0.8%(1/131), the differences were statistically significant (χ 2=12.805, 10.238; P=0.003, 0.008). In intracorporeal anastamosis group, the incidence of respiratory system infection was 1.3%(1/79), the incidence of urinary system infection was 2.5%(2/79), the incidence of surgical incision infection was 1.3%(1/79). In extracorporeal anastamosis group was 3.1%(4/131), 0.8%(1/131) and 3.1%(4/131), respectively.There were no significant difference between the two groups (χ 2 value were 0.662, 0.420 and 0.662, respectively; P value were 0.364, 0.587 and 0.364, respectively). Conclusion:Laparoscopic right hemicolectomy with intracorporeal anastamosis and extracorporeal anastamosis have the same surgical effect, but intracorporeal anastamosis may increase the risk of postoperative abdominal infection.

Objective:To compare the effect of midcaudal combined approach and the cephalic middle approach in laparoscopic complete mesocolic excision (CME) in the treatment of right colon cancer complicated with incomplete intestinal obstruction.Methods:From January 2014 to January 2019, 90 patients with right colon cancer complicated with incomplete intestinal obstruction admitted to the Third People′s Hospital of Dalian were retrospectively analyzed.All patients underwent laparoscopic right hemicolectomy, CME plus D3 lymph node dissection.According to the choice of different surgical approaches, 44 patients were treated with the midcaudal combined approach (observation group) and the other 46 patients were treated with cephalic middle approach (control group). The intraoperative, postoperative and complications of the two groups were compared statistically.Results:Compared with the control group, the bleeding volume in the observation group was significantly reduced ((105.3±22.6) ml vs.(309.6±28.0) ml, t=13.698), the operation time was significantly shortened ((165.2±17.9) min vs.(219.5±21.5) min, t=8.327), and the differences were statistically significant (all P<0.05). There were no significant differences in the number of lymph nodes dissected ((21.4±7.8)vs.(20.4±6.6), t=0.534), the proportion of lymph nodes dissected≥12(86.4%(38/44)vs.84.8%(39/46), χ 2=0.208), the complications after operation(6.8%(3/44)vs.10.9%(5/46), χ 2=0.318), the length of hospital stay after operation ((11.8±1.6) d vs.(12.5±2.3) d, t=0.986), the difference was statistically significant (all P>0.05). Conclusion:It is safe and feasible to use the middle caudal approach in laparoscopic CME for right colon cancer complicated with incomplete ileus. Compared with the cephalic middle approach, it can reduce thebleeding volume and shorten the operation time.