ObjectiveTo investigate the mechanisms by which Bushen Tongluo Jiangzhuo prescription improves renal fibrosis in rats with chronic kidney disease （CKD） through the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsSeventy specific pathogen-free （SPF） Sprague-Dawley （SD） rats were randomly divided into a control group （n=15） and a modeling group （n=55）. Rats in the modeling group were administered a 2.5% adenine suspension at a dose of 200 mg·kg^-1·d^-1 by gavage for 4 weeks to establish a CKD model. Successfully modeled rats were randomly divided into a model group， an irbesartan group （20.25 mg·kg^-1·d^-1）， and Bushen Tongluo Jiangzhuo prescription low-， medium-， and high-dose groups （5.82， 11.64， and 23.28 g·kg^-1·d^-1， respectively）， with 10 rats in each group. Each group was administered an equal volume of physiological saline， the corresponding concentration of irbesartan， or Bushen Tongluo Jiangzhuo prescription by gavage for 12 weeks. Body weight and renal function indices were dynamically monitored. Serum creatinine （SCr）， blood urea nitrogen （BUN）， urine albumin-to-creatinine ratio （ACR）， 24-hour urinary total protein （24 hUTP）， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） levels were measured using an automatic biochemical analyzer. Renal histopathological changes were observed by hematoxylin-eosin （HE） and Masson staining. Immunohistochemistry （IHC） was used to detect the expression of PI3K， Akt， phosphorylated Akt （p-Akt）， and mTOR in renal tissues. Western blot was performed to assess the protein expression of PI3K， p-Akt， Akt， phosphorylated mTOR （p-mTOR）， and mTOR in renal tissues. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to determine the mRNA expression levels of PI3K， Akt， and mTOR in renal tissues. ResultsCompared with the model group， rats in the irbesartan group and the low-， medium-， and high-dose Bushen Tongluo Jiangzhuo prescription groups showed significantly decreased levels of SCr， BUN， ACR， 24 hUTP， IL-1β， IL-6， and TNF-α （P<0.01）. AST levels were significantly increased （P<0.01）， while no significant difference was observed in ALT levels. Histopathological examination revealed that， compared with the model group， renal tubular epithelial cell edema and necrosis and Bowman's capsule dilation were alleviated， inflammatory cell infiltration was reduced， and interstitial and glomerular fibrosis was markedly improved in all treatment groups， with the most pronounced effect observed in the high-dose Bushen Tongluo Jiangzhuo prescription group. Real-time PCR results showed that mRNA expression levels of PI3K， Akt， and mTOR were significantly downregulated in the high-dose group （P<0.01）. IHC results demonstrated that PI3K and p-Akt expression levels in renal tissues were significantly decreased in the high-dose group （P<0.01）. Western blot analysis further confirmed that the expression levels of PI3K， p-Akt/Akt， and p-mTOR/mTOR were significantly reduced in the high-dose group （P<0.01）. ConclusionBushen Tongluo Jiangzhuo prescription improves renal function indices in CKD rats， reduces collagen deposition in renal tissues， and decreases serum inflammatory factor levels. Its protective effect on renal function may be achieved by activating autophagy through downregulation of the PI3K/Akt/mTOR signaling pathway， thereby alleviating renal fibrosis.

Objective To investigate the changes in metabolites detected by magnetic resonance spectroscopy(MRS)in the dorsal thalamus of patients with cervical spondylotic myelopathy(CSM)and to analyze their correlation with spinal cord injury based on diffusion tensor imaging(DTI).Methods A total of 93 patients with CSM(patient group)and 67 healthy volunteers(control group)were selected.DTI parameters of the spinal cord and MRS parameters of the thalamus were compared between the two groups.Correlation analysis were performed among clinical features,conventional imaging features,DTI parameters,and metabolites in CSM patients.Multifacto-rial linear regression equations for thalamic metabolites based on the aforementioned characteristics were established.Results The fractional anisotropy(FA)value was significantly lower in the patient group than in the control group(P=0.005,t=2.874).The N-acetyl aspartate/creatine(NAA/Cr)ratio(P<0.001,Z=-5.922),choline/Cr(Cho/Cr)ratio(P<0.001,Z=-6.857),and myo-inositol/Cr(MI/Cr)ratio(P<0.001,Z=-6.573)were significantly lower in the patient group than in the control group.The NAA/Cr ratio(r=0.444,P<0.001),Cho/Cr ratio(r=0.308,P=0.003),and MI/Cr ratio(r=-0.489,P<0.001)were corre-lated with the FA value in the patient group.There was a correlation between the NAA/Cr ratio and the duration(r=-0.365,P<0.001).Multifactorial linear regression equations for each metabolites in the thalamus:NAA/Cr=0.833+1.520×FA-0.007×duration;Cho/Cr=0.209+0.774×FA;MI/Cr=1.566-1.722×FA+0.008×modified Japanese Orthopaedic Association(mJOA)score;glu-tamate/Cr(Glx/Cr)=0.942+0.009×duration.Conclusion CSM patients exhibit metabolic alterations in the dorsal thalamus,which are linearly correlated with the degree of spinal cord injury.

Objective:To observe the effect of combining heat-sensitive moxibustion with action observation therapy in the treatment of spastic wrist and hand dysfunction post-stroke.Methods:Ninety stroke survivors with spasmodic wrist and hand dysfunction were randomly assigned to a heat-sensitive moxibustion group, an action observation group, or a combination group, each of 30. In addition to routine rehabilitation treatment, the groups received heat-sensitive moxibustion, action observation therapy or moxibustion followed by action observation therapy in 6 sessions a week over 6 weeks. Surface electromyography signals (iEMG and RMS) were recorded from the affected wrist and hand muscles before and after the treatment. All of the participants were also assessed using the Fugl-Meyer motor assessment for the upper extremities (FMA-UE).Results:After treatment, a significant improvement was observed in the average FMA-UE values, with that of the combination group (17.2±2.1) significantly higher than those of the other two groups. The average iEMG of the wrist flexors and extensors, the extensors of the fingers, and abductor pollicis brevis had increased significantly, with the combination group′s averages significantly higher than those of the other two groups. The average RMS values of those muscles had decreased significantly after the treatment, with those of the combination group significantly lower than the others.Conclusions:Combining heat-sensitive moxibustion and action observation therapy can significantly reduce muscle tension, and promote strength and better functioning of spastic wrist and hand muscles after a stroke. The combination is worthy of clinical application and promotion.

Objective To investigate the changes in metabolites detected by magnetic resonance spectroscopy(MRS)in the dorsal thalamus of patients with cervical spondylotic myelopathy(CSM)and to analyze their correlation with spinal cord injury based on diffusion tensor imaging(DTI).Methods A total of 93 patients with CSM(patient group)and 67 healthy volunteers(control group)were selected.DTI parameters of the spinal cord and MRS parameters of the thalamus were compared between the two groups.Correlation analysis were performed among clinical features,conventional imaging features,DTI parameters,and metabolites in CSM patients.Multifacto-rial linear regression equations for thalamic metabolites based on the aforementioned characteristics were established.Results The fractional anisotropy(FA)value was significantly lower in the patient group than in the control group(P=0.005,t=2.874).The N-acetyl aspartate/creatine(NAA/Cr)ratio(P<0.001,Z=-5.922),choline/Cr(Cho/Cr)ratio(P<0.001,Z=-6.857),and myo-inositol/Cr(MI/Cr)ratio(P<0.001,Z=-6.573)were significantly lower in the patient group than in the control group.The NAA/Cr ratio(r=0.444,P<0.001),Cho/Cr ratio(r=0.308,P=0.003),and MI/Cr ratio(r=-0.489,P<0.001)were corre-lated with the FA value in the patient group.There was a correlation between the NAA/Cr ratio and the duration(r=-0.365,P<0.001).Multifactorial linear regression equations for each metabolites in the thalamus:NAA/Cr=0.833+1.520×FA-0.007×duration;Cho/Cr=0.209+0.774×FA;MI/Cr=1.566-1.722×FA+0.008×modified Japanese Orthopaedic Association(mJOA)score;glu-tamate/Cr(Glx/Cr)=0.942+0.009×duration.Conclusion CSM patients exhibit metabolic alterations in the dorsal thalamus,which are linearly correlated with the degree of spinal cord injury.

Objective:To observe the effect of combining heat-sensitive moxibustion with action observation therapy in the treatment of spastic wrist and hand dysfunction post-stroke.Methods:Ninety stroke survivors with spasmodic wrist and hand dysfunction were randomly assigned to a heat-sensitive moxibustion group, an action observation group, or a combination group, each of 30. In addition to routine rehabilitation treatment, the groups received heat-sensitive moxibustion, action observation therapy or moxibustion followed by action observation therapy in 6 sessions a week over 6 weeks. Surface electromyography signals (iEMG and RMS) were recorded from the affected wrist and hand muscles before and after the treatment. All of the participants were also assessed using the Fugl-Meyer motor assessment for the upper extremities (FMA-UE).Results:After treatment, a significant improvement was observed in the average FMA-UE values, with that of the combination group (17.2±2.1) significantly higher than those of the other two groups. The average iEMG of the wrist flexors and extensors, the extensors of the fingers, and abductor pollicis brevis had increased significantly, with the combination group′s averages significantly higher than those of the other two groups. The average RMS values of those muscles had decreased significantly after the treatment, with those of the combination group significantly lower than the others.Conclusions:Combining heat-sensitive moxibustion and action observation therapy can significantly reduce muscle tension, and promote strength and better functioning of spastic wrist and hand muscles after a stroke. The combination is worthy of clinical application and promotion.

Objective To observe the effects of Levo-tetrahydropalmatine(l-THP)on the expression,regression and relapse of conditioned place preference(CPP)in ketamine induced rats,and to detect the content of dopamine(DA)in the striatum(caudate putamen,CPu)of the rat brain at different time points.Methods Ketamine addiction rat model was established by CPP.The effects of l-THP on the expression,regression and relapse of ketamine induced rat CPP were investigated using CPP score as the index.The content of DA in CPu of rats was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry(UPLC-MS/MS)after ketamine administration and l-THP intervention at 30 min,60 min,90 min,120 min and 150 min.Results It indicated that 1-THP could decrease the expression of CPP in ketamine induced rats,promote the process of CPP resolution and inhibit the process of relapse.In addition,l-THP combined with ketamine administration significantly inhibited the ketamine-induced increase in DA content in the CPu of the rats.Conclusion The mechanism of l-THP inhibiting the reward effect of ketamine may be related to blocking DA receptors and reducing the release of DA neurotransmitters.l-THP has potential implications for the treatment of ketamine addiction.

Objective:To investigate clinical characteristics of and genetic variants in the NF1 gene in children with neurofibromatosis type 1 (NF1) .Methods:Clinical data were collected from 22 children with NF1, who were admitted to the Department of Dermatology, Children's Hospital, Capital Institute of Pediatrics from January 2022 to September 2023, and were analyzed. Next-generation sequencing was performed to detect NF1 mutations in the probands, and the variants were verified in the family members by Sanger sequencing. A homology modeling software was used to predict the three-dimensional protein structure, and analyze the characteristics of gene mutations.Results:Among the 22 children with NF1, there were 14 males and 8 females, and they were aged from 3 months to 12 years at the clinic visit. All the 22 children presented with multiple café-au-lait spots, and their age at onset ranged from birth to 2 years. Nine patients were accompanied by freckles in the axillary or inguinal regions, 2 by cutaneous neurofibromas, 2 by juvenile xanthogranuloma, 2 by learning disabilities, and Lisch nodules of the iris, central precocious puberty and scoliosis occurred in 1 case each; 5 cases showed characteristic manifestations of neurofibroma on brain magnetic resonance imaging. A total of 5 types of NF1 gene variants were identified in the 22 patients, including complete heterozygous deletion of the NF1 gene (1 patient), missense variants (4 patients, one of whom carried 2 types of missense variants), frameshift variants (8 patients), nonsense variants (6 patients), and classical splicing variants (3 patients). Among the 22 variants, 7 were unreported variants, including c.758T>A (p.Val253Glu), c.2360dupC (p.Thr788Asnfs*5), c.5513T>G (p.Leu1838*), c.2774dupT (p.Leu925Phefs*11), c.6894dupT (p.Val2299Cysfs*7), c.6882_6883delCT (p.Phe2295Leufs*10), and c.6448A>T (p.Lys2150*). Of the unreported variants, 6 were frameshift or nonsense variants leading to different degrees of truncated protein expression, and severely affecting protein function; based on the three-dimensional protein structure prediction analysis, it was uncertain if the missense variant c.758T>A (p.Val253Glu) affected protein conformation. In 2 children, the NF1 variants were inherited from their mothers; 1 child carried 2 NF1 missense variants, 1 of which was a spontaneous mutation potentially causing the disease, while the other one with unknown pathogenicity was inherited from the phenotypically normal father; the remaining 19 children all carried spontaneous mutations.Conclusions:Children with NF1 mainly present with multiple café-au-lait spots at the early stage, and some characteristic manifestations such as cutaneous neurofibroma, juvenile xanthogranuloma, and Lisch nodules of the iris can also occur. NF1 gene pathogenic variants are complex and diverse, and 22 variants were identified in this study, enriching the spectrum of NF1 gene variants.

One case of 46, XY partial gonadal dysgenesis due to a congenital defect of DEAH-box RNA helicase 37(DHX37) was reported. The clinical and genetic data of a boy who was admitted to the Department of Endocrinology and Metabolism, the First Affiliated Hospital of Henan University of Science and Technology due to ambiguous external genitalia in September 2020 were collected and analyzed. This 3-month-old male patient showed a micropenis, bilateral cryptorchidism, 46, XY karyotype, a decrease in testosterone, anti-Müllerian hormone, inhibin B, an increase in follicle stimulating hormone. Testis biopsy indicated gonadal dysgenesis. The proband harbored a de novo heterozygous mutation in the DHX37 gene c. 923G>A(p.Arg308Gln). DHX37 variants need to be considered for 46, XY gonadal dysgenesis.

Objective To evaluate the efficacy of alendronate sodium combined with dietary and exercise intervention in postmenopausal osteoporosis. Methods 88 postmenopausal osteoporosis patients were enrolled and treated with alendronate sodium and Vitamin D combined with dietary and exercise intervention for 12 months. Bone mineral density (BMD) of lumber spine and femur neck were measured before and after the treatment. Results Medication combined with dietary and exercise intervention significantly increased bone mineral density of postmenopausal osteoporosis patients, and the serum levels of bone alkaline phosphatase (BLAP), alkaline phosphatase (AKP) and tartrate resistant acid phosphatase (TRACP) were significantly higher than those pre-treatment, with significant differences (P<0.05). Conclusion Compared to simple medication treatment, medication combined with dietary and exercise intervention is more effective to enhance medication efficacy and BMD level.

Objective To investigate the clinical effects of lactobacillus acidophilus combined with glutathione in the treatment of nonalcoholic fatty liver disease.Methods 120 patients with nonalcoholic fatty liver disease were selected,and they were randomly divided into control group (60 patients used glutathione alone) and observation group (60 patients received lactobacillus acidophilus on the basis of control group).The clinical efficacy,liver function index,blood lipid index and the ultrasonography grading of fatty liver before and after treatment of the two groups were compared.Results The clinical total effective rates of the control group and the observation group were 76.67％,91.67％,respectively.The total effective rate of the observation group was significantly higher than that of the control group(x2 =10.52,P ＜ 0.05).The levels of AST,ALT and GGT of the observation group after treatment were significantly lower than those of the control group and before treatment [(36.89 ± 7.14) U/L,(36.89 ± 7.14) U/L,(36.89 ±7.14) U/L vs.(49.36 ± 11.08) U/L,(45.91 ± 10.24) U/L,(90.28 ± 20.70) U/L;(36.89 ± 7.14) U/L,(36.89 ± 7.14) U/L,(36.89 ± 7.14) U/L vs.(92.90 ± 24.3) U/L,(81.11 ± 17.37) U/L,(147.27 ± 34.19) U/L,t =2.88,2.54,2.91;3.01,3.36;3.18,3.48;3.41,3.87;all P ＜0.05).The levels of TG,TC,HDL-C and LDL-C of the observation group after treatment were significantly better than those of the control group and before treatment [(1.66 ± 0.42) mmol/L,(4.05 ± 0.77) mmol/L,(1.69 ± 0.60) mmol/L,(2.44 ± 0.38) mmol/L vs.(2.13 ± 0.80) mmol/L,(4.64 ± 0.94) mmol/L,(1.45 ± 0.48) mmol/L,(2.97 ± 0.57) mmol/L;(1.66 ± 0.42) mmol/L,(4.05 ± 0.77) mmol/L,(1.69 ± 0.60) mmol/L,(2.44 ± 0.38) mmol/L vs.(2.71 ± 1.33) mmol/L,(5.42 ± 1.27) mmol/L,(1.08 ± 0.36) mmol/L,(3.49 ± 0.71) mmoL/L,t =2.43.2.13,2.55,2.07;3.02,3.41;3.11,3.65;2.81,3.30;2.87,3.15;all P ＜ 0.05).In the control group,normal in 6 cases,mild in 24 cases,moderate in 21 cases and severe in 9 cases as fatty liver degree;in the observation group,normal in 13 cases,mild in 30 cases,moderate in 13 cases and severe in 4 cases as fatty liver degree.The ultrasonography grading of fatty liver of the observation group after treatment were significantly better than those of control group and before treatment (U =3.74,5.20,all P ＜ 0.05).Conclusion Lactobacillus acidophilus combined with glutathione in the treatment of nonalcoholic fatty liver disease can efficiently promote the recovery process of liver function,regulate blood lipid levels and is helpful to improve the imaging grading.