Shugan Tongluo Qiangjing recipe protects against varicocele of EVC rats through modulating sperm DNA damage, telomere expression and oxidative stress.

Varicocele (VC) refers to expansion and tortuosity of spreading venous plexus in spermatic cord due to poor blood flow. This study aimed to investigate effects of Shugan Tongluo Qiangjing recipe (SGTL) on sperm DNA damage and oxidative stress in experimental VC (EVC) rats. EVC model was established by partial ligation of left renal vein. Spermatic vein diameter, testicular weight, sperm DNA fragmentation index (DFI) were evaluated. Telomere reverse transcriptase (TERT) expression, telomere gene transcription, and testicular tissue morphology were determined·H2O2, catalase, SOD, T-AOC were measured with colorimetry. SGTL significantly decreased spermatic vein diameter (P=0.000) and increased testicular weight (P=0.013) of rats compared those of EVC rats. SGTL maintained testicular tissue morphology in EVC rats. SGTL markedly reduced sperm DFI value in sperm of rats compared to EVC rats (P=0.000). SGTL significantly enhanced TERT expression and telomere gene transcription (P=0.028) in testis of rats compared to EVC rats. SGTL reduced H2O2 levels (P=0.001) and promoted CAT activity (P=0.016), SOD activity (P=0.049), and T-AOC activity (P=0.047) of rats, compared to EVC rats. In conclusion, SGTL could reduce pathogenic process of EVC by reducing sperm DNA damage and regulating telomere length in EVC rats, which may be related to oxidative stress regulation.

Exploring the mechanism of Semen Strychni in treating amyotrophic lateral sclerosis based on network pharmacology.

Semen Strychni (SS), known as an agonist of central nervous system, is a traditional herb widely used in treating amyotrophic lateral sclerosis (ALS) in small doses to relieve muscle weakness and improve muscle strength. However, the potential mechanisms and the main components of SS in treating ALS remain unclear. To explore the underlying mechanism of SS in treating ALS based on network pharmacology and molecular docking. The active components of SS were obtained using TCMSP, Herb, ETCM, and BATMAN-TCM. The targets of SS were gained from PharmMapper. The targets of ALS were searched on Genecards, Drugbank, DisGeNET, OMIM, TTD and GEO database. After obtaining the coincidence targets, we submitted them to the STRING database to build a protein-protein interaction network. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed subsequently. The active components and targets were further investigated using molecular docking technology. 395 targets of SS and 1925 targets of ALS were obtained with 125 common targets. The protein-protein interaction analysis indicated that SRC, AKT1, MAPK1, EGFR, and HSP90AA1 received the higher degree value and were considered the central genes. The Ras, PI3K-Akt, and MAPK signaling pathway could be involved in the treatment of ALS. Brucine-N-oxide obtained the lowest binding energy in molecular docking. This study explored the mechanism of SS in the treatment of ALS and provides a new perspective for future study. However, further experimental studies are needed to validate the therapeutic effect.

Ginsenoside-Rg1 combined with a conditioned medium from induced neuron-like hUCMSCs alleviated the apoptosis in a cell model of ALS through regulating the NF-κB/Bcl-2 pathway.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting both upper and lower motor neurons in the brain and spinal cord. One important aspect of ALS pathogenesis is superoxide dismutase 1 (SOD1) mutant-mediated mitochondrial toxicity, leading to apoptosis in neurons. This study aimed to evaluate the neural protective synergistic effects of ginsenosides Rg1 (G-Rg1) and conditioned medium (CM) on a mutational SOD1 cell model, and to explore the underlying mechanisms. We found that the contents of nerve growth factor, glial cell line-derived neurotrophic factor, and brain-derived neurotrophic factor significantly increased in CM after human umbilical cord mesenchymal stem cells (hUCMSCs) were exposed to neuron differentiation reagents for seven days. CM or G-Rg1 decreased the apoptotic rate of SOD1G93A-NSC34 cells to a certain extent, but their combination brought about the least apoptosis, compared with CM or G-Rg1 alone. Further research showed that the anti-apoptotic protein Bcl-2 was upregulated in all the treatment groups. Proteins associated with mitochondrial apoptotic pathways, such as Bax, caspase 9 (Cas-9), and cytochrome c (Cyt c), were downregulated. Furthermore, CM or G-Rg1 also inhibited the activation of the nuclear factor-kappa B (NF-κB) signaling pathway by reducing the phosphorylation of p65 and IκBα. CM/G-Rg1 or their combination also reduced the apoptotic rate induced by betulinic acid (BetA), an agonist of the NF-κB signaling pathway. In summary, the combination of CM and G-Rg1 effectively reduced the apoptosis of SOD1G93A-NSC34 cells through suppressing the NF-κB/Bcl-2 signaling pathway (Fig. 1 is a graphical representation of the abstract).

Prevalence of multiple sclerosis in Guangzhou, China: A population-based case-finding prospective study.

BACKGROUND: Multiple sclerosis (MS) is rare in China, and the prevalence previously reported may be biased. Currently, few studies that have investigated the prevalence of MS in China based on the latest diagnostic criteria. METHODS: Through a population-based survey from August 8, 2021 to December 31, 2021, we calculated the prevalence of multiple sclerosis in 18,676,605 residents of Guangzhou, China. MS patients were identified through the health insurance system of the Guangzhou Health Insurance Bureau, and we surveyed 17 large tertiary hospitals using a case-finding approach. All MS patients were diagnosed according to the 2017 McDonald criteria. RESULTS: A total of 143 patients in the resident population of Guangzhou were diagnosed with MS, with a crude prevalence of 0.77 per 100,000 (95% confidence interval (CI): 0.65-0.90), and the prevalence was higher in in females (1.14/100,000) than in males (0.44/100,000). The age-adjusted prevalence was 0.92 per 100,000 (95% CI: 0.77-1.10). The prevalence peaked at the age of 25-29 years (2.86/100,000) for both males and females (1.44/100,000 and 4.42/100,000, respectively). CONCLUSIONS: This is the first study to report the prevalence of MS in Guangzhou, China, according to the criteria. Our study shows that the prevalence of MS in Guangzhou is lower than that in other cities in China.

Fertility Does Not Alter Disease Progression in ALS Patients of Childbearing Age: A Three Centers Retrospective Analysis in Southern China.

Background: Limited data exists on the clinical features of patients with amyotrophic lateral sclerosis (ALS) during reproductive ages. Objective: Our study characterized the clinical features of ALS and the effects of pregnancy on disease progression in patients with ALS. Methods: We performed a retrospective study of female patients with ALS in three ALS research centers in southern China from 2009 to 2021. Data regarding fertility status, and clinical and genetic features, were collected. Age-matched male patients with ALS served as controls. The patients were divided into the following two subgroups: patients with symptom onset within 1 year of pregnancy and patients with symptom onset over 1 year group after pregnancy. Results: A total of 52 female and 52 matched male patients were enrolled. There were no differences in female and male patients in the mean age of symptom onset, the mean baseline ALSFRS-R score, or median reduction of ALSFRS-R score (p > 0.05). The mean age of first pregnancy was 25.57 ± 4.40) years. The mean age of first pregnancy in the over 1 year group was lower than that in the within 1 year group (p= 0.01). There was no difference in the median reduction of ALSFRS-R between the two subgroups. In the univariate analysis, diagnostic delay was highly correlated with the disease progression, with short delay representing rapid progress. No multicollinearity was found among every variable. In addition, 40.38% patients carried ALS-related gene variants. The proportion with gene mutations in the within 1 year group was higher than that in the over 1 year group (p < 0.01). Furthermore, SETX was the most frequently mutated gene in this cohort (16.67%) including 4 uncertain mutation. Conclusion: Pregnancy and fertility were not associated with disease progression. Diagnostic delay was correlated with disease progression in this cohort. In addition, SETX might be a gene of concern for ALS patients of childbearing age.

Painful Diabetic Peripheral Neuropathy Study of Chinese Outpatients (PDNSCOPE): A Multicentre Cross-Sectional Registry Study of Clinical Characteristics and Treatment in Mainland China.

INTRODUCTION: This aim of this study was to delineate current clinical scenarios of painful diabetic peripheral neuropathy (PDN) and associated anxiety and depression among patients in Mainland China, and to report current therapy and clinical practices. METHODS: A total of 1547 participants were enrolled in the study between 14 June 2018 and 11 November 2019. Recruitment was conducted using a multilevel sampling method. Participants' demographics, medical histories, glucose parameters, Douleur Neuropathique 4 Questionnaire (DN4) scores, visual analogue scale (VAS) pain scores, Patient Health Questionnaire 9 (PHQ-9) scores, Generalised Anxiety Disorder 7 (GAD-7) scores and therapies were recorded. RESULTS: The male-to-female ratio was 1.09:1 (807:740), and the mean age at onset was 61.28 ± 11.23 years. The mean DN4 score (± standard deviation) was 4.91 ± 1.88. The frequencies of DN4 sub-item phenotypes were: numbness, 81%; tingling, 68.71%; pins and needles, 62.90%; burning, 53.59%; hypoaesthesia to touch, 50.16%; electronic shocks, 43.31%; hypoaesthesia to pinprick, 37.94%; brushing, 37.82%; painful cold, 29.61%; and itching, 25.86%. Age, diabetic duration, depression history, PHQ-9 score and GAD-7 score were identified as risk factors for VAS pain score. Peripheral artery disease (PAD) was a protective factor for VAS pain score. For all participants currently diagnosed with PDN and for those previously diagnosed PDN, fasting blood glucose (FBG) was a risk factor for VAS; there was no association between FBG and VAS pain score for PDN diagnosed within 3 months prior to recruitment. Utilisation rate of opium therapies among enrolled participants was 0.71% , contradiction of first-line guideline recommendation for pain relief accounted for 9.43% (33/350) and contradiction of second-line guideline recommendation for opium dosage form was 0.57% (2/350). CONCLUSION: Moderate to severe neuropathic pain in PDN was identified in 73.11% of participants. Age, diabetic duration, depression history, PHQ-9 score, GAD-7 score and FBG were risk factors for VAS pain scores. PAD was protective factor. The majority of pain relief therapies prescribed were in accordance with guidelines. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03520608, retrospectively registered, 2018-05-11.

Cerebrospinal fluid MFG-E8 as a promising biomarker of amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a fatal progressive neurodegenerative disease resulting in the dysfunction of upper and lower motor neurons. Biomarkers in fluid have been used to monitor the disease and its progression. Milk fat globule-EGF factor 8 (MFG-E8) is an inflammation modulator, which is involved in the pathogenesis of neurodegenerative diseases. We here took this study to evaluate the predictive value of MFG-E8 in ALS. METHODS: This study consisted of 19 patients with ALS and 15 healthy controls. Cerebrospinal fluid (CSF) were collected from all participants and tested for the levels of MFG-E8, neurofilament light (NFL), and heavy chain (NFH). The correlations between MFG-E8 and NFL, NFH, ALS severity, cognitive status, and forced vital capacity (FVC) were analyzed. RESULTS: We found that MFG-E8 performs well in distinguishing ALS from controls, with relatively higher level of MFG-E8 in ALS subjects, than controls. Moreover, MFG-E8 negatively correlated with the revised ALS function rating scale (ALS-FRS), but not with the levels of NFL and NFH, disease duration, progression rate, mini-mental state examination (MMSE), and FVC. CONCLUSIONS: The study proved that CSF MFG-E8 helps distinguish ALS from controls. However, the protein in CSF negatively predicted disease severity.

PRISMA - Practical meta-analysis of applying local triamcinolone acetonide injection for stenosis after esophageal cancer surgery.

OBJECTIVES: To explore the practical method of endoscopic triamcinolone acetonide (TA) injection immediately after endoscopic surgery and combined with endoscopic dilation (ED) in the management of stenosis after esophageal cancer surgery based on their efficacy and safety. METHODS: A comprehensive search was performed in electronic databases including MEDLINE, EMBASE, the Cochrane Library, Web of Science, and China National Knowledge Infrastructure for possible controlled studies. Meta-analyses of the included studies were completed using Reviewer Manager software and were reported based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses. RESULTS: Eight randomized studies and five controlled studies containing 575 patients were obtained. In five studies (n=282), TA injected after surgery reduced the risk of stenosis (risk difference [RD] =-0.51, 95% CI [-0.64, -0.39], P<0.01) and the required ED sessions (RD =-3.66, 95% CI [-5.87, -1.46], P<0.01). In eight studies (n=293), TA injection combined with ED reduced the risk of recurrence of stenosis (RD =-0.28, 95% CI [-0.47, -0.08], P<0.01) and the required ED sessions (RD =-0.71, 95% CI [-1.39, -0.04], P<0.05). TA injection therapy did not increase the risk of complications in seven studies (n=380; RD =-0.01, 95% CI [-0.04, 0.02], P=0.53) compared with control. CONCLUSION: TA injection therapy after esophageal cancer surgery and combined with ED are both effective and safe in the management of stenosis, as they reduce the risk of stenosis and sequentially the required ED sessions without increasing complications.

[Tongjingling reduces ROS level and improves mitochondrial function in spermatogenic cells of varicocele rats with liver-qi stagnation].

OBJECTIVE: To explore the effects of the Chinese herbal compound Tongjingling (TJL) on the ROS level, mitochondrial membrane potential (MMP) and mitochondrial ultrastructure in spermatogenic cells in varicocele (VC) rats with liver-qi stagnation (LQS). METHODS: Totally, 72 male SPF Wistar rats were randomly divided into six groups of equal number, sham operation, VC+LQS model, low-, medium- and high-dose TJL, and L-carnitine (LC) control. The VC+LQS model was established by the Saypol method combined with tail-clamping. At 4 weeks after modeling, the rats in the low-, medium- and high-dose TJL groups were treated intragastrically with TJL at 0.6, 1.2 and 2.4 g/ml respectively, those in the sham operation and VC+LQS model groups with 0.9% saline, and those in the LC control group with LC oral liquid at 2.1 ml/kg, qd, for 8 weeks. Then the ROS level and MMP in the spermatogenic cells were measured by flow cytometry and the mitochondrial ultrastructure observed under the transmission electron microscope. RESULTS: The ROS level in the spermatogenic cells was significantly higher in the VC+LQS model and low-dose TJL groups than in the sham operation group (ï¼»62.72 ± 9.90ï¼½% and ï¼»52.25 ± 8.15ï¼½% vs ï¼»36.53 ± 5.25ï¼½%, P < 0.01), but remarkably lower in the medium-dose TJL (ï¼»41.65 ± 4.89ï¼½%), high-dose TJL (ï¼»39.60 ± 5.19ï¼½%) and LC control (ï¼»38.33 ± 7.46ï¼½%) than in the VC+LQS model group (P < 0.01). MMP in the spermatogenic cells was significantly lower in the VC+LQS model and low-dose TJL than in the sham operation group (ï¼»34.80 ± 20.18ï¼½% and ï¼»44.39 ± 19.60ï¼½% vs ï¼»60.24 ± 22.25ï¼½%, P < 0.01 and P < 0.05), but markedly higher in the medium-dose TJL (ï¼»50.62 ± 14.83ï¼½%), high-dose TJL (ï¼»52.42 ± 7.55ï¼½%) and LC control (ï¼»50.75 ± 15.65ï¼½%) than in the VC+LQS model group (P < 0.05). The mitochondria in the spermatogenic cells of the VC+LQS model rats exhibited swelling, vacuolization, rupture or disappearance of the mitochondrial cristae, and breakdown of the internal structure. The pathological injury of the mitochondrial structure was improved in different degrees in the TJL and LC groups. CONCLUSIONS: TJL can reduce the ROS level, increase MMP and improve pathological injury of the mitochondrial ultrastructure in the spermatogenic cells of VC rats with LQS, which may be the underlying molecular mechanism of TJL improving fertility in infertile VC patients.

[Tongjingling improves sperm DNA integrity and reduces oxidative stress in the testis of experimental varicocele rats].

OBJECTIVE: To explore the protective effect of Tongjingling (TJL) against sperm DNA damage and oxidative stress in the rat model of experimental varicocele (EVC). METHODS: We randomly divided 75 Wistar male rats into five groups of equal number: sham operation, EVC model, high-dose TJL, mid-dose TJL, and low-dose TJL. The EVC model was established in the rats by partial ligation of the left renal vein, followed by 8 weeks of medication from the 4th week after modeling. Then we observed the general status of the rats, detected the sperm DNA fragmentation index (DFI) in the epididymis by sperm chromatin structure assay (SCSA), and measured the content of hydroperoxide (H2O2) and the activities of catalase (CAT) and superoxide dismutase (SOD) in the testis by colorimetry. RESULTS: Compared with the sham operation group, the EVC models showed significantly increased sperm DFI in the epididymis (P <0.01) and elevated level of H2O2 and activities of CAT and SOD in the testis (P <0.01). In comparison with the EVC models, the rats of the TJL groups exhibited remarkably reduced sperm DFI and H2O2 content, but increased activities of SOD and CAT. CONCLUSIONS: TJL can improve sperm DNA integrity by increasing the activities of SOD and CAT and reducing the H2O2 level and hence oxidative stress in the testis tissue.

[Correlation between Fractional Anisotropy and Amyotrophic Lateral Sclerosis, and Effect of Inte- grative Medical Treatment on ALS].

OBJECTIVE: To explore whether fractional anisotropy (FA) value could be taken as a quantitative indicator for tracing and reexamining amyotrophic lateral sclerosis (ALS), and to analyze the correlation between FA value and integrative medical treatment. METHODS: Totally 18 ALS patients were recruited in this study. All patients received diffusion tensor imaging (DTI) using 3. OT (Propeller HD) MRI twice. Six regions of interest (ROI) were selected to measure FA values. Survival analyses were performed in 11 cases of end point events. RESULTS: (1) Three ROI (cerebral peduncle, posterior limb of internal capsule, and corona radiata) all indicated that FA value was the highest in patients with mild health status scale of amyotrophic lateral sclerosis (ALS/HSS). (2) There was statistical difference in the means of FA values in cerebral peduncle, posterior limb of internal capsule, and corona radiata of 18 cases between initial examination and reexamination (P < 0.01). (3) Kaplan-Meier survival curve showed the survival rate of ALS patients decreased as time went by, with the median survival time of 48 months. CONCLUSIONS: FA value was inversely proportional to the severity of ALS, the more severe, the lower FA values. FA value was an objective indicator for assessing the severity of ALS. ALS is an incurable disease till now. Integrative medical treatment might become one direction for ALS patients.

Considerations on intervention goal and efficacy evaluation of traditional Chinese medicine in the treatment of neurological diseases.

In the last several years, traditional Chinese medicine (TCM) has made much progress in the treatment of neurological diseases. The living space of TCM in neurological diseases lies in refractory diseases, aging and chronic diseases caused by multiple factors as well as sub-health state and chronic fatigue state. The effect model of TCM mainly consists of whole effect, self-organization, self-stable model, holographic effect and butterfly effect. The effective point of TCM in neurological diseases lies mainly in end-points and health-related events. Moreover, TCM has advantages in the evaluation of symptoms, syndrome and quality of life (QOL). Some key indexes should be included when evaluating the efficacy of TCM in neurological diseases. Meanwhile, the advantages of TCM such as end-points, health-related events and QOL should be highlighted. Multi-subject researching methods could be adopted to make a comprehensive evaluation of subjective and objective indexes. The clinical evidence on the TCM efficacy evaluation may come from RCTs, and other types of designs can also be considered.

[Thinking and challenge induced by the hypothesis of breaking stagnant and eliminating blood stasis in Treating acute cerebral hemorrhage by rF VII a].

Definite therapeutic effect has obtained by TCM in treating acute cerebral hemorrhage (ACH) according the TCM theory of "blood circulating outside the vessels is the stasis" using breaking stagnant and eliminating blood stasis (Poxue Zhuyu) method, but no material involving the natural development of stoke in superacue stage (0 - 4 hrs after onset of the disease) being presented so far. It has been proved by randomized, double-blinded multi-centeric clinical trials that recombinant activated factor VII (rF VII a) could decreased the morbidity and disability of patients suffered from ACH, suggesting that use hemostasis treatment in ACH during superacu stage should be stressed, and the drugs for Poxue Zhuyu should be used cautiously in the period of 0 - 4 hrs after onset. The hemorrhagic disorder could be eliminated by using drugs for Poxue Zhuyu and other medicines in rational combination.