Combinations of scalp acupuncture location for the treatment of post-stroke hemiparesis: A systematic review and Apriori algorithm-based association rule analysis.

Background: Post-stroke hemiparesis strongly affects stroke patients' activities of daily living and health-related quality of life. Scalp acupuncture (SA) is reportedly beneficial for post-stroke hemiparesis. However, there is still no standard of SA for the treatment of post-stroke hemiparesis. Apriori algorithm-based association rule analysis is a kind of "if-then" rule-based machine learning method suitable for investigating the underlying rules of acupuncture point/location selections. This study aimed to investigate the core SA combinations for the treatment of post-stroke hemiparesis by using a systematic review and Apriori algorithm-based association rule analysis. Methods: We conducted a systematic review to include relevant randomized controlled trial (RCT) studies investigating the effects of SA treatment in treating patients with post-stroke hemiparesis, assessed by the Fugl-Meyer Assessment (FMA) score. We excluded studies using herbal medicine or manual acupuncture. Results: We extracted 33 SA locations from the 35 included RCT studies. The following SA styles were noted: International Standard Scalp Acupuncture (ISSA), WHO Standard Acupuncture Point Locations (SAPL), Zhu's style SA, Jiao's style SA, and Lin's style SA. Sixty-one association rules were investigated based on the integrated SA location data. Conclusions: SAPL_GV20 (Baihui), SAPL_GV24 (Shenting), ISSA_MS6_i (ISSA Anterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_MS7_i (ISSA Posterior Oblique Line of Vertex-Temporal, lesion-ipsilateral), ISSA_PR (ISSA Parietal region, comprised of ISSA_MS5, ISSA_MS6, ISSA_MS7, ISSA_MS8, and ISSA_MS9), and SAPL_Ex.HN3 (Yintang) can be considered the core SA location combination for the treatment of post-stroke hemiparesis. We recommend a core SA combination for further animal studies, clinical trials, and treatment strategies.

Combined Administration of Curcumin and Chondroitin Sulfate Alleviates Cartilage Injury and Inflammation via NF-κB Pathway in Knee Osteoarthritis Rats.

Objective: Osteoarthritis (OA) is a degenerative chronic disease that most often occurs in the knee joint. Studies have shown that some food supplements, such as curcumin and chondroitin sulfate, are effective in treating knee osteoarthritis (KOA) by exhibiting different protective effects. In this study, we further investigated the combined therapeutic effects of curcumin and chondroitin sulfate on cartilage injury in rats with arthritis. Methods: An experimental KOA model was induced by monosodium iodoacetate (MIA) in rats. All rats were randomly divided into five groups: Ctrl (control), model (saline), Cur (20 mg/kg curcumin in saline), CS (100 mg/kg chondroitin sulfate in saline), and CA (20 mg/kg curcumin and 100 mg/kg chondroitin sulfate in saline); drugs were given 2 weeks after MIA injection. The histomorphological changes of cartilage were observed by safranin fast green staining, H&E staining, and micro-CT scanning. Also, the levels of PGE2, TNF-α and IL-1ß in the arthral fluid and serum were determined by the ELISA kits. The activities of SOD, CAT, COMP, MMP-3, and type II collagen were detected by biochemical kits. The expressions of TLR4, p-NF-κB, NF-κB, and COX-2 in cartilage were detected by Western blot. Results: Data show that serum levels of IL-1ß (p < 0.05), SOD (p < 0.0001), and MMP-3 (p < 0.001) were downregulated significantly in the CA group when compared to those in the model group. Meanwhile, obvious repair of cartilage with higher contains collagen II (p < 0.0001) could be observed in the CA group than the ones in Cur or CS group. In addition, significant downregulation of the expression of p-p65/p65 (p < 0.05) was found in the CA group. Conclusion: Our findings showed that combined administration of curcumin and chondroitin sulfate could exert better repair for KOA in rat models. This may hold great promise for discovering potential drugs to treat KOA and may improve treatment options for it.

Asperuloside inhibited epithelial-mesenchymal transition in colitis associated cancer via activation of vitamin D receptor.

BACKGROUND: Asperuloside is a natural compound extracted from various herbs with several bioactivities. Its effects on anti-inflammation and anti-tumor indicated that asperuloside might prevent colorectal cancer developing from inflammatory bowel diseases (IBD). But there were few reports about the efficacy and mechanism of asperuloside on improving colorectal cancer. It has been reported that vitamin D receptor (VDR) could regulate the expression of SMAD3. In previous study, asperuloside could significantly improve the expression of VDR and reduced Smad3 mRNA in IEC-6 cell. PURPOSE: The present study was aimed to investigate the potential mechanism of asperuloside on inhibiting epithelial-mesenchymal transition (EMT) in colitis associated cancer. STUDY DESIGN: First, in LPS-injured IEC-6 cell, asperuloside inhibited phosphorylated p65 (p-p65) level, improved VDR expression and reduced Smad3 mRNA. Second, we wonder the relationship between VDR signaling and nucleus factor-kappaB (NF-κB) signaling during asperuloside on reducing Smad3 mRNA. And then, the effect of asperuloside on inhibiting EMT development through VDR/Smad3 was investigated. Finally, we testified the effect of asperuloside on protecting against colitis associated cancer (CAC) by inhibiting EMT development through VDR/Smad3. METHODS: Pyrrolidinedithiocarbamate ammonium (PDTC) was used for established NF-κB-inhibited IEC-6 cell. This cell was applied for investigating the relationship between NF-κB and VDR of asperuloside on inhibiting Smad3. VDR-inhibited cell was established by small interfering RNA (siRNA) of VDR and was employed to investigate the role of VDR for asperuloside on decreasing Smad3. Transforming growth factor ß1 (TGFß1) was used for inducing EMT/fibrosis in IEC-6 cell. TGFß1-stimulated cell was used for testifying the effect of asperuloside on inhibiting EMT development. AOM/DSS-induced CAC was established to investigate the effect of asperuloside on suppressing cancer development. RESULTS: Asperuloside inhibited the level of p-p65 which was up-regulated by LPS. Asperuloside could up-regulate VDR signaling and reduce Smad3 mRNA in NF-κB-knockdown IEC-6 cells. Asperuloside failed to reduce Smad3 mRNA due to VDR knockdown, which implied that asperuloside might down-regulate Smad3 mRNA dependently on activation of VDR signaling and independently on inhibiting NF-κB signaling. Asperuloside exhibited significant prevention of EMT development in TGFß1-induced IEC-6 cell (EMT cell) and mice CAC. Asperuloside reduced the transform of epithelial phenotype into motile mesenchymal phenotype in EMT cell along with decreasing levels of EMT markers by inhibiting Smad3 mRNA via activation of VDR. In mice with CAC, expression of VDR in colon was improved by asperuloside. Symptoms of colitis, tumor number and tumor size were significantly inhibited by asperuloside. Suppressed EMT development was determined by reduced α-SMA expression and decreased mRNAs of several EMT markers. CONCLUSION: Asperuloside might prevent CAC through inhibiting EMT development via regulation of VDR/Smad3 pathway.

Acupuncture and Traditional Chinese Herbal Medicine Integrated With Conventional Rehabilitation for Post-stroke Functional Recovery: A Retrospective Cohort Study.

Background: Stroke leads to tremendous impacts on patients and the healthcare system. It is crucial to explore the potential management of rehabilitation. Acupuncture and traditional Chinese herbal medicine (TCHM) integrated with conventional rehabilitation benefit post-stroke functional recovery. Methods: We retrospectively reviewed the medical records of all patients included in the Integrated Traditional Chinese-Western Medicine care program for stroke (ITCWM-stroke care program) in 2019 in Taipei Tzu Chi Hospital to investigate the effects of acupuncture and TCHM integrated with conventional rehabilitation on National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores before and after the program. Results: A total of 255 stroke inpatients were retrieved and divided into acupuncture and acupuncture + TCHM group by hemorrhagic and ischemic stroke types, respectively. All the patients were recruited in the program at the early subacute phase after stroke onset. Of the hemorrhagic and ischemic stroke subjects, the NIHSS and BI total scores were significantly improved in the acupuncture and acupuncture + TCHM groups. The subgroup analysis results showed that in subjects with a baseline BI score ≤ 40, the acupuncture + TCHM group significantly improved BI total score better than the acupuncture group in both hemorrhagic (p < 0.05) and ischemic (p < 0.05) stroke subjects. Conclusion: Acupuncture and TCHM integrated with conventional rehabilitation significantly improve stroke patients' functional recovery at the early subacute phase. Acupuncture + TCHM contributes to better activities of daily living (ADL) improvements in stroke patients with a baseline BI score ≤ 40. We suggest integrating acupuncture and TCHM into the post-stroke rehabilitation strategy, especially for stroke patients with poor ADL function.

Chicoric Acid Attenuated Renal Tubular Injury in HFD-Induced Chronic Kidney Disease Mice through the Promotion of Mitophagy via the Nrf2/PINK/Parkin Pathway.

As the main factor in the pathogenesis of chronic kidney disease (CKD), the excessive apoptosis of renal tubular epithelial cells (RTECs) and its underlying mechanism of action are worth further investigation. Chicoric acid (CA), a major active constituent of the Uyghur folk medicine chicory, was recorded to possess a renal protective effect. The precise effect of CA on renal tubular injury in obesity-related CKD remains unknown. In the current study, CA was proven to ameliorate metabolic disorders including overweight, hyperglycemia, hyperlipidemia, and hyperuricemia in high fat diet (HFD)-fed mice. Furthermore, the reverse effect of CA on renal histological changes and functional damage was confirmed. In vitro, the alleviation of lipid accumulation and cell apoptosis was observed in palmitic acid (PA)-exposed HK2 cells. Treatment with CA reduced mitochondrial damage and oxidative stress in the renal tubule of HFD-fed mice and PA-treated HK2 cells. Finally, CA was observed to activate the Nrf2 pathway; increase PINK and Parkin expression; and regulate LC3, SQSTM1, Mfn2, and FIS1 expression; therefore, it would improve mitochondrial dynamics and mitophagy to alleviate mitochondrial damage in RTECs of obesity-related CKD. These results may provide fresh insights into the promotion of mitophagy in the prevention and alleviation of obesity-related CKD.

Improvement of Skin Barrier Dysfunction by Phenolic-containing Extracts of Lycium barbarum via Nrf2/HO-1 Regulation.

Lycium barbarum have received an increasing popularity due to its powerful biological activity and medicinal use. However, the effect of Lycium barbarum on skin remains largely uncharacterized. The general purpose of this paper was to characterize the phenolic compounds in Lycium barbarum extract (LBE) using LC-HRMS/QTOF method and to investigate whether topical administration of LBE can repair skin barrier dysfunction in mice. Our data demonstrated that LBE could not only decrease ROS level and matrix metalloproteinase expression, but also strengthen intrinsic antioxidant defense system including SOD, GSH-Px and CAT, thereby resulting in increased skin collagen content and an improvement of UV-induced skin erythema, thickness and wrinkles. Improved skin barrier functions were highly correlated with increased expression of filaggrin, involucrin and loricrin as well as antioxidant proteins such as Nrf2 and HO-1 in UV-irradiated mice, suggesting that LBE may be promising natural products at a lower cost for the topical application in the treatment of skin diseases with defective barrier function.

[Analysis and considerations on revision of instructions for traditional Chinese medicine injections].

According to the notice on revision of the instructions for traditional Chinese medicine injections(TCMIs) issued by the National Medical Products Administration(NMPA) from January 2006 to May 2020, the revised contents in the instructions for 29 varieties involved in the notice were sorted out, and the existing problems in the instructions for TCMIs were analyzed, so as to provide the basis for dynamic revision of the instructions. It was found that the revised items of instructions for 29 varieties all involved adverse reactions, contraindications and precautions, and warnings were added for 82.76% of 29 TCMIs preparations, indicating that all the revised contents were related to safety issues. In addition, 33.33% of the drugs risks mentioned in the precautions were not indicated in the adverse reactions; 82.76% instructions did not indicate drug interactions; 17.24% instructions lacked medication notes for special populations; 48.28% instructions did not indicate traditional Chinese medicine(TCM) syndromes of the main disease; 44.83% instructions did not indicate the type and stage of indication; and 86.21% instructions did not indicate the course of treatment. It could be concluded that the instructions for TCMIs have known risks of drugs that are not fully reflected in adverse reactions and the effective information is not comprehensive. The risk control measures proposed in the precautions need to have aftereffect evaluation and there is a lack of drug interactions and medications for special populations. As an important part of the full life-cycle management of drugs, the revision of instructions for TCMIs should be continuously improved to provide the basis for safe and reasonable application of TCMIs. Based on the above problems, it is proposed that the marketing license holder as the main body of the revision of instructions should actively carry out post-marketing basic and clinical research in accordance with the characteristics of TCM, combine the updated research with the guidance of TCM theory and improve the revision level of instructions for TCMIs to provide the basis for post-marketing evaluation.

Ergostatrien-3ß-ol (EK100) from Antrodia camphorata Attenuates Oxidative Stress, Inflammation, and Liver Injury In Vitro and In Vivo.

Hepatic ischemia/reperfusion (IR) injury is a complication that occurs during liver surgery, whereby hepatic tissue is injured by oxygen deficiency during ischemia, then further damaged by a cascade of inflammatory and oxidative insults when blood is resupplied during reperfusion. Antrodia camphorata is an indigenous fungus in Taiwan and an esteemed Chinese herbal medicine with various bioactivities. This study examined the effect of ergostatrien-3ß-ol (EK100), an active compound found in both the fruiting body and mycelia of A. camphorata, on IR injury pathologies in rats and cell models of oxidative and inflammatory stress. Male Sprague-Dawley rats were randomly assigned to receive a vehicle or 5 mg/kg EK100 prior to hepatic IR injury induced by 1 h ischemia followed by 24 h reperfusion, or a sham operation. RAW 264.7 murine macrophages and HepG2 hepatocytes were pretreated with EK100, then inflammation was induced with lipopolysaccharides in the former and oxidative stress was induced with hydrogen peroxide in the latter. EK100 decreased IR-induced elevation in serum levels of alanine aminotransferase and aspartate aminotransferase and lowered levels of the inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-1ß. In addition, EK100 significantly reduced hepatic mRNA levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2, as well as nitrite production and iNOS gene expression in both hepatocyte and macrophage cell lines. We demonstrated that EK100 exhibits potent protec-tion against hepatic IR injury, which may be used to design strategies to ameliorate liver damage during liver surgery.

Chinese olive (Canarium album L.) fruit regulates glucose utilization by activating AMP-activated protein kinase.

A growing body of evidence demonstrates obesity-induced insulin resistance is associated with the development of metabolic diseases. This study was designed to investigate ethyl acetate fraction of Chinese olive fruit extract (CO-EtOAc)-mediated attenuation of obesity and hyperglycemia in a mouse model. About 60% HFD-fed mice were treated intragastrically with CO-EtOAc for last 6 weeks, and body weight, blood biochemical parameters as well as hepatic inflammation response were investigated. Our results showed that CO-EtOAc treatment significantly reduced the formation of hepatic lipid droplets, body weight gain, blood glucose, and improved serum biochemical parameters in HFD-induced obese and insulin resistant mice. We further explored the molecular mechanism underlying the blood glucose modulating effect of CO-EtOAc using L6 myotubes model. We conclude that CO-EtOAc effectively increases the glycogen content and glucose uptake by stimulating the membrane translocation of glucose transporter 4. In addition, CO-EtOAc depolarizes the mitochondrial membrane and decreases the mitochondrial oxygen consumption, which may result in AMPK activation and the consequent mitochondrial fission. This study shows that CO-EtOAc prevents the development of obesity in mice fed with HFD and is also capable of stimulating glucose uptake. The possible mechanism might be due to the effects of CO-EtOAc on activation of AMPK and promotion of mitochondrial fission.

D-methionine improves cisplatin-induced anorexia and dyspepsia syndrome by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration.

BACKGROUND: Cisplatin is a widely used antineoplastic drug. However, cisplatin-induced dyspepsia syndromes, including delayed gastric emptying, gastric distension, early satiety, nausea, and vomiting, often force patients to take doses lower than those prescribed or even refuse treatment. D-methionine has an appetite-enhancing effect and alleviates weight loss during cisplatin treatment. METHODS: This work established a model of anorexia and dyspepsia symptoms with intraperitoneal injection of cisplatin (5 mg/kg) once a week for three cycles. Presupplementation with or without D-methionine (300 mg/kg) was performed. Orexigenic and anorexigenic hormones (ghrelin, leptin, and glucagon-like peptide-1), tryptophan hydroxylase 1 (TPH1), 5-hydroxytryptamine receptors (5-HT2C and 5-HT3 ), and hypothalamic feeding-related peptides were measured by immunohistochemistry staining, enzyme-linked immunosorbent assay, and real-time PCR assay. KEY RESULTS: Cisplatin administration caused marked decrease in appetite and body weight, promoted adipose and fat tissue atrophy, and delayed gastric emptying and gastric distension, and D-methionine preadministration prior to cisplatin administration significantly ameliorated these side effects. Besides, cisplatin induced an evident increase in serum ghrelin level, TPH1 activity, and 5-HT3 receptor expression in the intestine and decreased plasma leptin levels and gastric ghrelin mRNA gene expression levels. D-methionine supplementation recovered these changes. The expression of orexigenic neuropeptide Y/agouti-related peptide and anorexigenic cocaine- and amphetamine-regulated transcript proopiomelanocortin neurons were altered by D-methionine supplementation in cisplatin-induced anorexia rats. CONCLUSIONS AND INFERENCES: D-methionine supplementation prevents cisplatin-induced anorexia and dyspepsia syndrome possibly by attenuating intestinal tryptophan hydroxylase 1 activity and increasing plasma leptin concentration. Therefore, D-methionine can be used as an adjuvant therapy for treating cisplatin-induced adverse effects.

Efficacy of Two-Stage Treatment of Onychomycosis Using a Long-Pulsed Nd:YAG 1064-nm Laser.

OBJECTIVES: Onychomycosis is a fungal infection of the nail bed, nail matrix, and nail plate. Lasers have recently been studied as future clinical options for onychomycosis. We sought to evaluate the efficacy of the long-pulsed Nd:YAG 1064-nm laser on onychomycosis using a two-stage treatment. METHODS: A total of 100 affected nails (88 toenails and 12 fingernails from 22 patients) were treated using a long-pulsed Nd:YAG 1064-nm laser. The self-controlled treatment schedule included the first stage (1 session per week for 8 weeks) and the second stage (1 session every 4 weeks for 16 weeks). Patients were followed up with for 12 weeks after the last laser treatment. Direct microscopy, cultures, and clinical assessments were performed at various time points. RESULTS: Of the nails studied, 84% were infected by Trichophyton rubrum, while others were coinfected with T. rubrum and other fugal strains. The mycological clearance rate and the clinical efficacy rate of the nails were 29% and 21% after the first stage, 69% and 35% after the second stage, and 67% and 39% during follow-up, respectively. The second stage of laser treatment significantly improved the mycological clearance and clinical efficacy. CONCLUSION: Long-pulsed Nd:YAG 1064-nm laser two-stage treatment was effective for onychomycosis, with significantly improved mycological clearance and clinical efficacy. This trial is registered with ChiCTR 1900021669.

Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway.

Salvianolic acid A (Sal A), a bioactive compound isolated from the Chinese medicinal herb Danshen, is used for the prevention and treatment of cardiovascular diseases. However, the protective function of Sal A on preserving the role of blood-spinal cord barrier (BSCB) after spinal cord injury (SCI) is unclear. The present study investigated the effects and mechanisms of Sal A (2.5, 5, 10mg/kg, i.p.) on BSCB permeability at different time-points after compressive SCI in rats. Compared to the SCI group, treatment with Sal A decreased the content of the Evans blue in the spinal cord tissue at 24h post-SCI. The expression levels of tight junction proteins and HO-1 were remarkably increased, and that of p-caveolin-1 protein was greatly decreased after SCI Sal A. The effect of Sal A on the expression level of ZO-1, occluding, and p-caveolin-1 after SCI was blocked by the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP). Also, Sal A inhibited the level of apoptosis-related proteins and improved the motor function until 21days after SCI. In addition, Sal A significantly increased the expression of microRNA-101 (miR-101) in the RBMECs under hypoxia. AntagomiR-101 markedly increased the RBMECs permeability and the expression of the Cul3 protein by targeting with 3'-UTR of its mRNA. The expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and HO-1 was significantly increased after agomiR-101 treatment. Therefore, Sal A could improve the recovery of neurological function after SCI, which could be correlated with the repair of BSCB integrity by the miR-101/Cul3/Nrf2/HO-1 signaling pathway.

[LUTS in BPH patients with histological prostatitis before and after transurethral resection of the prostate].

OBJECTIVE: To investigate the effects of transurethral resection of the prostate (TURP) on lower urinary tract symptoms (LUTS) in patients with benign prostatic hyperplasia (BPH) complicated by histological prostatitis. METHODS: This study included 432 cases of BPH pathologically confirmed after TURP. Excluding those with LUTS-related factors before and after surgery and based on the international prostatitis histological classification of diagnostic criteria, the remaining 144 cases were divided into groups A (pure BPH, n = 30), B (mild inflammation, n = 55), C (moderate inflammation, n = 31), and D (severe inflammation, n = 28). Each group was evaluated for LUTS by IPSS before and a month after surgery. RESULTS: A total of 399 cases (92.4%) were diagnosed as BPH with histological prostatitis, 269 (67.4%) mild, 86 (21.6%) moderate and 44 (11.0%) severe. The preoperative IPSS was 21.43 +/- 6.09 in group A, 21.75 +/- 5.97 in B, 27.84 +/- 4.18 in C and 31.00 +/- 2.92 in D, with statistically significant differences among different groups (P < 0.001) except between A and B (P = 1.000); the postoperative IPSS was 5.60 +/- 2.16 in A, 7.36 +/- 2.77 in B, 11.55 +/- 3.39 in C and 16.89 +/- 3.37 in D, with statistically significant differences among different groups (P < 0.01), and remarkably lower than the preoperative one (P < 0.001). Almost all the infiltrating inflammatory cells in BPH with histological prostatitis were lymphocytes. CONCLUSION: BPH is mostly complicated with histological chronic prostatitis. The severity of LUTS is higher in BPH patients with histological prostatitis than in those without before and after TURP, and positively correlated with the grade of inflammation. Those complicated with moderate or severe histological prostatitis should take medication for the management of LUTS.

Ultrasound-assisted extraction of phillyrin from Forsythia suspensa.

Forsythia suspensa (Thunb.) Vahl is one of the most widely used traditional Chinese medicines, and possesses important biological activities, such as antibacterial, antiviral, anti-inflammatory and antioxidant activities. Phillyrin is the main bioactive component of Forsythia suspensa. In this paper, ultrasound-assisted extraction of phillyrin from Forsythia suspensa was studied with HPLC-photodiode array detection. Effects of several experimental parameters, such as type and concentration of extracting solvent, ratio of liquid to material, extraction temperature, and time of sonication on extraction efficiencies of phillyrin from Forsythia suspensa were evaluated. The optimal extraction conditions were 1g plant sample with 10 ml of 20% methanol and the extraction for 60 min at 60°C under ultrasonic irradiation. Under the optimum conditions, the yield of phillyrin was 0.713±0.009 mg/g. The results indicated that the ultrasound-assisted extraction is a very useful method for the extraction of important phytochemicals from plant materials.