Chemical Synthesis and Antigenicity Evaluation of an Aminoglycoside Trisaccharide Repeating Unit of Pseudomonas aeruginosa Serotype O5 O-Antigen Containing a Rare Dimeric-ManpN3NA.

Pseudomonas aeruginosa bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent medical need. While the immunological activity of lipopolysaccharide O-antigens in P. aeruginosa is well-known, the specific protective epitopes remain unidentified. Herein, we present the first chemical synthesis of highly functionalized aminoglycoside trisaccharide 1 and its acetamido derivative 2 found in the P. aeruginosa serotype O5 O-antigen. The synthesis of the trisaccharide targets is based on balancing the reactivity of disaccharide acceptors and monosaccharide donors. Glycosylations were analyzed by quantifying the reactivity of the hydroxyl group of the disaccharide acceptor using the orbital-weighted Fukui function and dual descriptor. The stereoselective formation of 1,2-cis-α-fucosylamine linkages was achieved through a combination of remote acyl participation and reagent modulation. The simultaneous SN2 substitution of azide groups at C2' and C2″ enabled the efficient synthesis of 1,2-cis-ß-linkages for both 2,3-diamino-D-mannuronic acids. Through a strategic orthogonal modification, the five amino groups on target trisaccharide 1 were equipped with a rare acetamidino (Am) and four acetyl (Ac) groups. Glycan microarray analyses of sera from patients infected with P. aeruginosa indicated that trisaccharides 1 and 2 are key antigenic epitopes of the serotype O5 O-antigen. The acetamidino group is not an essential determinant of antibody binding. The ß-D-ManpNAc3NAcA residue is a key motif for the antigenicity of serotype O5 O-antigen. These findings serve as a foundation for the development of glycoconjugate vaccines targeting P. aeruginosa serotype O5.

Chemical Synthesis and Antigenicity Evaluation of Shigella dysenteriae Serotype 10 O-Antigen Tetrasaccharide Containing a (S)-4,6-O-Pyruvyl Ketal.

Shigella is the second most common etiologic pathogen responsible for childhood acute diarrhea. An anti-Shigella vaccine is still eagerly awaited due to the increasing drug resistance of this pathogen. The Shigella O-antigen is a promising vaccine target. To identify the immune epitopes of the glycan, the first total synthesis of Shigella dysenteriae serotype 10 O-antigen tetrasaccharide containing a (S)-4,6-O-pyruvyl ketal was completed. The 1,2-trans-ß-glycosylation & C2 epimerization and conformational locking strategies facilitated the construction of two 1,2-cis-ß-glycosidic linkages. The reactivities of both the glycosyl donor and acceptor were improved by adding electron-donating benzyl groups, enabling an efficient assembly of the tetrasaccharide. The (S)-4,6-O-pyruvyl ketal was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency. In addition, (R)-4,6-O-pyruvylated and nonpyruvylated tetrasaccharides and three further fragments were synthesized. Glycan microarray screening revealed that the tetrasaccharide repeating unit is the key antigenic epitope of the O-antigen. Moreover, the (S)-4,6-O-pyruvyl ketal is an essential structural feature of this antigen for designing carbohydrate-based vaccines against S. dysenteriae serotype 10. The comparison of the (S)-4,6-O-pyruvylated glycan and its (R)-epimer will set an example for biological evaluation of other bacterial glycans containing pyruvyl ketals.

Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide.

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2→5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via α-stereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2-deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.

Effectiveness of Paroxetine for Poststroke Depression: A Meta-Analysis.

OBJECTIVE: The purpose of our study is to evaluate the efficacy of paroxetine in poststroke depression (PSD) patients by conducting a meta-analysis. METHODS: We searched Web of Science (science and social science citation index), PubMed, the Cochrane Central Register of Controlled Trials, Embase up to August 2019. Randomized controlled trials that paroxetine compared to other antidepressants or control treatments as monotherapy for patients with PSD. RESULTS: This review identified a total of 4 studies including 212 patients. This meta-analysis presented that paroxetine exhibits beneficial efficacy than routine treatment in PSD patients in terms of the reducing score of Hamilton Depression Scale (HAMD). Control treatment is more effective than paroxetine. No significant advantage was found with paroxetine. CONCLUSIONS: The efficacy of paroxetine maybe not very significant compared to other pharmacological and nonpharmacological interventions. Further high quality and large sample size studies are needed to evaluate the efficacy and safety of paroxetine in treating PSD in future.

[Effects of Geniposide on the Neuroinflammation in Chronic Cerebral Hypoperfusion Rat Model].

OBJECTIVE: To investigate the effects and the mechanism of geniposide on the neuroinflammation occured in the neurodegeneration course of a chronic cerebral hypoperfusion rat model. METHODS: Permanent bilateral common carotid arteries occlusions was performed to induce gradient cognitive deficit in rats. The sham group was used as control group. Then 18 rats that met the Screening Criteria were randomly selected 8 weeks post surgery, and were randomly divided into three groups, the 2-VO rats with saline solution group (2-VO+saline group), 2-VO rats with 50 mg/kg per day geniposide group (2-VO+G50) and 2-VO rats with 100 mg/kg per day geniposide group (2-VO+G100). All intervention groups were daily administered with geniposide or saline for 4 weeks. The sham-operated rats were administrated with saline. Then the rats were tested for Morris water maze to evaluate the memory and learning ability. Rats were sacrificed to obtain cortex and hippocampus tissues for HE staining and to detect expression level of glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-κB), and the level of inflammatory factors tumor necrosis factor-α (TNF-α) and interleukin (IL)-6. RESULTS: The 2-VO+saline group rats showed significant longer escape latency and less percent time in target quadrant, compared with sham-operation group ( P<0.05). The escape latency of 2-VO+G50 and 2-VO+G100 groups were shorter than the 2-VO+saline group ( P<0.05), but still longer than the sham group ( P<0.05), the percent time in target quadrant of which were more than the 2-VO+saline group and less than the sham group. However, there was no significant difference between these two groups. HE staining of sham group showed that neurons in the cortex and hippocampus lined up in order, cellar nucleus were big and globular. HE staining results showed that there were obviously neuoral cells loss, severe cytomorphosis, structural disappearance and nuclear fragmentation in the 2-VO+saline group. The 2-VO+G50 and 2-VO+G100 groups showed less neurodamage than the 2-VO+saline group with less neuoral cells loss, cytomorphosis and ambiguous nucleus. GFAP, iNOS, NF-κB were all highly expressed in the process of cognitive dysfunction in rats after chronic cerebral ischemia, however geniposide intervention (50 and 100 mg/kg per day) significantly decreased the expression of the above proteins. In addition, much more TNF-α and IL-6 were released in brain induced by chronic cerebral ischemia, and the levels were decreased after chronic geniposide oral treatment. No significant differences were detected between 2-VO+G50 and 2-VO+G100 groups. CONCLUSION: These findings demonstrated that geniposide significantly prevented cognition deterioration induced by chronic cerebral hypoperfusion in rats. Geniposide inhibited neuroinflammation occurred in the process of chronic cerebral ischemia probably via reducing iNOS and NF-κB expression and suppressing the release of inflammatory factor TNF-α and IL-6.

Chemical Synthesis Elucidates the Key Antigenic Epitope of the Autism-Related Bacterium Clostridium bolteae Capsular Octadecasaccharide.

The gut pathogen Clostridium bolteae has been associated with the onset of autism spectrum disorder (ASD). To create vaccines against C. bolteae, it is important to identify exact protective epitopes of the immunologically active capsular polysaccharide (CPS). Here, a series of C. bolteae CPS glycans, up to an octadecasaccharide, was prepared. Key to achieving the total syntheses is a [2+2] coupling strategy based on a ß-d-Rhap-(1→3)-α-d-Manp repeating unit that in turn was accessed by a stereoselective ß-d-rhamnosylation. The 4,6-O-benzylidene-induced conformational locking is a powerful strategy for forming a ß-d-mannose-type glycoside. An indirect strategy based on C2 epimerization of ß-d-quinovoside was efficiently achieved by Swern oxidation and borohydride reduction. Sequential glycosylation, and regioselective and global deprotection produced the disaccharide and tetrasaccharide, up to the octadecasaccharide. Glycan microarray analysis of sera from rabbits immunized with inactivated C. bolteae bacteria revealed a humoral immune response to the di- and tetrasaccharide, but none of the longer sequences. The tetrasaccharide may be a key motif for designing glycoconjugate vaccines against C. bolteae.

Chemical Synthesis and Immunological Evaluation of Helicobacter pylori Serotype O6 Tridecasaccharide O-Antigen Containing a dd-Heptoglycan.

The development of glycoconjugate vaccines against Helicobacter pylori is challenging. An exact epitope of the H. pylori lipo-polysaccharide (LPS) O-antigens that contain Lewis determinant oligosaccharides and unique dd-heptoglycans has not yet been identified. Reported here is the first total synthesis of H. pylori serotype O6 tridecasaccharide O-antigen containing a terminal Ley tetrasaccharide, a unique α-(1→3)-, α-(1→6)-, and α-(1→2)-linked heptoglycan, and a ß-d-galactose connector, by an [(2×1)+(3+8)] assembly sequence. Seven oligosaccharides covering different portions of the entire O-antigen were prepared for immunological investigations with a particular focus on elucidation of the roles of the dd-heptoglycan and Ley tetrasaccharide. Glycan microarray analysis of sera from rabbits immunized with isolated serotype O6 LPS revealed a humoral immune response to the α-(1→3)-linked heptoglycan, a key motif for designing glycoconjugate vaccines for H. pylori serotype O6.

Study on uranium leaching from uranium purification residue with ammonium hydrogen fluoride.

Residues generated from the uranium purification process, characterized by a high uranium content, pose a significant challenge for recovery through leaching and present a considerable environmental threat. After using XRD and SEM-mapping characterization analysis combined with the BCR continuous graded extraction test to analyze the content of different states of uranium, it was found that the main reason why the uranium in the residue was difficult to leach because it was encapsulated by SiO2 crystals. Using NH4HF2 as a leaching agent, a leaching study of uranium in the residue was carried out, and the results showed that the H+ and F- produced by NH4HF2could react with SiO2, destroying the crystal lattice of SiO2 and causing the encapsulated uranium to come into contact with the leaching agent, facilitating the leaching of uranium in the residue. The optimum conditions for uranium leaching were 10% mass fraction of NH4HF2, a liquid-solid ratio of 30:1, a reaction temperature of 30 °C and a reaction time of 120 min, and the leaching efficiency of uranium from the residue was as high as 98.95%. The leaching kinetics of uranium by NH4HF2 were consistent with the mixed controlled model in the shrinking core models, indicating that the surface chemical reaction and mass diffusion dominated both uranium leaching processes. This may provide a viable method for resource recovery and the treatment of uranium purification residues.

Effectiveness and safety of thoracic manipulation in the treatment of neck pain: An updated systematic review and meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). OBJECTIVE: The purpose of this meta-analysis was to evaluate the effectiveness and safety of thoracic manipulation (TM) in patients with neck pain (NP). METHODS: Seven electronic databases were searched from their inception through October 2023 by two authors. The methodological quality assessments were performed with the Physiotherapy Evidence Database (PEDro) scale. Pain, cervical range of motion (ROM), disability, and quality of life (QOL) were estimated for TM treatment in patients with NP. RESULTS: Eighteen randomized controlled trials (RCTs) with 914 patients were included with a PEDro score of 6.923 ± 3.120. Pooled effect sizes of pain (SMD =-0.481, 95% CI -0.653 to -0.309, P= 0.000), disability (SMD =-1.435, 95% CI -2.480 to -0.390, P= 0.007), QOL-physical component score (PCS) (SMD = 0.658, 95% CI 0.290 to 1.025, P= 0.000), ROM of flexion (SMD = 0.921, 95% CI 0.287 to 1.555, P= 0.000), ROM of extension (SMD = 0.572, 95% CI 0.321 to 0.822, P= 0.000), ROM of left lateral flexion (SMD = 0.593, 95% CI 0.075 to 1.112, P= 0.025) and ROM of left rotation (SMD = 0.230, 95% CI 0.010 to 0.450, P= 0.04) were favored by the TM group. CONCLUSIONS: TM provides short-term effect on relieving neck pain, increasing cervical ROM, and disability in patients with NP without serious side effects. Continuous therapy and distraction therapy are recommended as optimal choice on reducing pain and improving cervical ROM, especially in patients with chronic NP (> 3 months). The TM-induced improvements in the QOL of patients with NP should be verified by more further high-quality RCTs.

Efficacy and safety of kinesiology tape for hemiplegic shoulder pain: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this study was to examine the efficacy and safety of kinesiology tape in treating hemiplegic shoulder pain. METHODS: Web of Science, MEDLINE, Embase, Cochrane Library, six other English databases and three Chinese databases (CNKI, VIP, Wan Fang) were searched for randomized controlled trials published prior to December 13, 2020 in English or Chinese on the use of kinesiology tape for hemiplegic shoulder pain. RESULTS: Fourteen randomized controlled trials (679 patients) of good PEDro quality (6.43 ± 1.09) were included in this meta-analysis. The pooled results for pain (SMD -0.92, 95% CI -1.10 to -0.74, P< 0.001, 10 RCTs, 539 patients), range of motion (SMD 2.27, 95% CI 1.23 to 3.32, P< 0.001, 7 studies, 320 patients), the acromion humeral distance (SMD -0.62, 95% CI -0.88 to -0.37, P< 0.001, 7 RCTs, 246 patients) and the FMA-UE score (SMD 0.66, 95% CI 0.41 to 0.91, P< 0.001, 5 RCTs, 263 patients) suggested that therapeutic kinesiology tape relieved pain, increased ROM, shortened the acromion humeral distance and improved upper extremity motor function to a greater extent than the sham or blank control conditions. The pooled results for individual activity (SMD 0.42, 95% CI -0.22 to 1.07, P= 0.199, 5 RCTs, 199 patients) and quality of life (SMD 0.308, 95% CI -0.288 to 0.903, P= 0.311, 1 RCT, 44 patients) showed that the kinesiology tape group was not significantly different from the sham or blank control group. Publication bias was not observed. No adverse events were reported in any of the included studies. CONCLUSION: KT relieved pain and improved the ROM, DAH and FMA-UE score in patients with HSP to a greater extent than did the sham KT or blank control conditions. The effects on independence in activities of daily living and quality of life and whether this method is superior to active treatment in patients with HSP were not verified. More rigorous, reasonably designed RCTs with large sample sizes are still needed in the future.

The optimum parameters and neuroimaging mechanism of repetitive transcranial magnetic stimulation to post-stroke cognitive impairment, a protocol of an orthogonally-designed randomized controlled trial.

OBJECTIVE: Repetitive Transcranial Magnetic Stimulation (rTMS) has been used in cognition impairment due to various neuropsychiatric disorders. However, its optimum parameters and the neuroimaging mechanism are still of uncertainty. In order to simulate a study setting as close to real world as possible, the present study introduces a new orthogonally-designed protocol, consisting of the rTMS intervention with four key parameters (stimulating site, frequency, intensity and pulse number) and three different levels in each one, and aims to investigate the optimum parameters and the brain activity and connectivity in default mode network (DMN), dorsal attention network (DAN), central executive network (CEN) following rTMS intervention to post-stroke cognition impairment (PSCI). METHODS: A single-center, orthogonally-designed, triple-blind randomized controlled trial will be conducted and forty-five PSCI patients will be recruited and randomly assigned to one of nine active rTMS groups based on four rTMS paraments: stimulating site, frequency, intensity and pulse number. Neuropsychological, activities of daily living, quality of life and functional magnetic resonance imaging (fMRI) evaluations were be performed pre-, post- and 3 months after rTMS. DISCUSSION: This study evaluates the optimum parameters of rTMS for patients with post-stroke cognition impairment and explores the alteration of neural function in DMN, DAN, CEN brain network. These results would facilitate the standardized application of rTMS in cognition impairment rehabilitation.

Effect of Specific Acupuncture Therapy Combined with Rehabilitation Training on Incomplete Spinal Cord Injury: A Randomized Clinical Trial.

Acupuncture therapies were used to treat spinal cord injury (SCI) and its complications. To assess the effect of a specific acupuncture therapy combined with rehabilitation training for inpatients with incomplete SCI, we conducted an assessor-blinded, randomized controlled clinical trial in the Department of Rehabilitation Medicine Center in West China Hospital, Sichuan University. Seventy-two participants diagnosed with incomplete SCI were randomly assigned into 3 groups of 24 patients each, with data collection completed in December, 2019. Participants were randomly assigned (1 : 1 : 1) to 3 groups to receive treatment for 4 weeks, 5 times/week of acupuncture for Continuous Acupuncture Treatment (CAT) group, 3 times/week for Intermittent Acupuncture Treatment (IAT) group, and no acupuncture for Control group; all 3 groups received routine rehabilitation training. The primary outcome was the change of American Spinal Injury Association (ASIA) motor score from baseline to week 4. Secondary outcomes included sensory score, Modified Barthel Index (MBI). At week 4, CAT group had a higher motor score and MBI score increase than the control group (mean difference 10.52, 17.36; p < 0.001, p < 0.01, respectively). CAT group had more increase in motor score and MBI than IAT group (mean difference 5.55, 14.77; p < 0.05, p < 0.05, respectively). But the difference among groups in the increase of sensory score was not statistically significant. Acupuncture resulted in a higher motor score and MBI after 4 weeks. And the dosage of 5/week led to more improvement in motor score and MBI than that of 3/week. The results suggested that a dosage of 5/week of acupuncture is safe and more effective for SCI than 3/week. But further research is needed to determine the best intervention dosage, long-term efficacy, and underlying mechanism. This trial is registered with ChiCTR1900021530.

Conjugation of Synthetic Trisaccharide of Staphylococcus aureus Type 8 Capsular Polysaccharide Elicits Antibodies Recognizing Intact Bacterium.

Staphylococcus aureus causes a wide range of life-threatening diseases. One of the powerful approaches for prevention and treatment is to develop an efficient vaccine as antibiotic resistance greatly increases. S. aureus type 8 capsular polysaccharide (CP8) has shown great potential in vaccine development. An understanding of the immunogenicity of CP8 trisaccharide repeating unit is valuable for epitope-focused vaccine design and cost-efficient vaccine production. We report the chemical synthesis of conjugation-ready CP8 trisaccharide 1 bearing an amine linker, which effectively served for immunological evaluation. The trisaccharide 1-CRM197 conjugate elicited a robust immunoglobulin G (IgG) immune response in mice. Both serum antibodies and prepared monoclonal antibodies recognized S. aureus strain, demonstrating that synthetic trisaccharide 1 can be an efficient antigen for vaccine development.

Preparation of Nano-Copper Sulfide and Its Adsorption Properties for 17α-Ethynyl Estradiol.

In the present work, a tubular nano-copper sulfide was successfully synthesized by hydrothermal method. The physical and chemical properties of the prepared materials were characterized by XRD, SEM, TEM, and BET. The synthesized copper sulfide was used as an adsorbent for removing 17α-ethynyl estradiol (EE2) and exhibited excellent adsorption properties. At 25 °C, 15 mg of adsorbent was applied for 50 mL of 5 mg/L EE2 solution, adsorption equilibrium was reached after 180 min, and the adsorption rate reached nearly 90%. In addition, the kinetics, isothermal adsorption, and thermodynamics of the adsorption process were discussed on the basis of theoretical calculations and experimental results. The theoretical maximum adsorption capacity of copper sulfide was calculated to be 147.06 mg/g. The results of this study indicated that copper sulfide was a stable and efficient adsorbent with promising practical applications.

Acupuncture Treatment for Post-Stroke Dysphagia: An Update Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: To explore the effectiveness and safety of acupuncture in patients with post-stroke dysphagia by an update meta-analysis. METHODS: Potentially eligible RCTs aimed to evaluate the effects of acupuncture vs. non-acupuncture treatments, such as rehabilitation training or routine medication on the swallowing difficulty after stroke were searched from PubMed, Cochrane Library, China National Knowledge Infrastructure, and other database from the earliest record to June 2016. Patient demographics, regimens for acupuncture, type of controls, methods of randomization, and measurements of the clinical symptoms of dysphagia were retrieved. The relative risk (RR) and 95% confidence interval (CI) of effective rate of dysphagia was calculated after intervention performed following admission. Subgroup analyses and a metaregression analysis were performed to describe the heterogeneity. RESULTS: Twenty-nine RCTs comprising 2,190 patients were included. The included studies had a medium quality grade based on the Consolidated Standards of Reporting Trials (CONSORT) and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) checklist. Acupuncture therapy provided a higher effective rate compared with nonacupuncture treatments [RR=1.33, 95% confidence interval (CI), 1.25 to 1.43]. Subgroup and meta-regression analyses suggested that acupuncture intensity and measurement method were main sources of heterogeneity and resulted in a significant difference for pooled effect size. No severe adverse events were documented in these RCTs. CONCLUSIONS: Our meta-analysis provides a new evidence supporting the efficacy and safety of acupuncture in treatment to post-stroke dysphagia in short-term compared with rehabilitation or medication. More high-quality and large-scale research studies are needed.

Acupuncture for cerebral palsy: A meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy and safety of acupuncture therapy for children with cerebral palsy. DATA SOURCES: We conducted electronic searches of PUBMED (1950/2017), EMBASE (1974/2017), ScienceDirect (1986/2017), Academic Source Premier (1887/2017), the Cochrane Library (Issue 4, April 2017), Science Citation Index Expanded (1900/2017), China National Knowledge Infrastructure (1915/2017), China Biological Medicine (1990/2017-04), WanFang (1980/2017), VIP (1989/2017), and Chinese Science Citation Database (1989/2017). DATA SELECTION: We included randomized controlled trials that aimed to compare the effect of acupuncture plus rehabilitation training versus rehabilitation training alone. Data about functional motor abilities, daily activity/social participation, effective rate, intellectual development, and adverse effects were included. We used Revman 5.2 software for statistical analysis. OUTCOME MEASURES: The primary outcomes included functional motor abilities, daily activity, and effective rate. The secondary outcomes included intellectual development and adverse effects. RESULTS: Twenty-one studies with a total of 1718 participants met the inclusion criteria. The effect size of gross motor function (SMD = 0.64, 95% CI: 0.52 to 0.76, P < 0.00001; I2 = 0%, P = 0.69; in 13 studies with 1144 patients) and the total effective rate (RR = 1.28, 95% CI: 1.20 to 1.37, P < 0.00001; I2 = 18%, P = 0.27; in 12 studies with 1106 patients) suggested that acupuncture plus rehabilitation produced a significant improvement in gross motor function and a high total effective rate. The pooled fine motor function (SMD = 3.48, 95% CI: 2.62 to 4.34, P < 0.00001; I2 = 64%, P = 0.10; in 2 studies with 193 patients), modified Ashworth scale scores (SMD = -0.31, 95% CI: -0.52 to -0.11, P = 0.003; I2 = 74%, P = 0.004; in 5 studies with 363 patients) and activities of daily living (SMD = 1.45, 95% CI: 1.20 to 1.71, P < 0.00001; I2 = 78%, P = 0.004; in 4 studies with 313 patients) also indicated improvements in children with cerebral palsy. Publication bias was not observed. Only mild adverse events related to acupuncture were reported. CONCLUSION: Acupuncture plus rehabilitation training improved gross motor function, reduced muscle spasms, and enhanced daily life activities in children with cerebral palsy. However, this conclusion should be interpreted with caution due to the small number of randomized controlled trials available and the small sample sizes. More high-quality and large-scale studies are needed.

The standardization of acupuncture treatment for radiation-induced xerostomia: A literature review.

OBJECTIVE: To assess the relative standardization of acupuncture protocols for radiation-induced xerostomia. METHODS: A literature search was carried out up to November 10, 2012 in the databases PubMed/MEDLINE, EMBASE and China National Knowledge Infrastruction with the terms: radiation-induced xerostomia, acupuncture, acupuncture treatment, and acupuncture therapy. Five ancient Chinese classic acupuncture works were also reviewed with the keywords "dry mouth, thirst, dry tongue, dry eyes and dry lips" to search the effective acupuncture points for dry mouth-associated symptoms in ancient China. RESULTS: Twenty-two full-text articles relevant to acupuncture treatment for radiation-induced xerostomia were included and a total of 48 acupuncture points were searched in the 5 ancient Chinese classic acupuncture works, in which the most commonly used points were Chengjiang (CV24), Shuigou (GV 26), Duiduan (GV 27), Jinjin (EX-HN 12), and Yuye (EX-HN 13) on head and neck, Sanjian (LI 3), Shangyang (LI 1), Shaoshang (LU 11), Shaoze (SI 1), Xialian (LI 8) on hand, Fuliu (KI 7), Dazhong (KI 4), Zuqiaoyin (GB 44), Taichong (LR 3), Zhaohai (KI 6) on foot, Burong (ST 19), Zhangmen (LR 13), Tiantu (CV 22), Qimen (LR 14) on abdomen, Feishu (BL 13), Danshu (BL 19), Xiaochaogshu (BL 27), Ganshu (BL 18) on back, Shenmen (TF 4), Shen (CO10, Kidney), Yidan (CO11, Pancreas) and Pi (CO13, Spleen) on ear. CONCLUSION: There were considerable heterogeneities in the current acupuncture treatment protocols for radiation-induced xerostomia. Based on the results of the review and the personal perspectives, the authors provide a recommendation for manual acupuncture protocols in treating radiationinduced xerostomia patients with head and neck cancer.

[Different stimulation intensities of acupuncture at Hegu (LI 4) for central facial nerve paralysis after ischemic stroke: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy of acupuncture at Hegu (LI 4) on central facial nerve paralysis after ischemic stroke, and explore dose-effect relationship among different stimulation intensities of acupuncture at Hegu (LI 4) as well as its optimal treatment plan. METHODS: According to different acupuncture stimulation intensities which were based on treatment time and needle insertion direction, fifty patients were randomly divided into a Hegu 1 group, a Hegu 2 group, a Hegu 3 group, a Hegu 4 group and a control group, ten cases in each one. Different stimulation intensities of acupuncture at Hegu (LI 4) combined with facial paralysis acupoints, including Yingxiang (LI 20), Dicang (ST 4), Jiache (ST 6) and Quanliao (SI 18), were applied in Hegu 1 to 4 groups; meanwhile acupuncture at stroke acupoints, including Neiguan (PC 6), Shuigou (GV 26) and Sanyinjiao (SP 6), and medication treatment were adopted. Except acupuncture at Hegu (LI 4), the treatment of the control group was identical as Hegu groups. The treatment duration lasted for 14 days. The House-Brackmann facial never grading systems (H-B), Toronto facial grading system (TFGS), degrees of facial never paralysis (DFNP), facial disability index (FDI) and clinical efficacy were compared among groups. RESULTS: (1) Compared before the treatment, H-B, TFGS, DFNP and physical function score in FDI were all improved significantly in the Hegu 1 to 4 groups (all P < 0.05), but social function score in FDI was not obviously improved (all P > 0.05); all the scores in the control group were not evidently changed (all P > 0.05). (2) Compared with the control group, differences of H-B before and after treatment in the Hegu 1 to 4 groups, differences of TFGS in the Hegu 2 group and differences of DFNP in the Hegu 1 and Hegu 2 group were significantly improved (all P < 0.05). The differences of any scale among Hegu 1 to 4 groups were not significant (all P > 0.05), in which the most evident change was found in Hegu 2 group. (3) The total effective rate was 90.0% (9/10), 100.0% (10/10), 90.0% (9/10) and 80.0% (8/10) in Hegu 1 to 4 groups, which were significantly higher than 60.0% (6/10) in the control group (all P < 0.05). CONCLUSION: Acupuncture at Hegu (LI 4) has affirmative clinical efficacy on central facial nerve paralysis after ischemic stroke, in which oblique insertion along the opposite direction of meridian for 5 s of twirling manipulation has the best clinical effect.

A Study on the Effect of Neurogenesis and Regulation of GSK3ß/PP2A Expression in Acupuncture Treatment of Neural Functional Damage Caused by Focal Ischemia in MCAO Rats.

170 SD rats were randomly divided to five groups. Rats in model group, no-acupuncture group, and acupuncture group were subjected to MCAO surgery. Acupuncture group received 3 consecutive acupuncture treatments at a parameter that deep in 2 mm towards apex nasi and thrust/lifted at 3 times per second for 1 minute, while model group and no-acupuncture group were no-intervention control groups. Serious neural functional damage and sharp decrease of cerebral blood flow, obvious infarction volume, increased nestin mRNA expression, and immunopositive cells population (nestin(+), BrdU(+) and nestin/BrdU(+)) were found in MCAO rats which had not been observed in normal group and sham-operated group. However, the damage was attenuated by rat's "self-healing" capacity 3 days after MCAO. And the "self-healing" capacity can be strengthen by acupuncture treatment through increasing cerebral blood flow, neurogenesis, and regulation of gene transcription or GSK-3ß and PP2A expression. In conclusion, the present study indicates that the underlying mechanism of acupuncture treatment on neural functional damage caused by focal ischemia injury is a multiple interaction which may involve improved cerebral blood supply, neurogenesis, and regulation of gene transcription or GSK-3ß and PP2A expression in MCAO rats.

Orthogonal design to sift the optimal parameter of Neiguan acupuncture for cerebral infarction.

The individual difference and non-repeatability in acupuncture have not only restricted the development of acupuncture, but have also affected the specificity of acupoints. The present study used instruments to control needle depth, lifting and thrusting frequency, and the duration of acupuncture. Effects of the quantified acupuncture were observed at Neiguan (PC6) with different stimulation parameters. A frequency of 1, 2, or 3 Hz and duration of 5, 60, or 180 seconds were used to observe cerebral blood flow and ratio of infarct volume recovery. Results showed that stimulation at Neiguan with a frequency of 1 Hz and long duration of 180 seconds or 2/3 Hz and long duration of 5/60 seconds significantly increased cerebral blood flow and decreased the ratio of infarct volume. Interactions between frequency and duration play a critical role in quantified acupuncture therapy.