Efficacy and safety of acupuncture combined with rehabilitation in the treatment of strephenopodia after stroke: A protocol for systematic review and meta-analysis.

BACKGROUND: Strephenopodia is a common complication after stroke, which is easily neglected in the early stage of the disease and seriously affects the rehabilitation process of patients' limbs, and brings huge security risks and family burden. A large number of studies have confirmed that acupuncture combined with rehabilitation (ACR) has a significant effect on strephenopodia after stroke (SAS), but there is still a lack of systematic scientific evidence to support this argument. In this systematic review, we aimed to evaluate the efficacy and safety of ACR in the treatment of SAS, to provide evidence-based medical evidence for the clinical treatment of the disease. METHODS: We will search the following databases of 8 electronic databases from inception to January 2022: PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge infrastructure (CNKI), Technology Periodical Database (VIP), WanFang Data, and China Biology Medicine (CBM). All relevant randomized controlled trials (RCTs) focus on ACR in the treatment of strephenopodia after stroke will be included. The primary outcome will be the Measurement of strephenopodia angle and Clinical Spasm Index Scale (CSI). The Secondary outcomes will include Holden Functional Walking Classification (FAC), Berg Balance Scale (BBS), and Modified Barthel Index Score (MBI). Two reviewers will independently conduct the Study selection and data extraction. The risk of bias will be evaluated according to the Cochrane tool. Risk ratio and 95% confidence intervals will be used to estimate the efficacy of treatment, and the grading of recommendations, assessment, development, and evaluation approach to rate the certainty of evidence. The data analysis will be analyzed using by RevMan5.4. RESULT: This study will provide a comprehensive evaluation of the efficacy and safety of ACR in the treatment of SAS, with a view of providing more reliable evidence-based solutions for SAS. CONCLUSIONS: The conclusion of this study will provide evidence to judge whether ACR is effective and safe in treating SAS. PROSPERO REGISTRATION NUMBER: CRD42021290960.

Effectiveness and safety of auricular therapy for post-stroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke depression is a common and serious complication after stroke. Its main clinical manifestations are depression or instability, loss of interest, loss of appetite, sleep disorders, pessimism, and unworthiness, and even suicidal tendencies. Auricular therapy (AT), as part of traditional Chinese acupuncture, has achieved good results in the treatment of depression, but different clinical studies have shown mixed results. Therefore, the aim of this systematic review is to assess the effectiveness and safety of AT for post-stroke depression. METHODS: Two reviewers will electronically search the following databases: the Cochrane Central Register of Controlled Trials; Medline (via PubMed); Excerpt Medica Database; China National Knowledge Infrastructure; Chinese Biomedical Literature Database; Chinese Scientific Journal Database; and Wan-Fang Database from the inception to January 1, 2022. Study selection, data extraction, and assessment of study quality will be performed independently by 2 reviewers. If it is appropriate for a meta-analysis, Review Manager Version 5.3 statistical software will be used; otherwise, a descriptive analysis will be conducted. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The results will be presented as risk ratio with 95% confidence intervals for dichotomous data and weight mean difference or standard mean difference 95% confidence intervals for continuous data. RESULT: This study will provide a comprehensive review of the available evidence for the treatment of AT with post-stroke depression. CONCLUSIONS: The conclusions of our study will provide an evidence to judge whether AT is an effective and safe intervention for patients with post-stroke depression. TRIAL REGISTRATION NUMBER: PROSPERO CRD42021289870.

Comparison of the efficacy of acupuncture-related Therapies for post-stroke motor aphasia: A Bayesian network meta-analysis.

Background: Motor aphasia, which can affect the communication ability of patients and even triggers severe psychological disorders, is one of the most common sequelae after stroke. Acupuncture (a typical complementary alternative therapy) is frequently combined with speech training (ST) to treat post-stroke motor aphasia (PSMA) and presents significant efficacy. However, the most effective acupuncture intervention is still unknown. This study aims to analyze the efficacy of several acupuncture approaches combined with ST for PSMA to identify the best intervention for clinical decision-making by using network meta-analysis (NMA). Methods: Eight major databases were searched from the time of their establishment to March 2022. Clinical efficacy rate (CER) was used as the primary outcome indicator. R software (version 4.13.0) and STATA software (version 16.0) were used to analyze the data. Results: A total of 29 randomized controlled trials (RCTs) and six treatment regimens were included in this study. In the pair-wise meta-analysis, we found that the efficacy of scalp-tongue acupuncture (STA) combined with ST [OR = 8.30; 95% Credible interval (CrI): 3.87, 17.33], tongue acupuncture (TA) combined with ST (OR = 3.95; 95% CrI: 2.27, 6.89), scalp-body acupuncture (SBA) combined with ST (OR = 3.75; 95% CrI: 2.26, 6.22), scalp acupuncture (SA) combined with ST (OR = 2.95; 95% CrI: 1.74, 5.0), and body acupuncture (BA) combined with ST (OR = 2.30; 95% CrI: 1.26, 4.19) were significantly superior to that of ST. In addition, the efficacy of STA + ST was significantly superior to that of SA +ST (OR = 2. 82; 95% CrI: 1.24, 6.38) and BA + ST (OR = 3.61; 95% CrI: 1.40, 9.29). According to the surface under the cumulative ranking curve (SUCRA), STA + ST (SUCRA = 97.9%) may be the best treatment regimen to improve the clinical outcome in patients with PSMA. Conclusion: The NMA showed that STA combined with ST may be the best treatment to improve CER, compared with other combination treatments. However, since the overall quality and number of studies are limited, further RCTs with a large sample and multicenter are needed for further validation. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=316081, identifier CRD42022316081.

EMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with the post-stroke shoulder-hand syndrome: A Bayesian network meta-analysis.

Background: Post-stroke shoulder-hand syndrome (SHS), although not a life-threatening condition, may be the most distressing and disabling problem for stroke survivors. Thus, it is essential to identify effective treatment strategies. Physical therapy is used as a first-line option for treating SHS; however, it is unclear which treatment option is preferred, which creates confusion in guiding clinical practice. Our study aims to guide clinical treatment by identifying the most effective physical therapy interventions for improving clinical symptoms in patients with post-stroke SHS using Bayesian network meta-analysis. Methods: We conducted a systematic and comprehensive search of data from randomized controlled trials using physical therapy in patients with SHS from database inception to 1 July 2022. Fugl-Meyer Upper Extremity Motor Function Scale (FMA-UE) and pain visual analog score (VAS) were used as primary and secondary outcome indicators. R (version 4.1.3) and STATA (version 16.0) software were used to analyze the data. Results: A total of 45 RCTs with 3,379 subjects were included, and the intervention efficacy of 7 physical factor therapies (PFT) combined with rehabilitation training (RT) was explored. Compared with the control group, all the PFT + RT included were of statistical benefit in improving limb motor function and pain relief. Also, our study indicated that EMG biofeedback combined with RT (BFT + RT) [the surface under the cumulative ranking curve (SUCRA) = 96.8%] might be the best choice for patients with post-stroke SHS. Conclusion: EMG biofeedback combined with rehabilitation training may be the best physical therapy for improving upper limb motor function and relieving pain in patients with post-stroke SHS according to our Bayesian network meta-analysis results. However, the above conclusions need further analysis and validation by more high-quality RCTs. Systematic review registration: www.crd.york.ac.uk/prospero/, identifier: CRD42022348743.

The Nup98 Homolog APIP12 Targeted by the Effector AvrPiz-t is Involved in Rice Basal Resistance Against Magnaporthe oryzae.

BACKGROUND: The effector AvrPiz-t of Magnaporthe oryzae has virulence function in rice. However, the mechanism underlying its virulence in host is not fully understood. RESULTS: In this study, we analyzed the function of AvrPiz-t interacting protein 12 (APIP12) in rice immunity. APIP12 significantly bound to AvrPiz-t and APIP6 in its middle portion and N-terminus, respectively, in yeast two-hybrid assay. Glutathione S-transferase (GST) pull-down assay further verified the interactions of APIP12 with AvrPiz-t and APIP6. APIP12 encodes a homologue of nucleoporin protein Nup98 without the conserved domain of Phe-Gly repeats and has no orthologue in other plants. Both knockout and knockdown of APIP12 caused enhanced susceptibility of rice plants to virulent isolates of M. oryzae. The expression of some pathogenesis-related (PR) genes was reduced in both knockout and knockdown mutants, suggesting that APIP12 is required for the accumulation of transcripts of PR genes upon the infection. It is worth noting that neither knockout/knockdown nor overexpression of APIP12 attenuates Piz-t resistance. CONCLUSIONS: Taken together, our results demonstrate that APIP12 is a virulence target of AvrPiz-t and is involved in the basal resistance against M. oryzae in rice.

Autophagy-associated alpha-arrestin signaling is required for conidiogenous cell development in Magnaporthe oryzae.

Conidiation patterning is evolutionarily complex and mechanism concerning conidiogenous cell differentiation remains largely unknown. Magnaporthe oryzae conidiates in a sympodial way and uses its conidia to infect host and disseminate blast disease. Arrestins are multifunctional proteins that modulate receptor down-regulation and scaffold components of intracellular trafficking routes. We here report an alpha-arrestin that regulates patterns of conidiation and contributes to pathogenicity in M. oryzae. We show that disruption of ARRDC1 generates mutants which produce conidia in an acropetal array and ARRDC1 significantly affects expression profile of CCA1, a virulence-related transcription factor required for conidiogenous cell differentiation. Although germ tubes normally develop appressoria, penetration peg formation is dramatically impaired and Δarrdc1 mutants are mostly nonpathogenic. Fluorescent analysis indicates that EGFP-ARRDC1 puncta are well colocalized with DsRed2-Atg8, and this distribution profile could not be altered in Δatg9 mutants, suggesting ARRDC1 enters into autophagic flux before autophagosome maturation. We propose that M. oryzae employs ARRDC1 to regulate specific receptors in response to conidiation-related signals for conidiogenous cell differentiation and utilize autophagosomes for desensitization of conidiogenous receptor, which transmits extracellular signal to the downstream elements of transcription factors. Our investigation extends novel significance of autophagy-associated alpha-arrestin signaling to fungal parasites.

The wheat durable, multipathogen resistance gene Lr34 confers partial blast resistance in rice.

The wheat gene Lr34 confers durable and partial field resistance against the obligate biotrophic, pathogenic rust fungi and powdery mildew in adult wheat plants. The resistant Lr34 allele evolved after wheat domestication through two gain-of-function mutations in an ATP-binding cassette transporter gene. An Lr34-like fungal disease resistance with a similar broad-spectrum specificity and durability has not been described in other cereals. Here, we transformed the resistant Lr34 allele into the japonica rice cultivar Nipponbare. Transgenic rice plants expressing Lr34 showed increased resistance against multiple isolates of the hemibiotrophic pathogen Magnaporthe oryzae, the causal agent of rice blast disease. Host cell invasion during the biotrophic growth phase of rice blast was delayed in Lr34-expressing rice plants, resulting in smaller necrotic lesions on leaves. Lines with Lr34 also developed a typical, senescence-based leaf tip necrosis (LTN) phenotype. Development of LTN during early seedling growth had a negative impact on formation of axillary shoots and spikelets in some transgenic lines. One transgenic line developed LTN only at adult plant stage which was correlated with lower Lr34 expression levels at seedling stage. This line showed normal tiller formation and more importantly, disease resistance in this particular line was not compromised. Interestingly, Lr34 in rice is effective against a hemibiotrophic pathogen with a lifestyle and infection strategy that is different from obligate biotrophic rusts and mildew fungi. Lr34 might therefore be used as a source in rice breeding to improve broad-spectrum disease resistance against the most devastating fungal disease of rice.

Repression of microRNA biogenesis by silencing of OsDCL1 activates the basal resistance to Magnaporthe oryzae in rice.

The RNaseIII enzyme Dicer-like 1 (DCL1) processes the microRNA biogenesis and plays a determinant role in plant development. In this study, we reported the function of OsDCL1 in the immunity to rice blast, the devastating disease caused by the fungal pathogen, Magnaporthe oryzae. Expression profiling demonstrated that different OsDCLs responded dynamically and OsDCL1 reduced its expression upon the challenge of rice blast pathogen. In contrast, miR162a predicted to target OsDCL1 increased its expression, implying a negative feedback loop between OsDCL1 and miR162a in rice. In addition to developmental defects, the OsDCL1-silencing mutants showed enhanced resistance to virulent rice blast strains in a non-race specific manner. Accumulation of hydrogen peroxide and cell death were observed in the contact cells with infectious hyphae, revealing that silencing of OsDCL1 activated cellular defense responses. In OsDCL1 RNAi lines, 12 differentially expressed miRNAs were identified, of which 5 and 7 were down- and up-regulated, respectively, indicating that miRNAs responded dynamically in the interaction between rice and rice blast. Moreover, silencing of OsDCL1 activated the constitutive expression of defense related genes. Taken together, our results indicate that rice is capable of activating basal resistance against rice blast by perturbing OsDCL1-dependent miRNA biogenesis pathway.

Comparative genomics identifies the Magnaporthe oryzae avirulence effector AvrPi9 that triggers Pi9-mediated blast resistance in rice.

We identified the Magnaporthe oryzae avirulence effector AvrPi9 cognate to rice blast resistance gene Pi9 by comparative genomics of requisite strains derived from a sequential planting method. AvrPi9 encodes a small secreted protein that appears to localize in the biotrophic interfacial complex and is translocated to the host cell during rice infection. AvrPi9 forms a tandem gene array with its paralogue proximal to centromeric region of chromosome 7. AvrPi9 is expressed highly at early stages during initiation of blast disease. Virulent isolate strains contain Mg-SINE within the AvrPi9 coding sequence. Loss of AvrPi9 did not lead to any discernible defects during growth or pathogenesis in M. oryzae. This study reiterates the role of diverse transposable elements as off-switch agents in acquisition of gain-of-virulence in the rice blast fungus. The prevalence of AvrPi9 correlates well with the avirulence pathotype in diverse blast isolates from the Philippines and China, thus supporting the broad-spectrum resistance conferred by Pi9 in different rice growing areas. Our results revealed that Pi9 and Piz-t at the Pi2/9 locus activate race specific resistance by recognizing sequence-unrelated AvrPi9 and AvrPiz-t genes, respectively.

Precise mapping Fhb5, a major QTL conditioning resistance to Fusarium infection in bread wheat (Triticum aestivum L.).

Qfhi.nau-5A is a major quantitative trait locus (QTL) against Fusarium graminearum infection in the resistant wheat germplasm Wangshuibai. Genetic analysis using BC(3)F(2) and BC(4)F(2) populations, derived from selfing two near-isogenic lines (NIL) heterozygous at Qfhi.nau-5A that were developed, respectively, with Mianyang 99-323 and PH691 as the recurrent parent, showed that Qfhi.nau-5A inherited like a single dominant gene. This QTL was thus designated as Fhb5. To fine map it, these two backcross populations and a recombinant inbred line (RIL) population derived from Nanda2419 × Wangshuibai were screened for recombinants occurring between its two flanking markers Xbarc56 and Xbarc100. Nineteen NIL recombinants were identified from the two backcross populations and nine from the RIL population. In the RIL recombinant selection process, selection against Fhb4 present in the RIL population was incorporated. Genotyping these recombinant lines with ten markers mapping to the Xbarc56-Xbarc100 interval revealed four types of Mianyang 99-323-derived NIL recombinants, three types of PH691-derived NIL recombinants, and four types of RIL recombinants. In different field trials, the percentage of infected spikes of these lines displayed a distinct two-peak distribution. The more resistant class had over 55% less infection than the susceptible class. Common to these resistant genotypes, the 0.3-cM interval flanked by Xgwm304 and Xgwm415 or one of these two loci was derived from Wangshuibai, while none of the susceptible recombinants had Wangshuibai chromatin in this interval. This interval harboring Fhb5 was mapped to the pericentromeric C-5AS3-0.75 bin through deletion bin mapping. The precise localization of Fhb5 will facilitate its utilization in marker-assisted wheat breeding programs.

Fine mapping Fhb4, a major QTL conditioning resistance to Fusarium infection in bread wheat (Triticum aestivum L.).

Qfhi.nau-4B is a major quantitative trait locus (QTL) against Fusarium graminearum infection identified in the Fusarium head blight-resistant germplasm Wangshuibai. To fine map this QTL, a recombinant inbred line (RIL) population of 530 lines derived from Nanda2419 x Wangshuibai and the BC(3)F(2) population derived from the cross of a Qfhi.nau-4B near isogenic line (NIL) with susceptible cultivar Mianyang 99-323 as the recurrent parent were screened for recombinants occurred between microsatellite markers Xbarc20 and Xwmc349 that flank Qfhi.nau-4B. A total of 95 recombinants were obtained, including 45 RIL recombinants obtained through reverse-selection of Qfhi.nau-5A and 50 NIL recombinants from the BC(3)F(2) population. Genotyping these recombinant lines with 22 markers mapping to the Xbarc20 and Xwmc349 interval revealed fourteen genotypes of the RIL recombinants as well as of the NIL recombinants. Two-year field evaluation of their resistance to Fusarium infection showed that these lines could be clearly classified into two groups according to percentage of infected spikes. The more resistant class had over 60% less infection than the susceptible class and were common to have Wangshuibai chromatin in the 1.7-cM interval flanked by Xhbg226 and Xgwm149. None of the susceptible recombinants had this Wangshuibai chromatin. Qfhi.nau-4B was thus confined between Xhbg226 and Xgwm149 and named Fhb4. The interval harboring Fhb4 was mapped to 4BL5-0.86-1.00 bin using Chinese Spring deletion lines, a region with about 5.7 times higher recombination rate than the genome average. This study established the basis for map-based cloning of Fhb4.