Activated conduction by small incision and moderate stimulation for treatment of cerebral palsy in 182 cases

BACKGROUND： Intemationally, methods to treat cerebral palsy （CP） are basically the same, including correction of deformity with orthopaedic operation, selective posterior rhizotomy（SPR）, rehabilitation therapy and so on. Domestic methods to treat CP are basically close to the international methods. Traditional Chinese medical therapies, such as, acupuncture and moxibustion, acupoint injection, massage and so on, also have good curative effects. OBJECTIVE ： To observe the effect of activated conduction by small incision and moderate stimulation （ACSIMS） on limb function and living ability in patients with spastic CP at different degrees.DESIGN： Retrospective case analysis.SETTING： Department of Medical Education, Shanxi Medical College for Continuing Education.PARTICIPANTS ： A total of 182 patients with CP, including 97 males and 85 females, aged 3 to 23 years, who received treatment in Beijing Haidian District Diaoyutai Hospital during October 1996 to September 2005, were involved in this trial. The involved patients met the diagnostic criteria proposed in 2004 National Special Seminar of Cerebral Palsy. According to typing criteria of CP purposed in 1990 Brioni International Conference, the involved patients were typed： 117 with spastic CP, 14 with involuntary movement CP, 19 with defective coordination CP, 5 with hypotonia CP and 27 with mixed type CP. The guardians of underage patients and adult patients themselves were all informed of the therapeutic regimens. METHODS： ①According to CP typing assessment quantitative criteria of Li, the involved patients were assigned from limb position, daily living and movement 3 aspects： mild 23, moderate 75, severe 62 and extremely severe 22. ② Operation methods： The lower limb of moderate spastic CP patient was taken as an example. A median incision or paramedian incision was made between L2 and S1, and it was also the first incision in lower limb. The second incision was made at the center of buttock or at the midpoint of the line of sciatic tuber and greater trochanter. The third incision was determined according to the posture of shank of patients. The located region was locally anesthetized, then in which a small incision was made. Moderate stimulation was performed by a smooth mental instrument in muscular layer from different angles. Surgical catgut-embedding therapy was used after stimulation in CP patients who had hyperexplexia and obvious muscular atrophy. Anti-inflammatory was taken orally 3 to 5 days; physical treatment was daily conducted 10 to 15 minutes within 5 to 7 days, one course of treatment. Operation was needed once or twice in mild CP patients, twice or three times in moderate CP patients, three or four times in severe CP patients and three to five times in extremely severe CP patients. ③Assessment criteria of therapeutic effect of CP： cured, significantly effective, effective and non-effective based on a favorable tum in the limb position, daily living and movement 3 aspects. ④Chi-square test was used for difference comparison of enumeration data. MAIN OUTCOME MEASURES ： Comparison of therapeutic effect of patients with CP at different degrees after ACSIMS treatment.RESULTS ： Totally 182 CP patients were involved in the result analysis. ① Effective rate： ACSIMS had remarkably therapeutic effect in treatment of spastic CP. The effective rate of mild, moderate, severe and extremely severe CP was 100.0%, 97.3%, 95.2%, and 90.9%, respectively. The total effective rate reached 96.2%. The effective rate of CP at different degrees was close after treatment （P 〉 0.05）. ② Operation frequency： The mild patients began to recover within one to three days after one or two operations and moderate patients within one week to one month after two or three operations. After one to three times of treatments, the function of lower limbs of patients with mild or moderate CP was close to normal; After three to five times of operations, patients with severe or extremely severe CP began to recover within one week to three months, and their muscular tensions were decreased by one or two degrees, and walking was obviously improved as compared with preoperation. CONCLUSION ： ACSIMS has different therapeutic effects in treatment of spastic CP at different degrees. It can improve the limb function and daily living ability of CP patients. It needs fewer operations and has rapid response to treat mild CP with ACSIMS; on the contrary, it needs more operations and has slow response to treat severe CP with ACSMS.

Will Glacier No.1 Tianshan exist in the 22^(nd) century?

Mountains have been described as the water towers of the world. Almost all major rivers have their sources in mountains; glaciers are important water resources that contribute meltwater to river discharge. Glaciers participate in the global water cycle and, with their solid water storage, are an important component of the water balance. As solid reservoirs, glaciers continue to receive the mass nourishment of solid precipitation from the atmosphere, and their meltwater feed and regulate fiver discharge. Physical changes in glaciers are an indicator of climate change. Over the past half century, the global temperature has increased by 1-2 ℃, which emphasizes the urgent task of monitoring glaciers and predicting their trend. As an example, we have investigated, researched, and surveyed Glacier No. 1 in the Urumqi River source, Tianshan （abbr. Glacier No. 1 Tianshan or Glacier No.l） for half a century. We have found an increase by degrees of the glacial regression during the last 400 years and discovered a terminal moraine which is forming today. The global temperature is rising continually, while the local glacial temperature is 0.4 times that of the global temperature change. Thus, we forecast that Glacier No. 1 Tianshan will disappear during the late 21 st Century （2074-2100 A.D.）.

青藏高原高寒植物对生长季偶发性霜冻事件表现出深度过冷却现象

气候变暖促进了植物的春季物候,打破了气候与植物生长之间原有的平衡。随着极端气候事件出现更加频繁,气候与植物生长之间的不匹配性会影响植物的生存、生长和繁殖。为了防止生长季节在细胞内结冰,植物会采用过冷却策略。然而,气候事件的严重程度和物候期可能会影响植物在霜冻事件后的恢复。本研究通过实验探究了4种不同严重程度的极端霜冻事件如何影响青藏高原上两种优势物种钉柱委陵菜(Potentilla saundersiana,仲夏开花)和小龙胆(Gentiana parvula,夏末开花)的过冷却点和枯黄期。探讨了物候期如何影响钉柱委陵菜对霜冻事件的反应。结果发现,两个物种在遭受霜冻损害时都表现出过冷现象。钉柱委陵菜的平均过冷却点为−6.9℃,并受最低温度、持续时间和物候期的影响,而小龙胆的平均过冷却点为−4.8℃,最低温度和持续时间对其过冷却点影响不显著。此外,两个物种在最低温度(−10℃)处理持续4小时后均快速枯黄。本研究首次探索并定量了青藏高原高寒植物的过冷却点。鉴于高寒植物遭遇霜冻事件的概率不断增加,上述结果对了解高寒植物的生长和生存如何应对极端气候的不利影响具有重要意义。

Astrocytic pyruvate dehydrogenase kinase-lactic acid axis involvement in glia-neuron crosstalk contributes to morphine-induced hyperalgesia in mice

The activation of spinal astrocytes accounts for opioid-induced hyperalgesia(OIH),but the underlying mechanisms remain elusive.The presence of astrocyte-neuron lactate shuttle(ANLS)makes astrocytes necessary for some neural function and communication.The aim of this study was to explore the role of ANLS in the occurrence and maintenance of OIH.After 7 days consecutive morphine injection,a mice OIH model was established and astrocytic pyruvate dehydrogenase kinase 4(PDK4),phosphorylated pyruvate dehydrogenase(p-PDH)and accumulation of L-lactate was elevated in the spinal dorsal horn.Intrathecally administration of inhibitors of PDK,lactate dehydrogenase 5 and monocarboxylate transporters to decrease the supply of L-lactate on neurons was observed to attenuate hypersensitivity behaviors induced by repeated morphine administration and downregulate the expression of markers of central sensitization in the spinal dorsal horns.The astrocyte line and the neuronal line were co-cultured to investigate the mechanisms in vitro.In this study,we demonstrated that morphine-induced hyperalgesia was sustained by lactate overload consequent upon aberrant function of spinal ANLS.In this process,PDK-p-PDH-lactate axis serves a pivotal role,which might therefore be a new target to improve long-term opioid treatment strategy in clinical practice.

Unique genes carried by abundant species enhance CH_(4) emissions during the growing season at the Tibetan Plateau

CH_(4) emission rates followed an increased pattern during the growing season at Tibetan Plateau.•Unique genes carried by abundant species were positively correlated with CH_(4) emission rates.•Climate factors influenced CH_(4) emission rates by regulating microbial community and their genes.Microorganisms play pivotal roles in soil methane(CH_(4))emissions and their functional genes are origins of a key mechanism for soil CH4-cycling.However,understanding of the roles of specific genes(e.g.,unique or shared genes carried by species)underlying CH_(4)-cycling remains elusive.Here,we measured CH_(4) emission rates and investigated variations in microbial community and the abundance of genes carried by species during the growing season in alpine meadow on the Tibetan Plateau.We discovered that CH_(4) emission rates increased from 394.4,745.9,and 1092.7µg CH4 m−2 h−1,in April,June,and August,respectively,and had a positive correlation with unique genes carried by abundant species during the growing season.Moreover,we found that unique genes carried by abundant species involved in methanogenesis processes have a higher abundance than methanotrophic processes.Further analysis indicated that climate factors(i.e.,mean monthly temperature(MMT)and mean monthly precipitation(MMP))influenced microbial community and their functional genes,and therefore affected the CH_(4) emission rates.Overall,the present study provides a novel insight into the variation of soil CH4 emissions from a functional gene perspective,highlighting the important roles of unique genes carried by abundant species in CH4 emissions in the Tibetan Plateau under seasonal variation.

Total mesh excision via divergent approaches:Two case reports and literature review

Dear Editor,The introduction of mesh procedures to treat stress urinary incontinence(SUI)in women represents a significant milestone breakthrough and currently serves as the primary surgical approach for addressing SUI.Since the FDA's statement on mesh sling complications in 2008,an increasing number of patients have sought total excision of the polypropylene(PP)sling from their bodies.Currently,there are a few reports on PP sling removal through different routes,but a unified and specific surgical technique has not yet been established.The aim of this article is to report the successful techniques and approaches used in two cases involving the total removal of PP meshes resulting from tension-free vaginal tape(TVT)and transobturator tape(TOT)via different approaches.Additionally,we discuss the clinical outcomes and review relevant literature on this topic.

微生物硫循环网络的研究进展

硫元素是所有生物的基本组成成分,是生物体必需的营养元素之一。硫氧化还原微生物的数量多、分布广、代谢途径多样化,硫化合物之间的平衡依赖于微生物代谢网络中的各种硫转化反应与代谢过程。此外,硫循环与碳、氮循环紧密相关,对地球生态循环起到了至关重要的作用。本文综述了近期微生物硫循环网络的研究进展,包括所涉及的主要微生物、硫循环的生物化学途径、硫循环的环境意义和工业应用潜能等,深入了解自然和人工生态系统中存在的硫循环过程,可为控制工农业生产中硫元素的增减与利用提供理论基础与应用方案。

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

PD-1 blockade has demonstrated impressive clinical outcomes in colorectal cancers that have high microsatellite instability.However,the therapeutic efficacy for patients with tumors with low microsatellite instability or stable microsatellites needs further improvement.Here,we have demonstrated that low-dose decitabine could increase the expression of immune-related genes such as major histocompatibility complex genes and cytokine-related genes as well as the number of lymphocytes at the tumor site in CT26 colorectal cancer-bearing mice.A more significant inhibition of tumor growth and a prolongation of survival were observed in the CT26 mouse model after treatment with a combination of PD-1 blockade and decitabine than in mice treated with decitabine or PD-1 blockade alone.The anti-tumor effect of the PD-1 blockade was enhanced by low-dose decitabine.The results of RNA sequencing and whole-genome bisulfite sequencing of decitabine-treated CT26 cells and tumor samples with microsatellite stability from the patient tumor-derived xenograft model have shown that many immune-related genes,including antigen-processing and antigen-presenting genes,were upregulated,whereas the promoter demethylation was downregulated after decitabine exposure.Therefore,decitabine-based tumor microenvironment re-modulation could improve the effect of the PD-1 blockade.The application of decitabine in PD-1 blockade-based immunotherapy may elicit more potent immune responses,which can provide clinical benefits to the colorectal cancer patients with low microsatellite instability or stable microsatellites.

TLR4 is essential for dendritic cell activation and anti-tumor T-cell response enhancement by DAMPs released from chemically stressed cancer cells

The combination of immunotherapy and chemotherapy is regarded as a promising approach for the treatment of certain types of cancer. However, the underlying mechanisms need to be fully investigated to guide the design of more efficient protocols for cancer chemoimmunotherapy. It is well known that danger-associated molecular patterns （DAMPs） can activate immune cells, including dendritic cells （DCs）, via Toll-like receptors （TLRs）; however, the role of DAMPs released from chemical drug-treated tumor cells in the activation of the immune response needs to be further elucidated. Here, we found that colorectal cancer （CRC） cells treated with oxaliplatin （OXA） and/or 5-fluorouracil （5-Fu） released high levels of high-mobility group box 1 （HMGB1） and heat shock protein 70 （HSP70）. After OXA/5-Fu therapy, the sera of CRC patients also exhibited increased levels of HMGB1 and HSP70, both of which are well-known DAMPs. The supernatants of dying CRC cells treated with OXA/5-Fu promoted mouse and human DC maturation, with upregulation of HLA-DR, CD80 and CD86 expression and enhancement of IL-lp, TNF-a, MIP-la, MIP-lp, RANTES and IP-IO production. Vaccines composed of DCs pulsed with the supernatants of chemically stressed CRC cells induced a more significant IFN-y-producing Thl response both in vitroand in vivo. However, the supernatants of chemically stressed CRC cells failed to induce phenotypic maturation and cytokine production in TLR4-deficient DCs, indicating an essential role of TLR4 in DAMP-induced DC maturation and activation. Furthermore, pulsing with the supernatants of chemically stressed CRC cells did not efficiently induce an IFN-y-producing Thl response in TLR4-deficient DCs. Collectively, these results demonstrate that DAMPs released from chemically stressed cancer cells can activate DCs viaTLR4 and enhance the induction of an anti-tumor T-cell immune response, delineating a clinically relevant immuno-adjuvant pathway triggered by DAMPs.

Efficient induction of a Her2-specific anti-tumor response by dendritic cells pulsed with a Hsp70L1–Her2_(341–456) fusion protein

Heat shock proteins(HSPs)have been shown to interact with antigen-presenting cells(APCs),especially dendritic cells(DCs).HSPs act as potent adjuvants,inducing a Th1 response,as well as antigen-specific CD8^(+) cytotoxic T lymphocytes(CTL)via cross-presentation.Our previous work has demonstrated that Hsp70-like protein 1(Hsp70L1),a new member of the Hsp70 subfamily,can act as a powerful Th1 adjuvant in a DC-based vaccine.Here we report the efficient induction of tumor antigen-specific T cell immune response by DCs pulsed with recombinant fusion protein of Hsp70L1 and Her2_(341–456),the latter of which is a fragment of Her2/neu(Her2)containing E75(a HLA-A2 restricted CTL epitope).The fusion protein Hsp70L1–Her2_(341–456) promotes the maturation of DCs and activates them to produce cytokines,such as IL-12 and TNF-a,and chemokines,such as MIP-1a,MIP-1b and RANTES.Taken together,these results indicate that the adjuvant activity of Hsp70L1 is maintained in the fusion protein.Her2-specific HLA-A2.1-restricted CD8^(+) CTLs can be generated efficiently either from the Peripheral blood lymphocytes(PBL)of healthy donors or from the splenocytes of immunized HLA-A2.1/K^(b) transgenic mice by in vitro stimulation or immunization with DCs pulsed with the Hsp70L1–Her2_(341–456) fusion protein.This results in more potent target cell killing in an antigen-specific and HLA-A2.1-restricted manner.Adoptive transfer of splenocytes from transgenic mice immunized with Hsp70L1–Her2_(341–456)-pulsed DCs can markedly inhibit tumor growth and prolong the survival of nude mice with Her2^(+)/HLA-A2.1^(+) human carcinomas.These results suggest that Hsp70L1–Her2_(341–456)-pulsed DCs could be a new therapeutic vaccine for patients with Her2^(+) cancer.

Correction to: Low-dose decitabine enhances the effect of PD1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

In the published version of this paper,we repeatedly copied the image of the DAC-7 day as the DAC-14 day.The corrected Fig.6 is provided below.The figure legend was revised in order to avoid confusion and is shown below for reference.Although we regret our mistake during figure assembly and would like to apologize for any inconvenience it may have caused,we did not manipulate our data in any way.This unintentional error also has no bearing on the work's scientific conclusions.

PtHAK5, a candidate for mediating high-affinity K^+ uptake in the halophytic grass, Puccinellia tenuiflora

Puccinellia tenuiflora is a typical salt-excluding halophytic grass with strong salt-tolerance, which enhances tolerance by restricting Na^+influx as well as having a strong selectivity for K^+ over Na^+. The HAK5 K^+ transporters generally modulate effective K^+acquisition in plants, especially under low K^+ condition. In this study,Pt HAK5 from P. tenuiflora was isolated by RT-PCR and characterized using yeast complementation. The results showed Pt HAK5 consisted of 784 amino acids and shared over 80% homology with the identified high-affinity K^+ transporter HAK5 from other higher plants. The expression of PtHAK5 rescued the K^+ -uptake-defective phenotype of yeast strain CY162. In conclusion, PtHAK5 is a candidate for mediating high-affinity K^+ uptake under low K^+ conditions.

The role of herbivores in the grassland carbon budget for Three-Rivers Headwaters region,Qinghai-Tibetan Plateau,China

Background:An accurate assessment of the carbon budget is a crucial part of projecting future climate change and its impact on ecosystems.Grasslands foster multiple ecological functions including support for wild animals and livestocks.Herbivores intake forage biomass carbon,then digest and metabolize,and finally retain some carbon.The carbon processes have not been well quantified,resulting in uncertainties in the estimation of regional carbon budgets for grassland ecosystems.Methods:An animal metabolic carbon flux model was developed for herbivores in the Three-Rivers Headwaters region of China.The forage intake and metabolic carbon rates were estimated through metabolic body weight and daily digested measures for the main herbivore species.Results:The carbon intake was 5.52 Tg C year−1(45%)from partial aboveground biomass(12.2 Tg C year−1),in which 39.31%was released into the atmosphere by respiration CO_(2),43.77%was returned to the ecosystem as feces and urine,and 16.96%was retained in herbivores for population regeneration or for human well-being.Conclusions:This study,as the first research on this topic,quantified the carbon flux of herbivores and found livestock accounts for a major part of consumed carbon on grasslands,which is important for understanding regional carbon budgets to mitigate and adapt to climate change over grasslands worldwide.

Elevated Kir2.1/nuclear N2ICD defines a highly malignant subtype of non-WNT/SHH medulloblastomas

Medulloblastoma(MB)is one of the most common childhood malignant brain tumors(WHO grade IV),traditionally divided into WNT,SHH,Group 3,and Group 4 subgroups based on the transcription profiles,somatic DNA alterations,and clinical outcomes.Unlike WNT and SHH subgroup MBs,Group 3 and Group 4 MBs have similar transcriptomes and lack clearly specific drivers and targeted therapeutic options.The recently revised WHO Classification of CNS Tumors has assigned Group 3 and 4 to a provisional non-WNT/SHH entity.In the present study,we demonstrate that Kir2.1,an inwardly-rectifying potassium channel,is highly expressed in non-WNT/SHH MBs,which promotes tumor cell invasion and metastasis by recruiting Adam10 to enhance S2 cleavage of Notch2 thereby activating the Notch2 signaling pathway.Disruption of the Notch2 pathway markedly inhibited the growth and metastasis of Kir2.1-overexpressing MB cell-derived xenograft tumors in mice.Moreover,Kir2.1^(high)/nuclear N2ICD^(high)MBs are associated with the significantly shorter lifespan of the patients.Thus,Kir2.1^(high)/nuclear N2ICD^(high)can be used as a biomarker to define a novel subtype of non-WNT/SHH MBs.Our findings are important for the modification of treatment regimens and the development of novel-targeted therapies for non-WNT/SHH MBs.

Plant genome editing:CRISPR,base editing,prime editing,and beyond

The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein 9(Cas9)system is a fast-growing,genome editing technology that has wide applications in identifying gene functions as well as improving agricultural production and crop breeding.Here,we summarized recent advances in the development and applications of genome editing technologies in plants.We briefly described CRISPR/Cas9 technology and examined the base and prime editing techniques that have been developed from CRISPR technology.Some new prime editing-derived techniques were assessed.