INTRODUCTION

Osteoarthritis (OA) is the most common type of arthritis, with 1 in 3 people over age 65 affected and a higher prevalence in women[1,2]. The knees are among the most commonly affected joints in OA[3,4]. Knee osteoarthritis (KOA) is characterized as pain, joint stiffness, functional impairment and even disability, contributing to a heavy burden on healthcare service[5,6]. Considering the severe socioeconomic burden, nonpharmacological, pharmacological and surgical approaches were applied[7]. Physical therapy has been known to play a vital role in pain relief and restoration of mobility and function in KOA patients[8]. Manual therapy is a widely used physical treatment for KOA[9]. Several studies have reported positive effects of manual physical therapy on KOA[9-11]. The American College of Rheumatology recommends the combination of manual therapy with exercise for KOA patients under the supervision of a physiotherapist[12]. Besides, for the patients with deficits in range of motion (ROM), manual therapy plays a role to restore or maximize ROM improvement before surgeries[13].

Maitland and Mulligan mobilization are two types of manual therapy used in OA treatment[14]. Mulligan mobilization allows the patients to perform the offending movements in a functional position, hence, leading to a rewarding outcome[15].Maitland mobilization aims to reestablish the spinning, gliding and rolling motions of the two joints[14]. In clinical practice, movement quality can be increasedimproving joint stability of weak muscles by applying Maitland mobilization combined with psychological effects (self-confidence and motivating factors) and corrected mechanical loading. Maitland and Mulligan mobilization therapies have been used to treat multiple diseases, such as primary adhesive capsulitis of the shoulder[16], hip osteoarthritis[17] and knee osteoarthritis[18]. As reported by previous studies, Maitland or Mulligan mobilizations were used by 99.8% of physical therapists to treat cervicogenic dizziness[19].

Recently, some reviews have found that the manual therapies might be effective and safe in ameliorating osteoarthritis symptoms[16,18,20]. A meta-analysis by Qinguang Xu[18] demonstrated that manual therapy effectively and safely alleviated pain,reduced stiffness and restored physical function in KOA patients, and thus it could be considered as a complementary and alternative option. In the studies on primary adhesive capsulitis of the shoulder, Noten[16] identified the efficacy of mobilization techniques. Although Maitland mobilization was recommended in these studies[16,20], there still was no systematic review and meta-analysis to compare the efficacy of different mobilization techniques, such as MaitlandMulligan mobilization. Therefore, this study used an evidence-based method to determine the efficacy of Maitland and Mulligan mobilization methods in adults with KOA.

MATERIALS AND METHODS

This systematic review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA)[21] and the Cochrane Collaboration Handbook[22]. The protocol of this systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews(PROSPERO: CRD42020182532) on April 28, 2020.

質(zhì)量標(biāo)準(zhǔn)的制定應(yīng)考慮日常檢驗的經(jīng)濟(jì)適用性，不能一味地求全、求新。目前，有些標(biāo)準(zhǔn)過于復(fù)雜，應(yīng)研究方法簡化標(biāo)準(zhǔn)，如一測多評、一標(biāo)多測方法。標(biāo)準(zhǔn)起草完成后，應(yīng)征求企業(yè)意見，既要注重保證藥品安全性與檢測方法的專屬性和靈敏度相結(jié)合，還要注意環(huán)保，盡量不使用毒性較大的試劑，并進(jìn)行耐用性考察，提高標(biāo)準(zhǔn)的經(jīng)濟(jì)和實用性、避繁就簡、綠色檢驗。

Information sources

Two reviewers performed literature search individually in the following electronic databases: PubMed, The Cochrane Library, Web of Science, Embase and Google Scholar, from the time of inception to September 20, 2020. We also reviewed the reference lists of relevant reviews and meta-analyses[23,24].

紫玉蘭的分布信息主要來源于標(biāo)本數(shù)據(jù)庫的搜索、相關(guān)文獻(xiàn)記載。通過查詢中國數(shù)字植物標(biāo)本館(http://www.cvh.org.cn/)、中國自然標(biāo)本館(http://www.cfh.ac.cn/)和全球生物多樣性信息網(wǎng)(http://www.gbif.org/)，分別獲得501條、2487條、134條信息。結(jié)合文獻(xiàn)資料記載，排除錯誤鑒定、人工引種及信息模糊不清的標(biāo)本，最終獲得紫玉蘭39個自然分布點，其地理位置信息落實到鄉(xiāng)鎮(zhèn)行政單位。利用Google Earth衛(wèi)星圖拾取39個分布點的經(jīng)緯度。

由于溫度變量沒有明確的界限,因此其分類可以通過模糊集理論的軟劃分來實現(xiàn)。根據(jù)溫度變量的相似度或親疏性質(zhì),模糊聚類分析通過模糊相似關(guān)系來實現(xiàn)溫度變量的分類。為了使處理過程簡單直觀,一般將相似關(guān)系轉(zhuǎn)化為模糊矩陣,然后進(jìn)行模糊聚類分析。

電位傳感技術(shù)是利用離子選擇性電極的電位隨溶液中被測離子含量不同而變化的傳感技術(shù)。這種傳感技術(shù)，因選擇性識別能力強(qiáng)、測量參數(shù)單一、易于小型甚至芯片化和應(yīng)用范圍廣等優(yōu)點，成為最具有發(fā)展?jié)摿Φ囊环N生物和化學(xué)傳感技術(shù)[1]。但是，由于傳統(tǒng)的離子選擇性電極因受電極的選擇性和靈敏度的限制，以及通常電極需要內(nèi)充液而不易微型化，所以傳統(tǒng)的電位傳感技術(shù)在過去的一段時間發(fā)展緩慢。

國家能源局《特殊和稀缺煤類開發(fā)利用管理暫行規(guī)定》中明確要求特殊和稀缺煤類全部洗選，經(jīng)洗選加工的優(yōu)質(zhì)特殊和稀缺煤類優(yōu)先用于冶金、化工、材料等行業(yè)，限制直接燃燒?！笆濉逼陂g要求單位國內(nèi)生產(chǎn)總值CO2排放降低17%，COD、SO2排放分別減少8%。對于選煤廠來說，節(jié)能減排意味著減少浪費，節(jié)約成本，更有利于煤炭行業(yè)的健康、持續(xù)發(fā)展。

Search strategy

July 9, 2021

Eligibility criteria

Trials were considered eligible if the following items were met: (1) Adult patients with KOA at any stage according to Kellgren and Lawrence grading system; (2) Containing data about Maitland joint mobilization or mobilization with movement technique with or without other interventions; (3) Reporting pain, range of motion, functional performance/ability or other relevant outcomes; and (4) Controlled clinical trials.

Since our aim was to explore the different efficacy of these two techniques in ROM,pain and functional performance in KOA, some experiments containing the combination of joint mobilization (Maitland or Mulligan) with other common treatments were also included, as long as they mainly focused on assessing the effect of these two types of joint mobilization methods.

Study selection

Two independent reviewers (Li LL, Hu XJ) removed duplication, screened titles,abstracts and full texts and agreed on the final eligibility. Negotiation was required when there was disagreement[25]. We recorded the reasons for exclusion of full texts.

Data collection process and data items

Two independent reviewers (Li LL, Di YH) extracted the data from included articles using a pre-designed form, including the following parameters: Author’s name,publication year, sample size, study design, type/frequency/duration of the intervention and outcome assessment. Any disagreements were discussed and resolved by the two authors.

Risk of bias in individual studies

The quality of the included articles was assessed by two reviewers individually using PEDro scale. The results given by the two reviewers were compared and any disagreements were resolved by all three authors. The PEDro scale is based on the Delphi list and reported to be reliable for randomized controlled trials (RCTs) of physical therapy in systematic reviews. The PEDro scale consists of 11 items,including: (1) Specified eligibility criteria of studies; (2) Random allocation of studies;(3) Concealed allocation; (4) Similarity between groups at baseline; (5) Blinding of all subjects; (6) Blinding of all therapists; (7) blinding of all assessors; (8) Less than 15%dropouts; (9) Intention-to-treat analysis; (10) statistical comparisons between groups;and (11) Point measures and variability data. PEDro score was calculated by assessing the items 2-11. Each item was scored as either 1 or 0 according to whether the item was met or not, respectively. The total score of the scale is 10. Articles were classified into three distinct categories, including high (7-10), moderate (4-6) and low (0-3) quality.

Statistical analysis

All data were analyzed by using Cochrane Collaboration software (Review Manager Version 5.2 for Windows). Only continuous variables (range of motion, pain, function scale) were identified, therefore, the difference in means between the intervention groups with 95% confidence intervals (CI) was used as the main summary measures to determine the effect size of the results[26]. The final value and the standard deviation of the results were recorded as well as the number of patients in each treatment group at the last time of the follow-up. To evaluate the heterogeneity of the included studies,the chi2 statistical test andstatistic were performed. The extent of heterogeneity was measured by theIstatistical test and presented as the total percentage of variation between the studies. Thevalue was considered low ifwas 0%-25%, moderate ifwas 25%-50% and high ifwas 50%-90%. A random effect model was employed if the heterogeneity was relatively high. Conversely, in case of low heterogeneity, a fixed effect model was used to analyze the data with inverse variance weighting[27].Sensitivity analysis was conducted to identify the potential sources of high heterogeneity[28]. The statistical significance was assessed by using the Z index of overall effects[27]. Funnel plots was used to assess potential publication biases. If the included trials were < 10, we did not test for publication bias[29].

RESULTS

A total of 341 articles were screened from five electronic databases. After removing 333 articles, of which 125 were duplicates, 206 articles were screened out through title and abstract review, 10 articles were still for further consideration. After excluding two studies, eight trials involving 471 subjects were included in the present systematic review and meta-analysis (the reasons for their exclusion were given in Figure 1).

Characteristics of included studies

The characteristics regarding the study population, intervention, follow-up period and main results of the studies are presented in Table 1.

翌日上午取回采樣紙，用工業(yè)顯微鏡把附著藥液的1.2mm2試紙放大160倍，讀入計算機(jī)中，利用圖像處理技術(shù)統(tǒng)計上面的霧滴的粒數(shù)和當(dāng)量粒徑；再利用Excel軟件統(tǒng)計和計算平均粒徑的大小及粒數(shù)[3]。由于霧滴在采樣紙上的痕跡大致為圓形，應(yīng)校正為球體直徑，按下列公式計算，即

Risk of bias

For ROM, Mulligan mobilization might have the same efficacy as Maitland mobilization. Mulligan and Maitland mobilization, as two kinds of manual therapies,have been found to improve the mechanical loading, joint stability and strength of weak muscles through mechanical, self-confidence and motivating factors. In a cohort study, KOA patients received a manual physical therapy program focusing on passive extension mobilization of the knee, and the restoration effects in Mulligan mobilization group was not better than that in the exercise group[38]. In another study, ROM in Mulligan mobilization was improved in the long term[33]. According to the studies by Stathopoulos[17], Mulligan mobilization could only ameliorate joint dysfunctions of the upper and lower extremities and facilitated the immediate recovery of full and pain-free ROM. However, no studies have focused on the treatment period and the site of arthritis. In our study, we focused on the ROM of knees and included studies with various treatment periods. Besides, the high heterogeneity might decrease the reliabilities of the results. Further study and follow-ups will be needed to validate the conclusion.

Pain

Seven studies[14,15,30-34] with continuous data on pain degree were included in the meta-analysis, with a total of 354 participants. Five studies[14,15,30,31,33] reported the severity of pain using visual analogue scale, while the other two studies[32,34]adopted another Numeric Pain Rating Scale. The Numeric Pain Rating Scale is a segmented numeric version of the visual analogue scale, and both scales use a horizontal bar or line to rate the degree of pain. Thus, these two scales could be considered as the same. According to the forest plot (Figure 2), the pooled standardized mean difference (SMD) was 0.60 (SMD = 0.60; 95%CI: 0.17 to 1.03;=0.007).

ROM

Data were collected from five studies[14,30,31,33,35] with continuous data containing a total population of 204 participants. According to the forest plot (Figure 3), random effect model showed that there was no difference in the effect of the two mobilization methods on improving ROM (SMD = 9.63; 95%CI: -1.23 to 20.48;= 0.08).

Western Ontario and McMaster Universities (WOMAC) function score

Six studies, with 297 participants, reported WOMAC function score[14,15,31-33,35],and one study[14] reported WOMAC function and pain score. According to the forestplot (Figure 4), Mulligan dynamic joint mobilization was more effective in improving the WOMAC function score of patients with knee arthritis. (SMD = 7.41; 95%CI: 2.36 to 12.47;= 0.004).

Publication bias

The analysis of the funnel plot for publication bias suggested the absence of bias because of plot symmetry (Figure 5).

DISCUSSION

Summary of evidence

In this systematic review and meta-analysis of eight randomized controlled trials including 471 KOA patients, Mulligan mobilization was found to be a promising alternative option for KOA treatment. Particularly, the Mulligan mobilization has been recommended to be applied in alleviating pain and improving WOMAC function score. Because of the poor methodological quality of included studies, more studies are needed to assess the effect of manual therapies on pain, WOMAC function score and ROM.

Unsolicited article; Externally peer reviewed.

All the articles included were assessed with the PEDro Scale (Table 2). The total score of methodological quality varied from 5 to 10 out of 11. The score of most studies exceeded the cut-off point 6, but only two studies scored 9. Many studies missed points on blinding of patients[14,15,30-32], therapists[14,15,30-34] and assessors[14,15,30,32]. In addition, there was often a lack of the concealment of allocation. These are shortcomings for RCTs.

Overall, KOA is regarded as a complex disorder with multiple risk factors, such as generalized constitutional factors (age, female sex,)[39] and local adverse mechanical factors (trauma, malalignment,.)[40]. Confined to the current evidence,we did not limit sex, age, body weight or even history, which may influence the representativeness and application of conclusions. In addition, it was found that the heterogeneity of most included RCTs was high. Thus, the positive effects of the Mulligan mobilization should be interpreted with caution. Finally, because manual therapies require hands-on treatments, it is not possible to perform the study in a blinded way, resulting in the poor score on the PEDro Scale. In the future clinical trials, attention should be paid to all the points above in study design.

Strengths and limitations

Our research has several strengths. First, as far as we are aware, this is the first systematic review and meta-analysis aiming to determine the efficacy of MaitlandMulligan mobilization with movement in KOA patients. Secondly, this meta-analysis included as many relevant outcomes as possible and was completed according to the accepted guideline[41]. Thus, the results were relatively comprehensive.

However, similar to other meta-analyses, there were also limitations[42]. Firstly,since not all the grey literature could be searched, some studies might have been missed[43]. This may be negligible with comprehensive and reliable research strategy.Secondly, the sample size in this review might not be enough, which could affect the quality of evidence. Thirdly, due to less than 10 included studies, interpretation of publication bias assessment should be done with caution[29]. Finally, we did not report the cost due to the lack of data. Thus, more RCTs should be conducted,including novel interventions, and more data on adverse effects (AEs) safety will be of necessity.

變壓器油化驗中，由于對應(yīng)變壓器油的應(yīng)用中存在著很多的影響因素，通過對變壓器油的物理性能檢測分析，能夠衡量出變壓器油應(yīng)用是否存在著缺陷性。一般情況下，變壓器油在應(yīng)用過程中，其初始油顏色為淡黃色，隨著變壓器應(yīng)用的時間逐漸增長，其對應(yīng)的油體顏色也會出現(xiàn)新的變化，按照變壓器油應(yīng)用的時間變化其油體顏色會逐漸加深，這是由于變壓器應(yīng)用中，其對應(yīng)的油體出現(xiàn)了老化現(xiàn)象，并且生成了二氧化碳和雜質(zhì)，造成了整體的變壓器油應(yīng)用質(zhì)量下降，影響最終的變壓器油應(yīng)用效果。因此，在進(jìn)行變壓器油的化驗過程中，對應(yīng)的化驗人員及時地按照變壓器油化驗的物理性能變化將其物理性能上的影響處理好，降低變壓器油應(yīng)用的故障。

CONCLUSION

Mulligan joint mobilization is a promising intervention with the potential to improve the pain and joint function for patients with KOA. Based on real-world and other epidemiological settings, more data and surveillance will be necessary to identify the efficacy. Also, further studies are necessary to explore the cost of KOA in other ethnicities.

Our meta-analysis revealed that Mulligan mobilization will be a promising alternative option for KOA treatment. Unfortunately, because of the poor methodological quality of included studies, more data and surveillance will be necessary to identify the efficacy. Also, further studies are needed to explore the cost of KOA in other ethnicities.

The Mulligan mobilization has been recommended to be applied in alleviating pain and improving Western Ontario and McMaster Universities function score.

課程創(chuàng)新以創(chuàng)造性實踐活動為落腳點，而創(chuàng)造性實踐活動的成效一方面有賴于創(chuàng)造性思維水平，另一方面取決于創(chuàng)造性實踐能力。因此，應(yīng)用型本科院校實施課程創(chuàng)新，不僅要關(guān)注師生創(chuàng)造性思維的訓(xùn)練，而且要重視師生創(chuàng)新實踐能力的培養(yǎng)。由于能力形成、發(fā)展于活動之中，故應(yīng)用型本科院校一方面要鼓勵和支持教師從事創(chuàng)新實踐活動，另一方面要組織學(xué)生開展創(chuàng)新實踐活動。

We would like to thank all authors of the included primary studies.