2020年 · 第133卷第08期

Osteoarthritis (OA) is currently considered as more than a degenerative disorder of weight-bearing joints, instead one organ disease of "all-joint" due to cause(s) of aging, injury, inflammation, metabolic disorders,etc. Its prevalence is high: 9.6% in men and 18.0% in women aged over 60 years. Most health professionals say that OA is incurable and focus exclusively on palliative treatment, as we lack effective disease modifying osteoarthritis drugs (DMOADs).^[1]But should we hope that treating OA precisely in China is possible through intensive research and drug development?

Rheumatoid arthritis (RA), a systemic autoimmune disease characterized by synovial inflammation, can cause cartilage and bone damage as well as disability. The aim of this study was to explore whether serum glucose-6-phosphate isomerase (GPI) is correlated with disease activity and the value of GPI in the evaluation of infliximab treatment in patients with RA.

Sixty-two patients with RA who had an inadequate response to methotrexate (MTX) were enrolled in Peking University People’s Hospital from July 1, 2016 to July 31, 2018. Infliximab (3 mg/kg, intravenous at weeks 0, 2, and 6 and then every 8 weeks) was administered to patients with stable background MTX therapy. Serum samples were obtained at baseline and week 18. Serum GPI levels were determined using enzyme-linked immunosorbent assay. The associations between serum GPI levels and clinical features were analyzed.

Serum GPI was positively correlated with Disease Activity Score in 28 joints (DAS28), swollen joint count, tender joint count and C-reactive protein level (P < 0.001, P < 0.001, P < 0.001, and P = 0.033, respectively). The change of DAS28 in GPI-positive patients was greater than that in GPI-negative patients (P < 0.001). Compared with those for patients receiving MTX monotherapy at baseline, the GPI levels were significantly declined when MTX was combined with infliximab (P < 0.001).

Serum GPI is related to disease activity and clinical response to infliximab treatment.

Despite the recent advances in treatments for rheumatoid arthritis (RA), there are still unmet needs in disease outcomes. This study aimed to analyze the satisfaction with drug therapies for RA according to the levels of disease severity (patientassessed) and proportions of treatment cost to household income.

This was a subgroup study of a cross-sectional study in patients with RA and their physicians. The patients were subdivided into different subgroups based on their self-assessed severity of RA and on the proportions of treatment cost to household income (<10%, 10-30%, 31-50%, and >50%). The Treatment Satisfaction Questionnaire for Medication version II was used to assess patients’ treatment satisfaction.

When considering all medications, effectiveness, convenience, and global satisfaction scores were lower in the severe and moderate RA subgroups than those in the mild and extremely mild RA subgroups (all P < 0.001). Effectiveness, side effects, and convenience scores were higher in the <10% subgroup compared to those in the >50% subgroup (all P < 0.05). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 13.183, P = 0.004). For biological diseasemodifying anti-rheumatic drugs, effectiveness and convenience scores were lower in the severe RA subgroup than those in the extremely mild RA subgroup (both P < 0.05). Convenience score was higher in the <10% subgroup compared to that in the 31% to 50% and >50% subgroups (F = 12.646, P = 0.005). Global satisfaction score was higher in the <10% subgroup than that in the 31% to 50% subgroup (F = 8.794, P = 0.032).

Higher disease severity and higher financial burden were associated with lower patient satisfaction.

Treatment of coronary bifurcation lesions remains challenging; a simple strategy has been preferred as of late, but the disadvantage is ostium stenosis or even occlusion of the side branch (SB). Only a few single-center studies investigating the combination of a drug-eluting stent in the main branch followed by a drug-eluting balloon in the SB have been reported. This prospective, multicenter, randomized study aimed to investigate the safety and efficacy of a paclitaxel-eluting balloon (PEB) compared with regular balloon angioplasty (BA) in the treatment of non-left main coronary artery bifurcation lesions.

Between December 2014 and November 2015, a total of 222 consecutive patients with bifurcation lesions were enrolled in this study at ten Chinese centers. Patients were randomly allocated at a 1:1 ratio to a PEB group (n = 113) and a BA group (n = 109). The primary efficacy endpoint was angiographic target lesion stenosis at 9 months. Secondary efficacy and safety endpoints included target lesion revascularization, target vessel revascularization, target lesion failure, major adverse cardiac and cerebral events (MACCEs), all-cause death, cardiac death, non-fatal myocardial infarction, and thrombosis in target lesions. The main analyses performed in this clinical trial included case shedding analysis, base-value equilibrium analysis, effectiveness analysis, and safety analysis. SAS version 9.4 was used for the statistical analyses.

At the 9-month angiographic follow-up, the difference in the primary efficacy endpoint of target lesion stenosis between the PEB (28.7% ± 18.7%) and BA groups (40.0% ± 19.0%) was -11.3% (95% confidence interval: -16.3% to -6.3%, P_superiority <0.0001) in the intention-to-treat analysis, and similar results were recorded in the per-protocol analysis, demonstrating the superiority of PEB to BA. Late lumen loss was significantly lower in the PEB group than in the BA group (-0.06 ± 0.32 vs. 0.18 ± 0.34 mm, P < 0.0001). For intention-to-treat, there were no significant differences between PEB and BA in the 9-month percentages of MACCEs (0.9% vs. 3.7%, P = 0.16) or non-fatal myocardial infarctions (0 vs. 0.9%, P = 0.49). There were no clinical events of target lesion revascularization, target vessel revascularization, target lesion failure, all-cause death, cardiac death or target lesion thrombosis in either group.

In de novo non-left main coronary artery bifurcations treated with provisional T stenting, SB dilation with the PEB group demonstrated better angiographic results than treatment with regular BA at the 9-month follow-up in terms of reduced target lesion stenosis.

ClinicalTrials.gov, NCT02325817; https://clinicaltrials.gov

Cervical posterior decompression surgery is used to relieve ventral compression indirectly by incorporating a backward shift of the spinal cord, and this indirect decompression is bound to be limited. This study aimed to determine the decompression limit of posterior surgery and the effect of the decompression range.

We retrospectively reviewed the data of 129 patients who underwent cervical open-door laminoplasty through 2008 to 2012 and were grouped as follows: C4-C7 (n = 11), C3-C6 (n = 61), C3-C7 (n = 32), and C2-C7 (n = 25). According to the relative location of spinal levels within a decompression range, the type of decompression at a given level was categorized as external decompression (ED; achieved at the levels located immediately external to the decompression range margin), internal decompression (ID; achieved at the levels located immediately internal to the decompression range margin), and central decompression (CD; achieved at the levels located in the center, far from the decompression range margin). The vertebral-cord distance (VCD) was used to evaluate the decompression limit. The C2-C7 angle and VCD on post-operative magnetic resonance images were analyzed and compared between groups. The relationship between VCD and decompression type was analyzed. Moreover, the relationship between the magnitude of the ventral compressive factor and the probability of post-operative residual compression at each level for different decompression ranges was studied.

There was no significant kyphosis in cervical curvature (>-5°), and there was no significant difference among the groups (F = 2.091, P = 0.105). The VCD of a specific level depended on the decompression type of the level and followed this pattern: ED < ID < CD (P < 0.05). The decompression type of a level was sometimes affected by the decompression range. For a given magnitude of the ventral compressive factor, the probability of residual compression was lower for the group with the larger VCD at this level.

Our study suggests that the decompression range affected the decompression limit by changing the decompression type of a particular level. For a given cervical spinal level, the decompression limit significantly varied with decompression type as follows: ED < ID < CD. CD provided maximal decompression limit for a given level. A reasonable range of decompression could be determined based on the relationship between the magnitude of the ventral compressive factor and the decompression limits achieved by different decompression ranges.

Gastric cancer (GC) is one of the most globally prevalent cancers in the world. The pathogenesis of GC has not been fully elucidated, and there still lacks effective targeted therapeutics. The influence of altered kinesin superfamily protein 22 (KIF22) expression in GC progression is still unclearly. The aim of this study was to investigate the KIF22 effects on GC and related mechanisms.

Gastric carcinoma tissues and matching non-cancerous tissues were collected from patients with GC who have accepted a radical gastrectomy in Lanzhou University Second Hospital from May 2013 to December 2014. The expression of KIF22 was examined in GC of 67 patients and 20 para-carcinoma tissues by immunochemical staining. The relationship between the expression of KIF22 and clinicopathologic characteristics was next investigated in the remaining 52 patients except for 15 patients who did not complete follow-up for 5 years. Cell viability was performed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) test and colony formation assay in the MGC-803 and BGC-823 GC cells. Cell scratch and trans-well invasion assay was performed to assess migration ability in the MGC-803 and BGC-823 GC cells. Gene set enrichment analysis (GSEA) pathway enrichment analysis was performed to explore the potential functions. Cell cycle was detected by flow cytometry. In addition, the two GC cell lines were used to elucidate the underlying mechanism of KIF22 in GC in vitro via assessing the effects on mitogenactivated protein kinase and extracellular regulated protein kinases (MAPK/ERK) signal transduction pathway-related expressions by Western blotting assays. The differences were compared by t tests, one-way analysis of variance, and Chi-squared tests.

The study showed that KIF22 was up-regulated in GC, and KIF22 high expression was significantly related to differentiation degree (χ² = 12.842, P = 0.002) and poorly overall survivals. GSEA pathway enrichment analysis showed that KIF22 was correlated with the cell cycle. Silence of KIF22 decreased the ability of the proliferation and migration in gastric cells, induced G1/S phase cell cycle arrest via regulating the MAPK-ERK pathways.

KIF22 protein level was negatively correlated with prognosis. KIF22 knockdown might inhibit proliferation and metastasis of GC cells via the MAPK-ERK signaling pathway.

Takayasu arteritis-induced renal arteritis (TARA), commonly seen in Takayasu arteritis (TA), has become one of the main causes of poor prognosis and early mortality in patients with TA. TARA progressing into Takayasu arteritis-induced renal artery stenosis (TARAS), could lead to severe complications including malignant hypertension, cardiac-cerebral vascular disease, and ischemic nephropathy. Since there existed no guidelines on treatments, this study aimed to review the comprehensive treatments for TARA.

We searched systematically in databases including PubMed, Ovid-Medline, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and SinoMed, from inception to May 2018. Literature selection, data extraction, and statistical analysis were performed.

Eighty-two literatures were recruited focusing on medical treatments (n = 34) and surgical treatments (n = 48). We found that combined medical treatments of glucocorticoids and conventional synthetic disease-modifying anti-rheumatic drugs could reach high rates of remission in patients with TARA, and biological disease-modifying anti-rheumatic drugs were preferred for refractory patients. After remission induction, surgical treatment could help reconstruct renal artery and recover renal function partly. Percutaneous transluminal angioplasty was the first choice for patients with TARAS, while open surgery showed a good longterm survival.

Patients with TARA should benefit both from medical treatments and from surgical treatments comprehensively and sequentially. Multidisciplinary team coordination is recommended especially in patients with severe complications.

Hyperuricemia and gout have become public health concerns; many important guidelines have recommended xanthine oxidase inhibitors (XOIs) as the first-line urate-lowering therapies (ULTs) to treat chronic gout with hyperuricemia. However, whether treating hyperuricemia and gout with ULTs modifies cardiovascular risks remains controversial. The aim of this study was to assess the incident risk of cardiovascular (CV) events (CVE) in hyperuricemia population, assess the cardiovascular benefit-risk of ULTs in hyperuricemia patients with or without gout in diverse cardiovascular risk sub-groups, and specify the safety of different ULTs.

We searched PubMed, Embase, the Cochrane Library, Wanfang, Chongqing VIP (CQVIP, en.cqvip.com), and China National Knowledge Infrastructure Database for prospective cohort studies and randomized controlled trials (RCTs) in English and Chinese. Potential medications included XOIs, and uricosurics. RCTs were divided into sub-groups analysis based on blinding status and patients’ history of CV diseases. Risk ratios (RRs) were calculated and were reported with corresponding 95% confidence intervals (CIs) by fixed-effects or random-effects model.

Seven prospective cohort studies and 17 RCT studies were included. The risks of both major adverse cardiovascular events (MACE) (RR = 1.72, 95% CI 1.28-2.33) and CVE (RR = 1.35, 95% CI 1.12-1.62) were higher in the hyperuricemia population than non-hyperuricemia one. In seven RCT studies where XOIs were compared with no-treatment or placebo, the results of five low CV risk studies showed that XOIs lowered the risks of both MACE (RR = 0.35, 95% CI 0.20-0.62) and CVE (RR = 0.61, 95% CI 0.44-0.85); whereas two high CV risk studies showed that XOIs lowered the risk of CVE (RR = 0.69, 95% CI 0.54-0.88) rather than MACE (RR = 0.62, 95% CI 0.29-1.35). In nine RCT studies where the cardiovascular safety between febuxostat and allopurinol were compared, no statistical difference was found in the risk of MACE or CVE.

The hyperuricemia population does have a higher incidence of CVE, and the results suggested that XOIs might reduce the incidence of MACE and total CVE. In addition, from the perspective of cardiovascular safety, febuxostat equaled allopurinol in our meta-analysis.

A 50-year-old Chinese woman who experienced intermittent fever with xerostomia and xerophthalmia for 24 years, paroxysmal loss of consciousness for 11 years, aggravation for 1 year was admitted to the Peking University First Hospital in 2019. She started to have intermittent fever (38-39°C) every 2 to 3 months 24 years before first rheumatological evaluation, and the temperature can return to normal without intervention. After she had an episode of epilepsy with abdominal pain 23 years ago, she had severe weight loss, fatigue, weakness, skin pigmentation, and low blood pressure (80/45 mmHg). Laboratory test showed normal potassium, hyponatremia 133 mmol/L (normal range 135-145 mmol/L), low serum cortisol concentration in the early morning 0.56 μg/mL (normal range 4.40-9.20 μg/dL), low 24-h urine-free cortisol 259.6 μg/d (normal range 370.0-639.0 μg/d) and high adrenocortico-tropic-hormone (ACTH) 128.37 pg/mL (normal range 7.20-63.30 pg/mL). She also had anemia with hemoglobin 77 g/L, thrombocytopenia with platelet 70 × 10⁹/L to 90 × 10⁹/L and dramatically prolonged activated partial thromboplastin time (APTT) 105.1 s (normal range 22.7-31.8 s). Serum creatinine was elevated from 110 to 135 μmol/L (normal range 44-133 μmol/L). Both blood cultures and purified protein derivative test were negative. With prednisolone 30 mg daily along with supportive therapy, the patient’s blood pressure was back to normal with no more fever, and serum creatinine decreased to 120 μmol/L. Meanwhile, the patient’s fatigue and skin pigmentation were also alleviated, but her armpit and pubic hairs shed. Further autoimmune tests showed positive anti-nuclear antibodies (ANA) 1:1000 and anti-SSA antibody; however, normal serum complements levels. Since she was diagnosed as autoimmune adrenal insufficiency (AI), prednisone replacement therapy (5 mg 8 AM and 5 mg 4 PM each day) has been maintained for more than 20 years.

There was an enormous increase in reports confirming the safety and efficacy of using peroral endoscopic myotomy (POEM) to treat achalasia since the pioneering of the technique in 2010.^[1]However, the reports focused on short to medium-term follow-ups, and data on long-term outcomes of POEM for achalasia were very limited. It still remains unknown whether the satisfactory short-term outcomes are long lasting. Additionally, some achalasia patients receiving POEM noted that they could benefit from post-operative dietary recommendations that would be helpful for symptom remission. Therefore, this study aimed to determine the long-term treatment outcomes of using POEM to treat achalasia, and to assess postoperative Eckardt scores over this period. We also crafted a set of post-POEM dietary recommendations according to the feedback from achalasia patients who underwent this treatment to achieve better symptom remission for post-POEM patients.

Peripheral nervous system injuries can cause partial or complete transection of the nerve, thereby lead to paralysis, poor or abnormal sensation, and painful neuropathies. Platelet-rich fibrin (PRF) is defined as a second-generation platelet concentrates with high regenerative potential.^[1]Moreover, PRF is easy to prepare without chemical preprocessing, as inducing faster nerve repair is critical in the clinical use of nerve conduits for peripheral nerve repair. However, PRF membrane nerve conduit (PRF-NGC) has not been well studied. In this study, PRF-NGC was compared with autologous nerve grafts (ANG) and polyurethane (PUR) nerve conduit to investigate the potential effect of PRF-NGC on peripheral nerve repair. Regenerated nerves were analyzed by immunofluorescent staining and transmission electron microscopy. Measurements of wet weight and Masson’s trichrome stained sections of gastrocnemius muscle were collected for deterministic quantification of sciatic nerve functional recovery.

To the Editor:Rheumatic diseases are disorders characterized by joint inflammation, but other organs are also affected.^[1]Rheumatic diseases are common in China, and the clinical application of azathioprine (AZA), a purine analog immunosuppressant, for these diseases is attracting increasing attention. Although AZA is widely used in the treatment of rheumatic diseases, its clinical application is limited by adverse effects, especially leukopenia.

A 29-year-old Chinese woman complained of recurring dizziness for 5 months and gait disturbance for 2 months. On admission (April 2016), she was found to have a widebased gait, horizontal nystagmus and positive heel-kneeshin test. Initial hematological, biochemical, microbiological, hormonal investigations and tumor serum markers were unremarkable. Oligoclonal bands were observed in cerebrospinal fluid (CSF) without other pathological changes, while magnetic resonance imaging (MRI) of cervical spine and brain were normal. An anterior mediastinal mass was noted by computed tomography (CT) [Figure 1A]. Despite a lack of paraneoplastic antibodies in CSF or serum, such as anti-neuronal nuclear autoantibody type 1 (ANNA-1, also known as "anti-Hu" ), ANNA-2 (also known as "anti-Ri" ), Purkinje cell antibody type 1 (PCA-1, also known as "anti-Yo" ), anti-CV2 (also known as "collapsin response mediator protein 5 [CRMP5]" ), anti-Ma, anti-Amphiphysin, anti-Tr (also known as "delta/notch-like epidermal growth factorrelated receptor [DNER]" ) and anti-glutamic acid decarboxylase (GAD), her neurological manifestation still pointed toward one of the paraneoplastic neurological syndromes (PNSs).

In the article entitled "Long non-coding RNA HOTAIRM1 promotes proliferation and inhibits apoptosis of glioma cells by regulating the miR-873-5p/ZEB2 axis" published on issue 2, pages 174-182, volume 133 of Chinese Medical Journal,^[1]the author and affiliation section should be corrected as follows:

In the article titled "Protocol on transcranial alternating current stimulation for the treatment of major depressive disorder: a randomized controlled trial," published on pages 61-67, Issue 1, Volume 133 ofChinese Medical Journal,^[1]"Ninety-two" of Abstract, Study design, randomization, and blinding andFigure 1should be "One hundred," and "46" inFigure 1should be "50" ; and the Sample size calculation andFigure 1are corrected.