Volume 95  ·  Issue 34  ·  2015

Time flies, and the passage of time can't erase the footprints of the strugglers. In 2015, the Chinese Medical Journal ushered in a beautiful moment of its 100th anniversary, which is also a common festival for Chinese medical workers. Since its founding for a hundred years, to this day, Chinese Medical Journal has been affirmed by the majority of medical workers and readers for its strong scientific nature, high authority, great influence and wide coverage, and has played an important role in promoting the development and exchange of medical academic work in China. Although the burn discipline started late, after more than 50 years of construction and development, it has now become one of the few international advanced medical disciplines in China, adding new highlights and features to Chinese Medical Journal.

With the widespread application of D-dimer in clinical practice, the standardization of D-dimer detection and the reliability of results have attracted great attention of clinicians. 2001 Respiratory Disease Branch of Chinese Medical Association published "Guidelines for Diagnosis and Treatment of Pulmonary Thromboembolism (Draft)"^[1]In 2010, the Pulmonary Vascular Disease Group of the Cardiovascular Disease Branch of the Chinese Medical Association and the Cardiovascular Physicians Branch of the Chinese Medical Doctors Association jointly published the Chinese Expert Consensus on the Diagnosis and Treatment of Acute Pulmonary Thromboembolism^[2]In 2013, the Expert Consensus Group on Emergency Clinical Application of D-Dimer Detection published the Expert Consensus on Emergency Clinical Application of D-Dimer Detection^[3]Clinicians strongly demand that laboratories provide accurate and comparable test data that meet clinical needs. Due to the lack of testing guidelines and standards, the expert consensus published by domestic academic organizations is not clear enough for the requirements of laboratory testing, and the quality improvement of clinical laboratories encounters many difficulties. Therefore, from 2013 to 2015, the Clinical Laboratory Center (NCCL) of the Ministry of Health put forward the basic requirements for D-dimer detection in clinical laboratories on the basis of referring to foreign standards, consulting literatures, conducting questionnaire surveys and physical testing surveys, and through the industry standard project research of the Legal Affairs Department of the National Health and Family Planning Commission. The present situation of D-dimer detection and the basic requirements of laboratory detection standardization are briefly described and discussed.

Hemophilia, as a congenital hereditary disease, is recognized for its sex-associated heredity, post-traumatic hemorrhage and special changes in the laboratory. The development of hemophilia diagnosis and treatment level well reflects the development course of medicine, science and technology and society; It has experienced the yesterday of facing death, the today of improving quality of life and the tomorrow of looking forward to freedom from the bonds of disease.

The situation of uremia prevention and treatment in China is grim. According to the national blood purification case information registration data, by the end of 2014, there were nearly 340,000 hemodialysis patients in China. However, according to the data of the national epidemiological survey, there are 120 million patients with chronic kidney disease (CKD) in China, including more than 19 million patients with stage 3 or above CKD^[1]110 million diabetic patients^[2]250 million hypertensive patients^[3]。 Therefore, with the continuous improvement of the national medical security system, the number of maintenance hemodialysis patients will continue to grow at a high speed, which will surely bring a huge economic burden. Under this background, how to improve the quality of life and survival rate of hemodialysis patients and obtain the optimal health economics has become an important content of common concern between the government and the majority of blood purification scholars. Since the promulgation of the Standard Operating Procedures for Blood Purification (2010 Edition) in 2010, the National Center for Medical Quality Management and Control of Nephrology has carried out nationwide medical quality control of hemodialysis. The results show that the overall treatment level of hemodialysis in China needs to be improved, especially the detection of hemodialysis adequacy and its compliance rate. Therefore, based on the results of evidence-based medicine, referring to relevant international guidelines, and on the basis of refining the part of dialysis adequacy in the Standard Operating Procedure for Blood Purification (2010 Edition), the clinical practice guidelines for hemodialysis adequacy in China are put forward. The aim is to base on the principle of practical feasibility and guiding clinical practice, give more targeted guidance to clinical front-line workers, and promote the improvement of hemodialysis adequacy in China.

To evaluate the comparability of measurement results for coagulation factor Ⅷ (FⅧ)and factor Ⅸ (FⅨ)activity and the commutability of reference materials on different measurement systems.

The study was performed according to CLSI guideline EP30 and China health standard WS/T 356-2011.Clinical samples with different levels of FⅧ and FⅨ which covered over the clinical analytical range, five lots of homemade reference materials (F20140601-F20140605) and a coagulation reference material (SSCLOT4) provided by NIBSC were detected for FⅧ and FⅨ activity on three popular measurement systems in China, which including Stago STA-R Evolution, IL ACL TOP700 and Sysmex CA7000 automatic coagulation analyzers using supplementary reagents. The results between measurement systems were analyzed pairwise. To evaluate the comparability, the linear regression and the biases between the results of clinical samples from two measurement systems were calculated. The comparability was evaluated by the regression coefficient and the biases inside the acceptable range. After eliminated outliers from the results, linear regressions were run again and the 95% confidence intervals were calculated. The commutability of the homemade reference materials and NIBSC reference material were evaluated by comparing the results with the limits of the intervals.

The ranges of FⅧ and FⅨ level of clinical samples were 0.5%-218.0% and 1.6%-156.5%, which covered the sample levels in routine work and fit the requirements for commutability evaluation. The square of correlation coefficients (R²) of measurement results of clinical samples for FⅧ and FⅨ activity assays were 0.89-0.94 and 0.81-0.93. The proportions of outliers were all less than 10%. The comparability of measurement results of FⅧ and FⅨ in different measurement systems was acceptable.According to the acceptable criteria for bias, the measurement results of 42, 41 and 45 clinical samples for FⅧ and 44, 42 and 41 clinical samples for FⅨ were used in the commutability evaluation for homemade reference materials and NIBSC reference material after deleting the outliers. The five lots homemade reference materials and NIBSC reference material were all within the 95% prediction intervals from the linear regression of clinical samples' results.

Good correlation and comparability are found for FⅧ assay and those for FⅨ assay are acceptable. All homemade reference materials and NIBSC reference material are commutable for the three measurement systems.

To provide valuable test by evaluating the efficiency of lupus anticoagulant assays based on different principles.

370 citrated samples were recruited, LA were tested by dRVVT, SCT, APTT-Actin, APTT-Actin FSL and APTT-SS respectively, and 1∶1 mixing tests before incubation were studied in all the recruited subjects. For LA testing, the results of 1∶1 mixing test were expressed as index of circulating anticoagulant (ICA), and the confirm test results were expressed as percent of correction (C) and normalized ratio (NR). The reference interval (RI)/Cut-off values of all the assays were established, and the efficiency of all the assays were further studied.

The RI/Cut-off values of all assays were different. The sensitivity of dRVVT were the highest among all the assays (70.3%-93.1%), and the sensitivity of APTT (<55.0%) were the lowest. The sensitivity of APTT-SS (47.5%-53.5%) were higher than APTT-Actin (32.7%-39.6%) and APTT-Actin FSL (29.7%-36.6%). The specificity of dRVVT, SCT and three APTT were 91%-100%, 80.6%-100%, and 85.1%-98.5%, respectively. The specificity of SCT confirm test were 100%. Sensitivity of all the five methods were decreased in the weak positive LA. The sensitivity of dRVVT and SCT were more than 50.0%, however, the sensitivity of APTT-Actin and APTT-Acitn FSL were less than 16.0%. The sensitivity of APTT-SS were 23.7%-30.5%. Except the APTT-SS, dRVVT and SCT were correlated with thrombotic risk in APS patients (OR: 5.562-9.240, P<0.05).

Every Laboratory should establish local LA RI/Cut-off values. dRVVT is the best assay for LA test, and APTT-SS method is superior to the other APTT method. The different test combinations of dRVVT and SCT are correlated with thrombotic risk in APS patients.

To investigate the effectiveness and safety of inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy in idiopathic pulmonary alveolar proteinosis (PAP).

Ten PAP patients were enrolled, who were hospitalized in the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2012 to January 2014.All the patients were treated with inhaled GM-CSF therapy, high-dose therapy for 12 weeks, GM-CSF 150 μg twice a day on days 1-7, none for days 8-14, 6 cycles, low-dose therapy for 12 weeks, GM-CSF 150 μg inhaled once a day on days 1-7, none for days 8-14, 6 cycles, and followed-up for one year. Physiologic, serologic and radiologic features of the patients were analyzed.

After inhaled therapy, clinical symptoms, oxygenation indexes, pulmonary function of nine patients were improved, and high resolution CT (HRCT) showed ground-glass lesions reduced. After inhaled therapy for 6 months, the average level of arterial oxygen partial pressure (PaO₂) was significantly higher than that before therapy ((75.5±7.0) vs (63.6±8.9) mmHg (1 mmHg=0.133 kPa)), while alveolar-arterial oxygen pressure difference (P_(A-a)O₂) was lower than before ((25.1±7.1) vs (41.2±13.5) mmHg) (both P<0.01). Similarly, vital capacity (VC)%predicted, forced vital capacity (FVC)%predicted and carbon monoxide diffusing capacity (D_LCO)%predicted all improved after therapy ((77.3±16.6)% vs (63.3±16.6)%), (79.5±17.6)% vs (64.9±17.1)%), (69.4±23.0)% vs (50.0±19.9)%) (all P<0.01). The score of HRCT reduced after therapy for six months (P<0.05). While the levels of serum lactate dehydrogenase (LDH), carcinoembryonic antigen (CEA), CYFRA211 were unchanged. No serious adverse events occurred during observation.

Inhaled GM-CSF therapy is safe and effective.

To observe the clearance of BK viruria and long-term graftsurvival in renal transplant recipients with BK virus (BKV)infection under the protocol of our center.

Urine was taken from 229 renal transplant recipients, who were transplanted between March 2006 to October 2008, for BKV cytological testing and real-time PCR for BKV DNA at 1, 3, 6, 9, and 12 months after transplantation. Graft biopsies were analyzed for SV40-T by immunohistochemical method. Recipients were treated according to the BKV infection protocol of our center and were monitored for BKV and graft function. All the patients were followed for at least 5 years.

By 1 year post-transplant, urinary decoy cells, BK viruria, and BKV associated nephropathy(BKVAN) occurred in 78, 99, and 7 patients, respectively. The median followed-up time was 63.6(3.0-88.0)months. After reduction of immunosuppression, 81 (81.8%) patients cleared BK viruria with a mean time of (12.1±1.9) months. When compared with non-BKVAN patients, BKVAN patients had a higher median peak level of BK viruria (2.07×10⁹ vs 9.28×10⁵copies/ml, P=0.002), lower frequency of clearance (3/7 vs 78/92, P=0.006), longer BK viruria clearance time ((45.4±6.4) vs (8.7±1.5) months, P=0.001). The 1, 3, 5-yeargraft survival in BK viruria patients were 99.0%, 95.9% and 89.6% respectively, which were not significantly different from those in non-BK viruria patients(97.7%, 95.5% and 93.7% , P=0.289). Graft function of BK viruria patients were not statistical significance compared with non-BK viruria patients (serum creatinine level 5 years post-transplant: (105.7±30.9)vs (111.3±44.6)μmol/L,P=0.322). Graft function of BKVAN patients at 5 years post-transplantwas stable without significantly difference from non-BKVAN patients (serum creatinine level: (127.6±41.0)vs(108.3±39.3)μmol/L,P=0.204).

On the premise of intensively and regularly BKV monitoring and preemptive reduction of immunosuppression, BK viruria and BKVAN can not impact on the long-term graft survival in renal transplant recipients.

To assess the feasibity and efficacy of narrow band imaging (NBI) cystoscopy assisted holmium laser resection of primary non-muscle invasive bladder cancer (HoLRBt).

During the period of May 2013 to December 2014, 150 cases of primary non-muscle invasive bladder cancer (NMIBC) admitted in our hospital were randomly divided into NBI-HoLRBt and WLI-TURBt group. In NBI-HoLRBt group, all suspicious lesion identified by either WLI or NBI were resected during the surgery with WLI and in NBI mode for lesion only visible with NBI. At the end of the procedure, NBI cystoscopic examination was performed again to identify whether there was residual lesions at the margins of the resection areas. In WLI-TURBt group, only WLI and TURBt were applied. All patients from the two groups underwent routine intravesical instillation after surgery. A total of 124 patients were diagnosed NMIBC by pathological findings(NBI-HoLRBt group: n=60, WLI-TURBt group: n=64), they were followed-up at 3 months, at which both WLI and NBI cystoscopy were performed to examine the residual tumor, and cytology was checked for all patients. The residual tumor rates at the first follow-up (RR-fFU) were recorded and compared.

Baseline characteristics of the patient and the tumor were comparable between the two groups. The overall detection rate of NMIBC and carcinoma in situ (CIS) were significantly higher with NBI than WLI (94.5%(137/145) vs 75.8%(110/145), 16/17 vs 10/17, both P<0.05). The RR-fFU for NBI-HoLRBt and WLI-TURBt was 3.3%(2/60)and 17.2%(11/64), respectively (P<0.05).

NBI-HoLRBt was feasible, and more effective for identification of NMIBC as well as for the reduction of residual tumor rate compared with WLI-TURBt.

To observe the morphology changes of cerebral cortex in primary open-angle glaucoma (POAG) patients, and to explore the damage mechanism in the central nerve system.

30 patients, 19 males and 11 females (age ranged from 26 to 82 years old), who were diagnosed with POAG in the department of ophthalmology at Huashan Hospital of Fudan University from February 2011 to December 2012 were enrolled. Meanwhile, additional 30 age- and sex- matched patients were collected as controls. All subjects underwent a complete ophthalmic evaluation. As for magnetic resonance imaging (MRI), we adopted the scans of T1WI, T2WI and fluid attenuated inversion recovery (FLAIR) on a Siemens Magneton Verio 3T MRI machine with a 12-channel head coil. Subjects with space occupying or vascular lesion in brain imaging were excluded from the study. The three-dimensional magnetization prepared rapid acquisition gradient echo sequence (3D-MPRAGE) was used to acquire the volume data of whole brain of all subjects. SPM8 and VBM8 toolbox were used to analyze the image data. Voxel-based analysis was done for whole brain grey matter images.

Compared with the control group, the volume of grey matter from several brain regions of the POAG patients decreased. These structures included left lingual gyrus (t=3.207, P=0.002), left medial frontal gyrus (t=2.912, P=0.004), right superior frontal gyrus (t=2.745, P=0.005), left middle temporal gyrus (t=2.958, P=0.003), right precuneus (t=3.291, P=0.001), right postcentral gyrus (t=3.306, P=0.001), left inferior parietal lobule(t=2.716, P=0.006), left parahippocampa gyrus (t=2.815, P=0.005). The results were assessed with comparative t-test to perform statistical analysis. When t>2.479,P<0.01, the difference between the two groups was considered statistically significant.

The volume of grey matter in POAG patients' brain decreased in several regions. It is illustrated that POAG is a syndrome, which causes damages in the brain of POAG patients at multi-aspects and multi-levels. The damages contained not only injuries in the visual pathway, but also morphological and functional changes in many other brain regions.

TOX3 gene was considered to be breast cancer susceptibility gene in the European population and East Asian populations. This study was aimed to investigate the relevance of TOX3 gene rs3803662 single nucleotide polymorphisms and sporadic breast cancer susceptibility among the Han Nationality in Henan Province.

A case-control study was performed among 253 patients with sporadic breast cancer and 343 control subjects in Henan Province. The SNP rs3803662 in TOX3 was genotyped by imLDR technique. Association analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for the SNP between different alleles and breast cancer.

There was no statistically significant difference in the distribution of TOX3 rs3803662 allele in different Ki-67 value and HER2 gene status in the case group. The distribution of TOX3 rs3803662 allele between breast cancer and the control group were different. Compared with allele AA and GA, allele GG increased the risk of breast cancer in codominant inheritance(OR=2.19, 95%CI: 1.19-4.02) and recessive genetic models( OR=2.06, 95%CI: 1.15-3.70). Further stratifying analysis was conducted based on estrogen receptor status. The SNP rs3803662 showed significant associations with ER status, and was associated with positive ER status in the recessive (OR=1.92; 95%CI: 1.00-3.67; P=0.05) and codominant models (OR=2.07; 95%CI: 1.05-4.08; P=0.036). And this SNP was associated with negative ER status breast cancers in both recessive (OR=2.38; 95%CI: 1.10-5.15; P=0.028) and codominant models (OR=2.43; 95%CI: 1.08-5.48; P=0.032). But there was no statistically significant difference in each subgroup stratified by ER status.

This was a verification study in a Han population. In codominant and recessive genetic models, allele GG increased breast cancer risk and was associated with the pathogenesis of different ER status breast cancer. But there was no obvious correlation between this SNP and Ki-67 or HER2 gene .This is the first breast cancer susceptibility loci that is confirmed in Henan population. Our study only analyzes the correlation between the SNP and ER status in breast cancer. More studies and analyses about the association between SNPs and different characteristic of breast cancer should be performed.

To explore the possibility of using comprehensive anti-infection method during sacral neuromodulation(SNM)operation to prevent postoperative loacal incision infection.

SNM were performed for 23 patients (male 11 cases, and female 12 cases) who had intractable lower urinary tract dysfunctoin from January 2013 to Feburary 2015. During the treatment period (both in stage Ⅰ and stage Ⅱ), several steps were adopted to prevernt local incision infection after opertion, such as comprehensive skin disinfection, strict aseptic operating, intravenous infusion of antibiotics (cefoxitin or levofloxacin) prophylacticly at least 24 h, using sterile water to wash the incison in operation and taking oral antibiotics anti-infection as supplemental after operation. At the meantime, microbiological examination was performed in the explanted tined leads , extension wire connection and local gluteal tissue.

A total of 23 patients received SNM with local anesthesia, mean time of operation, hospitalization and test period were 1.5 h, 3.2 d and 37.1 d , respectively. All patients had no symptoms of clinical local infection after stageⅠtest period and all incisions were healing with Ⅰ/A standard. Eight patients were removed the inside electrodes because of poor effect at the end of test period with local anesthesia. Bacterial growth was not detected in all 8 patients of explanted tined leads and extension wire connection. And all 8 patients had their incision healed with Ⅰ/A standard. Fifteen patients received implantable pulse generator(IPG) with local anesthesia. Mean time of operation was 63 min and mean time of hospitalization was 2.2 d. Among them , 10 patients' extension wire connection and loacal tissue were send to microbiological examination and no bacterial growth was found. All stage Ⅱ incisions were healing with Ⅰ/A standard.

Perioperative comprehensive anti-infection method could prevent local incision infection after SNM.

To evaluate the association of obstructive sleep apnea hypopnea syndrome (OSAHS) with carotid atherosclerosis and the efficacy of continuous positive airway pressure (CPAP) treatment.

A total of 93 OSAHS patients diagnosed by polysomnography (PSG) were selected from Sleep Disorders Center at Affiliated Hospital of Xuzhou Medical College between March 2013 and December 2014. Based on the results of apnea-hypopnea index (AHI), they were divided into mild (n=22), moderate (n=37), and severe OSAHS group (n=34). Meanwhile, 28 healthy adult individuals matched for age and body mass index (BMI) were enrolled as the control group. The carotid intima-mesa thickness (IMT) was measured by color Doppler uhrasonography, and plasma levels of tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1) and nitric oxide (NO) were determined by Enzyme-Linked Immunosorbent Assay (ELISA). The correlations between carotid IMT and plasma levels of TNF-α, ET-1 and NO were analyzed. A total of 24 patients with moderate to severe OSAHS underwent CPAP treatment and the carotid IMT, plasma levels of TNF-α, ET-1 and NO were compared before and after CPAP treatment.

OSAHS patients had significant increase of carotid IMT with the increasing disease severity, and the carotid IMT in mild, moderate and severe OSAHS groups were all significantly higher than that in the control group ((0.73±0.31), (0.86±0.07), (1.07±0.14) vs (0.65±0.10) mm, all P<0.05). The plasma levels of TNF-α and ET-1 in mild to severe OSAHS group were significantly higher than those in controls ((17.45±3.02), (23.81±2.91), (35.16±3.43) vs (12.53±3.48) ng/L and (0.81±0.13), (1.06±0.21), (1.66±0.30) vs (0.64±0.12) ng/L, allP<0.05 ), whereas plasma levels of NO in the three OSAHS groups were significantly decreased compared with the control group ((35.46±10.12), (29.32±9.47), (20.16±7.41) vs (45.43±7.92) μmol/L, allP<0.05). Furthermore, there were significant differences in plasma levels of TNF-α, ET-1 and NO among the three OSAHS groups (allP<0.05). Carotid IMT was positively correlated with plasma TNF-α and ET-1 (r=0.56 and 0.51) and negatively correlated with plasma NO (r=-0.46) (all P<0.05). After 3 months of CPAP treatment, plasma levels of TNF-α and ET-1 in OSAHS patients were significantly reduced ((19.64±5.28), (0.94±0.21) vs (28.72±5.36), (1.36±0.36) ng/L), and plasma NO was markedly increased ((33.57±6.32) vs (24.34±4.46) μmol/L, allP<0.05). However, CPAP treatment did not have a significant effect on carotid IMT ((0.91±0.21) vs (0.96±0.14) mm),P>0.05).

Systemic inflammation and vascular endothelial dysfunction may play an important role in pathogenesis and development of carotid artery atherosclerosis in OSAHS. Short-term CPAP therapy alleviates systemic inflammation and improves endothelial function, but does not influence the increased carotid IMT in OSAHS patients.

To evaluate the efficacy and safety of trastuzumab plus capecitabine as first-line therapy for HER-2-positive metastatic breast cancer patients who have previously received anthracyclines and taxanes.

The patients who have HER-2-positive breast cancer recurrence and metastasis after treated by anthracyclines and taxanes were enrolled in this study. The patients received trastuzumab (6 mg/kg every 21 days following a loading dose of 8 mg/kg on cycle 1) and capecitabine (2 000 mg/m^2, days 1 to 14 every 21 days).

38 patients were enrolled. The median PFS for trastuzumab plus capecitabine was 8.6 months. The objective response rate (ORR) was 31.6%. Clinical benefit rate (CBR) was 65.8%. The most serious adverse event was leucopenia in one patient. Relatively common hematology toxicity was grade Ⅰ or Ⅱ leucopenia and neutropenia. The most common nonhematologic toxicity was hand-foot syndrome (HFS), which observed in 8 patients (21%). The morbidity of grade Ⅱ and Ⅲ HFS were 8% and 3% respectively.

Trastuzumab plus capecitabine is an effective and safe regimen as first-line treatment for HER-2-positive metastatic breast cancer patients whose cancer is resistant to treatment with anthracyclines and taxanes.

To analyze the testing results of hospitalized patients with suspected viral pneumonia using xTAG Respiratory Virus Panel Array (xTAG RVP).

133 hospitalized patients with suspected viral pneumonia from Peking Union Medical College Hospital from January 2013 to December 2014 were divided into two groups, including 42 young and middle-aged patients (17-49 years old) and 91 middle and old-aged patients (50-88 years old). The nucleic acids of sputum or bronchoalveolar lavage fluid (BALF) samples from the two group patients were screened by xTAG RVP and the results were analyzed.

Viruses can be detected from 50 out of all 133 samples, and the positive rate was 37.6%. Among the viral positive samples, the proportion of mixed infections was 12.0%. The detection rates of Influenza A virus (FluA) and Rhinovirus (RV) were higher than others (45.0% and 16.7%). The infection rate of young and middle-aged patients was significantly higher than that of the middle and old-aged patients (73.8% vs 31.9%, P<0.001). The viral detection rates of samples from spring, summer, autumn and winter were 25.0%, 6.7%, 20.0% and 38.3%, respectively. The positive rate difference among four seasons was not significant (P=0.257).

FluA and RV are dominant respiratory viruses in hospitalized patients with suspected viral pneumonia, and the infection rate of the young and middle-aged patients is higher than the middle and old-aged patients.

To investigate the effect of two methods on postoperative shoulder pain following laparoscopic cholecystectomy (LC).

A total of 99 patients undergoing LC were prospectively divided into three groups (33 patients in each group): Patients in group A underwent LC were control group, those in group B were inserted negative pressure drainage tube under the right inferior phrenic after LC, and patients in group C accepted warm and normal saline flush during operation under the right inferior phrenic. Shoulder pain occurrence and shoulder pain levels (visual analogue pain scale-VAS) were recorded on 1, 3, 6, 24, 48, 72 h after operation.

Postoperative shoulder pain occurrence was significantly higher in group A (14/33) than those in group B (6/33) and group C (1/33), and group C had the best effect (χ²=2.733, P=0.004) among the 3 groups. For shoulder pain levels, same result was achieved with group C had the best effect (P<0.05).

Warm and normal saline flush during operation under the right inferior phrenic could help to obviously reduce the occurrence of post LC shoulder pain probably by blocking some mechanisms causing postoperative shoulder pain after LC.

The patient, a 69-year-old man, went to our hospital for more than 2 months because he found a mass at the root of his left thigh. Outpatient examination: a mass can be palpable at the root of his left thigh, about 3 cm ×2 cm ×2 cm in size, tough in texture, without skin redness, swelling, damage, no tenderness, can be pushed, and the boundary is clear. B-ultrasound showed that there was a 37 mm ×20 mm hypoechoic mass at the root of the left thigh with a clear boundary (Figure 1), was admitted to our hospital on October 20, 2014 with a mass at the root of his left thigh. Admission examination: body temperature 37.0 ℃ pulse 74 beats/min, breathing 16 beats/min, blood pressure 130/80 mmHg (1 mmHg =0.133 kPa). Deny the history of contact with infectious diseases such as hepatitis, tuberculosis, schistosomiasis and typhoid fever. Laboratory tests: normal liver and kidney function. On the morning of October 22, a mass resection of the root of the left thigh was performed under general anesthesia. During the operation, the mass was hard, clearly defined, about 5 cm ×4 cm ×3 cm in size, and the capsule was intact. Intraoperative rapid pathology: mucinous malignancy, type awaiting routine pathology. Gross examination of postoperative mass: The mass was spherical, 4.5 cm ×4.0 cm ×2.5 cm in size, with incomplete capsule, adipose tissue attached to the surface, brittle cut surface, 0.8 cm diameter cyst cavity formed in the center, and a large amount of mucus was seen in the capsule and on the surface of the mass (Figure 2)。 Microscopically, the tumor cells were polygonal, small round and short fusiform mixed, diffusely distributed, small blood vessels proliferated, the interstitium was a large mucus lake, a small amount of residual lymphoid tissue was seen at the edge of the tumor, and the sinus structure could be seen after careful search (Figure 3)。 The results of immunoenzyme labeling showed that Vimentin, S-100 and Melanoma were positive in tumor cells, Actin, Desmin, CD56, epithelial membrane antigen (EMA), Cytokeratin (Pan), leukocyte common antigen (LCA), Ewing's sarcoma marker (CD99), chromaphin A (CgA) and synaptophysin (SY) were negative in tumor cells (Figure 4)。 Pathological diagnosis: Left inguinal lymph node metastatic mucinous malignant melanoma, it is recommended to find the primary lesion in the ipsilateral lower limb clinically. After careful clinical search, multiple stains were seen on the skin on the lateral side of the left lower leg, one of which was a larger irregular stain with a size of 2 cm ×2 cm (Figure 5), after asking the medical history, the pigmentation was more than 20 years old, and it was significantly enlarged with repeated erosion and crusting 3 years ago, and then healed by itself. On November 28th, the lesion skin resection at the lateral pigmentation of the left calf was performed under local anesthesia. A large number of melanophagic cells and collagen fibers were seen in the dermis under the microscope, but no clear malignant tumor cells were found (Figure 6), suggesting that it may be a malignant melanoma with local degeneration. Combined with secondary pathological examination, this case was finally diagnosed as a rare metastatic mucinous malignant melanoma of left inguinal lymph node with primary regression.

A 28-year-old female developed fever without obvious trigger in January 2014, with a body temperature of up to 39 ℃, occasional cough, phlegm difficult to cough up, accompanied by obvious dry eyes and dry mouth, no chills, weight loss, night sweats, no frequent urination, urgency, abdominal pain, diarrhea and other discomfort. She went to a hospital, and blood routine showed white blood cells 12.36×10⁹/L, hemoglobin 114 g/L, platelets 254×10⁹/L, and was treated with azithromycin, gaticarcin and cephalosporin antibiotics for more than 40 days, and his body temperature gradually dropped to normal. On February 28, 2014, he had fever again, with a maximum body temperature of 40.3℃, occasional cough and expectoration, no chills, night sweats, and joint pain all over the body, including knee joint, accompanied by swelling and pain of lymph nodes on the right neck, without rash, hair loss and other discomfort. Perfect examination showed that white blood cells were 2.6×10⁹/L, hemoglobin 83 g/L, platelets 52×10⁹/L, biochemistry showed alanine aminotransferase (ALT) 122 U/L, aspartate aminotransferase (AST) 55 U/L, glutamyl transferase (GGT) 139 U/L, triglyceride 2.23 mmol/L, fibrinogen 0.62 g/L, immunoglobulin G 18.70 g/L, erythrocyte sedimentation rate 30 mm/1 h, rheumatoid factor 22.6 kU/L. Immune correlation examination showed positive anti-nuclear antibody by indirect immunofluorescence (+) 1:320 (spot), anti-SSA antibody by immunospot (+), and negative remaining antibodies. Abdominal B-ultrasound showed splenomegaly. Perfect bone marrow cytology shows infected bone marrow images. Right cervical lymph node biopsy revealed lymph node reactive hyperplasia with atypical T-zone hyperplasia. During this period, penicillin + piperacillin tazobactam sodium, imipenem cilastatin sodium + teicoplanin were given to fight infection, but the effect was not good. The patient still had intermittent fever, and the three lines progressively declined. Further examination of serum ferritin 4 033 μ g/L, natural killer cell activity significantly decreased to 9%, soluble interleukin 2 receptor 41 394 ng/L, labial gland biopsy: partial acinar atrophy, interstitial scattered and focal lymphocyte infiltration (focal lymphocytes>50), small duct hyperplasia with dilatation (Figure 1)。 According to relevant diagnostic criteria^[1]Hemophagocytic lymphohistiocytosis (HLH) and Sjogren's syndrome (SS) were definately diagnosed. The patient was screened for HLH-related gene mutations by high-throughput (second-generation sequencing) sequencing method. The results showed that the deletion of the coding sequence of the 32nd exon of UNCl3D gene resulted in frameshift mutation (c.3229_3235del) and deletion of the corresponding amino acid (p.1077_1079del), which was verified by polymerase chain reaction combined with direct sequencing (Figure 2)。 After the patient was diagnosed with HLH and SS, he was given intravenous etoposide 100 mg and methylprednisolone to control inflammatory factor storm on March 20 and March 27, 2014, respectively. At the same time, he was given methotrexate 7.5 mg once a week and folic acid 5 mg 3 times a day to treat SS, supplemented by symptomatic supportive treatment. The condition was gradually under control. After discharge, the patient continued to take low-dose methylprednisolone and methotrexate for maintenance therapy. Follow-up until October 2014, the patient's condition remained stable.

Chronic altitude sickness (CMS) refers to the clinical syndrome with excessive increase of red blood cells as the main symptom of gradual loss of habit to the low oxygen environment of the plateau in people who have lived on the plateau for a long time or settlers who have lived at an altitude above 2 500 m. The Qinghai standard formulated by the Sixth International Congress of Plateau Medicine in 2004 is: in the absence of chronic lung disease and other causes of erythrocytosis, the hemoglobin concentration of male ≥210 g/L and female ≥190 g/L, and accompanied by three or more of the following symptoms: shortness of breath, palpitation, sleep disorder, cyanosis, headache, tinnitus and paresthesia, etc^[1]。 A large number of CMS cases show that arterial hypoxemia will gradually aggravate over time, eventually leading to various serious diseases such as microcirculation disorders, pulmonary hypertension, sleep breathing disorders and pulmonary heart disease^[2,3,4]。

Fibroblast growth factor 23 (FGF-23), a member of the family of hormonal fibroblast growth factors, is a 251 amino acid glycoprotein with a relative molecular mass of approximately 32,000. The FGF-23 gene is mapped to chromosome 12 and was originally discovered by gene mapping cloning in autosomal dominant rickets with hypophosphatemia^[1]。 The main physiological role of FGF-23 is to regulate mineral metabolism. In recent years, animal and clinical studies^[2,3]It was found that FGF-23 was closely related to the occurrence and development of cardiovascular diseases. Therefore, the correlation between FGF-23 and cardiovascular diseases has become a hot topic of attention. This article will review the research progress of FGF-23 and cardiovascular diseases.