Volume 93  ·   Issue 40  ·  2013

To evaluate the efficacy and safety of dose-reduced decitabine for the lower risk myelodysplastic syndrome (MDS) patients with transfusion dependent.

Twentyfive cases of lower risk (low or intermediate-1 risk in IPSS risk group) MDS patients with transfusion dependence from November 2009 to September 2012 were treated by dose-reduced decitabine (20 mg/m² intravenously once daily for 3 days).And their efficacy, side effects, quality-of-life and survival rate were evaluated.

Among them, the responses included complete remission (CR, n=3, 12%), transfusion independence (n=4, 16%), hematologic improvement (HI, n=8, 32%) and stable disease (SD, n=2, 8%).And the overall response rate (ORR) was 68% (17/25).Among 11 cases available for cytogenetic evaluation, 1 achieved partial cytogenetic remission (PRc).Ⅳ grade hematologic toxicity rate was 48% (12/25) and Ⅲ-Ⅳ grade infection rate 20% (5/25).No severe hematologic toxicity was observed.After treatment, the Karnofsky performance score (KPS) increased from 47±16 to 66±22 (P=0.001); more patients were reclassified as WPSS≤1 (44% vs 16%, P=0.031) or MDACC score≤7 (64% vs 8%, P=0.022).The median follow-up time was 467 (14-881) d.The 100 and 600-day expected survive rates of low and intermediate-1 risk in IPSS risk group were 100% versus 95.2% and 100% versus 90.5%.

Dose-reduced decitabine is well-tolerated and effective in transfusion dependent MDS patients in IPSS-lower risk.There is a low rate of severe hematologic toxicity and early mortality.It may prolong their survival time.

To explore the impact of prior-to-transplantation induction therapy (IT) on patient outcome after allogeneic hematopoietic stem-cell transplantation (Allo-HSCT) for higherrisk myelodysplastic syndromes (MDS).

A total of 49 consecutive patients underwent Allo-HSCT for MDS between November 2002 and December 2012.Twenty-six lower-risk MDS cases received supportive therapy (ST).And 17/23 cases of higher-risk MDS received IT prior to transplantation while anothers 6 only with ST.Their survival, relapse rate and incidence of transplantation-related mortality (TRM) were retrospectively analyzed according to International Prognostic Scoring System (IPSS) scores and marrow blast count.

The 5-year cumulative overall survival (OS), disease-free survival (DFS), relapse rate and incidence of transplantation related mortality (TRM) were 59.9%,59.2%,10.5% and 31.8% during a median follow-up period of 24.4 (6.2-72.0) months.The OS and DFS of higher-risk group with IT, ST and lower-risk group were different (72.1% vs 16.7% vs 68.1%, P=0.028| 72.1% vs 16.7% vs 67.9%, P=0.030).And the OS and DFS of higher-risk group with IT were similar to those of lower-risk group (P=0.526,0.504).For the higher-risk group, the patients on IT had improved survival than those on ST in terms of OS and DFS (both P=0.020).Moreover, the OS and DFS of remission group were higher than non-remission group in patients on IT (both 100% vs 46.7%, P=0.049).The number of marrow blasts significantly decreased after IT (P=0.010) without increased TRM (28.9% vs 33.6%,P=0.612).

Induction therapy prior to Allo-HSCT for MDS may reduce clone burden and improve the outcomes of higher-risk MDS without increased TRM.

To assess the prevalence and clinical characteristics of isocitrate dehydrogenase 1 and 2 (IDH 1 and IDH2) gene mutations in myelodysplastic syndrome (MDS) patients.

Pretreatment bone marrow specimens were enriched for mononuclear cells in 108 adult patients with de novo MDS from January 2006 to August 2012.Genomic DNA was extracted from mononuclear cells.And PCR and direct sequencing were performed to sequence exon 4 of IDH gene.

IDH mutations were discovered in 11 MDS patients (10.19%, 11/108) and all were heterozygous.The frequencies of IDH1 and IDH2 mutations were 5.56% (6/108) and 4.63% (5/108) respectively.Only one type of IDH1 mutation (c.394C→T, p.R132C) was identified in our cohort.All IDH2 mutations caused the changes of R140 (c.419G→A, p.R140Q).However IDH2 R172 mutation was not detected.The combined mutations of IDH1 and IDH2 were not simultaneously observed in the same patient.The prevalence of IDH mutation was higher in advanced-stage MDS than those earlystage MDS patients.Mutated and wild-type groups had significantly difference in bone marrow blast percentage (median 12.5% vs 6.0%,P=0.013) at diagnosis, but not in white blood cell count, hemoglobin level and platelet count, etc.In the normal karyotype group, the frequencies of IDH mutations were as similar as those in the abnormal karyotype group (10.61% (7/66) vs 10.00% (4/40),P>0.05).The median follow-up time was 472 d, our data indicated that IDH mutations were correlated with poor overall survival (median time 512 vs 740 d,P=0.017).IDH mutations were also an inferiorly predictive factor in the intermediate-1 group patients of International Prognostic Scoring System (IPSS)(median survival time 512 d vs not reached,P=0.038).There was also better efficacies than other treatments in IDH mutation positive patients (median survival time 623 vs 165 d, P=0.049).

IDH mutation is a vital biomarker for better risk stratification of MDS patients with and improving IPSS.Hypomethylating agents may be effective for treating IDH mutation positive patients.

To compare the results of fluorescence in situ hybridization (FISH) versus conventional cytogenetics (CC) in the detection of common chromosomal abnormalities and evaluate the significance of FISH in myelodysplastic syndrome (MDS).

A total of 344 patients with de novo MDS from June 2008 to October 2012 were detected by 6 pairs of probes, including CSF1R/D5S23-D5S721 (5q33), EGR1/D5S23-D5S721 (5q31), D7S486 (7q31)/CSP7, D7S522 (7q31)/CSP7, D20S108/CSP8 (20q12/CSP8) and CSPX/CSPY.The results were compared with those of CC.

CC revealed cytogenetic abnormalities in 168/344 cases (48.8%) and the frequency of common aberrations such as+ 8,20q-,-7/7q-,-5/5q- and -Y were 18.9% (65/ 344),9.3% (32/344),8.4% (29/344),8.4% (29/344) and 2.4% (5/206) respectively.While FISH revealed chromosome abnormalities in 147/344 patients (42.7%) and the frequency of +8,20q-,-7/7q-,- 5/5q- and -Y were 20.9% (72/344),11.6% (40/344),11.6% (40/344),10.2% (35/344) and 2.9% (6/206) respectively.Overall 187/344 patients (54.4%) carried clonal aberrations by a combination of CC and FISH.Among 158 patients with normal karyotype by CC, 14 cases (8.9%) were detected to have clonal aberrations by FISH.FISH also confirmed 4 carriers of clonal aberrations out of 9 patients with nonclonal abnormalities by CC.

FISH is effective for improving the probability of detecting chromosome abnormalities in MDS cases with normal karyotypes and karyotype failure.FISH may provide rationales for clonal abnormalities in patients with nonclonal aberrations by CC.A combination of FISH and CC shows complementary advantages.

To explore the diagnostic value of thyroid microcarcinoma with a tallerthan-wide shape (A/T≥1) in transverse ultrasonographic planes.

There were a total of 683 thyroid nodules in 491 patients undergoing consecutive ultrasonography and surgery at our hospital between 2011 and 2012.The ultrasonography examinations of thyroid nodules were routinely performed in the transverse planes.A taller-than-wide shape was defined as a ratio of anteroposterior diameter to transverse diameter in transverse plane≥1.The sensitivity and specificity for thyroid carcinoma were analyzed.The data of thyroid carcinoma were formulated as follows:group 1, nodules>1 centimeter; group 2,≤1 centimeter.Their ratiosof A/T werecompared.The data wereanalyzed with SPSS 17.0 statisticalsoftware package.Results Among 683 nodules, 499 were malignant and 184 benign.The sensitivity and specificity for malignancy were 61.5% and 84.2% respectively.There was significant difference (P=0.000).A taller-than-wide shape (A/T≥1) was more frequent in criterion 2 than criterion 1 (χ²=4.380, P=0.036).

A taller-than-wide shape (A/T≥1) is associated with thyroid malignancy especially thyroid microcarcinoma.And it is a useful ultrasonic feature for predicting thyroid microcarcinoma.

To explore the safety of omitting axillary lymph node dissection (ALND) in primary invasive breast cancer patients with negative sentinel lymph nodes (SLN).

Between June 2005 and June 2011, all SLN negative patients omitting ALND were analyzed retrospectively.They were all primary invasive breast cancer patients without clinicocytological evidence of axillary node involvement.SLN biopsy was performed prior to systemic treatment.And the tracer was ⁹⁹Tc^m labeled Ratuximab.

A total of 1807 eligible patients were enrolled.Their median age was 50 years (21-87).And the median number of SLN was 2.The patients of T1, T2 and T3 were 1069 (59.2%), 712 (39.4%) and 26 (1.4%) respectively.After a median follow-up of 36 months, 14 (0.77%) cases of ipsilateral axillary recurrence were observed.Among them, 10 (0.55%) had single axillary recurrence.Second primary cancer occurred in 22 patients (1.2%).And distant metastases were found in 26 patients (1.4%).The 3-year axillary recurrence rate was 0.7%, disease-free survival 96.4% (95% CI 95.4%-97.4%) and recurrence-free survival 97.1% (95% CI 96.1%-98.1%).

The omitting of ALND is safe in breast cancer patients with negative SLN.

To explore the effects of postprandial diaphragm training (DT) on esophageal acid exposure, esophageal motility and proximal gastric volume at different postprandial periods in patients with gastroesophageal reflux disease (GERD).

Thirty GERD patients and 9 healthy subjects (HS) with matched demographic characteristics were enrolled from June 2005 to June 2006 at Peking Union Medical College Hospital.Esophageal manometry with a Dentsleeve catheter and simultaneous esophageal pH monitoring were recorded in a 30-min fasting period and a 120-min postprandial period.The GERD patients were divided into 3 groups: 9 patients received diaphragm training at 1^st hour after meal (group DT_{1 h}) and another 10 at 2^nd hour after meal (group DT_{2 h}) whereas no diaphragm training after meal in 11 (group NDT).Ultrasonic imaging of proximal gastric volume was undertaken at 0, 30,60, 90 and 120 min after meal.

(1) The percentage time with pH<4 in group DT_{1 h}was lower than that in group NDT in the 120-min postprandial period (0.2% (0-4.1%), 6.6% (2.2%-18.2%), P<0.05) and no significant difference of esophageal acid exposure was observed between groups DT_{2 h}and NDT (3.7% (0.1%-17.8%), 6.6% (2.2%-18.2%), P>0.05). (2) Esophagogastric junction (EGJ) and crural diaphragm pressures at the 1^st hour after meal in group DT _{1 h}were both significantly higher than those in group NDT during diaphragm training ((44.4±8.1) vs (16.2±4.5) mm Hg, (38.2±4.2) vs (9.8±4.5) mm Hg, 1 mm Hg=0.133 kPa, both P<0.05).EGJ and crural diaphragm pressures at the 2^nd hour after meal in group DT_{2 h}were significantly higher than those in group N-DT during diaphragm training ((53.2±7.5) vs (14.0±3.7) mm Hg, (48.2±6.3) vs (8.9±2.7) mm Hg, both P<0.05).There was no change of lower esophageal sphincter pressure (all P>0.05). (3) After test meal, the groups DT_{1 h}, DT_{2 h}and N-DT had similar proximal stomach volume (all P>0.05).

Diaphragm training at the 1^st hour after meal might reduce the 120-min postprandial esophageal acid exposure in GERD patients.The reduction in esophageal acid exposure may result from enhanced antireflux barrier of EGJ function.Therefore postprandial diaphragm training provides a new approach to conservative treatment of GERD.

To explore the major risk factors for intra-abdominal infections after radical gastrectomy in patients with gastric cancer.

From October 2010 to January 2013, a total of 479 patients undergoing radical gastrectomy at Department of Gastric, Duodenal& Pancreatic Surgery, Hunan Provincial Tumor Hospital were divided into 2 groups according to an onset of postoperative intra-abdominal infections (n=32, 6.68%) or not (n=447, 93.32%).Their clinicopathological data, such as age, gender, co-morbidities, surgical duration, operative blood loss and pathological stage were retrospectively analyzed by Logistic regressive analysis with a case-control study model.

As compared with the control group, the patients had a greater age ((59±10) vs (53±11) years, P<0.01), lower lymphocyte count ((1.4±0.7) ×10⁹/L vs (1.7±0.6) ×10⁹/L, P=0.02), lower hemoglobin level ((108±28) vs (117±24) g/L, P=0.04), lower albumin level ((34±6) vs (37±5) g/L, P<0.01) and longer surgical duration ((244±43) vs (216±45) min, P<0.01) in the postoperative intra-abdominal infection group.Univariate Logistic regressive analysis found that a history of abdominal surgery, body mass index (BMI) >25 kg/m², comorbidities, diabetes mellitus, complications due to gastric cancer, lymphocyte count<1.5×10⁹/L, hemoglobin<100 g/L, albumin<30 g/L, ascites, perioperative transfusion, total mastectomy, combined organ resection and surgical duration>240 min were associated with the occurrence of postoperative intra-abdominal infections (all P<0.05).Further multivariate analysis identified 4 independent risk factors for intra-abdominal infections after radical gastrectomy, including combined multiorgan resection (OR=3.64, 95% CI: 1.39-9.55), BMI>25 kg/m² (OR=3.04, 95% CI: 1.17-7.92), diabetes mellitus (OR=3.41, 95% CI:1.05-11.09) and perioperative transfusion (OR=2.24, 95% CI:1.02-5.13).

A correction of modifiable risk factors may reduce the incidence of intra-abdominal infections after radical gastrectomy, shorten the length of hospital stays and improve outcomes in patients with gastric cancer.

To explore the correlation between serum levels of Cystatin C and metabolic syndrome.

This study was randomly conducted in 506 persons, including 191 patients with metabolic syndrome (MS), 210 with metabolic disorder (MD) and 105 persons in normal control (NC) group.According to serum levels of Cys C, the clinical data were also divided into 3 groups of lower tertile (T1,n=165), middle tertile (T2,n=172) and upper tertile (T3,n=169).Body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), fasting plasma glucose (FPG), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), high density lipoprotein (HDL), creatinine (Cr), estimated glomerular filtration rate (eGFR), microalbuminuria (MAU), systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP) were measured and their mutual relations evaluated.

Statistically significant differences (all P<0.01) existed among T1, T2 and T3 groups in the mean values of BMI, waist circumference, WHR, FPG, LDL-C, TG, Cr, eGFR, MAU, SBP, DBP and PP.As tertile levels of Cys C increased, MS morbidity rates became all remarkably augmented (P<0.01).The MS component scores had significant statistical differences among the patients of T1, T2 and T3 groups (P<0.01).As the MS component scores increased, the level of Cys C rose in these patients.The higher MS marks were, the higher serum concentration of Cys C was in these patients.The plasma concentration of Cys C in MS patients was closely related with WC, LDL-C, FBG and blood pressure (all P<0.05), not related with TG levels and negatively correlated with HDL-C levels (r=-0.352, P=0.01).WC, Cys C, LDL-C, MAU and PP were significantly associated with MS.And the value of OR between Cys C and MS was 2.943 (95% CI 1.276-3.914).

Cys C is significantly associated with MS.As MS scores rise, the level of Cys C increases.

To explore the influencing factors of glycemic variability in elderly patients with type 2 diabetes.

A total of 337 elderly patients received continuous glucose monitoring (CGM) from January 2007 to January 2011.The evaluation variables of glycemic variability included standard deviation of blood glucose (SDBG), mean amplitude of glycemic excursion (MAGE), absolute means of daily differences (MODD) and postprandial glucose excursion (PPGE).The normal reference value of glycemic variability was defined according to the diagnostic criteria of Chinese Diabetes Society guideline.

The difference of glycemic variability was compared by gender, age and diabetic duration.The values of SDBG, MAGE, MODD and PPGE in females were all higher than those in males (P<0.05) and no difference existed between various age groups.The level of glycemic variability increased gradually with the extension of diabetic duration (P<0.01).Logistic regression analysis showed that gender (MAGE:OR=0.44, P=0.023; SDBG: OR=0.39, P=0.023), diabetic duration (MAGE:OR=1.58,P=0.006; SDBG:OR=2.42,P<0.001) and HbA1c (MAGE:OR=2.44,P<0.001; SDBG:OR=2.68,P<0.001) were significant influencing factors of glycemic variability (MAGE/SDBG) in elderly patients with type 2 diabetes (P<0.05), but not age, body mass index (BMI) or diabetic neuropathy.

Gender, diabetic duration and HbA1c are significant influencing factors of glycemic variability while age, BMI or diabetic neuropathy has no association with glycemic variability in elderly patients with type 2 diabetes.

Tumor necrosis factor (TNF) locus has been a long-standing type 2 diabetes (T2D) candidate gene.Few studies have been conducted on TNF SNP (single nucleotide polymorphism) as rs1799964 (T-1031C), rs1800630 (A-863C) and rs1799724 (C-857T) in T2D.The purpose of this study is to examine the association of TNF SNP and T2D in a case control study and further explore whether these SNPs influence the clinical efficacy of insulin therapy.

A total of 109 newly diagnosed type 2 diabetics and 168 healthy individuals were recruited.Three tag SNPs (rs1799964 (T-1031C), rs1800630 (A-863C), rs1799724 (C-857T)) were selected across the TNF locus and polymerase chain reaction (PCR) directed sequencing was performed.The patients received Lispro 25 twice daily to achieve glycemic control and they were followed up for 1 year.Plasma glucose level, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR) and homeostatic model assessment for beta-cell function (HOMA-β) were compared among groups with different haplotypes of SNPs.

Haplotype of TNF-1031C-863C-857C increased the risk of T2D (OR=2.7, P<0.05).Comparing with homozygote of TNF-1031T-863C-857C diabetics (TCC), those carrying CCC allele had higher fasting serum insulin (16.1 (12.0-20.3) mU/L) and HOMA-IR (ln HOMA-IR 1.8±0.4) levels (TCC group:10.6 (8.1-14.3) mU/L and 1.42±0.54 respectively, P<0.05)).One-year insulin treatment decreased HbA1c effectively in both TCC and CCC groups (P<0.05).However, higher HOMA-IR was still observed in CCC group than that of TCC after normoglycemia (lnHOMA-IR:2.5 (0.9-3.9) vs 1.1 (0.8-1.8) respectively,P<0.05).Moreover HOMA-β showed no significant improvement in CCC group as it was in TCC group by the endpoint of follow-up.

TNF-1031C-863C-857C is a risk haplotype for T2D.CCC carrying patients failed to achieve HOMA-β improvement.And it might be due to increased endogenous HbOMA-IR level comparing with TCC homozygote.

To explore the microbiological and clinical characteristics of patients with candidemia and analyze their prognostic risk factors.

A retrospective analysis was conducted for hospitalized patients with candidemia from January 2008 to December 2012 at Affiliated Zhongshan Hospital, Fudan University.Pathogen spectrum, resistance pattern, underlying diseases, therapy received and patient prognosis were collected by chart review.The univariate and multivariate Logistic regression analyses were used to determine the prognostic risk factors of candidemia.

A total of 138 inpatients were identified.There were 98 males and 40 females with a mean age of (61.3±16.6) years.The morbidity rate of candidemia in annual discharged patients was 0.034%-0.051%.The most common pathogens were Candida albicans (n=72, 52.2%),Candida parapsilosis (n=29, 21.0%) and Candida tropicalis (n=16, 11.6%).The antibiotic susceptible rate of azole for Candida was 90.9%-97.4% while 55.6%-83.3% for Candida tropicalis.The overall case fatality rate of candidemia was 39.1% (54/138) while the attributable case fatality rate 31.9% (44/138).Multivariate Logistic regression analysis indicated acute physiology and chronic health evaluationⅡ (APACHEⅡ) score≥20 points (OR=8.025, 95% CI: 2.032-31.696, P=0.003), hypoproteinemia (OR=6.213, 95% CI:1.849-20.879, P=0.003), concurrent bacteremia (OR=5.541, 95% CI: 1.576-19.487, P=0.008) and indwelling urethral catheter (OR=13.776, 95% CI:1.402-135.352, P=0.024) were the independent risk factors of candidemia-related mortality, while removal or replacement of central venous catheter (OR=0.231, 59% CI: 0.075-0.716, P=0.011) and surgery within 30 days (OR=0.206, 95% CI: 0.050-0.857, P=0.030) were the protective factors.

Candida albicans is the most common causative agent.The case fatality rate of candidemia has remained high.APACHEⅡ score≥20 points, hypoproteinemia, indwelling urethral catheter and concurrent bacteremia are independent risk factors attributing to candidemia-related mortality while removal or replacement of central venous catheter and surgery within 30 days are the protective ones.

To explore the antitumor effects of 2-deoxyglucose (2-DG) plus docetaxel (Doc) on PC3 and DU145 cells and its mechanism.

The proliferation of cells was detected by methyl thiazolyl tetrazolium (MTT) assay.Then propidium iodide (PI) staining measured apoptotic cells on flow cytometry.ATP assay kit was used to detect ATP content.The expressions of proteins ubiquitinated protein (Ub) and Hsp70 were measured by Western blot.

2-DG could inhibit proliferation of PC3 and DU145 cells in a dose- and time-dependent manner.However, it could not induce apoptosis in PC3 or DU145.The inhibition rates for PC3 proliferation at 48 h by Doc with concentrations of 0.1, 0.5, 2.5 nmol/L were 10.71%, 25.32% and 56.46% respectively.The inhibition rates for DU145 cell proliferation at 48h by Doc with concentrations of 0.1,0.5,2.5 nmol/L were 12.28%, 23.94% and 63.43% respectively.The inhibition rates for PC3 cell proliferation by Doc plus 2-DG with a concentration of 1.0 g/L were 27.15%, 58.74% and 87.95% respectively and 29.53%, 59.41%, and 90.48% for DU145 respectively.2-DG could enhance the effectiveness of inhibition to PC3 and DU145 proliferation by Doc with a synergistic manner (all q>1.15).The apoptotic rates for PC3 and DU145 induced by Doc 0.5 nmol/L plus 2-DG 1.0 g/L at 48 h were 46.49% and 53.64% respectively.The apoptotic rates were significantly higher than Doc 0.5 nmol/L alone (21.30% for PC3 and 18.92% for DU145 respectively)(P<0.05).The ATP relative concentration for PC3 in 2-DG 1.0 g/L at 0, 12, 24, 48,and 72 h were 13.75, 11.23, 10.19, 9.81 and 9.02 and for DU145 15.00, 12.59, 11.38, 10.54 and 10.37 respectively.Simultaneously, Western blot showed that Ub and Hsp70 protein were expressed intensively.

2-DG can enhance the sensitivity of androgen-independent prostate cancer cells to docetaxel.Its mechanism may be associated with the decrease of proteasome function.

To explore the altered expressions of alkane monooxygenase (Alk B) and hypoxia-inducible factor-1α (HIF-1α) in a rat model of hypoxic pulmonary arterial hypertension.

Twenty Wistar rats were divided randomly into normal control and hypoxia groups after 1-week adaptive feeding.Hypoxia group was raised in a homemade organic glass tank with a 24-h continuous supply of air and nitrogen atmospheric mixed gas.And the oxygen concentration of (10.0±0.5)% was controlled by oxygen monitoring control system.The control group was maintained in room air.Both groups stayed in the same room with the same diet.After 8 weeks, the level of mean pulmonary pressure (m PAP) was measured by right-heart catheterization, right ventricular hypertrophy index (RVHI) calculated by the ratio of right ventricle to left ventricle plus septum and hypoxic pulmonary vascular remodeling (HPSR) observed under microscope.And the levels of Alk B and HIF-1αm RNA and protein in lungs were measured by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot.

At 8 weeks post-hypoxia, compared with the control group[11.0±0.7 mm Hg (1 mm Hg=0.133 kPa),0.210±0.035], the levels of mPAP and RVHI in hypoxia group (33.3±1.3 mm Hg, 0.448±0.013) increased significantly (both P<0.05), the expressions of AlkB mRNA and protein in pulmonary tissue decreased significantly (0.338±0.085 vs 0.688±0.020, P<0.01)(0.483±0.052 vs 0.204±0.010,P<0.01), and the expressions of HIF-1α mRNA and protein increased significantly (0.790±0.161 vs 0.422±0.096, P<0.01)(0.893±0.080 vs 0.346±0.008, P<0.01).

The down-regulation of AlkB in lung tissue may increase the activity of HIF-1 to participate in the occurrence and development of pulmonary hypertension.