‍ ObjectiveTo investigate the serum level of HBV RNA in untreated or treatment-experienced patients with chronic hepatitis B （CHB） and the correlation between serum HBV RNA level and the duration of antiviral therapy with nucleos（t）ide analogues （NAs）. MethodsA total of 300 patients with CHB who attended Department of Infectious Diseases in The First Affiliated Hospital of Shihezi University School of Medicine from February to July， 2022， were enrolled as subjects. Related clinical data were collected， and according to the duration of antiviral therapy， they were divided into untreated group with 73 patients， treatment duration ≤1 year group with 91 patients， and treatment duration >1 year group with 136 patients. Serum HBV RNA load， HBV DNA load， and HBsAg concentration were measured for all patients. The Mann-Whitney U test was used for comparison of continuous data between two groups， and the Kruskal-Wallis H test was used for comparison between multiple groups， further pairwise comparison using Bonferroni method； the chi-square test was used for comparison of categorical data； a Spearman correlation analysis was used to investigate the degree of correlation between various indicators. ResultsThe positive rate of HBeAg was 18.3%， and among the patients with negative HBV DNA， the patients with positive HBV RNA accounted for 44.1% （86/195）. There was a significant difference in the distribution of the serum levels of HBV RNA， HBV DNA， and HBsAg between the positive HBeAg group and the negative HBeAg group （Z=10.740， 6.300， and 7.280， all P<0.05）. There was a significant difference in the distribution of DNA level between the untreated group and the treatment duration ≤1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA and HBV DNA levels between the untreated group and the treatment duration >1 year group （P<0.05）； there was a significant difference in the distribution of HBV RNA， HBV DNA， and HBsAg levels between the treatment duration ≤1 year group and the treatment duration >1 year group （P<0.05）. The correlation analysis between the duration of antiviral therapy and the levels of HBV RNA， HBV DNA， and HBsAg showed that the duration of antiviral therapy had an extremely weak negative correlation with the levels of HBV RNA and HBsAg （r=-0.247 and -0.138， both P<0.05） and a strong negative correlation with the level of HBV DNA （r=-0.771， P<0.001）. There was a low degree of correlation between the serum level of HBV RNA and the serum levels of HBV DNA and HBsAg （r=0.360 and 0.442， both P<0.001）. Further stratified analysis showed that in the untreated group， there was a strong positive correlation between HBV RNA and HBV DNA （r=0.752， P<0.001） and a moderate positive correlation between HBV RNA and HBsAg （r=0.559， P<0.001）； in the treatment duration ≤1 year group， there was a low degree of positive correlation between HBV RNA and HBV DNA/HBsAg （r=0.396 and r=0.388， both P<0.001）； in the treatment duration >1 year group， there was a low degree of positive correlation between HBV RNA and HBsAg （r=0.352， P<0.001）. ConclusionSerum HBV RNA is negatively correlated with the duration of treatment with NAs， and the correlation of HBV RNA with HBV DNA and HBsAg gradually decreases with the increase in the duration of treatment. Therefore， it can be used as a supplementary indicator for monitoring the level of virologic response in CHB patients to a certain extent， with a relatively high accuracy in reflecting the level of viral replication in untreated patients.

Objective To analyze the correlation between the expression of soluble glycoprotein A(GPA)in plasma of healthy blood donors and anti-M and anti-"Mia"antibodies.Methods Plasma from healthy donors from February 9,2022 to February 15,2023 was collected:irregular antibody-negative NN type(group Ⅰ,n=118)and MM type(group Ⅱ,n=51),anti-M antibody positive NN type(group Ⅲ,n=145)and anti-"Mia"antibody positive companion type(group Ⅳ,n= 87),the GPA content in plasma of different individuals in 4 groups was detected,and the difference in GPA expression was analyzed by t-test.Results The average plasma GPA contents in groupsⅠ,Ⅱ,Ⅲ and Ⅳ were 9.941±0.252,10.97±0.256,5.139±0.129 and 4.28±0.139ng/ml,respectively.The average GPA content of groups Ⅰ and Ⅱ was higher,and the average GPA content of groups Ⅲ and Ⅳ was lower,and the differences were statistically significant(all P＜0.01).Conclusion The GPA content in plasma of healthy donors with anti-M and anti-"Mia"antibodies was significantly lower than that of the antibody-negative group.The results of this study lay a foundation for further investigation of whether GPA in plasma has the ability to neutralize anti-M and anti-"Mia"antibodies,improve disease diagnosis and safe blood transfusion.

Objective To analyze the situation of perinatal birth defects in 13 monitoring hospitals in Changsha City from 2011 to 2020, and to explore the composition characteristics and changes of birth defects in Changsha. Methods The monitoring data of perinatal birth defects in 13 surveillance hospitals in Changsha City from 2011 to 2020 were collected and statistically analyzed. Results From 2011 to 2020, the total number of perinatal infants in the 13 surveillance institutions in Changsha was 541,234, showing a trend of rising first and then falling. A total of 15 725 cases of birth defects were found, and the incidence rate of birth defects in perinatal period was 290.54/10 000. The incidence of birth defects in 2020 decreased by 41.93% compared with 2011. The incidence of perinatal birth defects in males (326.59/10,000) was higher than that in females (248.96/10 000), and the difference was statistically significant (χ²=288.955, P＜0.05). The incidence of perinatal birth defects in urban areas (312.65/10,000) was higher than that in rural areas (262.26/10 000), and the difference was statistically significant (χ²=119.974, P＜0.05). The incidence of birth defects in perinatal infants born to mothers under 20 years old was higher than that in other age groups. The top five major birth defects were congenital heart disease, polydactyly, external ear malformation, clubfoot, and hypospadias. Conclusion The incidence of perinatal birth defects in Changsha shows an overall downward trend , and the prevention and control measures for birth defects have shown effectiveness. To consolidate the achievements and control the incidence at a low level, the tertiary prevention of birth defects should be further strengthened.

Objective:To compare the effects of enhanced heat preservation strategies and conventional heat preservation strategies in the operation room on body temperature, coagulation function, and myocardial injury in patients with cervical spinal cord injuries.Methods:A retrospective cohort study was conducted to analyze the clinical data of 160 patients with cervical spinal cord injuries admitted to Second Affiliated Hospital of Xi′an Jiaotong University and Affiliated Honghui Hospital of Xi′an Jiaotong University from February to October 2022, including 82 males and 78 females, aged 38-64 years [(50.6±8.7)years]. Injured segments included C 3 in 19 patients, C 4 in 33, C 5 in 39, C 6 in 38, and C 7 in 31. According to American Spinal Injury Association (ASIA) classification, 10 patients were classified into grade A, 83 grade B, 39 grade C, and 28 grade D. All the patients underwent cervical laminoplasty, decompression and bone graft fusion surgery. According to different heat preservation strategies intraoperatively, the patients were divided into conventional heat preservation group ( n=80) and enhanced heat preservation group ( n=80). The body temperature changes before surgery, at 2 hours during surgery, immediately after surgery, at 2 and 24 hours after surgery were compared between the two groups. The changes of coagulation function before surgery and at 4 hours after surgery were compared between the two groups, including the prothrombin time (PT), thrombin time (TT), and activated partial thromboplastin time (APTT). The incidence of myocardial injury and the number of patients with myocardial injury measured by the indicators of cardiac troponin I (cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) at 48 hours after surgery. Before surgery and at 14 days after surgery, ASIA classification was used to evaluate the neurological functions, including sensory and motor functions between the two groups. The incidence of cardiovascular events at 12 months after surgery were compared between the two groups. Results:A total of 145 patients were followed up for 12-18 months [(15.7±1.6)months]. At 12 months after operation, there were 7 patients in the enhanced heat preservation group were lost to follow-up, compared to 8 patients in the conventional heat preserration group. There was no statistically significant difference in body temperature between the two groups before surgery or at 24 hours after surgery ( P>0.05). At 2 hours during surgery, immediately after surgery and at 2 hours after surgery, the body temperature was (36.90±0.12)℃, (37.00±0.06)℃, and (37.16±0.06)℃ in the enhanced heat preservation group, which were significantly higher than those in the conventional heat preservation group [(36.56±0.03)℃, (36.74±0.08)℃, and (36.84±0.08)℃] ( P<0.01). The serum levels of PT, TT and APTT were not significantly different between the two groups before surgery ( P>0.05), while they were (13.1±1.2)seconds, (19.2±1.1)seconds, and (36.2±3.3)seconds in the enhanced heat preservation group at 4 hours after surgery, which were significantly lower than those in the conventional heat preservation group [(14.3±1.0)seconds, (20.2±1.1)seconds, and (38.7±3.4)seconds] ( P<0.01). The incidence of myocardial injury in the enhanced heat preservation group was 5.0% (4/80) at 48 hours after surgery, which was lower than 12.5% (12/80) in the conventional heat preservation group ( P<0.05). With cTnI as the indicator of myocardial injury, there were 2 patients [2.6%(2/76)] with myocardial injury in the enhanced heat preservation group, which was much lower than 8 patients [11.8%(8/68)] in the conventional heat preservation group ( P<0.05). With hs-cTnT as the indicator of myocardial injury, 8 patients [10.5%(8/76)] in the enhanced heat preservation group experienced myocardial injury, similar with 10 patients [14.7%(10/68)] in the conventional heat preservation group ( P>0.05). There were no statistically significant differences in the ASIA scores of the sensory and motor functions between the two groups before surgery and at 14 days after surgery ( P>0.05). The incidence of cardiovascular events at 12 months after surgery in the conventional heat preservation group was 27.8% (20/72), which was significantly higher than 9.6% (7/73) in the enhanced heat preservation group ( P<0.01). Conclusion:For patients with cervical spinal cord injuries, compared with conventional heat preservation strategies, the enhanced heat preservation strategies in the operating room can improve the patients′ core body temperature and coagulation function, and significantly reduce the incidence of myocardial injury and cardiovascular events.

Objective:To investigate the repeatability of corneal topographic parameters with the Pentacam HR in patients with keratoconus of different severity.Methods:A diagnostic test study was performed.A total of 120 eyes from 98 patients with subclinical keratoconus or keratoconus were enrolled at Henan Eye Hospital from January 2019 to March 2022.The patients were divided into subclinical keratoconus group, mild keratoconus group, moderate keratoconus group and severe keratoconus group, with 30 eyes in each group.An additional 30 eyes of 30 subjects undergoing refractive surgery were selected as a control group.Three consecutive Pentacam HR measurements were performed by the same clinician.The recordings included a total of 53 parameters in anterior corneal surface, posterior corneal surface, thickness, composite index, and corneal densitometry.The within-subject standard deviation (Sw), repeatability limit ( r) and tolerance index (TI) were calculated to evaluate the repeatability of the parameters between different groups.This study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[5]).All subjects were informed of the purpose and significance of the study and signed an informed consent form before enrollment. Results:Compared with the control group, the TI of the subclinical, mild, moderate and severe keratoconus groups were 54.71%(29/53), 66.04%(35/53), 90.57%(48/53) and 94.34%(50/53), respectively, higher than 0.31.The steep keratometry (Ks), the maximum keratometry (Kmax) of the anterior corneal surface, the anterior corneal radius of curvature, the flat keratometry (Kf) of the posterior corneal surface, the posterior corneal radius of curvature (PRC), the thinnest corneal thickness (TCT), the average densitometry for the anterior 120 μm in the 0-2 mm area (A.0-2 mm), average densitometry for the anterior 120 μm in the 2-6 mm area (A.2-6 mm), average densitometry for the central tissue in the 0-2 mm area (C.2-6 mm), average densitometry for the total cornea in the 0-2 mm area (T.0-2 mm) and average densitometry for the total cornea in the 2-6 mm area (T.2-6 mm) showed good repeatability in the subclinical and mild keratoconus groups (TI<0.31).Kmax Zonal Mean 3 mm, posterior corneal surface mean keratometry, central keratoconus index showed good repeatability in subclinical, mild and moderate keratoconus groups.Kmax Zonal Mean 4 mm and Kmax Zonal Mean 5 mm showed good repeatability in all groups (TI<0.31).Conclusions:For patients with subclinical and mild keratoconus, Kf of the posterior corneal surface, PRC and TCT are recommended to monitor disease progression.To monitor the condition of patients with moderate and severe keratoconus, we may focus on the detection of Kmax Zonal Mean 4 mm and Kmax Zonal Mean 5 mm.

Sepsis is a systemic inflammatory syndrome induced by infection and other factors， with the number of patients worldwide exceeding 10 million each year. The pathophysiological mechanism is of this disease complex. Sepsis is often accompanied by endotoxin translocation， gastrointestinal dysfunction， inflammatory cytokine activation， immune dysregulation， coagulation disorder， multiple organ function impairment and many other body imbalances， as well as systemic inflammation， apoptosis， oxidative stress injury and other cell damage mechanisms. This disease causes a heavy medical burden due to the difficult diagnosis and treatment and the poor prognosis. Great progress has been achieved in the diagnosis and treatment of sepsis with traditional Chinese medicine （TCM） and western medicine. The value of western medicine in the diagnosis and treatment of sepsis is limited due to antibiotic resistance， hormone abuse， and high medical costs. Sepsis is classified as a warm disease or typhoid fever in TCM. Da Chengqitang is a classical formula in the Treatise on Typhoid Fever to deal with the excess syndrome of Yang brightness Fu-organ. Modern medicine has proved that Da Chengqitang has the effect of inhibiting oxidative stress， reducing inflammation， and delaying apoptosis by improving gastrointestinal dynamics and regulating intestinal microecology. On the basis of the previous theoretical basis and the rich experience in the medication， medical practitioners have proposed a new therapeutic concept of using Da Chengqitang in combination with western drugs from a holistic view involving both bacteria and toxicity for treating both the symptoms and the root cause， which has a wide range of application. The article reviews the classical research and latest findings of Da Chengqitang in the treatment of sepsis， with a view to clarifying the mechanism and advantages of this formula in the adjuvant treatment of sepsis， exploring its potential efficacy， and providing timely， adequate， and scientific theoretical support for the promotion of this formula in the clinical practice.

Objective:To investigate the clinical characteristics of patients with keratoconus, and to explore the factors influencing keratoconus severity.Methods:A cross-sectional study was performed.A total of 908 patients (1 476 eyes) with primary keratoconus were enrolled in Henan Eye Hospital from January 2019 to December 2021.The medical history data of patients were collected by face-to-face questionnaire survey.Refractive parameters were measured by subjective optometry.Intraocular pressure (IOP) was measured by a non-contact tonometer, and corrected IOP was calculated by Dresden formula.Corneal topography parameters was obtained using Pentacam HR.The subgroup analysis of clinical characteristics of all patients was performed by age (<21 years, 21~<31 years, ≥31 years) and gender.Disease severity was graded based on steep keratometry (Ks), namely mild (Ks<48 D), moderate (48 D≤Ks<55 D) and severe (Ks≥55 D). The influencing factors of disease severity in keratoconus were analyzed by ordered Logistic regression.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2019[5]). All subjects or guardians were informed of the purpose and significance of the study and written informed consent was obtained.Results:Of the 908 patients, 622 were with bilateral keratoconus and 286 were with unilateral keratoconus.The median age of onset was 20(17, 26) years, and the median age of diagnosis was 21(18, 27) years.The ratio of males to females was 3.05∶1.There were 9.80%(89/908) of the patients having a history of allergy, 25.55%(232/908) having a history of other systemic diseases, and 1.98%(18/908) having a family history of keratoconus.Of the 1 476 affected eyes, 27.57%(407/1 476) were diagnosed as severe keratoconus, and 61.94%(568/917) had a history of eye rubbing.The medians of sphericity, cylindricity, IOP, corrected IOP, Ks, thinnest corneal thickness (TCT), anterior corneal surface elevation (AE) and posterior corneal surface elevation (PE) were -4.00(-7.00, -1.75)D, -3.50(-6.00, -1.50)D, 12.00(10.30, 13.80)mmHg, 15.40(13.60, 17.00)mmHg, 49.85(46.40, 54.90)D, 460.00(425.00, 490.00)μm, 21.00(13.00, 34.75)μm, 51.00(33.00, 75.00)μm, respectively.The spherical refraction, IOP and corrected IOP were lower and the cylindrical refraction was higher in patients at age <21 years than in patients at age 21~<31 years, and the TCT of patients at age <21 years was higher than that at age ≥31 years, and the differences were statistically significant (all at P<0.05). Compared with female patients, male patients had younger onset age, lower spherical refraction, IOP and corrected IOP, as well as higher cylindrical refraction, AE and PE, showing statistically significant differences (all at P<0.05). The spherical refraction and IOP of male patients were lower than those of female patients at age <21 years, and the cylindrical refraction was higher in males than in females among the patients at age 21~<31 years, and the differences were statistically significant (both at P<0.05). Among the patients with onset age <21 years and diagnosis age <21 years, the ratio of males to females in patients with severe keratoconus was higher than those with mild and moderate disease, and the difference was statistically significant (both at P<0.05). Older age of onset was a protective factor for disease severity in keratoconus (odds ratio=0.981, 95% confidence interval: 0.963~0.999). Conclusions:The younger the onset age of keratoconus patients, the more severe the disease.Among the patients with severe keratoconus, there were more male patients, and males have a younger onset age and severer conditions.It is suggested that early screening of keratoconus in children and adolescents should be strengthened in clinical work, and more active prevention and treatment measures should be taken for younger patients, especially males.

Objective:To study the epidemic status about genotype of the astrovirus, and to provide the epidemic data and control epidemic of infectious disease.Methods:Screening for astrovirus positive nucleic acids was performed using an astrovirus real-time fluorescent PCR kit. RT-PCR amplification was performed with astrovirus-specific primers Mn289/270. The positive products were recovered and purified and directly sequenced. Sequence analysis and phylogenetic analysis of astrovirus sequences were performed using Clustal and MEGA3.0 biological software.Results:From 2016 to 2018, we collected 496 fecal specimens from children with diarrhea from different regions, of them 136 cases had viral diarrhea, and in 17 of them astrovirus (3.4%) was detected, there were more males than females. All the 17 cases were under 5 years of age, and 12 cases (70.58%) were younger than 1 year old. In regional distribution, samples from Xining accounted for 64.70% (11/17), Huangzhong county for 29.41% (5/17), Huangnan Prefecture for 5.88%(1/17). The positive cases were mainly found in April to June, and there was another peak from October to December, which was consistent with the time distribution of rotavirus in past years. Seven strains were HAstV-1, one strain was HAstV-2, and the homology among four strains of HAstV-1 was 99.0%-100%. The homology with the other two strains of the same type was 88.4-95.7%.Conclusions:The dominant genotype of Astrovirus was HAstV-1 in infants with diarrhea in Qinghai, meanwhile there was also HAstV-2.

Objective:To investigate the predictive value of blood routine and blood biochemical indicators for immunotherapy combined with chemotherapy-related interstitial pneumonia (IP) in patients with diffuse large B-cell lymphoma (DLBCL).Methods:The data of 151 newly-diagnosed DLBCL patients treated with rituximab combined with chemotherapy in the First Affiliated Hospital of Soochow University from December 2017 to October 2020 were retrospectively analyzed. According to whether IP occurred, the patients were divided into IP group and non-IP group. The patient's clinical data and baseline laboratory test results were collected. The differences in clinicopathological features and laboratory indicators between IP group and non-IP group were analyzed. In addition, the relationship between the variety of blood routine and blood biochemical indicators and the occurrence of IP was analyzed. The receiver operating characteristic (ROC) curve of the selected indicators to predict the occurrence of IP was drawn, and the predictive performance of each indicator was analyzed.Results:The incidence of IP was 9.3% (14/151) in DLBCL patients after receiving immunotherapy combined with chemotherapy. The lymphocyte count (LYM) in IP group at the first diagnosis was higher than that in non-IP group [1.60×10 9/L (1.40×10 9/L, 2.51×10 9/L) vs. 1.28×10 9/L (0.89×10 9/L, 1.78×10 9/L), U=-2.194, P=0.028], but there was no significant difference in the levels of platelet count, neutrophil count, monocyte count, lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH), serum albumin (ALB) and the proportion of patients with elevated C-reactive protein (CRP) between the two groups (all P > 0.05). Compared with the laboratory indicators in non-IP group before the 4th cycle of treatment, LYM and ALB in IP group were significantly reduced at IP onset [0.72×10 9/L (0.46×10 9/L, 0.92×10 9/L) vs. 0.93×10 9/L (0.71×10 9/L, 1.15×10 9/L), 32.9 g/L (28.6 g/L, 34.9 g/L) vs. 40.3 g/L (36.1 g/L, 43.1 g/L)], but LDH and α-HBDH increased [332 U/L (255 U/L, 396 U/L) vs. 233 U/L (200 U/L, 286 U/L), 277 U/L (206 U/L, 315 U/L) vs. 189 U/L (159 U/L, 229 U/L)], and the differences were statistically significant (all P<0.05). The proportion of patients with elevated CRP in IP group was high than that in non-IP group [100.0% (14/14) vs. 56.9% (78/137), P=0.001]. The area under ROC curve of LYM, ALB, LDH and α-HBDH alone for predicting the occurrence of IP was 0.668, 0.820, 0.789 and 0.802. The best cut-off values of ALB, LDH and α-HBDH was 34.6 g/L, 241 U/L and 199 U/L. ALB had the highest sensitivity for predicting the occurrence of IP (81.8%). The areas under ROC curve of ALB+LDH, ALB+α-HBDH, LDH+α-HBDH, ALB+LDH+α-HBDH for predicting the occurrence of IP was 0.850, 0.844, 0.777 and 0.851, respectively. LDH+α-HBDH had the highest predictive sensitivity (92.9%), but the specificity was low (53.3%). The prediction sensitivity (both 78.6%) and specificity (both 86.1%) of ALB+LDH and ALB+LDH+α-HBDH were high. Conclusions:DLBCL patients are at risk of IP during immunotherapy combined with chemotherapy. The increased LYM at initial diagnosis is a risk factor for the occurrence of IP. The variety of LYM, ALB, LDH, α-HBDH and CRP during the treatment may be related to the occurrence of IP. Among them, ALB, LDH and α-HBDH have important predictive values for the occurrence of IP.

Objective:To investigate the prognosis of severe hyperbilirubinemia in full-term infants who met the exchange transfusion criteria and were treated by blood exchange transfusion and phototherapy.Methods:A total of 168 full-term infants with severe hyperbilirubinemia who met the criteria for exchange transfusion and were hospitalized in the Neonatology Department of seven tertiary hospitals in Hebei Province from June 2017 to December 2018 were retrospectively included. According to the treatment protocol, they were divided into two groups: exchange transfusion group (38 cases) and phototherapy group (130 cases). Two independent sample t-test and Chi-square test were used to compare the clinical manifestations and follow-up results between the two groups. Multivariate logistic regression was used to analyze the risk factors for poor prognosis. Results:Neonatal severe hyperbilirubinemia in the exchange transfusion and phototherapy group were both mainly caused by hemolytic disease [42.1%(16/38) and 29.2%(38/130)], sepsis [28.9%(11/38) and 11.5%(15/130)] and early-onset breastfeeding jaundice [15.8%(6/38) and 11.5%(15/130)]. Total serum bilirubin level on admission in the exchange transfusion group was significantly higher than that in the phototherapy group [(531.7±141.3) vs (440.0±67.4) μmol/L, t=3.870, P<0.001]. Moreover, the percentage of patients with mild, moderate and severe acute bilirubin encephalopathy in the exchange transfusion group were higher than those in the phototherapy group [15.8%(6/38) vs 3.8%(5/130), 7.9%(3/38) vs 0.8%(1/130), 13.2%(5/38) vs 0.0%(0/130); χ2=29.119, P<0.001]. Among the 168 patients, 135 were followed up to 18-36 months of age and 12 showed poor prognosis (developmental retardation or hearing impairment) with four in the exchange transfusion group (12.9%, 4/31) and eight in the phototherapy group (7.7%, 8/104). Multivariate logistic regression analysis showed that for full-term infants with severe hyperbilirubinemia who met the exchange transfusion criteria, phototherapy alone without blood exchange transfusion as well as severe ABE were risk factors for poor prognosis ( OR=14.407, 95% CI: 1.101-88.528, P=0.042; OR=16.561, 95% CI: 4.042-67.850, P<0.001). Conclusions:Full-term infants who have severe hyperbilirubinemia and meet the exchange transfusion criteria should be actively treated with blood exchange transfusion, especially for those with severe ABE, so as to improve the prognosis.