Tumor immune microenvironment is a local external tumor environment composed of tumor immune cells and the cytokines secreted by these cells， and it plays a regulatory role in the development and progression of tumors. In the treatment of hepatocellular carcinoma， amino acid metabolism and its reprogramming of proliferating cell metabolism have attracted more and more attention， showing potential in regulating the tumor immune microenvironment. Although amino acid metabolic reprogramming is regarded as a novel approach for tumor therapy， its specific mechanism remains unclear in the regulation of tumor immunity in hepatocellular carcinoma. This article discusses the mechanism of action of amino acid metabolism in the tumor immune microenvironment of hepatocellular carcinoma and its application prospect in clinical practice， in order to provide new ideas for immunotherapy for liver cancer.

Objective:To evaluate pulmonary hypertension (PH) in Chinese people living with human immunodeficiency virus (HIV) receiving long-term anti-retroviral therapy (ART) and those who had not received ART for HIV infection, and to analyze the risk factors for PH in HIV infected individuals, so as to provide evidence for the monitoring and management of cardiovascular diseases in people living with HIV in China.Methods:HIV infected individuals who received long-term ART were from the NCT04463810 study cohort. In addition, using propensity score matching method, gender matched HIV infected individuals who had not received ART were selected as controls from the NCT00872417 and NCT01844297 studies. This study was a retrospective and observational clinical study. Basic data, clinical visit and cardiac Doppler ultrasonography data were collected to analyze the prevalence of PH and risk factors for PH in people living with HIV. Chi-square test and multivariate logistic regression were used for statistical analysis.Results:Among the 318 HIV infected individuals, 159 underwent long-term ART and 159 did not receive ART, which were divided into long-term ART group and ART-na?ve group, respectively. Among 318 HIV infected individuals, 30 cases (9.4%) experienced PH, including 23 cases (7.2%) with critical PH, six cases (1.9%) with mild PH, one case (0.3%) with moderate PH, and there was no severe PH. The prevalence of PH in the long-term ART group was 5.0%(8/159), which was lower than that in the ART-na?ve group (13.8%, 22/159). The difference was statistically significant ( χ2=7.21, P=0.012). Multivariate analysis showed that older age (odds ratio ( OR)=1.064, 95% confidence interval ( CI) 1.019 to 1.111, P=0.016) and unsuppressed HIV status ( OR=2.660, 95% CI 1.041 to 6.797, P=0.041) were independent risk factors for PH of people living with HIV. Conclusions:The prevalence of PH in people living with HIV with long-term ART is lower than that of ART-na?ve people living with HIV. Older age and unsuppressed HIV status are independent risk factors for PH in people living with HIV. Cardiac Doppler ultrasonography is helpful for the early screening of PH in people living with HIV. ART should be actively performed to reduce the incidence of PH in people living with HIV.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

The World Health Organization (WHO) classification serves as the internationally recognized standard for diagnosing and classifying hematopoietic and lymphoid tissue tumors(WHO-HEAM). Since 2001, it has undergone multiple upgrades and revisions, updating, clarifying, and refining previous tumor diagnostic and classification standards while incorporating numerous new genetic and molecular biological subtypes. In 2022, two classification proposals emerged due to a wealth of clinical and scientific research results: the fifth edition of the WHO hematopoietic and lymphoid tissue classification (WHO-HAEM5), published in Leukemia journal; and the International Consensus Classification (ICC), published in Blood journal. These two schemes differ in their approach to classifying hematopoietic and lymphoid tissue tumors, posing challenges for clinical laboratory diagnosis and treatment.

Objective:To explore the risks of cardiovascular disease (CVD) and influencing factors in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients with long-term combination anti-retroviral therapy (cART).Methods:The baseline data from the multi-center prospective cohort of HIV/AIDS patients who received long-term cART from 2018 to 2020 were collected. cART-naive HIV/AIDS patients were matched by age and gender using the propensity score matching (PSM) as controls. Data collection adverse events of anti-human immunodeficiency virus drugs reduced model (D: A: D[R]) score, Framingham risk score (FRS) and atherosclerotic cardiovascular disease (ASCVD) risk score were used to assess the 10-year CVD risk in patients with long-term cART treatment and in cART-naive patients. Logistic regression analysis was used to assess the risk factors related to high 10-year CVD risk.Results:A total of 301 HIV/AIDS patients received long-term cART and 300 cART-naive HIV/AIDS patients were included, with an average age of 39.8 years old. There were 490 male accounting for 81.5%. Based on the D: A: D [R] score, 4.3%(13/301) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 6.3%(19/300) of patients in the cART-naive group. Based on the FRS, 13.4%(36/269) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥10%, and 10.6%(28/264) in the cART-naive group. Based on the ASCVD risk score, 10.4%(14/135) of patients in the long-term cART group had a 10-year CVD risk assessment of ≥7.5%, and 13.8%(17/123) in the cART-naive group. There was no significant difference in the prevalence of high 10-years CVD risk between the long-term cART group and the cART-naive group assessed by any of risk equations (all P>0.050). By multivariate logistic regression analysis, the risk factors associated with 10-year CVD risk ≥10% assessed by D: A: D[R] model were age≥50 years, smoking, hypertension, diabetes, dyslipidemia and CD4 + T lymphocyte count <200×10 6 cells/L (adjusted odds ratio ( AOR)=697.48, 4 622.28, 23.11, 25.95, 27.72 and 18.25, respectively, all P<0.010). The risk factors associated with 10-year CVD risk ≥10% assessed by FRS were age≥50 years, male, smoking, hypertension, diabetes and dyslipidemia ( AOR=53.51, 4.52, 36.93, 36.77, 6.15 and 3.84, respectively, all P<0.050). The risk factors associated with 10-year CVD risk ≥7.5% assessed by ASCVD risk score were age≥50 years, male, smoking, hypertension, diabetes ( AOR=18.48, 14.11, 14.81, 13.42 and 12.41, respectively, all P<0.050). Conclusions:Long-term cART has no significant effect on the 10-year CVD risk in HIV/AIDS patients. Higher CVD risk in HIV/AIDS patients are mainly associated with CD4 + T lymphocyte counts<200×10 6 cells/L and traditional CVD risk factors, including age≥50 years old, smoking, hypertension, diabetes and dyslipidemia.

Objective:To investigate the current status of treatment choice and responses in patients with chronic myeloid leukemia (CML) in China.Methods:From the end of April to mid-May in 2020, a cross-sectional survey, by filling out a survey questionnaire, was conducted to explore the first-line choice of tyrosine kinase inhibitors (TKI) , current medications, drug switch and major molecular responses (MMR) as well as the variables associated with them in patients in China.Results:Data of 2933 respondents with CML from 31 provinces, municipalities, and autonomous regions across the country were included in this study. 1683 respondents (57.4%) were males. Median age was 38 (16-87) years old. 2481 respondents (84.6%) received imatinib as first-line TKI; 1803 (61.5%) , the original new drug (branded drug) . When completing the questionnaire, 1765 respondents (60.2%) were receiving imatinib; 1791 (61.1%) , branded drug. 1185 respondents (40.4%) had experienced TKI switch. With a median follow-up of 45 (3-227) months, 1417 of 1944 (72.9%) respondents with newly diagnosed CML in the chronic phase achieved MMR. Multivariate analysis showed that the respondents with urban household registration ( OR=0.6, 95% CI 0.5-0.8, P<0.001) , ≥ bachelor degree ( OR=0.5, 95% CI 0.4-0.7, P<0.001) , and in the advanced phase at diagnosis ( OR=0.5, 95% CI 0.3-0.8, P=0.001) less preferred Chinese generic TKI, while the respondents from the central region in China more preferred Chinese generic TKI more than those from the eastern region ( OR=1.7, 95% CI 1.4-2.0, P<0.001) . Moreover, the respondents in the advanced phase at diagnosis more preferred second-generation TKI ( OR=5.4, 95% CI 3.6-8.2, P<0.001) ; those ≥60 years old, less preferred second-generation TKI ( OR=0.4, 95% CI 0.2-0.7, P=0.002) . Being in the advanced phase at diagnosis ( OR=2.2, 95% CI 1.6-3.2, P<0.001) , first-line choice of imatinib ( OR=2.0, 95% CI 1.6-2.6, P<0.001) or Chinese generic drugs ( OR=1.3, 95% CI 1.1-1.6, P=0.002) , longer interval from diagnose of CML to starting TKI treatment ( OR=1.2, 95% CI 1.1-1.2, P<0.001) and longer duration of TKI therapy ( OR=1.1, 95% CI 1.0-1.1, P<0.001) were significantly associated with TKI switch; urban household registration ( OR=0.7, 95% CI 0.6-0.8, P<0.001) , ≥MMR ( OR=0.6, 95% CI 0.5-0.8, P<0.001) and unknown response ( OR=0.7, 95% CI 0.6-0.9, P=0.003) , no TKI switch. Female sex ( OR=1.4, 95% CI 1.1-1.7, P=0.003) , urban household registration ( OR=1.6, 95% CI 1.3-2.0, P<0.001) , front-line imatinib therapy ( OR=1.4, 95% CI 1.1-1.9, P=0.016) and longer duration of TKI treatment ( OR=1.2, 95% CI 1.2-1.3, P<0.001) were significantly associated with achieving a MMR or better response; age ≥ 60 years old ( OR=0.7, 95% CI 0.4-1.0, P=0.047) and TKI switch ( OR=0.6, 95% CI 0.5-0.7, P<0.001) , achieving no MMR. Conclusions:By 2020, the majority of Chinese CML patients received imatinib as the fist-line TKI therapy and continue to take it. More than half of TKIs were branded drugs. Socio-demographic characteristics and clinical variables affect their TKI choice, drug switch, and treatment response.

Objective:Through the investigation of the injured persons in explosion accidents, the impact of wearing the ear protectors device (anti-noise earplugs) on the auditory organs and hearing loss of the injured person was understood, which could provide reference for the clinical diagnosis, treatment and prevention of the explosive hearing impairment.Methods:A retrospective survey was conducted on 39 directly injured persons who were injured in 23 explosion accidents involving a steel plant from 1990 to 2016 as the explosive hearing loss, taking the time of the patient＇s injury and 3-6 months after the injury as the time of investigation and evidence collection, and according to whether to wear the ear protectors device for group comparison and statistical analysis.Results:There was no significant difference between the two groups in hearing loss, tinnitus, earache, headache, some patients with dizziness and craniocerebral injury, regardless of whether the injured person wore anti-noise earplugs or not ( P=0.444-1) , the shock (coma) patients in the non-protected group were more common (34.8%, 8/23) , and the difference was statistically significant ( P=0.012) ; Although auricle injury was detected in both groups and there was no significant difference between the two groups ( P=1) , but the external ear canal injury, tympanic membrane perforation were more common in the non-protected group, and there was no external ear canal and tympanic membrane perforation in the wearing earplug group, and the difference between the two groups was significant ( P=0.000) . After 3-6 months, the rehabilitation of auditory system and other symptoms in patients showed that the hearing loss, tinnitus, earache, headache, dizziness and other symptoms all disappeared in patients wearing earplugs, while the above symptoms in the non-protected group were improved but more persisted, and the difference between the two groups was statistically significant ( P=0.000-0.012) , and there was no significant difference in rehabilitation conditions such as craniocerebral injury between the two groups ( P=1) ; There were patients with unhealed auricle injury in both groups in 3-6 months after the injury, and there was no significant difference between the two groups ( P=1) , however, in the non-protected group, 69.57% (16/23) of the patients with external auditory canal injury were still unhealed and none of the patients with tympanic membrane perforation recovered, and the difference between the two groups was obvious ( P=0.000~0.001) ; Pure tone air conduction examination showed that the hearing of the earplugs wearers was well recovered at the time of the explosion, while irreversible hearing impairment was common in the non-protective group, the difference was statistically significant ( P=0.000) . Conclusion:Ear protector plays an important role in protecting the auditory organs and hearing of workers in explosion accident, and it is an effective protective measure to prevent and reduce the damage of external ear canal, perforation of tympanic membrane and explosive hearing loss caused by explosion accidents.

Objective:To investigate the effect of sound insulation improvement on the noise exposure of workers in the operation room of hot rolling line for wide and heavy plate.Methods:From September 2019 to September 2017, based on the occupational health Survey, the data of 25 fixed operation rooms and workers in operation rooms of a steel rolling production line were collected retrospectively, the noise exposure levels before and after the improvement of sound insulation were statistically analyzed.Results:The noise exposure value of the workers, the qualified rate of 0 Grade 8 hours equivalent noise (L EX, 8 h) ≤85 dB (A) and the qualified rate of the design limit value of the operation room were all higher than those before the modification, the difference was statistically significant ( P<0.01) , after the renovation, the Class II and above noise hazards were eliminated, the equivalent continuous a sound level (L Aeq, 8 h) >75 dB (A) of the workers in the operation room was 8h, and the noise level in the operation room still did not meet the Ergonomics limit standard. Conclusion:The improvement of sound insulation can effectively improve the working environment of noise workplace operating room and reduce the workers'noise exposure level.

Objective:Through the investigation of the injured persons in explosion accidents, the impact of wearing the ear protectors device (anti-noise earplugs) on the auditory organs and hearing loss of the injured person was understood, which could provide reference for the clinical diagnosis, treatment and prevention of the explosive hearing impairment.Methods:A retrospective survey was conducted on 39 directly injured persons who were injured in 23 explosion accidents involving a steel plant from 1990 to 2016 as the explosive hearing loss, taking the time of the patient＇s injury and 3-6 months after the injury as the time of investigation and evidence collection, and according to whether to wear the ear protectors device for group comparison and statistical analysis.Results:There was no significant difference between the two groups in hearing loss, tinnitus, earache, headache, some patients with dizziness and craniocerebral injury, regardless of whether the injured person wore anti-noise earplugs or not ( P=0.444-1) , the shock (coma) patients in the non-protected group were more common (34.8%, 8/23) , and the difference was statistically significant ( P=0.012) ; Although auricle injury was detected in both groups and there was no significant difference between the two groups ( P=1) , but the external ear canal injury, tympanic membrane perforation were more common in the non-protected group, and there was no external ear canal and tympanic membrane perforation in the wearing earplug group, and the difference between the two groups was significant ( P=0.000) . After 3-6 months, the rehabilitation of auditory system and other symptoms in patients showed that the hearing loss, tinnitus, earache, headache, dizziness and other symptoms all disappeared in patients wearing earplugs, while the above symptoms in the non-protected group were improved but more persisted, and the difference between the two groups was statistically significant ( P=0.000-0.012) , and there was no significant difference in rehabilitation conditions such as craniocerebral injury between the two groups ( P=1) ; There were patients with unhealed auricle injury in both groups in 3-6 months after the injury, and there was no significant difference between the two groups ( P=1) , however, in the non-protected group, 69.57% (16/23) of the patients with external auditory canal injury were still unhealed and none of the patients with tympanic membrane perforation recovered, and the difference between the two groups was obvious ( P=0.000~0.001) ; Pure tone air conduction examination showed that the hearing of the earplugs wearers was well recovered at the time of the explosion, while irreversible hearing impairment was common in the non-protective group, the difference was statistically significant ( P=0.000) . Conclusion:Ear protector plays an important role in protecting the auditory organs and hearing of workers in explosion accident, and it is an effective protective measure to prevent and reduce the damage of external ear canal, perforation of tympanic membrane and explosive hearing loss caused by explosion accidents.

Objective:To investigate the effect of sound insulation improvement on the noise exposure of workers in the operation room of hot rolling line for wide and heavy plate.Methods:From September 2019 to September 2017, based on the occupational health Survey, the data of 25 fixed operation rooms and workers in operation rooms of a steel rolling production line were collected retrospectively, the noise exposure levels before and after the improvement of sound insulation were statistically analyzed.Results:The noise exposure value of the workers, the qualified rate of 0 Grade 8 hours equivalent noise (L EX, 8 h) ≤85 dB (A) and the qualified rate of the design limit value of the operation room were all higher than those before the modification, the difference was statistically significant ( P<0.01) , after the renovation, the Class II and above noise hazards were eliminated, the equivalent continuous a sound level (L Aeq, 8 h) >75 dB (A) of the workers in the operation room was 8h, and the noise level in the operation room still did not meet the Ergonomics limit standard. Conclusion:The improvement of sound insulation can effectively improve the working environment of noise workplace operating room and reduce the workers'noise exposure level.