[Cryotherapy combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis: a case report].

Nasopharyngeal tuberculosis refers to the tuberculosis in the nasopharynx, which is mainly treated with systemic chemotherapy with anti-tuberculosis drugs. Here, we reported a case of nasopharyngeal tuberculosis treated by cryosurgery combined with local spraying of isoniazid on the basis of systemic chemotherapy with anti-tuberculosis drugs. By reviewing the case data and relevant literature, we understood the clinical manifestations, diagnosis and differential diagnosis of the disease, improved everyone's understanding of the disease, and proposed a new method of cryosurgery combined with local spraying of isoniazid for the treatment of nasopharyngeal tuberculosis for clinical discussion.

[Progress in platelets and tuberculosis].

Platelets are important cells in hemostatic and coagulative reactions. Interestingly, platelets-related immunopathological mechanism and clinical research have become one of the hot research topics in tuberculosis at home and abroad in recent years. Platelets get involved in host chronic inflammation and pulmonary immune response, thus playing a negative regulatory role in tuberculosis. This is achieved through direct internalization of Mycobacterium tuberculosis and indirect interaction with immune cells. In addition, patients with tuberculosis often have thrombocytosis, and there is increasing evidence that anti-platelet therapy as a host-directed therapy has demonstrable clinical benefit in tuberculosis control. Platelet inhibition may be an emerging therapeutic strategy for tuberculosis. This review aims to highlight the research progress in platelets and tuberculosis.

[Analysis of clinical characteristics and risk factors of death in critical burn patients complicated with invasive fungal infection].

Objective: To investigate the clinical characteristics and risk factors of critical burn patients complicated with invasive fungal infection. Methods: A retrospective case series study was conducted. From January 2017 to December 2022, 88 critical burn patients combined with invasive fungal infection who met the inclusion criteria were admitted to Zhengzhou First People's Hospital, including 61 males and 27 females, aged 26-74 years. Data on invasive fungal infection sites and the detection of pathogens in patients were recorded. According to the survival outcome within 28 days after admission, the patients were divided into survival group (63 cases) and death group (25 cases). The following data of patients were compared between the two groups, including the basic data and injuries of patients at admission such as age, sex, body weight, total burn area, combination of inhalation injury, combination of hypertension and diabetes, acute physiology and chronic health status evaluation Ⅱ (APACHE Ⅱ) score, and admission time after burns, the levels of blood biochemical indexes within 24 h after admission such as white blood cell count, platelet count, red blood cell count, monocyte count, neutrophil count, lymphocyte count, alanine transaminase, aspartate transaminase, glucose, creatinine, urea nitrogen, D-dimer, galactomannan (GM), 1,3-ß-D glucan, and creatine kinase, the application of invasive procedures and vasoactive drugs during the treatment such as continuous renal replacement therapy, ventilator-assisted breathing, tracheotomy, deep vein catheterization, skin grafting >2 times, the levels of infection indicators on post admission day (PAD) 1, 3, 7, and 14 including C-reactive protein (CRP), procalcitonin, lactic acid, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), and the detection of pathogens in the process of treatment. Data were statistically analyzed with independent sample t test, analysis of variance for repeated measurement, chi-square test, Mann-Whitney U test, and Bonferroni correction. Multivariate logistic regression analysis was performed to screen the independent risk factors that affected death of critical burn patients complicated with invasive fungal infection. Results: The main sites of invasive fungal infection were the wounds (67 cases) and blood stream (46 cases), with Candida fungi (58 strains) as the main strain for fungi infection, and there were a total of 30 cases of infection with mixed pathogenic bacteria. Compared with those in survival group, the APACHE Ⅱ score, proportions of combination with inhalation injury and hypertension of patients in death group were significantly increased (t=2.11, with χ2 values of 6.26 and 9.48, respectively, P<0.05), while the other basic data and injury condition had no significant changes (P>0.05). Compared with those in survival group, the levels of D-dimer, GM, and 1,3-ß-D glucan of patients in death group were significantly increased within 24 h after admission (with t values of 2.42, 2.05, and 2.21, respectively, P<0.05), while the other blood biochemical indexes within 24 h after admission, as well as the proportions of applying invasive procedures and application of vasoactive drugs during the treatment process were not significantly changed (P>0.05). The levels of infection indicators of patients on PAD 1 and 3 were similar between the two groups (P>0.05). The procalcitonin level on PAD 7 and the levels of CRP, procalcitonin, lactic acid, IL-6, and TNF-α on PAD 14, as well as the proportion of infection with mixed pathogenic bacteria of patients in death group were significantly higher than those in survival group (with t values of 4.69, 3.89, 6.70, 6.14, 4.65, and 3.26, respectively, χ2=12.67, P<0.05). Multivariate logistic regression analysis showed that combination with inhalation injury, combination with hypertension, and infection with mixed pathogenic bacteria were independent risk factors for death of critical burn patients complicated with invasive fungal infection (with odds ratios of 5.98, 4.67, and 6.19, respectively, 95% confidence intervals of 1.42-15.39, 1.41-25.28, and 1.86-20.58, respectively, P<0.05). Conclusions: The main sites of infection in critical burn patients complicated with invasive fungal infection are the wounds and blood stream, with Candida fungi as the main strain for fungi infection, and a large proportion of infection with mixed pathogenic bacteria. The combined inhalation injury, combined hypertension, and infection with mixed pathogenic bacteria are the independent risk factors for the death of those patients.

[Bronchial tuberculosis complicated with massive hemorrhage after Dieulafoy's disease biopsy: a case report].

Compared with simple bronchial Dieulafoy's disease, bronchial tuberculosis with Dieulafoy's disease is rarer and more complex, with non-specific clinical manifestations. In this article, we reported a case of right lateral basal segment bronchial tuberculosis complicated with Dieulafoy's disease. The clinical manifestations, microscopic features, and rescue procedures in the event of massive hemorrhage in this case were described in detail, and the shortcomings in the clinical diagnosis and treatment of this case were analyzed. The aim of this study was to improve clinicians' understanding of bronchial tuberculosis combined with Dieulafoy's disease.

The evolutionary history of hepaciviruses.

In the search for natural reservoirs of hepatitis C virus (HCV), a broad diversity of non-human viruses within the Hepacivirus genus has been uncovered. However, the evolutionary dynamics that shaped the diversity and timescale of hepaciviruses evolution remain elusive. To gain further insights into the origins and evolution of this genus, we screened a large dataset of wild mammal samples (n = 1,672) from Africa and Asia, and generated 34 full-length hepacivirus genomes. Phylogenetic analysis of these data together with publicly available genomes emphasizes the importance of rodents as hepacivirus hosts and we identify 13 rodent species and 3 rodent genera (in Cricetidae and Muridae families) as novel hosts of hepaciviruses. Through co-phylogenetic analyses, we demonstrate that hepacivirus diversity has been affected by cross-species transmission events against the backdrop of detectable signal of virus-host co-divergence in the deep evolutionary history. Using a Bayesian phylogenetic multidimensional scaling approach, we explore the extent to which host relatedness and geographic distances have structured present-day hepacivirus diversity. Our results provide evidence for a substantial structuring of mammalian hepacivirus diversity by host as well as geography, with a somewhat more irregular diffusion process in geographic space. Finally, using a mechanistic model that accounts for substitution saturation, we provide the first formal estimates of the timescale of hepacivirus evolution and estimate the origin of the genus to be about 22 million years ago. Our results offer a comprehensive overview of the micro- and macroevolutionary processes that have shaped hepacivirus diversity and enhance our understanding of the long-term evolution of the Hepacivirus genus.

[Reference values for carotid artery intima-media thickness among community adult dwellers in Shenzhen City].

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was meanCIMT=0.324 7+0.006 9×age and SDCIMT=0.076 9+0.001 2×age. For women, the regression was meanCIMT=0.354 9+0.005 4×age and SDCIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.

MHD instability dynamics and turbulence enhancement towards the plasma disruption at the HL-2A tokamak.

The evolutions of MHD instability behaviors and enhancement of both electrostatic and electromagnetic turbulence towards the plasma disruption have been clearly observed in the HL-2A plasmas. Two types of plasma disruptive discharges have been investigated for similar equilibrium parameters: one with a distinct stage of a small central temperature collapse ([Formula: see text] 5-10%) around 1 millisecond before the thermal quench (TQ), while the other without. For both types, the TQ phase is preceded by a rotating 2/1 tearing mode, and it is the development of the cold bubble from the inner region of the 2/1 island O-point along with its inward convection that causes the massive energy loss. In addition, the micro-scale turbulence, including magnetic fluctuations and density fluctuations, increases before the small collapse, and more significantly towards the TQ. Also, temperature fluctuations measured by electron cyclotron emission imaging enhances dramatically at the reconnection site and expand into the island when approaching the small collapse and TQ, and the expansion is more significant close to the TQ. The observed turbulence enhancement near the X-point cannot be fully interpreted by the linear stability analysis by GENE. Evidences suggest that nonlinear effects, such as the reduction of local [Formula: see text] shear and turbulence spreading, may play an important role in governing turbulence enhancement and expansion. These results imply that the turbulence and its interaction with the island facilitate the stochasticity of the magnetic flux and formation of the cold bubble, and hence, the plasma disruption.

[Effects of surgical procedures and general anesthesia exposure within 2 hours in early childhood on neurodevelopmental outcomes in school-age].

Objective: To observe the effect of surgical procedures and general anesthesia exposure (<2 h) in early childhood on neurodevelopmental outcomes in school-age. Methods: A total of 147 children aged 6-12 years old, who received surgery under general anesthesia (<2 h) at the age of 0-2 years in Children's Hospital of Nanjing Medical Universityfrom June 2009 to December 2012 were retrospectively enrolled in this study (from June 2018 to December 2021) as exposure group, including 76 males and 71 females, with a mean age of (8.8±1.6) years. All the cases were divided into single-exposure group (n=65) and multiple-exposure group (≥2 times, n=82) according to different times of anesthesia exposure. According to the cohort of exposure group, 160 healthy children of the same age with no history of surgery under general anesthesia were recruited from the community from June 2018 to December 2021 as the control group, including 87 males and 73 females, and aged (8.6±1.9) years. A variety of standardized neurological tests including Wechsler intelligence scale for children fourth edition (WSC-Ⅳ), integrated visual and auditory continuous performance test (IVA-CPT), Swanson Nolan and Pelham, version Ⅳ (SNAP-Ⅳ), children sensory integration capacity development rating scale (CSIC), and social living ability scale were performed in all subjects by a child health specialist who failed to know the details. The primary outcome was the full-scale IQ (FSIQ) in WISC-Ⅳ, and the secondary outcomes were IVA-CPT, SNAP-Ⅳ, CSIC, and social living ability scale. Results: The FSIQ of single-exposure, multiple-exposure and control groups was 105.4±14.1, 100.9±10.2 and 103.6±13.5, respectively, with no statistically significant difference (F=2.37, P=0.095). The FSIQ of different first age exposure groups (aged 0-6 months, 7-12 months and 1-2 years) was 99.8±10.2, 104.5±10.5 and 104.4±14.5, respectively, with no statistically significant difference (F=2.39, P=0.095). The FSIQ of different exposure duration groups (0-59 min, 60-119 min and control group) was 102.8±11.3, 103.0±13.7 and 103.6±13.5, respectively, with no statistically significant difference (F=0.13, P=0.882). As for the secondary outcomes, the scores of visual persistence quotient in single-exposure, multiple-exposure and control groups were 94.8±10.5, 94.0±10.9 and 100.6±17.7, with a statistically significant difference (F=6.96, P=0.001). In terms of locomotion in social living ability scale, the score of the three groups was 10.0±0.2, 10.2±0.6 and 10.4±0.7, respectively, with a statistically significant difference (F=10.61, P<0.001), but all were within the standard range. Conclusions: The surgical procedures and general anesthesia exposure within 2 hours in early childhood has no effect on the overall FSIQ in school age, but has a slight impacts on the visual persistence quotient of IVA-CPT and the locomotion score of social living ability scale.

[Liver transplantation for the treatment of acute liver failure in 3 cases with NBAS gene deficiency and literature review].

Objective: To investigate the clinical efficacy of liver transplantation in the treatment of acute liver in children with NBAS gene deficiency disease and their outcome. Methods: This retrospective study enrolled children with NBAS gene deficiency who were admitted to the Children's Hospital of Fudan University for liver transplantation from January 2013 to June 2022. The clinical data were collected and analyzed. Medical literature published before June 2022 was searched with the keywords of "NBAS" "neuroblastoma amplified sequence recurrent" "acute liver failure" "SOPH syndrome" "short stature with optic nerve atrophy" "Pelger-Huët anomaly" in PubMed, China National Knowledge Infrastructure and Wanfang database. Results: Liver transplantation was performed in 3 patients (2 males and 1 female) with NBAS deficiency. All patients presented with fever-triggered recurrent acute liver failure. The genetic detection found compound heterozygous NBAS gene pathogenic variants in them. The total episodes of acute liver failure before liver transplantation were 11, 2, and 4 respectively, and the age at liver transplantation was 3.5, 2.3, and 2.0 years respectively. During liver transplantation, patient 1 was in the convalescent phase of acute liver failure, patient 2 was in the acute phase, presenting with hepatic encephalopathy (grade V) and respiratory failure, and patient 3 was considered to be in the acute phase. After liver transplantation, patient 1 recovered normal liver function within 1 month and had no liver transplantation-related complications. Patient 2 had secondary epilepsy, intellectual disability, movement disorder, and transiently elevated transaminases. Patient 3 died of severe infection within 1 month. There was no literature in Chinese, 6 in English, 8 NBAS-deficient patients who were treated with liver transplantation. Total 11 patients presented with fever-triggered recurrent acute liver failure. Their age at liver transplantation ranged from 0.9 to 5.0 years. Postoperative complications occurred in 3 patients. Until the last visit, they were followed up for 0.7 to 14.0 years. Total 2 patients died and the 9 surviving patients did not develop acute liver failure. Conclusions: Liver transplantation is effective for the treatment of acute liver failure associated with NBAS gene disease. However, postoperative complications of liver transplantation may occur. The timing of liver transplantation still needs further research.

[A real-world study of the effects of endocrine therapy on liver function in breast cancer].

Objective: To compare the effect of different endocrine therapy drugs on liver function in patients with early breast cancer. Methods: A retrospective cohort study was conducted to include 4 318 patients with early breast cancer who received adjuvant endocrine therapy in Department of Breast Surgery, Peking Union Medical College Hospital from January 1, 2013 to December 31, 2021. All the patients were female, aged (51.2±11.3) years (range: 20 to 87 years), including 1 182 patients in the anastrozole group, 592 patients in the letrozole group, 332 patients in the exemestane group, and 2 212 patients in the toremifene group. The mixed effect model was used to analyze and compare the liver function levels of patients at baseline, 6, 12, 18, 24, 36, 48, 60 months of medication, and 1 year after drug withdrawal among the three aromatase inhibitors (anastrozole, letrozole, exemestane) and toremifene. Results: ALT and AST of the 4 groups were significantly higher than the baseline level at 6 months (all P<0.01), and there were no significant differences in total bilirubin, direct bilirubin and AST levels among all groups one year after drug withdrawal (P: 0.538, 0.718, 0.061, respectively). There was no significant difference in the effect of all groups on AST levels (F=2.474, P=0.061), and in the effect of three aromatase inhibitors (anastrozole, letrozole, and exemestane) on ALT levels (anastrozole vs. letrozole, P=0.182; anastrozole vs. exemestane, P=0.535; letrozole vs. exemestane, P=0.862). Anastrozole and letrozole had significantly higher effects on ALT levels than toremifene (P<0.01, P=0.009). The proportion of abnormal liver function in each group increased significantly at 6 months compared with baseline, and then the proportion showed a decreasing trend over time. Conclusions: Three aromatase inhibitors (anastrozole, letrozole, and exemestane) and toremifene can significantly increase the level of ALT and AST in patients with breast cancer, and the levels can gradually recover to the baseline after 1 year of drug withdrawal. The effect of non-steroidal aromatase inhibitors (anastrozole, letrozole) on ALT levels is greater than toremifene.

[One-stage revision using intra-articular vancomycin infusion effectively treats chronic prosthetic joint infection caused by Enterococcal].

Objective: To investigate the clinical effects of one-stage revision combined with intra-articular infusion of vancomycin in the treatment of chronic prosthetic joint infection (PJI) caused by Enterococcal. Methods: From May 2013 to June 2020,the clinical data of 9 patients (2 males and 7 females) with chronic Enterococcal PJI treated with one-stage revision using intra-articular infusion of vancomycin at Department of Orthopaedics,First Affiliated Hospital of Xinjiang Medical University were retrospectively analyzed,including 8 hips and 1 knee.A total of 9 patients with age of (63.9±11.7)years (range:43 to 76 years) were included, and the body mass index was (23.6±4.3)kg/m2 (range:18 to 30 kg/m2).There were 6 cases with antibiotic history and 5 cases with sinus tract.The joint fluid,infected tissue around the prosthesis and ultrasonic shock fluid of the prosthesis were collected during operation for microbial culture identification and drug sensitivity test.After thorough debridement of the infected site and removal of the infected prosthesis,a new prosthesis was implanted,then the drainage tube in the operation area was placed.After surgery,vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin(0.5 g,qd) in monomicrobial PJI,and vancomycin(1.0 g,q12 h) was combined with intra-articular vancomycin (0.5 g,qd) and imipenem/meropenem (0.5 g,qd),and the interval between the two drugs was 12 hours in polymicrobial PJI.Hip and knee functions were evaluated by Harris Hip Score or Knee Society Score(KSS),respectively.The comparison of hip function scores before and after operation was performed by paired t-test. Results: All patients were followed up for (60±39)months(range:24 to 110 months).Two cases were infected with Enterococcus faecium and 7 cases were infected with Enterococcus faecalis.There were 7 cases of monomicrobial infection and 2 cases of polymicrobial infection.Erythromycin(5/9),tetracycline(4/9),ciprofloxacin and ß-lactam antibiotics(3/9) were the top three antibiotics in Enterococci resistance rate.The sensitive antibiotics for Enterococcal were vancomycin,linezolid and tigecycline.The average duration of intravenous antibiotics was (14±1)days (range:13 to 17 days),and the average duration of antibiotics in articular cavity was (15±2)days(range:11 to 20 days).Mean duration of oral antibiotic use after discharge was (2±1)months(range:1 to 3 months).One case of polymicrobial PJI treatment failed,with a failure rate of 1/9.At last follow-up,the Harris score of patients with hip PJI increased from (43±6)points to (84±6)points(t=-11.899, P<0.01). KSS score of knee function was improved from 33 point pre-operatively to 85 point post-operatively;overall function score was improved from 35 point pre-operatively to 80 point post-operatively.During the treatment,no formation of sinus tract of the hip joint caused by a catheter,skin necrosis at the knee puncture site or leakage of joint fluid;no complications such as deep vein thrombosis and pulmonary embolism occurred. Conclusions: One-stage revision combined with intra-articular infusion of vancomycin can achieve acceptable infection control rate and joint function in patients with chronic Enterococcus PJI.However,the treatment of polymicrobial PJI still needs to be further verified.

[A multicenter study on the tolerance of intravenous low-dose cyclophosphamide in systemic lupus erythematosus].

OBJECTIVE: To compare the safety of low-dose cyclophosphamide and high-dose cyclophosphamide in the treatment of systemic lupus erythematosus (SLE). METHODS: A total of 1 022 patients with systemic lupus erythematosus from 24 hospitals in China between March 2017 to July 2018 were enrolled. Their clinical manifestations, laboratory tests, adverse events, reasons for stopping receiving intravenous cyclophosphamide and comorbidities were collected. Among them, 506 SLE patients received short-interval low-dose intravenous cyclophosphamide therapy (SILD IV-CYC, 400 mg every two weeks), and 256 patients underwent high-dose cyclophosphamide therapy (HD IV-CYC, 500 mg/m2 of body surface area every month), the side effects between the two groups were compared, the remaining 260 SLE patients were treated with IV-CYC irregularly. Moreover, a total of 377 patients in SILD IV-CYC group and 214 patients in HD IV-CYC group had medical records of the reasons for stopping recei-ving IV-CYC. The reasons for stopping receiving IV-CYC in these two groups were analyzed. RESULTS: In this study, only 40.27%(238/591)of the SLE patients stopped receiving intravenous cyclophosphamide for the causes of disease improvement, however, up to 33.67% (199/591) of the patients for the reason of drug-related side effects. There were 83 patients out of 214 (38.79%) with high-dose intravenous cyclophosphamide treatment who stopped receiving IV-CYC for the drug-related side effects, which was significantly higher than that in the low-dose cyclophosphamide group (30.77%, 116/337, P=0.048). Of theses 506 patients in SILD IV-CYC group, 88 (17.39%) patients experienced gastrointestinal reactions, 66 (13.04%) suffered from infections, 49 (9.68%) had myelosuppression and 68 (13.44%) had alopecia, respectively. Among the 256 patients in the HD IV-CYC group, 80 (31.25%) experienced gastrointestinal reactions, 57 (22.27%) suffered from infections, 51 (19.92%) had myelosuppression and 49 (19.14%) had alopecia. Moreover, 71 (25.18%) of 282 female patients with age between 16 to 45 years in SILD IV-CYC group had abnormal menstruation, while menstrual disorder occurred in 39.72% (56/141) patients of HD IV-CYC group. There was no difference of drug-induced hepatic injury, hemorrhagic cystitis and fatigue between the two groups. CONCLUSION: Low-dose cyclophosphamide showed a lower prevalence of adverse events than high-dose cyclophosphamide in systemic lupus erythematosus patients.

[The prognostic value of dynamic minimal residual disease after autologous hematopoietic stem cell transplantation in patients with multiple myeloma in novel-agent era].

Objective: To investigate the clinical prognostic value of dynamic minimal residual disease (MRD) after autologous hematopoietic stem cell transplantation (AHSCT) in patients with multiple myeloma (MM). Methods: Patients with MM who underwent AHSCT in Beijing Chao-Yang Hospital from February 2016 to December 2019 were enrolled in this study. All the patients in the study had complete baseline data at the diagnosis. AHSCT was performed after induction chemotherapy. Response evaluation was performed after induction therapy. All the patients were assessed at approximately 100 days after AHSCT. Bone marrow MRD by NGF was performed every three months and dynamically monitored for at least 12 months. All the patients were divided into different groups according to cytogenetics and MRD status. Survivals in different groups were analyzed by IBM SPSS 22.0 statistical software. Results: A total of 150 patients with MM were enrolled in this study at last, including 66 patients in the cytogenetic standard risk group and 84 patients in the cytogenetic high-risk group. The median age was 54 years (range 30-68 years) and 87 male patients (58.0%) was in the study. The median follow-up was 36 months (range 16-72 months). Patients in the standard-risk group had better clinical prognosis than those in the high-risk group [median PFS in the standard-risk group was not achieved, and median PFS in the high-risk group was 45 months (P<0.001); median OS of both groups was not reached, and the estimated 3-year OS rate of the standard-risk group and the high-risk group was 95.2% and 78.9%, respectively (P=0.001)]. According to MRD status of patients, patients in each group were divided into three subgroups: persistent positive (Ppos), transient negative (Tneg) and persistent negative (Pneg). The median OS and median PFS of all subgroups in the standard-risk group was not reached (P=0.324 and P=0.086). In high-risk group, the median OS of MRD Pneg subgroup was not reached, and the estimated 3-year OS rate was 100%; The median OS of MRD Ppos subgroup was 52 months, and MRD Tneg subgroup only 31 months (P=0.002); the median PFS of MRD Pneg group was not reached, and the estimated 3-year PFS rate was 85.4%; median PFS of MRD Ppos subgroup was 40 months, and MRD Tneg subgroup only 17 months (P=0.001). Conclusions: MRD Pneg might overcome the adverse prognosis of MM patients with high-risk cytogenetics. However, MRD Tneg might be a poor prognostic factor for the patients with cytogenetic high-risk MM.

[Effects of oral bacterial metabolites on systemic diseases].

The oral cavity is the second largest microbial habitat in the whole body. Due to the divergence of oxygen, metabolic substrates and rate-limiting enzymes, oral bacteria are classified into sugar-metabolizing and nitrogen-compound-metabolizing bacteria according to their metabolic characteristics. The metabolites include organic acids, carbon dioxide, amino acids, proteins, and ammonia. Oral bacterial metabolites are very important for oral bacteria growth and reproduction, and also play an important role in systemic diseases such as periodontitis, oral cancer, intestinal diseases, diabetes and atherosclerosis. Therefore, in-depth exploration of oral bacterial metabolism is of great significance to understand the impact of oral cavity on systemic health. This article reviews the metabolic characteristics of oral bacteria and their correlation with systemic diseases.

[Association between short-term exposure to ambient nitrogen dioxide and the risk of heart failure hospitalization].

Objective: To assess the association between short-term exposure level of nitrogen dioxide and the hospitalization risk of heart failure. Methods: Based on China-PEACE Retrospective Heart Failure Study, 117 364 hospitalized patients with heart failure were recruited from 92 hospitals in 62 cities throughout China between January 1, 2015 and December 31, 2015. The daily exposure level of nitrogen dioxide, temperature, and humidity in the same cities during the same period were also collected. We applied the generalized additive model and Bayesian hierarchical model to quantify the lagged effect and cumulative effect of short-term (0-3 days) exposure to ambient nitrogen dioxide on the hospitalization risk of heart failure. We further conducted stratified analyses by age, region, and season to identify any difference in the associations between short-term nitrogen dioxide exposure and heart failure among subgroups. Results: The mean age for participants in the analysis was (70.32±12.22) years. The median, minimum and maximum of daily nitrogen dioxide concentration in 62 cities from January 1, 2015 to December 31, 2015 was 26.4 µg/m3, 2.33 µg/m3 and 150.25 µg/m3, respectively. The exposure level of nitrogen dioxide at the same day was associated with the hospitalization risk of heart failure (OR=1.022, 95%CI: 1.012, 1.031). Significant effects were also observed in the moving average concentrations from lag 0-1 to lag 0-3 day (OR=1.020, 95%CI: 1.009, 1.030; OR=1.016, 95%CI: 1.004, 1.028; OR=1.013, 95%CI: 1.001, 1.026). Moreover, all of the associations between short-term exposure to nitrogen dioxide and the risk of heart failure hospitalization were statistically significant, with no significant difference in all subgroups stratified by age, region, and season. Conclusion: A higher level of short-term exposure to nitrogen dioxide could trigger more hospitalizations with heart failure.

[Effects of continuous goal-directed analgesia on fluid resuscitation of massive burn patients during shock].

Objective: To investigate the effects of continuous goal-directed analgesia on fluid resuscitation during shock stage in patients with massive burns, providing a basis for rational optimization of analgesia protocols in patients with burn shock. Methods: A retrospective case series study was conducted. One hundred and thirty-six patients with massive burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital from January 2015 to December 2020, and the patients were divided into continuous analgesia (CA) group (68 cases,with average age of 44 years old) and intermittent analgesia (IA) group (68 cases,with average age of 45 years old) according to whether sufentanil injection was continuously used for intravenous analgesia during the shock stage. The patients in the 2 groups were predominantly male. Before and at 72 h of treatment, the severity of disease and trauma pain of patients in the 2 groups were scored by the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and the visual analogue scale (VAS). Hematocrit, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), oxygen saturation in central venous blood (ScvO2), rehydration coefficient, blood lactate value, hourly urine output, and the adverse reactions such as hypotension, nausea, vomiting, dizziness, skeletal muscle tonicity, respiratory depression, bradycardia, pruritus, and drug addiction of patients in the 2 groups during the treatment were recorded at the 1st, 2nd, and 3rd 24 h post-injury. Data were statistically analyzed with analysis of variance for repeated measurement, paired or independent sample t test, Bonferroni correction,chi-square test and Mann-Whitney U test. Results: Before treatment, APACHE Ⅱ and VAS scores of patients in the 2 groups were close (with t values of -0.67 and 0.32, respectively, P>0.05); At 72 h of treatment, APACHE Ⅱ and VAS scores of patients in CA group were 8.5±2.2 and 2.5±1.6, both of which were significantly lower than (15.2±3.0) and (7.9±2.0) of patients in IA group, respectively (with t values of -14.94 and -17.46, respectively, P<0.01). Compared with the pre-treatment period, the APACHE Ⅱ and VAS scores of patients in IA group decreased significantly at 72 h of treatment (with t values of 11.35 and 30.59, respectively, P<0.01); the changes in APACHE Ⅱ and VAS scores of patients at 72 h of treatment in comparison with those of patients before treatment in CA group were all similar to those of patients in IA group (with t values of 4.00 and 4.82, respectively, P<0.01). Compared with those of patients in IA group, there were no significant changes in CVP, hematocrit, heart rate, ScvO2, and MAP of patients in CA group at all three 24 h post-injury (with t values of <0.01, 0.12, 2.10, 1.55, 0.03; 0.13, 0.22, <0.01, 0.17, 0.49; 0.63, 0.06, 0.04, 2.79, and 2.33, respectively, P>0.05). Compared with those of patients in IA group at the 1st 24 h post-injury, CVP, ScvO2 and MAP of patients were significantly higher at the 2nd and 3rd 24 h post-injury (with t values of -10.10, -9.31, -8.89; -10.81, -4.65, and -9.43, respectively, P<0.01), and the heart rate of patients was significantly lower at the 2nd and 3rd 24 h post-injury (with t values of 7.53 and 7.78, respectively, P<0.01), and the hematocrit of patients decreased significantly only at the 3rd 24 h post-injury (t=15.55, P<0.01); the changes of CVP, ScvO2, MAP and heart rate of patients at the 2nd and the 3rd 24 h post-injury, and HCT of patients at the 3rd 24 h post-injury, in comparison with those of patients at the 1st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of -12.25, -10.24, -8.99, 9.42, -8.83, -7.53, -11.57, 10.44, and 12.91, respectively, P<0.01). Compared with those of patients in IA group, the rehydration coefficient of patients in CA group was significantly higher only at the 3rd 24 h post-injury (t=5.60, P<0.05), blood lactate value of patients in CA group was significantly lower at the 1st and 2nd 24 h post-injury (with t values of 4.32 and 14.52, respectively, P<0.05 or P<0.01), the hourly urine output of patients in CA group increased significantly at the 1st, 2nd, and 3rd 24 h post-injury (with t values of 24.65, 13.12, and 5.63, respectively, P<0.05 or P<0.01). Compared with the those of patients at the 1st 24 h post-injury, the rehydration coefficient of patients in IA group decreased significantly at the 2nd and the 3rd 24 h post-injury (with t values of 33.98 and 36.91, respectively, P<0.01), the blood lactate values of patients in IA group decreased significantly at the 2nd and the 3rd 24 h post-injury (with t values of 8.20 and 11.68, respectively, P<0.01), and the hourly urine output of patients in IA group was significantly increased at the 2nd and the 3rd 24 h post-injury (with t values of -3.52 and -5.92, respectively, P<0.01); the changes of rehydration coefficients and blood lactate values of patients at the 2nd and the 3rd 24 h post-injury in comparison with those of patients at the 1st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of 35.64, 33.64, 9.86, and 12.56, respectively, P<0.01), but hourly urine output of patients in CA group increased significantly only at the 3rd 24 h compared with that of patients at the 1st 24 h post-injury (t=-3.07, P<0.01). Adverse reactions such as hypotension, nausea, vomiting, dizziness, bradycardia, and pruritus occurred rarely in patients of the 2 groups, and none of the patients had skeletal muscle tonicity, respiratory depression, or drug addiction. The incidence of adverse reactions of patients in CA group was similar to that in IA group (χ2=0.08, P>0.05). Conclusions: Continuous goal-directed analgesia can effectively relieve pain and improve vital signs of patients with large burns. Meanwhile it has little impact on volume load, which can assist in correcting ischemia and hypoxia during the shock period and help patients get through the shock period smoothly.

[Study on construction and application of technology system of chronic diseases and risk factor surveillance in China].

To study and establish a set technology systems of sampling, investigation, quality control, and data analysis of complex sampling for chronic diseases and risk factor surveillance in China based on the requirements of the WHO and China's national conditions, and provide evidence for the policy making and prevention and control evaluation of chronic diseases and technical support for the research of chronic diseases. Through the study of complex sampling technique, adjustment of surveillance points and evaluation of their representatives, a national and provincial representative surveillance system and a complex weighted data analysis were established. According to the relevant plans, actions, and policies in China and other countries, the surveillance content and index system were studied and constructed, which was in line with China's national conditions, "1 + X" steps surveillance, covering the content of questionnaire , physical measurement, and laboratory testing. Based on modern information technology, a three-level platform of information collection and a multi-center laboratory quality control technology system were established, including sampling, information collection, biological sample management, quality control, and result display. Relying on the above research techniques, a national epidemiological investigation was conducted in China, which covered cerebrovascular disease, mental disorders, digestive system disease, and diabetes complications, to obtain the national representative data. This study reflected the innovation of "combination of medicine and prevention" and multi department cooperation in the fields of clinical medicine and public health and provided some big data for the health policy making and the evaluation of the effects of chronic disease prevention and control.

[Characteristics of the alveolar bone defects evaluated by cone-beam CT in periodontitis patients with orthodontic treatment history of Angle class â ¡ malocclusion].

Objective: To evaluate the levels of alveolar bone defects by using cone-beam CT in periodontitis patients with history of orthodontic treatment and to find the special tooth positions, sites and periodontitis stages of alveolar bone defects, so as to provide reference for the formulation of clinical personalized diagnosis and treatment plans. Methods: Thirty patients who were diagnosed as Angle class Ⅱ malocclusion, treated by using labial fixed orthodontic appliances and also diagnosed as periodontitis (orthodontic group) were recuited from January 2009 to June 2019 at the School and Hospital of Stomatology, China Medical University in the present study. They were aged (27.0±5.4) years old (ranged 18-41 years old). Another 60 periodontitis patients without a history of orthodontic treatment matched according to age, gender and severity of periodontitis were selected as control group (non-orthodontic group). They were aged (26.7±5.2) years old (ranged 18-41 years old). Cone-beam CT images were used to measure the heights of the alveolar bone defects at each tooth position of the patients. The difference in the heights of the alveolar bone defects between the orthodontic group and the non-orthodontic group at the same position of the maxillary and mandibular alveolar bones were compared. The specificities of the defect heights in different positions of the maxillary and mandibular alveolar bones and different sites of the same tooth position were analyzed among orthodontic group. The specificities of the different tooth positions of the maxillary and mandibular alveolar bones of the different periodontitis stages among orthodontic group were compared. Results: The heights of the alveolar bone defects in the maxillary canine area and molar area, the mandibular incisor area, the canine area and the premolar area in the orthodontic group were higher than that in the non-orthodontic group, and the differences were statistically significant (P<0.05). In orthodontic group, the most severe teeth in the maxillary and mandibular alveolar bone defects were the canine areas [(3.75±1.00), (3.83±1.10) mm]. Secondly, the more severe tooth positions of the maxillary alveolar bone height defects were the molar area [(3.67±0.84) mm] and the incisor area [(3.39±0.83) mm] and the more severe tooth positions of the mandibular alveolar bone defects were the incisor area [(3.73±1.42) mm] and the molar area [(3.54±0.81) mm]. The height of the alveolar bone defect in the mandibular incisor area was greater than that in the maxillary (P<0.05). The bone defect in the maxillary molar area was severer than that of the mandibular area (P<0.05). The alveolar bone defects in the buccal and lingual sides were mostly larger than that of the mesial and distal sides both in maxillary and mandibular positions except for the maxillary incisor area(P<0.05). The most severe alveolar bone defect position changed with the periodontitis stage. The most severe tooth position of the maxillary in stage Ⅰ periodontitis was in the molar area [(3.26±0.63) mm], whereas the incisor area was the most severe tooth of the mandible [(3.14±1.04) mm]. In addition, among maxillary incisor area, canine area, premolar area, molar area, the most severe alveolar bone defect height was the canine area in stage Ⅱ, Ⅲ, Ⅳ mandibular (P<0.05). Conclusions: In periodontitis patients with a history of orthodontic treatment, the height of the alveolar bone defect was specific to the tooth positions and sites. With the periodontitis stage changing, the most severe defect position changed in both maxillary and mandibular alveolar bones. It is recommended to pay more attention to the alteration of alveolar bone in periodontitis patients with a history of orthodontic treatment and give timely targeted treatment plans.