Objective To analyze the clinical significance of subjective visual vertical (SVV) tests at different head deflection angles in assessing utricle function in patients with benign paroxysmal positional vertigo (BPPV). Methods A total of 61 BPPV patients who were treated at the Hearing Impairment and Vertigo Diagnosis and Treatment Center of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine from August 2022 to May 2023 were retrospectively included, and 29 healthy adults were selected as controls. SVV tests were performed on all research subjects at different head deflection angles: upright head (0°), left head 45° (L45°), right head 45° (R45°). The test results between the two groups were compared. Results SVV absolute value at R45° in BPPV group was lower than that in the control group (P＝0.003); there was no significant difference in SVV values at 0° and L45° between the two groups. There was no statistical difference in SVV values at different head deflection angles between the control group and the left BPPV group. SVV absolute value at R45° in right BPPV group was lower than that in the control group (P＜0.001); there was no statistical difference in SVV values at 0° and L45° between the two groups. Conclusions SVV test can provide subjective information about the utricle, and SVV tests at different head deflection angles can fine-tune evaluate the function of the utricle in BPPV patients.

Objective:To study the impact of early blood concentrations of tacrolimus on the survival of patients after liver transplantation.Methods:Clinical data of 159 patients with liver diseases undergoing classic orthotopic liver transplantation at the Department of Hepatobiliary Surgery, the 900th Hospital of the Joint Logistics Support Force between January 2010 and December 2019 were retrospectively analyzed, including 123 males and 36 females, aged (48.0±12.2) years. According to survival status, patients were divided into the surviving group ( n=108) and death group ( n=51). Inverse probability of treatment weighting (IPTW) was applied to adjust for confounding factors by weighting covariates between the two groups. Univariate and multivariate Cox regression analysis were used to examine the relationship between early tacrolimus concentrations and mortality, and restrict cubic spline (RCS) curves were employed to assess the nonlinear relationship further. Results:After IPTW weighting, multivariate Cox regression analysis indicated that early tacrolimus concentration ( HR=2.479, 95% CI: 1.354-4.537, P<0.001) and preoperative international normalized ratio ( HR=0.358, 95% CI: 0.162-0.792, P=0.011) levels were risk factors for post-transplant survival. The RCS curve revealed that the optimal thresholds for early tacrolimus concentration were 6.30 ng/ml and 8.28 ng/ml ( P<0.001). Patients were therefore divided into the optimal concentration group ( n=60) and the non-optimal concentration group ( n=99). After IPTW weighting, the optimal concentration group comprised 102 cases, and the non-optimal concentration group included 212 cases. The 1-year, 3-year and 5-year survival rates in the optimal concentration group and the non-optimal concentration group were 97.06%, 81.37% and 75.49%, and 86.32%, 64.62% and 50.94%, respecitvely ( χ2=8.37, P<0.001). Conclusion:Early tacrolimus concentration is an independent risk factor for post-transplant survival. A tacrolimus concentration >8.28 ng/ml or <6.30 ng/ml is associated with a relatively higher mortality rate.

Objective:To investigate the relationship between symptoms of vertigo and vestibular functions and short-term hearing outcomes in patients with flat descending sudden sensorineural hearing loss （SSNHL）. Methods:A retrospective review was conducted of the vestibular symptoms observed in 48 patients with unilateral flat-down sudden sensorineural hearing loss treated at the Department of Otolaryngology Head and Neck Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Symptoms of vertigo and the results of cervical vestibular-evoked myogenic potentials （cVEMP）, ocular VEMP （oVEMP）, caloric test and video head-impulse test （vHIT） were collected to determine whether these factors could predict therapeutic efficacy. Results:The symptoms of vertigo was not correlated with prognosis （P>0.05） or with abnormal vestibular functions （P>0.05）. Patients with abnormal cVEMP, oVEMP, caloric test or vHIT showed significantly lower effective rates （32.0%, 44.0%, 32.0%, and 24.0%, respectively）; the greater the number of abnormal tests, the poorer the outcome. Patients with all four tests abnormal gained only （3.13±15.97） dB HL in hearing recovery, whereas those with normal cVEMP, oVEMP, caloric test or vHIT showed better chances of hearing improvements by （29.22±20.31）, （31.18±21.59）, （26.17±21.31）, and （26.38±24.05） dB HL, respectively. Conclusion:Vestibular function effectively predicts prognosis in flat descending SSNHL. Patients with abnormal vestibular tests, regardless of symptoms of vertigo, responded poorly to treatment, whereas those with normal cVEMP, oVEMP, caloric test and vHIT results achieved better hearing recovery. Abnormal vestibular function implies more extensive and severe inner-ear lesions in patients with SSNHL.
Humans ; Male ; Female ; Retrospective Studies ; Prognosis ; Adult ; Middle Aged ; Vertigo/diagnosis* ; Hearing Loss, Sensorineural/diagnosis* ; Young Adult ; Hearing Loss, Sudden/diagnosis* ; Adolescent ; Aged ; Vestibular Evoked Myogenic Potentials

Objective: To examine the impact of temperature on the incidence of hand-foot-mouth disease (HFMD), so as to provide a basis for research on the impact of climate on HFMD. Methods: HFMD incidence data in Huzhou City, Zhejiang Province from 2010 to 2022 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. Concurrent meteorological data were obtained from the Huzhou Meteorological Bureau. A distributed lag non-linear model (DLNM) was employed to analyze the impact of temperature on HFMD incidence. Results: A total of 65 059 cases of HFMD were reported in Huzhou City from 2010 to 2022, with incidence peaks occurring from April to July and from October to November. The 5th, 25th, 50th, 75th, and 95th percentiles (P5, P25, P50, P75, and P95) of daily average temperature were 2.5, 9.4, 17.8, 24.7, and 30.6 ℃, respectively. The results from the DLNM analysis revealed a non-linear relationship between daily average temperature and HFMD incidence, which exhibited an irregular "M" shape. The incidence peaks were observed at 6.5 ℃ (RR=1.596, 95%CI: 1.154-2.207) and 25.7 ℃ (RR=3.257, 95%CI: 2.614-4.058), respectively. The maximum single-day effect was observed at a daily average temperature of -6.2 ℃ at lag 0 day (RR=1.250, 95%CI: 1.100-1.420), while the minimum single-day effect was observed at a daily average temperature of 34.6 ℃ at lag 0 day (RR=0.881, 95%CI: 0.826-0.940). The impact of daily average temperature at P5 on the incidence of HFMD showed RR values greater than 1 at lag 0, 3, 27, and 30 days, but less than 1 at lag 9 and 12 days, with no significant cumulative lag effect. In contrast, for the daily average temperature at P95, the RR values less than 1 at lag 15, 18, and 21 days, with significant cumulative lag effects identified. Conclusions The incidence of HFMD in Huzhou City peaks from April to July and again from October to November. There exists a nonlinear relationship and lag effect between temperature and HFMD incidence, with particular attention drawn to the impact of extreme temperatures on the disease's onset.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .

Objective:To study the impact of early blood concentrations of tacrolimus on the survival of patients after liver transplantation.Methods:Clinical data of 159 patients with liver diseases undergoing classic orthotopic liver transplantation at the Department of Hepatobiliary Surgery, the 900th Hospital of the Joint Logistics Support Force between January 2010 and December 2019 were retrospectively analyzed, including 123 males and 36 females, aged (48.0±12.2) years. According to survival status, patients were divided into the surviving group ( n=108) and death group ( n=51). Inverse probability of treatment weighting (IPTW) was applied to adjust for confounding factors by weighting covariates between the two groups. Univariate and multivariate Cox regression analysis were used to examine the relationship between early tacrolimus concentrations and mortality, and restrict cubic spline (RCS) curves were employed to assess the nonlinear relationship further. Results:After IPTW weighting, multivariate Cox regression analysis indicated that early tacrolimus concentration ( HR=2.479, 95% CI: 1.354-4.537, P<0.001) and preoperative international normalized ratio ( HR=0.358, 95% CI: 0.162-0.792, P=0.011) levels were risk factors for post-transplant survival. The RCS curve revealed that the optimal thresholds for early tacrolimus concentration were 6.30 ng/ml and 8.28 ng/ml ( P<0.001). Patients were therefore divided into the optimal concentration group ( n=60) and the non-optimal concentration group ( n=99). After IPTW weighting, the optimal concentration group comprised 102 cases, and the non-optimal concentration group included 212 cases. The 1-year, 3-year and 5-year survival rates in the optimal concentration group and the non-optimal concentration group were 97.06%, 81.37% and 75.49%, and 86.32%, 64.62% and 50.94%, respecitvely ( χ2=8.37, P<0.001). Conclusion:Early tacrolimus concentration is an independent risk factor for post-transplant survival. A tacrolimus concentration >8.28 ng/ml or <6.30 ng/ml is associated with a relatively higher mortality rate.

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

The effect of aspirin eugenol ester(AEE)on the metabolism of rats was investigated to provide theoretical references for the clinical rational use of the drug.Firstly,the appropriate con-centration of AEE suspension was prepared.Wistar rats were randomly divided into three groups:the normal group,the AEE low-dose group(18 mg/kg),and the AEE high-dose group(72 mg/kg).The rats in the dosing group were dosed once daily,and the Wistar rats in the normal group were dosed once daily with an equal volume of 0.5％sodium carboxymethylcellulose solution.The feces and urine were collected after 7 days of continuous gavage,and the feces and urine were ana-lyzed by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spec-trometry(UPLC-QTOF-MS/MS)for non-targeted metabolomics and Metabo Analyst 5.0 was used for metabolic pathway enrichment.The results showed that the dose of AEE selected in this experiment was not toxic to the growth of rats.The results of the metabolomics study found that 10 and 8 differential metabolites were identified in rat feces and urine,respectively,involving meta-bolic pathways such as phenylalanine,tyrosine and tryptophan biosynthesis,phenylalanine metabo-lism,steroid hormone biosynthesis,biosynthesis of unsaturated fatty acids,aminosugar and nucleo-tide sugar metabolism,fatty acid biosynthesis,and β-alanine metabolism.AEE had no significant effect on the body weight of rats(P＞0.05),but AEE could affect the metabolism of rat organ-ism.Fecal metabolites were mainly involved in metabolic pathways including unsaturated fatty acid biosynthesis,tyrosine metabolism,fatty acid biosynthesis,and steroid hormone biosynthesis;urina-ry metabolites were mainly involved in metabolic pathways including purine metabolism,fatty acid biosynthesis,arginine,and proline metabolism.Therefore,the metabolic effects of AEE on rats are mainly closely related to the regulation of lipid metabolism,amino acid metabolism,and energy metabolism.The results of this experiment can provide some references for the efficacy and clinical application of AEE in animals.