Neuropathic pain, a debilitating condition caused by dysfunction of the somatosensory nervous system, remains difficult to treat due to limited understanding of its molecular mechanisms. Bioinformatics analysis identified cerebellin 2 (CBLN2) as highly enriched in human and murine proprioceptive and nociceptive neurons. We found that CBLN2 expression is persistently upregulated in dorsal root ganglia (DRG) following spinal nerve ligation (SNL) in mice. In addition, transcription factor SOX11 binds to 12 cis-regulatory elements within the Cbln2 promoter to enhance its transcription. SNL also induced SOX11 upregulation, with SOX11 and CBLN2 co-localized in nociceptive neurons. The siRNA-mediated knockdown of Sox11 or Cbln2 attenuated SNL-induced mechanical allodynia and thermal hyperalgesia. High-throughput sequencing of DRG following intrathecal injection of CBLN2 revealed widespread gene expression changes, including upregulation of numerous NF-κB downstream targets. Consistently, CBLN2 activated NF-κB signaling, and inhibition with pyrrolidine dithiocarbamate reduced CBLN2-induced pain hypersensitivity, proinflammatory cytokines and chemokines production, and neuronal hyperexcitability. Together, these findings identified the SOX11/CBLN2/NF-κB axis as a critical mediator of neuropathic pain and a promising target for therapeutic intervention.
Animals ; Neuralgia/metabolism* ; Ganglia, Spinal/metabolism* ; Up-Regulation ; Mice ; NF-kappa B/metabolism* ; SOXC Transcription Factors/genetics* ; Male ; Neuroinflammatory Diseases/metabolism* ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics* ; Hyperalgesia/metabolism* ; Signal Transduction ; Spinal Nerves

Objective:To explore the value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective:To explore the value of metanephrine, normetanephrine, and some steroid hormones in the assessment of adrenal venous sampling (AVS).Methods:This retrospective study enrolled 101 patients with primary aldosteronism who underwent AVS at Peking Union Medical College Hospital between June 1, 2021, and October 1, 2024. Multiple hormones, including aldosterone, cortisol, metanephrine, normetanephrine and steroid hormone profiles, were measured in samples from the inferior vena cava and bilateral adrenal veins during AVS. Selectivity index and lateralization index were calculated based on the levels of different hormones to determine successful AVS cannulation (selectivity index≥2) and aldosterone hypersecretion lateralization (lateralization index≥2). Patients who underwent unilateral adrenalectomy were followed for at least 6 months. Clinical and biochemical outcomes were assessed according to the Primary Aldosteronism Surgical Outcome (PASO) criteria, with biochemical remission defined as achieving complete or partial biochemical remission postoperatively. The efficacy of different hormones relative to cortisol for calculating selectivity index and lateralization index was evaluated for subtype classification.Results:The age at diagnosis of the enrolled patients was (50.5±9.6) years, including 77 males. Regarding the selectivity index, five hormones including metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone demonstrated significantly higher selectivity index compared to cortisol (all P<0.05). Based on the cortisol-derived selectivity index, AVS cannulation was unsuccessful in 8 patients; using the five indices, unsuccessful cannulation occurred in 2, 2, 3, 4, and 5 patients, respectively. Based on postoperative follow-up, 55 patients were identified as having unilateral surgically relievable primary aldosteronism. In identifying these patients, the performance of metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone, and dehydroepiandrosterone was non-inferior to cortisol, correctly identifying 95% (52/55), 93% (51/55), 91% (50/55), 87% (48/55), and 89% (49/55) of cases, respectively. However, among these patients, there were no statistically significant differences in the success rate of intubation in AVS and the ability to identify patients with unilateral primary aldosteronism between the five indicators and cortisol (all P>0.05). Using cortisol-based lateralization as the reference standard, androstenedione and dehydroepiandrosterone both achieved an accuracy of 90% (84/93) for determining the lateralized side, while 17α-hydroxypregnenolone, normetanephrine, and metanephrine achieved accuracies of 89% (83/93), 81% (74/93), and 80% (73/93), respectively. Conclusion:Metanephrine, normetanephrine, androstenedione, 17α-hydroxypregnenolone and dehydroepiandrosterone could increase the success rate of intubation in AVS, with a high ability to identify patients with unilateral primary aldosteronism, and are expected to replace cortisol as new indicators of AVS.

The study focused on individuals with influenza-like symptoms (fever, cough, sore throat, runny nose, and other respiratory symptoms) in three kindergartens in Tongzhou District, Beijing City, in April 2023. Nasopharyngeal swab specimens were collected, and real-time fluorescent quantitative PCR was used to detect common respiratory pathogens in the collected specimens. Positive specimens were subjected to sequencing analysis of the highly variable region of human respiratory syncytial virus (HRSV) G protein, homology analysis and phylogenetic tree analysis. A total of 25 fever cases were collected from 3 kindergartens, aged 3-8 years old, with an age M ( Q1, Q3) of 4 (3.5, 5) years old. Ten confirmed cases of HRSV positive were screened and detected using the fluorescent quantitative PCR method, with a total detection rate of 40% (10/25). Typing identification and sequencing analysis confirmed that the main epidemic type was HRSV subtype B, which was highly homologous and closely related to previous epidemic strains in the region. Through pathogen investigation and analysis, it was preliminarily determined that this epidemic was dominated by HRSV subtype B.

The study focused on individuals with influenza-like symptoms (fever, cough, sore throat, runny nose, and other respiratory symptoms) in three kindergartens in Tongzhou District, Beijing City, in April 2023. Nasopharyngeal swab specimens were collected, and real-time fluorescent quantitative PCR was used to detect common respiratory pathogens in the collected specimens. Positive specimens were subjected to sequencing analysis of the highly variable region of human respiratory syncytial virus (HRSV) G protein, homology analysis and phylogenetic tree analysis. A total of 25 fever cases were collected from 3 kindergartens, aged 3-8 years old, with an age M ( Q1, Q3) of 4 (3.5, 5) years old. Ten confirmed cases of HRSV positive were screened and detected using the fluorescent quantitative PCR method, with a total detection rate of 40% (10/25). Typing identification and sequencing analysis confirmed that the main epidemic type was HRSV subtype B, which was highly homologous and closely related to previous epidemic strains in the region. Through pathogen investigation and analysis, it was preliminarily determined that this epidemic was dominated by HRSV subtype B.

Objective:To investigate the pathogen spectrum and the epidemiological characteristics of hospitalized severe acute respiratory tract infection (SARI) cases in a sentinel hospital in Tongzhou District of Beijing from 2019 to 2022, and provide reference for scientific prevention and control of SARI.Methods:This study enrolled SARI patients in the Beijing Luhe Hospital from January 2019 to December 2022. Nasopharyngeal swabs or respiratory secretions of the patients were collected and analyzed by quantitative real-time PCR to detect the pathogens and their types. The epidemiological and clinical characteristics of the cases were analyzed.Results:In this study, 1 124 SARI cases were enrolled, of which 379 were positive for respiratory pathogens with a detection rate of 33.72%. Most of the SARI cases were positive for bacteria pathogens, and the detection rates of Mycoplasma pneumoniae, Streptococcus pneumoniae, and Stenotrophomonas maltophilia were high. Influenza A virus, parainfluenza virus, and respiratory syncytial virus were the main viral pathogens detected in the cases. There were significant differences in the number of cases and the detection rate of respiratory pathogens among different age groups (χ 2=555, P=0.000 1). The predominant pathogens in different years were different. Mycoplasma pneumoniae [27.27% (51/187)] and influenza A virus [17.65% (33/187), ] were the predominant pathogens in 2019; parainfluenza virus [16.67% (10/60)], Mycoplasma pneumoniae [11.67% (7/60)], and Haemophilus influenzae [11.67% (7/60)] were the predominant pathogens in 2020; Stenotrophomonas maltophilia [24.39% (20/82)] and respiratory syncytial virus [19.51% (16/82)] were the predominant pathogens in 2021; Stenotrophomonas maltophilia [20% (10/50)] and parainfluenza virus [12% (6/50)] were the predominant pathogens in 2022. Conclusions:Most of the SARI cases in Tongzhou district of Beijing from 2019 to 2022 are caused by bacteria. More attention should be paid to the prevalence of Stenotrophomonas maltophilia and Mycoplasma pneumoniae, as well as the prevalence of respiratory syncytial virus, parainfluenza virus, and influenza A virus. The predominant pathogens change every year from 2019 to 2022. Therefore, the prevention and control strategies should be made accordingly. This study provides basis data for the national respiratory multipathogen surveillance program.

Objective To investigate the value of urea nitrogen to creatinine ratio(UCR)and blood lactate clearance rate(LCR)in predicting the mortality risk of elderly with severe pneumonia.Methods A total of 83 elderly patients with severe pneumonia who were admitted to the respiratory intensive care unit(RICU)of Lai'an Branch of Nanjing Drum Tower Hospital from May 2018 to March 2022 were enrolled in this study.The patients were divided into survival group(n=22)and death group(n=61)according to the prognosis on the 28th day after admission.The risk factors of death in elderly severe pneumonia were analyzed.The predictive value of UCR,LCR and the combination of them at 6 h after admission for the mortality risk of elderly patients with severe pneumonia was investigated.Results The Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score on admission,age,the proportion of patients with pneumonia severity index(PSI)grade＞3 on admission,high-sensitivity C-reactive protein(hs-CRP)at 6 h after admission,neutrophil-to-lymphocyte ratio(NLR),red cell distribution width(RDW),white blood cell count(WBC),and UCR in the death group were higher than those in the survival group(P＜0.05).The LCR at 6 h after admission in the death group was lower than that in the survival group(P＜0.05).PSI grade＞3 at admission,UCR increasing at 6 h after admission,and LCR decreasing at 6 h after admission were the risk factors for death in elderly patients with severe pneumonia(P＜0.05).The area under the curve(AUC)values of UCR and LCR at 6 h after admission and their combination for the prediction of death in elderly patients with severe pneumonia were 0.715,0.701 and 0.805,respectively(P＜0.05).Conclusion PSI grade＞3 at admission,UCR increasing at 6 after admission,and LCR decreasing at 6 h after admission are risk factors for death in elderly patients with severe pneumonia.UCR and LCR at 6 h after admission can be used for predicting the mortality risk of elderly patients with severe pneumonia,and the combination of UCR and LCR has higher predictive value.

Objective To observe the clinical efficacy and safety of sacubactril valsartan tablets combined with dapagliflozin tablets in the treatment of patients with type Ⅱ cardio-renal syndrome(CRS).Methods The patients with type Ⅱ CRS were divided into control group and treatment group according to cohort method.Control group was given dapagliflozin 10 mg per time,qd,orally.On the basis of control group,treatment group was given sacubactril valsartan sodium tablets 50 mg per time,bid,orally,and doubled every 2 to 4 weeks until 200 mg per time,bid.Two groups were treated for 3 months.The clinical efficacy,cardiac and renal function and safety were compared between the two groups.Results There were 89 cases in the control group and 87 cases in the treatment group.After treatment,the total effective rates of treatment and control groups were 91.95％(80 cases/87 cases)and 80.90％(72 cases/89 cases),and the difference was statistically significant(P＜0.05).After treatment,the cardiac output of treatment group and control group were(4.36±0.48)and(4.05±0.41)L·min-1,the left ventricular ejection fraction were(48.62±5.02)％and(43.21±4.51)％,the serum creatinine levels were(84.01±10.36)and(95.26±12.65)pmol·L-1,the blood urea nitrogen levels were(6.23±1.12)and(8.04±1.41)mmol·L-1,the urinary protein excretion rates were(79.03±8.27)and(86.05±10.32)μg·min-1,the urinary albumin/creatinine ratios were(90.04±15.13)and(102.16±17.26)mg·g-1,and the differences were statistically significant(all P＜0.05).The adverse drug reactions of treatment group were gastrointestinal reaction,hypotension and hypoglycemia,while those in the control group were hypoglycemia,gastrointestinal reaction and dizziness.The total incidences of adverse drug reactions in treatment and control groups were 8.05％and 6.74％without significant difference(P＞0.05).Conclusion Sacubatrol valsartan tablets combined with dapagliflozin tablets have a definitive clinical efficacy in the treatment of type Ⅱ CRS,which can improve patients'cardiac and renal function,without increasing the incidence of adverse drug reactions.

Objective To observe the clinical efficacy and safety of sacubactril valsartan tablets combined with dapagliflozin tablets in the treatment of patients with type Ⅱ cardio-renal syndrome(CRS).Methods The patients with type Ⅱ CRS were divided into control group and treatment group according to cohort method.Control group was given dapagliflozin 10 mg per time,qd,orally.On the basis of control group,treatment group was given sacubactril valsartan sodium tablets 50 mg per time,bid,orally,and doubled every 2 to 4 weeks until 200 mg per time,bid.Two groups were treated for 3 months.The clinical efficacy,cardiac and renal function and safety were compared between the two groups.Results There were 89 cases in the control group and 87 cases in the treatment group.After treatment,the total effective rates of treatment and control groups were 91.95％(80 cases/87 cases)and 80.90％(72 cases/89 cases),and the difference was statistically significant(P＜0.05).After treatment,the cardiac output of treatment group and control group were(4.36±0.48)and(4.05±0.41)L·min-1,the left ventricular ejection fraction were(48.62±5.02)％and(43.21±4.51)％,the serum creatinine levels were(84.01±10.36)and(95.26±12.65)pmol·L-1,the blood urea nitrogen levels were(6.23±1.12)and(8.04±1.41)mmol·L-1,the urinary protein excretion rates were(79.03±8.27)and(86.05±10.32)μg·min-1,the urinary albumin/creatinine ratios were(90.04±15.13)and(102.16±17.26)mg·g-1,and the differences were statistically significant(all P＜0.05).The adverse drug reactions of treatment group were gastrointestinal reaction,hypotension and hypoglycemia,while those in the control group were hypoglycemia,gastrointestinal reaction and dizziness.The total incidences of adverse drug reactions in treatment and control groups were 8.05％and 6.74％without significant difference(P＞0.05).Conclusion Sacubatrol valsartan tablets combined with dapagliflozin tablets have a definitive clinical efficacy in the treatment of type Ⅱ CRS,which can improve patients'cardiac and renal function,without increasing the incidence of adverse drug reactions.