Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective: The variety and efficacy of biomarkers available that may be used objectively to diagnose major depressive disorder (MDD) in adults are unclear. This systematic review aims to identify and evaluate the variety of objective markers used to diagnose MDD in adults. Methods: The search strategy was applied via PubMed and PsycINFO over the past 10 years (2013–2023) to capture the latest available evidence supporting the use of biomarkers to diagnose MDD. Data was reported through narrative synthesis. Results: Forty-two studies were included in the review. Findings were synthesised based on the following measures: blood, neuroimagingeurophysiology, urine, dermatological, auditory, vocal, cerebrospinal fluid and combinatory—and evaluated based on its sensitivity/specificity and area under the curve values. The best predictors of blood (MYT1 gene), neuroimagingeurophysiological (5-HT1A auto-receptor binding in the dorsal and median raphe), urinary (combined albumin, AMBP, HSPB, APOA1), cerebrospinal fluid-based (neuron specific enolase, microRNA) biomarkers were found to be closely linked to the pathophysiology of MDD. Conclusion A large variety of biomarkers were available to diagnose MDD, with the best performing biomarkers intrinsically related to the pathophysiology of MDD. Potential for future research lies in investigating the joint sensitivity of the best performing biomarkers identified via machine learning methods and establishing the causal effect between these biomarkers and MDD.

Objective:To investigate the relationship between oxygen consumption (VO 2), carbon dioxide production (VCO 2), and Oxygen Consumption/lactate (VO 2/Lac) with risk of death in patients with severe ARDS. Methods:A retrospective cohort study method was used, and the study subjects were hospitalized for >5 days adult patients with severe ARDS in the central intensive care unit of Henan Provincial People's Hospital from 1 March 2020 to 30 June 2023. The following patients were excluded: IC test was not completed on the 4th day of ICU admission, IC test results were unreliable, mechanical ventilation duration had exceeded 48 h at the time of ICU transfer or admission, palliative care patients and pregnant and parturient women. Using indirect calorimetry to determine VO 2 and VCO 2 values on the 4th day of admission, reviewing medical records to obtain general condition, disease information, blood gas analysis (including lactate value), diagnostic and therapeutic measures, and following up deaths by telephone and time of death. The primary outcome measure was death at 90 days, and the secondary outcome measure was death at 28 days, length of stay in ICU, total length of stay, and total hospitalization cost. Cox regression analysis and linear regression analysis were used to investigate the relationship between VO 2, VCO 2, VO 2/Lac and primary and secondary outcome indexes. Results:A total of 216 patients were enrolled, 78 patients (36.1%) died and 138 patients (63.9%) survived at 90 days. After correction for confounders, the results of multifactorial Cox regression analysis suggested that compared with the Q4 group, HR (95% CI) for 90-day risk of death in the VO 2 Q1 and Q2 groups was 3.21 (1.38, 7.49) and 3.24 (1.42, 7.38), and HR (95% CI) for 90-day risk of death in the VCO 2 Q1, Q2 and Q3 groups was 5.88 (2.33, 14.84), 4.26 (1. 60, 11.34) and 3.54 (1.34, 9.35), respectively, and the HR (95% CI) for 90-day risk of death in the VO 2/Lac Q1, Q2 and Q3 groups were 8.72 (3.01, 25.25), 8.43 (2.91, 24.47) and 4.04 (1.34, 12.17) respectively. P-trends were all <0.05, indicating that VO 2, VCO 2 and VO 2/Lac were linearly and negatively associated with the risk of 90-day mortality. In addition, VO 2, VCO 2, and VO 2/Lac were negatively associated with 28-day risk of death and higher VO 2/Lac was negatively associated with length of ICU stay. Conclusions:VO 2, VCO 2 and VO 2/Lac were negatively associated with 90-day mortality risk and 28-day mortality risk in patients with severe ARDS and may be independent risk factors predicting mortality risk of such patients.

Humans ; Esophageal Squamous Cell Carcinoma ; Esophageal Neoplasms/pathology* ; Carcinoma, Squamous Cell ; Microbiota

Objective:To evaluate risk factors for local recurrence and prognosis in patients with upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy combined with lymph node dissection (LND).Methods:The data of 237 patients who were diagnosed with UTUC in Peking University First Hospital and received radical nephroureterectomy combined with LND during January 2010 and March 2022 were retrospectively reviewed. Clinicopathologic characteristics and oncological outcomes were compared according to lymph node metastasis. There were 122 males and 115 females. The tumors of 122 cases were located on the left, while 115 cases were on the right. The tumors of 102 cases were in the renal pelvic, 124 cases in the ureter and 11 cases in both sites. The mean age was (65.52±10.14) years old. The overall survival (OS), cancer-specific survival (CSS), local recurrence-free survival (LRFS) of all patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between two groups were analyzed by log-rank test. Univariate and multivariate Cox proportional hazards regressions were performed to identify the independent risk factors for CSS and LRFS.Results:There were 122 males and 115 females. According to the lymph node metastasis, the patients were divided into lymph node negative group ( n=180, 75.9%) and lymph node positive group ( n=57, 24.1%). Lymph node positive group had a higher percentage in renal tumor [57.9%(33/57) vs. 38.1% (69/180)], stage T 3-4 [84.2%(48/57) vs. 32.8%(59/180)], G 3 [91.2%(52/57) vs. 55.6%(100/180)], glandular differentiation [17.5%(10/57) vs. 4.4%(8/180)], sarcomatoid differentiation [22.8%(13/57) vs. 9.4%(17/180)], necrosis [47.4%(27/57) vs. 16.1%(29/180)], lymphovascular invasion [40.4%(23/57) vs. 12.2%(22/180)] and the number of lymph node dissection [ 4(1, 10) vs. 2(1, 5)]. There were significant differences between the two groups ( P<0.05). Of 237 patients, 42 lost of follow up. The median follow-up time was 46(22, 79) months. Among the 195 patients, 52 patients died, and 42 died due to the tumor. Of all patients, 58(29.7%) had local recurrence, 34 had local recurrence alone, and 24 had concurrent distant metastasis. The 5-year OS and CSS were 67.4% and 71.3%, respectively. The 5-year OS and CSS were 70.5% and 75.1% respectively in the lymph node negative group, 57.5% and 59.4% respectively in the lymph node positive group ( P < 0.05). The 3-year LRFS was 68.0% for all the patients. The 3-year LRFS was 75.6% in the lymph node negative group and 44.5% in the lymph node positive group ( P<0.05). Multivariate analysis showed that tumor stage T 3-4( HR =3.924, 95% CI 2.045-7.529, P<0.001) and G 3( HR=2.871, 95% CI 1.193-6.909, P =0.019) were independent risk factors for LRFS. Multivariate analysis showed that age ≥70 years ( HR = 3.578, 95% CI 1.917-6.678, P<0.001) and pathological stage T 3-4 ( HR =2.366, 95% CI 1.278-4.381, P =0.006) were independent risk factors for CSS. Multivariate analysis showed that age ≥70 years ( HR = 3.874, 95% CI 2.190-6.853, P<0.001) and pathological stage T 3-4 ( HR = 2.757, 95% CI 1.565-4.857, P<0.001) were independent risk factors for OS. Conclusions:Patients with high T stage, high grade, as well as glandular differentiation, sarcomatoid differentiation, necrosis, lymphovascular invasion are more likely to have positive lymph node detection. Age ≥70 years and stage T 3-4 were independent risk factors for CSS and OS. Stage T 3-4 and G 3were independent risk factors for LRFS.

Objective:To evaluate the relationship between the euchromatic histone-lysine N-methyltransferase (G9a) and sodium-dependent activation of potassium channel (Slack) in the dorsal root ganglia (DRG) of rats with neuropathic pain (NP).Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 1 month, weighing 100-120 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (S group), vector plus sham operation group (VS group), vector plus NP group (VN group), and G9a CRISPR/Cas9 knockout plus NP group (GN group). Sham operation was performed at the age of 2 months in group S. In group VS, AAV5 1 μl was microinjected into L 4 and L 5 DRG at the age of 1 month, and sham operation was performed at the age of 2 months.In VN group and GN group, AAV5 and G9a CRISPR/Cas9 knockout plasmid 1 μl were microinjected into L 4 and L 5 DRG at the age of 1 month, and NP model was established by spinal nerve ligation (SNL) at the age of 2 months.Six rats in each group were selected to measure the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) before microinjection (T 0), before SNL (T 1), and at 3, 5 and 7 days after SNL (T 2-4). The animals were sacrificed after the last behavioral testing, the DRGs of lumbar segment (L 4, 5) were removed for determination of the expression of G9a, dimethylation of histone H3 at lysine 9(H3K9me2) and Slack (by Western blot). At 7 days after establishing the model, 6 rats from each group were selected to culture the primary DRG neurons.The frequency and amplitude of Slack current in DRG neurons and miniature excitatory post-synaptic currents (mEPSCs) in the spinal dorsal horn were measured by whole-cell patch-clamp technique. Results:Compared with group S, the TWL was significantly shortened and the MWT was decreased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was up-regulated, the expression of Slack was down-regulated, the amplitude and frequency of Slack currents in DRG neurons were decreased, and the frequency of mEPSCs was increased in group VN ( P<0.05), and no significant change was found in the parameters mentioned above in group VS ( P>0.05). Compared with group VN, the TWL was significantly prolonged and the MWT was increased at T 2-4, the expression of G9a and H3K9me2 in the spinal dorsal horn was down-regulated, the expression of Slack was up-regulated, the amplitude and frequency of Slack currents in DRG neurons were increased, and the frequency of mEPSCs was decreased in group GN ( P<0.05). Conclusion:The mechanism of NP is related to up-regulating the expression of G9a in DRG, thus inhibiting the expression and opening of Slack channels in rats.