Sepsis is a potentially fatal condition characterized by the failure of one or more organs due to a disordered host response to infection. The development of sepsis is closely linked to immune dysfunction. As a result, immunotherapy has gained traction as a promising approach to sepsis treatment, as it holds the potential to reverse immunosuppression and restore immune balance, thereby improving the prognosis of septic patients. However, due to the highly heterogeneous nature of sepsis, it is crucial to carefully select the appropriate patient population for immunotherapy. This review summarizes the current and evolved treatments for sepsis-induced immunosuppression to enhance clinicians' understanding and practical application of immunotherapy in the management of sepsis.

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.
Humans ; U937 Cells ; RUNX1 Translocation Partner 1 Protein ; Leukemia/genetics* ; Core Binding Factor Alpha 2 Subunit/genetics* ; Oncogene Proteins, Fusion/genetics* ; Leukemia, Myeloid, Acute/genetics*

Dry eye is a multifactorial disease characterized by loss of ocular surface homeostasis and increased tear film instability, accompanied by ocular symptoms such as ocular dryness, foreign body sensation, burning sensation, eye redness, pain, photophobia, tearing, eye fatigue, decreased visual acuity, increased secretion, and sensitivity to external stimuli. Its pathophysiological mechanisms are mainly tear film instability, elevated tear osmolarity(Tosm), ocular surface inflammation and injury, and neurosensory abnormalities. Tosm is an important factor in maintaining tear film stability and ocular surface comfort. Elevated Tosm can cause ocular discomfort, corneal epithelial damage, loss of goblet cells and ocular inflammatory response in dry eye patients, and the inflammatory response can further reduce tear film stability and increase Tosm, which puts dry eye in a vicious cycle. In order to have a more comprehensive understanding of the relationship between tear hyperosmolarity(THO)and dry eye, this article will focus on the role of THO in the pathogenesis, diagnosis, severity classification and targeted treatment of dry eyes from the aspect of pathophysiology.

Objective: To explore the pathogenesis and risk factors of gallstone formation. Methods: The findings of hepatobiliary ultrasound and related data were collected from healthy subjects who underwent a physical examination at Xuanwu Hospital of Capital Medical University from January 2012 to December 2021. A total of 98 344 healthy subjects were included in the study,including 48 241 males and 50 103 females,with a ratio of 1∶1.03,aged (42.0±15.6)years(range:14 to 97 years). The gender,age,body mass index,waist circumference,systolic pressure,diastolic pressure,ALT,AST,total bilirubin,fasting blood glucose,triglyceride,total cholesterol,low-density lipoprotein,high-density lipoprotein were collected.Healthy subjects were required to sit for at least 10 minutes before blood pressure was measured.Rresults of fasting venous blood were collected after 8 to 12 hours on an empty stomach.According to the presence of gallstones by ultrasound results, healthy subjects were divided into study group and control group. Data were analyzed by rank-sum tests and χ² test, and risk factors for gallstone formation were explored by Logistic regression analysis. Results: The incidence of gallstones in this group was 5.42%(5 333/98 344). Among them,the incidence of gallstones in people aged 60 years and above was significantly higher than that in people under 60 years old(15.31%(2 348/15 334) vs. 3.60%(2 985/83 010), χ²=3 473.46,P<0.05).The healthy subjects were divided by age for every 10 years,and the results showed that the incidence of gallstones increased with age. The incidence of gallstones in females was 5.68%(2 844/50 103),greater than 5.16%(2 489/48 241) in males(χ²=11.81,P<0.05). Among them,1 478 cases underwent gallbladder surgical resection due to gallstones,and the operation rate was 27.71%. The operation rate reached the peak between 60 and <70 years old,and decreased after 70 years old. The results of the multivariate analysis showed that,female(OR=1.38, P<0.01),age(OR=1.58, P<0.01),body mass index≥24 kg/m²(OR=1.31, P<0.01),waist circumference≥85 cm(OR=1.24, P<0.01),fasting blood glucose>6.1 mmol/L(OR=1.18,P<0.01),total cholesterol≥5.18 mmol/L(OR=0.87, P=0.019),low-density lipoprotein≥3.37 mmol/L(OR=1.15,P=0.001) were the risk factors for gallstone formation;high-density lipoprotein≥1.55 mmol/L(OR=0.87, P<0.01) was a protective factor for gallstone formation. Conclusions: The incidence of gallstones increases with age in male and female. Gender,age,body mass index,waist circumferenc,fasting blood glucose,total cholesterol,LDL,and HDL are related factors with gallstone formation.

AIM: To investigate the safety of bioequivalence (BE) studies of orally inhaled drug products (OIDPs) conducted by Phase I clinical Research Center of our hospital. METHODS: The safety data were collected from 482 healthy subjects enrolled in 20 OIDPs BE studies in Wuxi People's hospital from 2017 to 2022. The difference of adverse events (AEs) between test preparation and reference preparation were compared, as well as the influence of gender, age, mechanism of drug action and device type on AE were analyzed. RESULTS: A total of 102 cases of AEs were occurred in 77 subjects (16.0%, 77/482), 87 cases of AEs were related to experimental drugs, all AEs were mild or moderate, and no serious adverse events occurred. There was no difference in the incidence of AE between test preparation and reference preparation. In addition, gender, age, mechanism of drug action and device type had no significant effects on AEs. CONCLUSION: In 20 bioequivalence studies of OIDPs, OIDPs were safe and well tolerated in healthy subjects after dosing, and safety features of generic OIDPs and original drug were basically similar.

AIM: To explore the reasons for screening failure of healthy subjects in clinical trials of orally inhaled drug products (OIDPs). METHODS: Screening data of 1 432 healthy subjects who participated in clinical trials of OIDPs were collected. The main reasons for the screening failure, gender differences in screening failure rate and the correlation between age and screening failure rate were summarized and analyzed. RESULTS: The screening failure rate was 72.4 % and increased with age. The failure rate was slightly higher in females than in males. Besides abnormal vital signs (17.3%), abnormal laboratory test results (16.5%) and withdrawal of consent (7.6%), poor venous condition (13.9%), positive for cigarette test results (12.6%) and failure in inhalation training (7.1%) were also the other three main reasons affecting the screening success rate. Abnormal vital signs and poor venous conditions were the primary screening failure reasons for males and females, respectively. CONCLUSION: The screening success rate could be improved by informing fully and communicating effectively, selecting young subjects with strong understanding abilities, and enhancing the training skills of investigators.

Objective To investigate the serum C-type lectin domain family 4 member G(CLEC4G)level and its clinical value in patients with Atopic Dermatitis(AD).Methods The blood samples of 60 AD patients and 29 control patients were collected,and CLEC4G,Interleukin-33(IL-33),total immunoglobulin E(tIgE),specific IgE(specific IgE),and eosinophil levels were detected.The correlation between CLEC4G level and clinical data of AD patients and IL-33 was analyzed.The risk of AD was evaluated by Logistic regression analysis of CLEC4G,IL-33 and other indicators.Results Compared with the control group,the serum CLEC4G level in AD patients was significantly decreased(359.4±57.3 vs.521.8±48.1)pg/mL.There was no significant difference in CLEC4G level between child-hood,adolescent and adult,male and female AD patients.Compared with tIgE≤100 kU/L group,CLEC4G level was significantly decreased in 100～200 kU/L group and tIgE≥200 kU/L group,but there was no significant difference between 100～200 kU/L group and tIgE≥200 kU/L group.Serum CLEC4G level decreased significantly only in the moderate AD group,but had no significant difference among the other groups.The serum level of IL-33 was increased in AD patients,but there was no significant correlation between CLEC4G and IL-33(r = 0.090,P = 0.495).Age less than 14 years old and IL-33 were risk factors for the incidence of AD,with OR values of 2.756 and 1.241,95%CI of 1.076～7.060 and 1.030～1.495,respectively.CLEC4G was a protective factor for AD(OR = 0.890,95%CI:0.809～0.979).Conclusion CLEC4G may be a protective factor independent of IL-33 mediated AD pathogenesis.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective:To investigate the clinical characteristics of children with atopic dermatitis (AD) and the changes in serum levels of apolipoprotein A1 (Apo A1), 25-hydroxyvitamin D [25(OH)D] and eosinophil derived neurotoxin (EDN).Methods:200 children with AD treated in Zhuzhou Central Hospital from January 2016 to December 2019 were selected retrospectively as AD group and 100 healthy children as control group. The clinical characteristics of children with AD were analyzed, and the differences in serum Apo A1, 25 (OH)D and EDN levels between two groups were compared. The relationships between serum Apo A1, 25(OH)D, EDN levels and severity of AD were explored.Results:The male to female composition ratio of 200 AD patients was 1.41∶1, and the age of onset <3 months was the highest (64.50%). Inhalation allergens were detected in 118 cases (59.00%) and ingestion allergens in 82 cases (41.00%). The levels of Apo A1 and EDN in AD group were significantly higher than those in control group, while the level of 25(OH)D was significantly lower than that in control group ( P<0.05). With the aggravation of the disease, the serum Apo A1 and EDN levels in AD children increased gradually, while the serum 25(OH)D level decreased significantly (all P<0.05). Severity Scoring of Atopic Dermatitis (SCORAD) was positively correlated with Apo A1 and EDN levels ( P<0.05), and was negatively correlated with 25(OH)D level (all P<0.05). Conclusions:Apo A1, 25 (OH)D and EDN are involved in the pathogenesis of AD in children, and their serum levels are closely related to the severity of AD.

Objective: To investigate the impact of surgical treatment on quality of life in patients with locally recurrent rectal cancer (LRRC). Methods: A descriptive case series study was performed. The complete clinical data of 62 patients who met the diagnostic criteria of LRRC and treated by surgical procedures in Huashan Hospital of Fudan University from January 2012 to November 2019 were analyzed retrospectively. All the patients were followed up at least 12 months. Assessments of urinary function, sexual function, mobility function of lower limb and quality of life were documented. Patients with distant metastasis and surgical history of the urinary system were excluded. According to the criteria of Memorial Sloan Kettering Cancer Center (MSKCC), recurrence were divided into central (n=27), anterior (n=20), posterior (n=7), and lateral (n=8) subtypes. Baseline characteristics, surgical procedures and short-term complications were analyzed. International prostate symptom score (IPSS) and grade of voiding dysfunction were used to evaluate the urinary function. Higher score of IPSS and higher grade of voiding dysfunction indicated worse voiding function. Sexual function for both genders was assessed preoperatively and postoperatively. International index of erectile function-5 (IIEF-5) was used for assessment of male patients and higher score indicated better function. Female sexual function index (FSFI) was used in females and higher score indicated better function. Short-form health survey with 36 items (SF-36), yielding an 8-scale profile of functional health (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, emotional health and mental health) was used to evaluate the quality of life. The higher score indicated the better quality of life. Results: All the operations of 62 patients completed successfully and R0 resection rate was 88.7% (55/62). Postoperative surgical complications occurred in 16 cases (25.8%), including 3 patients of Clavien-Dindo classification III. At postoperative 3-month, 42 patients without ileum cystectomy or ureterostomy suffered from different grade of voiding dysfunction. IPSS increased significantly after the surgery (before surgery: 12.36±4.75, after surgery: 18.40±4.77, t=-9.128, P<0.001). There was no significant difference among the subtypes (P>0.05). At postoperative 12-month, IIEF-5 decreased from 14 (0~25) to 9 (0~19) in males (Z=-5.174, P<0.001) and FSFI deceased from 8.4 (2.0-27.0) to 2.0 (2.0-18.4) in females (Z=-3.522, P<0.001). Scores of physical functioning and role-physical decreased significantly [physical functioning: before surgery 70 (35-85), after surgery 65 (30-80), Z=-3.685, P<0.001; role-physical: before surgery 50 (0-50), after surgery 25(0-75), Z=-4.065, P<0.001], while those of social functioning role-emotional and mental health increased significantly after the surgery [social functioning: before surgery 44 (22-78), after surgery 56 (0-89), Z=-3.509, P<0.001; role-emotional: before surgery 17 (0-100), after surgery 33 (0-100), Z=-2.439, P=0.015; mental health: before surgery 40 (36-76), after surgery 52 (24-80), Z=-3.395, P<0.001]. All surgical procedures decreased the voiding function of LRRC patients and the sexual function of male patients (all P<0.01). However, only total pelvic exenteration and posterior pelvic exenteration decreased FSFI in female patients [before surgery: 8.4 (2.0-27.0) after surgery: 2.0 (2.0-18.4), Z=-2.810, P=0.005]. Conclusions: Multi-visceral resection in LRRC patients may damage voiding and sexual function. However, successful and effective surgical treatment can improve the psychosocial health of LRRC patients.
Female ; Humans ; Male ; Neoplasm Recurrence, Local ; Quality of Life ; Rectal Neoplasms/surgery* ; Rectum ; Retrospective Studies