Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

We wished to establish an expert consensus on late stage of critical care (CC) management. The panel comprised 13 experts in CC medicine. Each statement was assessed based on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) principle. Then, the Delphi method was adopted by 17 experts to reassess the following 28 statements. (1) ESCAPE has evolved from a strategy of delirium management to a strategy of late stage of CC management. (2) The new version of ESCAPE is a strategy for optimizing treatment and comprehensive care of critically ill patients (CIPs) after the rescue period, including early mobilization, early rehabilitation, nutritional support, sleep management, mental assessment, cognitive-function training, emotional support, and optimizing sedation and analgesia. (3) Disease assessment to determine the starting point of early mobilization, early rehabilitation, and early enteral nutrition. (4) Early mobilization has synergistic effects upon the recovery of organ function. (5) Early functional exercise and rehabilitation are important means to promote CIP recovery, and gives them a sense of future prospects. (6) Timely start of enteral nutrition is conducive to early mobilization and early rehabilitation. (7) The spontaneous breathing test should be started as soon as possible, and a weaning plan should be selected step-by-step. (8) The waking process of CIPs should be realized in a planned and purposeful way. (9) Establishment of a sleep-wake rhythm is the key to sleep management in post-CC management. (10) The spontaneous awakening trial, spontaneous breathing trial, and sleep management should be carried out together. (11) The depth of sedation should be adjusted dynamically in the late stage of CC period. (12) Standardized sedation assessment is the premise of rational sedation. (13) Appropriate sedative drugs should be selected according to the objectives of sedation and drug characteristics. (14) A goal-directed minimization strategy for sedation should be implemented. (15) The principle of analgesia must be mastered first. (16) Subjective assessment is preferred for analgesia assessment. (17) Opioid-based analgesic strategies should be selected step-by-step according to the characteristics of different drugs. (18) There must be rational use of non-opioid analgesics and non-drug-based analgesic measures. (19) Pay attention to evaluation of the psychological status of CIPs. (20) Cognitive function in CIPs cannot be ignored. (21) Delirium management should be based on non-drug-based measures and rational use of drugs. (22) Reset treatment can be considered for severe delirium. (23) Psychological assessment should be conducted as early as possible to screen-out high-risk groups with post-traumatic stress disorder. (24) Emotional support, flexible visiting, and environment management are important components of humanistic management in the intensive care unit (ICU). (25) Emotional support from medical teams and families should be promoted through"ICU diaries"and other forms. (26) Environmental management should be carried out by enriching environmental content, limiting environmental interference, and optimizing the environmental atmosphere. (27) Reasonable promotion of flexible visitation should be done on the basis of prevention of nosocomial infection. (28) ESCAPE is an excellent project for late stage of CC management.
Humans ; Consensus ; Critical Care/methods* ; Intensive Care Units ; Pain/drug therapy* ; Analgesics/therapeutic use* ; Delirium/therapy* ; Critical Illness

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*

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

Objective:To investigate the preliminary effects of sub-pectoral fascial breast augmentation and reconstruction.Methods:Six patients (10 breasts) of mammary dysplasia, mastatrophy, prophylactic mastectomy, unilateral breast defect with contralateral mastatrophy were included in the study from Oct. 2019 to July 2021. The mean patient age was 29 years (range, 20 to 35 years). All the textured and smooth cohesive gel implants were inserted under pectoralis major fascia by endoscopic-assisted, incisions were including axillary, around areola and inferior mammary fold approaches. The prophylactic mastectomy cases were performed nipple sparing mastectomy and sub-pectoral fascial breast restoration with implants. The fat and fascia tissue were well reserved to give a satisfying coverage of the appropriate implant. Negative pressure drainage and moulding dressing were used after the surgery.Results:Ten breast augmentation and restoration with a mean implant size of 200 cc (range, 180-300 cc). Less immediate postoperative pain and bleeding were reported. Patients were followed up for an average of 10 months (range, 6 to 21 months). There were no cases of major malpositions, double-bubble and bottom out symptoms. The overall outcome was with better symmetry and satisfaction with time passed by, and no secondary surgical procedures needed.Conclusions:Primary and satisfactory results have been obtained in subfascial breast augmentation and restoration for indications. With the endoscopic-assisted accurate pectoral fascial dissection, and well reserved soft tissue coverage, this technique could avoid the pectoralis major muscle ablation and keep the advantages of sub-glandular plane.

Objective:To investigate the application effect of reverse abdominal wall advancement flap in repairing chest wall soft tissue defect after breast tumor resection.Methods:From October 2020 to April 2021, the Department of Plastic Surgery and Breast Surgery of Hainan Cancer Hospital cooperated to repair the chest wall wounds of 4 female patients with unilateral giant breast tumors after primary lesion resection. Patients aged 40-63 years old, with an average of 51.5 years old. The size of the tumor estimated by physical examination was 7 cm × 6 cm-15 cm × 20 cm. The flaps were closely monitored after surgery, and complications were recorded. Local recurrence was followed-up.Results:The wound size of 4 patients after mastectomy was 16 cm×14 cm-20 cm×18 cm. Abdomen separation range reached anterior axillary line laterally and contralateral clavicle midline medially. Inferiorly, 1 case reached umbilical level, 1 case reached 2 cm below the umbilicus, and 2 cases reached 3 cm below the umbilicus. Three cases were diagnosed as breast lobulated tumors, and 1 case invasive lobular carcinoma. Among the 4 cases, 3 flaps survived completely and healed by first intention, while another flap healed under blister scab. There was no necrosis, infection, hematoma, seroma, or vascular crisis of the flap. All patients were satisfied. Three patients received radiotherapy and one received radiotherapy combined with oral chemotherapy. All patients were followed up for 3-6 months. No local recurrence was discovered. The abdomen was tighter than before operation, but no stiffness was found. There was no abdominal pain, abdominal wall bulging or abdominal hernia.Conclusions:Reverse abdominal wall advancedment flap was used to repair soft tissue defect of the chest wall after breast tumor resection. The operation was simple and fast, with no need for additional donor site incision. Quick recovery allowed shorter interval between surgery and next scheduled treatments.

Objective:To investigate the application effect of reverse abdominal wall advancement flap in repairing chest wall soft tissue defect after breast tumor resection.Methods:From October 2020 to April 2021, the Department of Plastic Surgery and Breast Surgery of Hainan Cancer Hospital cooperated to repair the chest wall wounds of 4 female patients with unilateral giant breast tumors after primary lesion resection. Patients aged 40-63 years old, with an average of 51.5 years old. The size of the tumor estimated by physical examination was 7 cm × 6 cm-15 cm × 20 cm. The flaps were closely monitored after surgery, and complications were recorded. Local recurrence was followed-up.Results:The wound size of 4 patients after mastectomy was 16 cm×14 cm-20 cm×18 cm. Abdomen separation range reached anterior axillary line laterally and contralateral clavicle midline medially. Inferiorly, 1 case reached umbilical level, 1 case reached 2 cm below the umbilicus, and 2 cases reached 3 cm below the umbilicus. Three cases were diagnosed as breast lobulated tumors, and 1 case invasive lobular carcinoma. Among the 4 cases, 3 flaps survived completely and healed by first intention, while another flap healed under blister scab. There was no necrosis, infection, hematoma, seroma, or vascular crisis of the flap. All patients were satisfied. Three patients received radiotherapy and one received radiotherapy combined with oral chemotherapy. All patients were followed up for 3-6 months. No local recurrence was discovered. The abdomen was tighter than before operation, but no stiffness was found. There was no abdominal pain, abdominal wall bulging or abdominal hernia.Conclusions:Reverse abdominal wall advancedment flap was used to repair soft tissue defect of the chest wall after breast tumor resection. The operation was simple and fast, with no need for additional donor site incision. Quick recovery allowed shorter interval between surgery and next scheduled treatments.

Objective To investigate the clinical efficacy of Dong's extra-point pricking bloodletting therapy for female chloasma of liver depression and qi stagnation type. Methods One hundred and twenty female patients with chloasma of liver depression and qi stagnation type were randomized to treatment and control groups, 60 cases each. The control group received Dong's extra-point pricking bloodletting therapy and the treatment group, conventional acupuncture. The symptom and sign score was recorded in the two groups before and after treatment. The clinical therapeutic effects were compared between the two groups. Results The total efficacy rate was 95.5％ in the treatment group and 81.7％ in the control group; there was a statistically significant difference between the two groups (P<0.05). The pre-/post-treatment symptom and sign score difference value was (0.98±0.23) in the treatment group and (0.81±0.18) in the control group; there was a statistically significant difference between the two groups (P<0.05). Conclusion Dong's extra-point pricking bloodletting therapy is an effective way to treat female chloasma of liver depression and qi stagnation type.

OBJECTIVETo analyze the CARL gene mutation in the patients with chronic myeloproliferative neoplasm(MPN) and to explore the clinical significance of CALR mutation.

METHODSThe peripheral blood of patients was collected and the genomic DNA was exacted, the 9 exon of CALR gene and the fragment of human thrombopoetic receptor(MPL) gene were amplified by PCR, the mutation of CALR and MPL genes was detected by using the direct sequencing, the JAK2 V617F mutation was detected by using allele spicific PCR.

RESULTSThe CALR mutations were detected in 13 patients out of 55 MPN patients (23.6%). The frequency of CALR mutation was 22.7% (10/44) in 44 essential thrombocythemia(ET) patients. A total of 3 types of CALR mutation were identified (type I c.1092_1143del52bp, n=5; type II c.1154_1155insTTGTC, n=4; type III c.1094_1139del46bp, n=1). CALR mutations occurred at a frequency of 27.2% in primary myelofibrosis (PMF), including type I (n=2) and type II (n=1). The incidence of JAK2 V617F was 58.1%(32/55), that in ET and PMF was 59.1%(26/44) and 54.5% (6/11), respectively. The mutations of MPL W515 were not detectable in all cases, and the simultaneous mutation of CARL and MPL W515 was not detected. The median age of patients with CALR mutation was significantly younger than that of patients with JAK2 mutations (48 vs 64 years of old, P<0.05). The levels of hemoglobin and leukocytes in patients with CARL mutations were significantly lower (P<0.05) but the level of plateletes was higher than that in patients with JAK2 V617F mutations (P<0.05). Deep venous thrombosis occurred in 4 of 35 ET patients with the JAK2 V617F mutation (n=4), but did not occurr in the patients with CALR mutation. Karyotype abnormality was detected in only one case among 48 patients by chromosome karyotype analysis.

CONCLUSIONThe incidence of CALR mutation is high in ET and PMF patients without JAK2 V617F and MPL W515K mutations, which is associated with younger median age, lower leucocyte and hemoglobin levels, higher platelet counts, and rare thrombocytosis, compared with the patients with JAK2 V617F mutation.