BACKGROUND: Treatment with chimeric antigen receptor-T (CAR-T) cells has shown promising effectiveness in patients with relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL), although the process of preparing for this therapy usually takes a long time. We have recently created CD19 Fast-CAR-T (F-CAR-T) cells, which can be produced within a single day. The objective of this study was to evaluate and contrast the effectiveness and safety of CD19 F-CAR-T cells with those of CD19 conventional CAR-T cells in the management of R/R B-ALL. METHODS: A multicenter, retrospective analysis of the clinical data of 44 patients with R/R B-ALL was conducted. Overall, 23 patients were administered with innovative CD19 F-CAR-T cells (F-CAR-T group), whereas 21 patients were given CD19 conventional CAR-T cells (C-CAR-T group). We compared the rates of complete remission (CR), minimal residual disease (MRD)-negative CR, leukemia-free survival (LFS), overall survival (OS), and the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) between the two groups. RESULTS: Compared with the C-CAR-T group, the F-CAR-T group had significantly higher CR and MRD-negative rates (95.7% and 91.3%, respectively; 71.4% and 66.7%, respectively; P = 0.036 and P = 0.044). No significant differences were observed in the 1-year or 2-year LFS or OS rates between the two groups: the 1-year and 2-year LFS for the F-CAR-T group vs.C-CAR-T group were 47.8% and 43.5% vs. 38.1% and 23.8% (P = 0.384 and P = 0.216), while the 1-year and 2-year OS rates were 65.2% and 56.5% vs. 52.4% and 47.6% (P = 0.395 and P = 0.540). Additionally, among CR patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CAR-T-cell therapy, there were no significant differences in the 1-year or 2-year LFS or OS rates: 57.1% and 50.0% vs. 47.8% and 34.8% (P = 0.506 and P = 0.356), 64.3% and 57.1% vs. 65.2% and 56.5% (P = 0.985 and P = 0.883), respectively. The incidence of CRS was greater in the F-CAR-T group (91.3%) than in the C-CAR-T group (66.7%) (P = 0.044). The incidence of ICANS was also greater in the F-CAR-T group (30.4%) than in the C-CAR-T group (9.5%) (P = 0.085), but no treatment-related deaths occurred in the two groups. CONCLUSION Compared with C-CAR-T-cell therapy, F-CAR-T-cell therapy has a superior remission rate but also leads to a tolerably increased incidence of CRS/ICANS. Further research is needed to explore the function of allo-HSCT as an intermediary therapy after CAR-T-cell therapy.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

Objective:To investigate the expression and phosphorylation level change of adenosine monophosphate activated protein kinase (AMPK) in skeletal muscle of severely scald rats and its roles in skeletal muscle atrophy in severely scalded rats.Methods:The experimental research method was applied. Totally 100 6-week-old male Wistar rats were divided into sham injury group and scald group according to the random number table, with 50 rats in each group. After weighing the body weight, rats in scald group were inflicted with full-thickness scald of 30% total body surface area on the back, and rats in sham injury group were simulated with scald. At 6 h and on 1, 3, 5, and 7 d post injury, 10 rats in each group were taken to measure their body weights and weights of extensor digitorum longus and soleus muscle. At 6 h and on 1, 3, 5, and 7 d post injury, the tibialis anterior muscles were collected, the mRNA expressions of muscle atrophy F-box protein (MAFbx) and muscle-specific RING finger protein 1 (MuRF1) were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction; the content of adenosine monophosphate (AMP), adenosine diphosphate, and adenosine triphosphate (ATP) were detected by high performance liquid chromatography, and AMP/ATP ratio and energy charge were calculated; the protein expressions of AMPK-α and phosphorylated AMPK-α (p-AMPK-α) were detected by Western blotting, and the p-AMPK-α/AMPK-α ratio was calculated, with sample number of 4 in each time point of each group. Data were statistically analyzed with analysis of variance for factorial design and least significant difference test.Results:The body weights of rats in 2 groups before injury and at each time point post injury were close ( P>0.05). At 6 h post injury, the weight of extensor digitorum longus of rats in scald group was (0.107±0.007) g, which was significantly heavier than (0.086±0.0607) g of sham injury group ( P<0.01). On 3 d post injury, the weight of extensor digitorum longus of rats in scald group was (0.083±0.016) g, which was significantly lighter than (0.102±0.005) g of sham injury group ( P<0.01). The weight of soleus of rats in 2 groups were close at each time point post injury ( P>0.05). Compared with those of sham injury group, the mRNA expression of MAFbx in tibialis anterior muscle of rats in scald group was significantly up-regulated at 6 h post injury ( P<0.01), and the mRNA expressions of MuRF1 in tibial anterior muscle of rats in scald group were significantly up-regulated at 6 h and on 1 d post injury ( P<0.01). At 6 h and on 7 d post injury, compared with those of false injury group, the AMP/ATP ratios of the tibial anterior muscle of rats in scald group were significantly increased ( P<0.05 or P<0.01), and energy charges of the tibial anterior muscle of rats in scald group were significantly decreased ( P<0.01). At each time point post injury, the protein expressions of AMPK-α of the tibial anterior muscle of rats in 2 groups were close ( P>0.05). The p-AMPK-α/AMPK-α ratios of the tibial anterior muscle of rats in scald group at 6 h and on 7 d post injury were significantly higher than those in sham injury group ( P<0.05 or P<0.01). Conclusions:The decrease in energy charge and increase in AMP/ATP ratio of skeletal muscle of rats after severe scald activate AMPK. The activation of AMPK in the early stage of injury is consistent with the up-regulation of MAFbx and MuRF1 expressions and down-regulation of skeletal muscle weight. The above-mentioned changes may be one of the molecular mechanisms of skeletal muscle atrophy in rats with severe scald

The injury mechanism of high-voltage electric burn in limbs is complex and special. The soft tissue and vascular injuries caused by high-voltage electric burn are serious and concealed. It is difficult to judge the severity and extent of injury before surgery, which affects the diagnosis and treatment effects and remains a major problem in burn field. In recent decades, a series of clinical studies have been conducted by scholars at home and abroad, using various imaging methods for the judgment of soft tissue and vascular injuries, which have their own advantages and disadvantages. According to the principle of accuracy, precision, safety, and easy operation, magnetic resonance imaging and magnetic resonance angiography are required at the same time in general for the imaging judgment of soft tissue and vascular injuries in limbs with high-voltage electric burn. The B-mode ultrasonography shall be performed if a precise judgment of vascular injury is needed.

Objective To explore the Chinese culture oriented palliative care content for people with heart failure. Methods After a comprehensive literature review and expert interviews, two-round expert consultation was conducted to confirm the Chinese culture oriented palliative care content indicators for people with heart failure. Results A scientific literature review was performed and finally 102 articles were included.Totally 13 experts were interviewed and 525 meaning units were identified in the interviews.The Chinese culture oriented palliative care content for people with heart failure contained 4 first-grade indicators,10 second-grade indicators and 42 third-grade indicators.The expert′s enthusiasm of the two rounds of expert consultation were both 100%,the authoritative coefficient were 0.82 and 0.83, the coordination coefficient of Kendall′s W were 0.14 to 0.40 (P<0.01). Conclusions The Chinese culture oriented palliative care content for people with heart failure contributes to the development of new models for integrated heart failure care and palliative care which set with Chinese culture.

Objective: To summarize the measures and experience of treatment in mass extremely severe burn patients. Methods: The clinical data and treatment of 8 extremely severe burn patients in August 2 Kunshan factory aluminum dust explosion accident who were admitted in the 100th Hospital of PLA on August 2nd, 2014, were retrospectively analyzed. There were 4 males and 4 females, aging 22-45 (34±7) years, with total burn area of 55%-98% [(89±15)%] total body surface area (TBSA) and full-thickness burn area of 45%-97% [(80±21)%] TBSA. All the 8 patients were accompanied with severe shock, inhalation injury, and blast injury. According to the requirements of former PLA General Logistics Department and Nanjing Military Command, a treatment team was set up including a special medical unit and a special care unit, with Chai Jiake from the First Affiliated Hospital of PLA General Hospital as the team leader, Zheng Qingyi from the 175th Hospital of PLA (the Affiliated Dongnan Hospital of Xiamen University) as the deputy leader, the 100th Hospital of PLA as the treatment base, and burn care, respiratory, nephrology, nursing specialists from the First Affiliated Hospital of PLA General Hospital, and the burn care experts and nursing staff from the 180th Hospital of PLA, 118th Hospital of PLA, 98th Hospital of PLA, and 175th Hospital of PLA, and nurses from the 85th Hospital of PLA, 455th Hospital of PLA, 101th Hospital of PLA, 113th Hospital of PLA as team members. Treatment strategies were adopted as unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns. With exception of one patient who received deep vein catheterization before admission, the other 7 patients were treated with deep vein catheterization 0.5 to 3.0 hours after admission to correct hypovolemic shock as soon as possible. Eight patients received tracheotomy, and 7 patients were treated with mechanical ventilation by ventilator in protective ventilation strategy with low tide volume and low volume pressure to assist breathing. Fiberoptic bronchoscopy was done one to three times for all the 8 patients to confirm airway injuries and healing status. Escharectomy and Meek dermatoplasty in the extremities of all the 8 patients were performed 3 to 6 days after injury for the first time. Escharectomy, microskin grafting, and covering of large pieces of allogeneic skin on the trunks of 4 patients were performed 11 to 16 days after injury for the second time. The broad-spectrum antibiotics were uniformly used at first time of anti-infective therapy, and then the antibiotics species were adjusted in time. The balance of internal environment was maintained and the visceral functions were protected. One special care unit was on responsibility of only one patient. Psychological intervention was performed on admission. The rehabilitative treatment was started at early stage and in company with the whole treatment. Results: Acute renal injury occurred in 5 patients within 36 hours after injury and their renal function was restored to normal 4 days after injury due to active adjustment of fluid resuscitation program. No pulmonary complications, such as severe pulmonary infection and ventilator-associated pneumonia, occurred in the survived patients. One of the 8 patients died, and the other 7 patients were cured successfully. The wounds were basically healed in 2 patients in 26 or 27 days by 2 or 3 times of operation, and in 5 patients by 4 or 5 times of operation. The basic wound healing time was 26-64 (48±15) days for all the 7 patients. Conclusions Treatment strategies of unified coordination by the superior, unified responsibility of team leader, division of labor and cooperation between team members, and multidisciplinary cooperation led by department of burns are the bases to successful treatment. Correcting shock as soon as possible is the prerequisite and closing wound as soon as possible is the key to successful treatment. Comprehensive treatment measures, such as maintaining and regulating the function of viscera, improving the body immunity, and preventing and treating the complications, are the important components to successful treatment. It is emphasized that in the treatment of mass extremely severe burn patients, specialist burn treatment should always be in the dominant position, and other related disciplines may play a part in auxiliary function.

OBJECTIVE: To explore the relationship between extend types and distant metastasis of nasopharyngeal carcinoma (NPC). METHOD: Retrospective analyze 260 patients with nasopharyngeal carcinoma, among which 162 cases were distant metastasis (metastasis group) and 98 cases were neither distant metastasis nor recurrence (disease-free group) over 5 years after radiotherapy. All these patients were staged depending on CT or MRI image before treatment and divided into local-regional type(T(1-2)N(0-1)) for 36 cases and upward invasion type (T(3-4)N(0-1)) for 68 cases and downward invasion type (T(1-2)N(2-3)) for 75 cases and mixed type (T(3-4)N(2-3)) for 81 cases. The differences between two groups was analyzed using Chi-square test. RESULT: The local-regional type and upward invasion type was 25.3% for the metastasis group and 64.3% for the disease-free group. The downward and mixed invasion was 74.7% for the metastasis group and 35.7% for the disease-free group. The rate(proportion) of N(2-3) was significantly higher in metastasis group than in disease-free group with limited extension (84.4% vs. 33.3%, P < 0.01). The rates(proportion) of N(0-1) and N(2-3) were also significantly higher in metastasis group than in disease-free group with severity extension (T(3-4) (60% vs. 36.1% and 68.4% vs. 40%, P < 0.01). CONCLUSION The extent of cervical lymph node metastases is one of the most important factors of NPC with distant metastasis, severity extension of primary disease should also be in consideration. Even the limitations of primary disease, once cervical lymph node metastasis occurs, the risk of distant metastasis is significantly increased.
Adolescent ; Adult ; Aged ; Carcinoma ; Female ; Humans ; Lymph Nodes ; pathology ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Carcinoma ; Nasopharyngeal Neoplasms ; pathology ; Neck ; Neoplasm Metastasis ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Young Adult

This paper is to introduce our experiences in treating 2 batches of 13 burn victims transferred from remote areas on postburn days 3 and 4. Methods Thirteen burn victims of 2 mass casualties were transferred to our burns institute from remote areas on postburn days 3 and 4 on June 27, 2001 and June 2, 2002, respectively. There were 4 males and 9 females, age ranged from 20 to 43 years, with a mean age of 31.1±6.2 years. The mean total burn area was 74.3%±24.7% TBSA (range, 25% to 97%). Among them, 10 patients suffered from serious burn with mean total burn area involving 86.0%±11.5% TBSA (range, 60% to 97%), and mean full-thickness burn of 63.9%±26.3% TBSA. Four patients also manifested signs of severe inhalation injury, and 6 patients with moderate inhalation injury. In three patients with mean total burn area covering 35.5%±10.0% TBSA (range, 25% to 45%), with mean full-thickness burn of 15.3%±5.0%, were al having moderate inhalation injuries. Among these 13 patients, 3 were having high body temperature (39℃), while 3 manifested hypothermia. The heart rate was 140-160/min, and respiratory rate 26 to 32/min in 6 patients. Abdominal distension or loss of bowel sound were found in 4 patients. Low white cell and platelet count were found in some patients. In 13 cases, liver function, renal function, myocardiac enzyme, and coagulation function were abnormal. Results Among 13 burn victims, one patient died of myocarditis on postburn day 29, and another one died of hepatic failure (history of chronic hepatitis B) on postburn day 45 with only 2% TBSA of burn wound remained open. Conclusion Burns victims occurred in mass casualties who were transferred from remote areas to our Burns Institute were all in critical condition, usually with multiple complications, demanding most meticulous care. Our strategies in this regard consisted of dispatch of experienced surgeons and nurses to the referring hospitals and the airport to receive the patients to offer appropriate care to them during the journey,organization of the medical staff so that each of them was ordained specific function, thus conditions of the patients were evaluated immediately and appropriate treatment started expeditiously for those lethal complications on arrival. Timely and exact comprehensive treatments were prerequisite to save the patients’ life. Adequate metabolic support should be emphasized, and coagulant of anticoagulant treatment should be carried out when indicated.

Objective To investigate the clinical characteristics of invasive bum wound infection with sepsis in patients with major burns and to summarize the successful expenences in the treatment of such patients. Methods Eight patients with major bums, complicated by invesive bum wound infection and sepsis were consecutively admitted to our hospital from September 1997 to October 1998. Among them, 6 patients developed multiple organ dysfunction syndrome (MODS) and 2 developed septic shock. The plasma concentrations of IL-6,IL-8,TNFα and lypopolysaccharibe (LPS) were assayed before and after surgical intervention, as well as when the patient' s vital signs became stable. Results The patients' conditions usually deterieorated abruptly when extensive invasive bum wound infection emerged. While multi-microbial infection was usually found, Pseudomonas aeruginosa was the predominant bactena isolated from the subeschar tissue. The plasma concentrations of IL-6, IL-8, TNFα and LPS before surgical intervention wore significantly higher than those after surgical intervention (P＜0.05).The lowest levels of the inflammatory mediators were abserved when the patients'conditions became stable,and the values were significantly lower than those before surgical intervention ( P＜0.001). Conclusion Since the main cause of burn wound sepsis is the presence of a large area of infected bum wound, they should be excised and covered as early as possible. LPS and pro-inflammatory mediators play an important role in the pathogenesis of burn sepsis. Athough favorable results should be attributed to compmhessive treatment, we believe that early, aggressive and thorough surgical excision of infected burn wounds, followed by sound and complete coverage of the area, play a crucial role.

5 mm) had a significant influence on the frequency and distribution of cervical lymph node metastasis. The local recurrent rate in palpable lymph node group was significantly higher than the non-palpable lymph node group. Conclusions Careful palpation, B type ultrasonography, exploratory operation and frozen section are very important factors to heighten diagnosis of PTMC. We believe that PTMC could be divided into two subsets: with the former of non-aggressive behaviors treated by conservative surgery, and the later of a potentially aggressive clinical course treated by a more aggressive procedure.