This study reports the diagnosis and treatment of a 26-year-old pregnant woman with severe malnutrition combined with acute pyelonephritis causing sepsis, refractory septic shock and multiple organ failure. A female patient, 26 years old, was admitted to hospital mainly due to "menelipsis for more than 19 weeks, nausea and vomiting for 20 days, fever with fatigue for 3 days". At the end of 19 weeks of intrauterine pregnancy, the patient presented with fever accompanied by urinary tract irritation. Laboratory tests showed elevated inflammatory indicators, and ultrasonography showed bilateral pelvicalyceal dilation. She was diagnosed with acute pyelonephritis, sepsis, acute kidney injury (AKI) and severe malnutrition. After a whole-hospital consultation, the patient was treated with meropenem and vancomycin as antimicrobial therapy, and bilateral nephrostomy drainage was performed simultaneously. After that, the patient suffered a sudden decrease in blood pressure, blood oxygen saturation, and rapid heart rate. Septic shock with multiple organ dysfunction was considered, and she was transferred to intensive care unit (ICU) immediately. After the patient was transferred to ICU, emergency tracheal intubation and ventilator-assisted ventilation were performed. Rapid fluid resuscitation was administered for the patient. While pulse indicator continuous cardiac output (PICCO) monitoring was performed, norepinephrine, terlipressin, and methylene blue were administered to maintain peripheral vascular resistance. Since the patient developed septic cardiomyopathy and cardiogenic shock later, levosimendan and epinephrine were admi-nistered to improve cardiac function. While etiological specimens were delivered, meropenem, teicoplanin and caspofungin were given as initial empiric antimicrobial therapy. Unfortunately, the intrauterine fetal death occurred on the night of admission to ICU. On the 3rd day of ICU admission, a still-born child was delivered vaginally with 1/5 defect of the fetal membrane. On the 6th day of ICU admission, the patient had fever again with elevated inflammatory indicators. After excluding infection in other parts, intrau-terine infection caused by incomplete delivery of fetal membrane was considered. Then emergency uterine curettage was performed and the infection gradually improved. Later the laboratory results showed that the nephrostomy drainage was cultured for Escherichia coli and uterine, cervical and vaginal secretions were cultured for Candida albicans. Due to severe infection and intrauterine incomplete abortion, the patient developed disseminated intravascular coagulation (DIC). Active antimicrobial therapy and blood product supplement were given. However, the patient was critically ill with significant decrease in hemoglobin and platelets combined with multiple organ failure. Thrombotic microangiopathy (TMA) was not excluded yet, so plasma exchange was performed for the patient in order not to delay treatment. The patient underwent bedside continuous renal replacement therapy (CRRT) for AKI. The patient was complicated with acute liver injury, and the liver function gradually returned to normal after liver protection, antimicrobial therapy and other treatments. Due to the application of large doses of vasoactive drugs, the extremities of the patient gradually developed cyanosis and ischemic necrosis. Local dry gangrene of the bilateral toes remained at the time of discharge. In general, the patient suffered from septic shock, cardiogenic shock, combined with DIC and multiple organ dysfunction. After infection source control, antimicrobial therapy, uterine curettage, blood purification treatment, nutritional and metabolic support, the patient was discharged with a better health condition.
Humans ; Female ; Pyelonephritis/complications* ; Pregnancy ; Adult ; Multiple Organ Failure/etiology* ; Shock, Septic/etiology* ; Sepsis/etiology* ; Pregnancy Complications ; Pregnancy Complications, Infectious ; Malnutrition/complications*

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

Cognitive dysfunction caused by blast traumatic brain injury (bTBI) is a serious neurological disease with high incidence, serious condition and poor prognosis. bTBI can lead to a series of symptoms such as short-term memory loss, inattention or multi-tasking difficulties. In severe cases, bTBI can develop into Alzheimer′s disease, which has a great impact on patients′ normal work and life. At present, researches on cognitive dysfunction caused by bTBI mainly involve model construction, pathogenesis, pathophysiological changes, diagnosis and treatment, etc., and the molecular mechanism of its occurrence remains to be further studied. Under normal physiological conditions, the release of excitatory and inhibitory neurotransmitters, the release and uptake of Ca 2+, oxidation and antioxidant systems, and the promotion and inhibition of apoptosis are in a dynamic balance. bTBI disturbs the balance, which will lead to the damage of nerve cells at the molecular level, thus resulting in the occurrence of cognitive dysfunction. To this end, the authors summarized the aspects of excitatory toxicity and Ca 2+homeostasis disorder, oxidative stress, inflammation and edema, apoptosis, etc., and reviewed the research progress on the molecular mechanism of cognitive dysfunction caused by bTBI, so as to provide a reference for the treatment and rehabilitation of cognitive dysfunction in patients with bTBI.

Background::Gastric cancer (GC), a malignant tumor with poor prognosis, is one of the leading causes of cancer-related deaths worldwide; consequently, identifying novel therapeutic targets is crucial for its corresponding treatment. NUF2, a component of the NDC80 kinetochore complex, promotes cancer progression in multiple malignancies. Therefore, this study aimed to explore the potential of NUF2 as a therapeutic target to inhibit GC progression. Methods::Clinical samples were obtained from patients who underwent radical resection of GC at Lanzhou University Second Hospital from 2016 to 2021. Cell count assays, colony formation assays, and cell-derived xenotransplantation (CDX) models were used to determine the effects of NUF2 on GC progression. Flow cytometry was used to detect the effect of NUF2 or quercetin on cell cycle progression and apoptosis. A live-cell time-lapse imaging assay was performed to determine the effect of NUF2 on the regulation of mitotic progression. Transcriptomics was used to investigate the NUF2-associated molecular mechanisms. Virtual docking and microscale thermophoresis were used to identify NUF2 inhibitors. Finally, CDX, organoid, and patient-derived xenograft (PDX) models were used to examine the efficacy of the NUF2 inhibitor in GC. Results::NUF2 expression was significantly increased in GC and was negatively correlated with prognosis. The deletion of NUF2 suppressed GC progression both in vivo and in vitro. NUF2 significantly regulated the mitogen-activated protein kinase (MAPK) pathway, promoted G2/M phase transition, and inhibited apoptosis in GC cells. Additionally, quercetin was identified as a selective NUF2 inhibitor with low toxicity that significantly suppressed tumor growth in GC cells, organoids, CDX, and PDX models. Conclusions::Collectively, NUF2-mediated G2/M phase transition and apoptosis inhibition promoted GC progression; additionally, NUF2 inhibitors exhibited potent anti-GC activity. This study provides a new strategy for targeting NUF2 to suppress GC progression in clinical settings.

Objective:To understand the current situation of spiritual nursing needs in elderly patients with primary glaucoma and its influencing factors, and to analyze its relationship with self-perceived burden and perceived social support, so as to provide a theoretical basis for reducing their spiritual distress and pain and meeting their spiritual nursing needs.Methods:A total of 218 elderly patients with primary glaucoma who were hospitalized in the department of ophthalmology of the First Hospital of Jilin University from March to September, 2022 were selected by convenience sampling. They were investigated by using general information questionnaire, the Nurse Spiritual Therapeutics Scale, the Self-Perceived Burden Scale, and the Perceived Social Support Scale. And multiple linear regression was used to analyze the influencing factors of spiritual nursing needs among elderly patients with primary glaucoma.Results:The total score of spiritual nursing needs of elderly patients with primary glaucoma was (30.73 ± 4.85). The highest dimension of item average score was "building a good atmosphere" (3.02 ± 0.59), and the lowest dimension was "helping religious practice" (1.95 ± 0.63). The total scores of spiritual nursing needs and self-perceived burden were negatively correlated ( r=-0.423, P<0.01), and positively correlated with the total scores of perceived social support ( r=0.515, P<0.01). Multivariate linear regression analysis showed that age, religious belief, educational level, treatment duration, residence, self-perceived burden, and perceived social support were the main influencing factors of spiritual care needs of elderly patients with primary glaucoma, ( t values were -5.23-7.04, all P<0.01), which could explain 44.5% of the total variation. Conclusions:The spiritual nursing needs of elderly patients with primary glaucoma were at a medium level. Therefore, it is recommended that nurses should carry out targeted spiritual nursing for them according to the differences and characteristics of different patients, to reduce their self-perceived burden, and to improve perceived social support level, in order to meet their spiritual nursing needs.

Objective To explore the safety and efficiency of robot-assisted laparoscopic resection of pediatric adrenal region masses.Methods Six cases with adrenal region mass underwent robot-assisted laparoscopic adrenalectomy(RALA)from October 2019 to March 2022 in our hospital by using the da Vinci Robotic Surgery System.The patient was routinely placed in the 60°position on the healthy side.Two robotic arms were used to operate,and additional auxiliary operation holes were added as needed.The tumor was revealed by the combination of sharp and blunt separation,and the tumor trophoblastic vessels were identified.The tumor vessels were isolated by clamping with silk wire or biological clips.The tumor was fully freed and excised completely.Smaller specimens were removed by a slightly enlarged operation hole,and larger specimens were removed by another incision in the lower abdomen.Results All the 6 cases of procedures were successfully performed without conversion to open surgery.The operative duration was 90-240 min(mean,133.3 min),and the blood loss was 15-50 ml(mean,31.7 ml).In 2 cases,the drainage tube was not placed.In the remaining 4 cases,the indwelling time of the drainage tube after surgery was 4-8 d(mean,5.5 d).The postoperative hospital stay was5-15 d(mean,8.7 d).There were no complications except for one patient with postoperative bleeding.All the patients were followed up for 10-24 months(mean,16.7 months).CT examinations showed no recurrence of tumors.Conclusion Robotic-assisted laparoscopic resection of pediatric adrenal region masses is safe with satisfactory results.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

【Objective】 To investigate the penile appearance, sexual function, psychological status and related influencing factors of adult patients who underwent hypospadias repair surgery in their minors, so as to provide reference for the diagnosis, treatment and prognosis of hypospadias. 【Methods】 This study included 50 adult hypospadias patients who underwent urethroplasty in our hospital during May 2005 and Aug. 2018. The present appearance, sexual function and psychological status were evaluated. The correlation and consistency between hypospadias objective scoring evaluation (HOSE) and pediatric penile perception score (PPPS) were analyzed. Factors affecting the results were determined with univariate and multivariate regression analysis. 【Results】 The satisfaction rate of HOSE was significantly correlated with the urethral length and complications (P=0.024, P=0.033). The satisfaction rate of PPPS was significantly correlated with the number of urethral operations and postoperative complications (P=0.041, P=0.023). There was a weak correlation between HOSE and PPPS (r=0.291, P=0.040), but almost no consistency (Kappa=0.2, P=0.107). Sixty percent of the patients paid attention to the ventral appearance of penis, whose dissatisfaction rate of PPPS was higher than those who did not pay attention to the ventral appearance of the penis (19/30 vs. 6/20, P=0.021). Patients with multiple operations (>1), postoperative complications or unsatisfactory penile appearance were more likely to have inferiority complex (52.6% vs. 22.6%, P=0.029; 59.1% vs.14.3%, P=0.001;61.5% vs. 24.3%, P=0.015). Multivariate regression analysis showed that dissatisfaction with the appearance of the penis was an independent risk factor for patients’ perception of their own physical defects. Among the patients who believed that they had physical defects, the percentage of patients with grade IV penile erectile hardness was significantly lower than that of those who denied they had physical defects (9/17 vs. 27/33, P=0.047). 【Conclusion】 The undesirable postoperative penis appearance is likely to have a negative impact on patients’ long-term psychological state, which might further damage the sexual function in adulthood. Surgeons should pay attention to the penile appearance during the conduction of hypospadias repair.

【Objective】 To explore the effects of nerve growth factor （NGF） on bladder function and axon injury repair in rats with traumatic spinal cord injury （t-SCI） so as to explore its molecular mechanism. 【Methods】 Traumatic spinal cord injury model was constructed in 30 male SD rats by modified Allen’s beating method. The rats were randomly divided into sham-operation group， injury group and NGF group， with 10 rats in each group. We used the BBB score to observe the motor function of the rats’ hind limbs before and after the operation. The BL-420 biometer experimental system detected the urodynamics. Six anterior roots of the left lumbar taken from the distal end of the anastomosis were stained with toluidine blue， and the number of myelinated axons was counted. We used HE to stain rat bladder tissue， TUNEL to stain the rats’ severely injured spinal cord， and observed the spinal cord apoptosis rate. Western blotting was used to detect the protein expressions of Raf-1， p-MEK-2， MEK-2， ERK1/2， and p-ERK1/2 in spinal cord tissue. 【Results】 The BBB score results showed that there was no difference in the scores of the sham-operation group， the injury group and the NGF group before the operation. After the operation， the scores of the injury group and the NGF group were significantly lower than those in the sham-operation group （P<0.05）. The maximum detrusive pressure and the number of axons were significantly lower in the injury group than in the sham-operation group and the NGF group （P<0.05）， but the residual urine volume and bladder cell apoptosis rate in the injury group were notablely higher than those in the other two groups （P<0.05）. HE staining results showed that bladder edema in the injury group was severe and the detrusor muscle structure was loose， while the NGF group had reduced bladder injury. Western blot results showed that the protein ratio of p-ERK1/2/ERK1/2 and p-MEK-2/MEK-2 and the expression of Raf-1 in the injury group were significantly higher than those in the sham operation group and NGF group （P<0.05）. However， there was no significant difference between the sham operation group and the NGF group in maximum detrusive pressure， the number of myelin axons， residual urine volume， bladder cell apoptosis rate， or protein （P>0.05）. 【Conclusion】 NGF may hinder the conduction of MAPK/ERK pathway， thereby affecting the repair of axon damage and improving the bladder function of t-SCI rats.