Patients with severe pneumonia caused by novel coronavirus infection are often complicated with acute respiratory distress syndrome (ARDS), which has a high mortality. ARDS is characterized by diffuse alveolar damage, pulmonary edema, and hypoxemia. Mitochondria are prone to morphological and functional abnormalities under hypoxia and viral infection, which can lead to cell apoptosis and damage, severely impacting the disease progression. Mitochondria maintain homeostasis through fission and fusion. In ARDS, hypoxia leads to the phosphorylation of dynamin-related protein 1 (Drp1), triggering excessive mitochondrial fission and damaging the alveolar epithelial barrier. Animal experiments have shown that inhibiting this process can alleviate lung injury, providing a potential direction for treatment. The pathology of novel coronavirus infection-related ARDS is similar to that of typical ARDS but more severe. Viral infection and hypoxia disrupt the mitochondrial balance, causing fission and autophagy abnormalities, promoting oxidative stress and mitochondrial DNA (mtDNA) release, activating inflammasomes, inducing the expression of hypoxia-inducible factor-1α (HIF-1α), exacerbating viral infection, inflammation, and coagulation reactions, and resulting in multiple organ damage. Mechanical ventilation and glucocorticoids are commonly used in the treatment of novel coronavirus infection-related ARDS. Mechanical ventilation is likely to cause lung and diaphragm injuries and changes in mitochondrial dynamics, while the lung protective ventilation strategy can reduce the adverse effects. Glucocorticoids can regulate mitochondrial function and immune response and improve the patient's condition through multiple pathways. The mitochondrial dynamics imbalance in novel coronavirus infection-related ARDS is caused by hypoxia and viral proteins, leading to lung and multiple organ injuries. To clarify the pathophysiological mechanism of mitochondrial dynamics imbalance in novel coronavirus infection-related ARDS and explore effective strategies for regulating mitochondrial dynamics balance to treat this disease, so as to provide new treatment targets and methods for patients with novel coronavirus infection-related ARDS. The existing treatments have limitations. Future research needs to deeply study the mechanism of mitochondrial dysfunction, develop new therapies and regulatory strategies, and improve the treatment effect.
Humans ; Respiratory Distress Syndrome/etiology* ; COVID-19 ; Mitochondrial Dynamics ; Mitochondria/metabolism* ; DNA, Mitochondrial ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Dynamins ; SARS-CoV-2

Objective:To investigate the efficacy and safety of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis.Methods:A retrospective analysis was carried out on 46 patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis who received endovascular treatment at the Strategic Support Force Medical Center from January 2015 to August 2022. Twenty-seven patients underwent balloon angioplasty alone and 19 patients underwent acute stent implantation. The baseline characteristics, modified thrombolysis in cerebral infarction (mTICI) score of the responsible vessels, modified Rankin scale (mRS) score 90 days after operation, incidence of symptomatic intracranial hemorrhage and mortality of the two groups were evaluated.Results:The proportion of effective recanalization of the offending vessels (mTICI≥2b) in the acute stenting group was slightly higher than that in the balloon angioplasty group (16/19 vs. 81.5%), but the difference was not statistically significant ( P>0.05). Besides, there was no significant difference in the median of mRS between the acute stenting group [3.0(0, 4.0)] and the balloon angioplasty group [4.0(1.0, 5.0)] 90 days after operation ( P>0.05). In terms of safety, the incidence of symptomatic intracranial hemorrhage and mortality were comparable between the two groups ( P>0.05). Conclusions:The effect of acute stent implantation during endovascular treatment for patients with emergent large vessel occlusion due to intracranial atherosclerotic stenosis is not inferior to that of balloon angioplasty, and it does not increase the risk of intracranial bleeding complications.

Objective:To investigate the efficacy and safety of different transcatheter arterial chemoembolization(TACE)-based regimens in patients with unresectable hepatocellular carcinoma(uHCC)and explore the optimal timing for combining TACE with tyrosine kinase inhibit-ors(TKIs)and immune checkpoint inhibitors(ICIs).Methods:A retrospective analysis was conducted on data from 555 patients with uHCC who underwent TACE-based treatment between April 2016 and December 2021 in Nanfang Hospital,Southern Medical University.The pa-tients were assigned into the following four groups according to different treatment regimens:TACE group(n=317),TACE combined with TKIs group(TACE+TKIs,n=66),TACE combined with ICIs group(TACE+ICIs,n=33),and TACE combined with TKIs+ICIs group(TACE+TKIs+ICIs,n=139).Subgroup analysis was performed within the TACE+TKIs+ICIs group,with patients being assigned into"pre-TACE"and"post-TACE"groups based on the timing of the combination therapy.Univariate and multivariate Cox regression analyses were conducted to identify pro-gnostic factors influencing overall survival(OS).Results:The TACE+TKIs+ICIs group showed the longest OS(21.9 months,95%confidence in-terval[CI]:17.2-26.6,P=0.030)and progression-free survival(PFS)(8.3 months,95%CI:7.3-9.3,P=0.004)compared to those in the other three groups.In the subgroup analysis,the"post-TACE"group had longer OS than the"pre-TACE"group(26.8 months vs.19.2 months,P = 0.011).The objective response rate(ORR)was 32.8%,41.1%,42.4%,and 52.5%(P=0.001)and the disease control rate(DCR)was 59.6%,71.2%,69.7%,and 82.7%(P<0.001)in the TACE,TACE+TKIs,TACE+ICIs,and TACE+TKIs+ICIs groups,respectively.The adverse events were similar to those reported in previous studies.Cox regression analysis revealed that tumor number,extrahepatic metastasis,and treatment regimen were independent factors influencing OS in patients(all P<0.05).Conclusions:TKIs or ICIs can improve OS and PFS in patients with uHCC receiving TACE,and the combination of TKIs+ICIs with TACE achieves better beneficial outcomes.The greatest OS was observed when the combination therapy TKIs+ICIs was initiated within 3 months after the first TACE procedure.

Objective:To analyze the clinical adverse events of the first carbon ion therapy system in radiotherapy for cancer patients in China.Methods:A retrospective analysis was conducted on the clinical trial monitoring data of the carbon ion therapy system obtained by the Pharmacovigilance Center of Gansu Province. A descriptive study was conducted on the demographic characteristics, radiotherapy techniques, irradiation site and dose parameters, postoperative follow-up, and adverse event information of 46 tumor patients who received carbon ion therapy and participated in the clinical trial in Wuwei Cancer Hospital, Gansu Province from November 2018 to February 2019. Frequency and percentage were used to describe and analyze the occurrence of adverse events after carbon ion therapy for cancer patients in different groups. All subjects who received radiotherapy were grouped according to the treatment dose and fractionation method.Results:The median age of the 46 patients was 47 years old, and the male to female ratio was 30∶16. There were 15, 5, 8, 9, and 9 patients with head and neck, chest, abdomen, pelvic cavity, and limb spinal tumors, respectively. The total duration of radiotherapy was 2-4 weeks for 10-16 times. There were 246 adverse events in 45 cases, with an incidence of 98%. No severe adverse events occurred. The adverse events definitely related to carbon ion devices accounted for 19.1%, and no severe adverse events related to carbon ion devices occurred. According to the evaluation criteria of common terminology criteria for adverse events (CTCAE), the main adverse events were CTCAE grade 2 and below, with only 1 (2%) head and neck tumor patient (nasopharyngeal malignant tumor) experienced CTCAE grade 3 adverse events after treatment. In addition, 43 patients developed acute adverse reactions, with an incidence of 93%, mainly involving the skin, mucosa, eyes, ears, pharynx and esophagus, upper gastrointestinal tract, lower gastrointestinal tract (including pelvic cavity), lung, genitourinary tract, heart, central nervous system and hematology (white blood cells, platelets and neutrophils), etc. Conclusion:The adverse reactions of patients treated with the first carbon ion therapy system are mainly CTCAE grade 2 and below, and the clinical adverse events are mild and controllable.

Objective:To explore the effect of the problem-originated clinical medical curriculum (PCMC) combined with feedback theory in nursing teaching of the Department of Endocrinology.Methods:From January 2018 to January 2020, convenience sampling method was used to select 150 nurses who interned in the Department of Endocrinology of Shanxi Provincial People's Hospital as the research subjects. The control group consisted of 76 nurses who interned from January 2018 to January 2019, and the observation group consisted of 74 nurses who interned from February 2019 to January 2020. The control group was taught using traditional teaching methods, while the observation group implemented PCMC combined with feedback theory on the basis of the control group. Before and after intervention, nursing assessment results, nursing ability and teaching satisfaction were compared between the two groups.Results:After intervention, the scores of theoretical knowledge, clinical practice, specialized nursing, job responsibility of the two groups were higher than those before intervention, and the scores of the observation group were higher than those of the control group, with statistically significant differences ( P<0.05). After intervention, the scores of problem detection, emergency response, problem-solving, and team collaboration of the two groups were higher than those before intervention, and the scores of the observation group were higher than those of the control group, with statistically significant differences ( P<0.05). After intervention, the satisfaction scores of nursing teaching content, teaching form, teaching attitude, and teaching ability of the observation group were higher than those of the control group, with statistical differences ( P<0.05) . Conclusions:PCMC combined with feedback theory applied in nursing teaching of the Department of Endocrinology shows good application effects, which can improve the nursing teaching effectiveness of the Department of Endocrinology and the satisfaction of intern nurses. It is worthy of clinical promotion and practice.

Objective To explore risk factors for developing neurogenic heterotopic ossification (NHO) after traumatic brain injury (TBI).Methods Thirty-three patients suffering from TBI no more than 6 months and admitted to Guangdong Work Injury Rehabilitation Hospital between December 2015 and December 2016 were selected.Those with and without NHO was assigned to an NHO group (n =12) and a control group (n =21) respectively.The two groups were compared in terms of the duration of coma and mechanical ventilation,the time to start rehabilitation and the occurrence of infection,pressure ulceration,deep vein thrombosis (DVT) or inflammation.Muscle tension,white blood cell (WBC) count,erythrocyte sedimentation rate (ESR),high sensitivity creactive protein (hsCRP) and alkaline phosphatase (ALP) were also measured.Independent sample T tests,chi-squared tests and binary logistic regression were used to compare the two groups seeking to isolate risk factors for NHO which might be predictive.Results Significantly prolonged coma and/or mechanical ventilation were observed in NHO group compared to the control group.Significant differences were also found in the average WBC,ESR,hsCRP and ALP levels,as well as in the occurrence of infection,DVT and inflammatory symptoms between the two groups.The incidences of infection,DVT and inflammatory reaction were higher in the NHO group,as were the levels of leukocyte,ESR,hsCRP and ALP.Those differences between the groups were statistically (and of course clinically) significant.The duration of coma and mechanical ventilation,infection,DVT,inflammation,and elevated levels of leukocytes,ESR or ALP can all usefully be considered risk factors for NHO,with infection,DVT and inflammation of the highest importance.Conclusion Duration of coma and utilization of mechanical ventilation,infection,DVT,inflammation,as well as an increase of leukocytes,ESR or ALP should be considered as risk factors for NHO after TBI.

OBJECTIVE:To reduce drug repercussion of outpatient pharmacy,and to promote safe drug use.METHODS:By quality control circle (QCC),the data of drug repercussion were selected from outpatient pharmacy of our hospital in Sept.2016.The drug repercussion reason check list was designed to master the situation of drug repercussion in outpatient department,formulate improvement measures and confirm effect through field inspection.The case number of drug repercussion and the improvement of circle members' ability were compared one month before and after QCC (Mar.2017).Finally,the effects of QCC were evaluated.RESULTS:Referring to the reasons for the repercussion of adjunct drugs for inspection and the repercussion of unsuitable drug use in our hospital,those problems were improved by formulating manual for drug use examination project,optimizing and examining drug delivery process in the department,etc.The case number of drug repercussion in outpatient pharmacy decreased from 31 cases per month to 12 cases per month;the rate of goal achievement was 119％;the rate of improvement was 61％.The ability of QCC members to solve problems and the ability to use QCC skills were increased positively.CONCLUSIONS:The development of QCC activity in our hospital reduces case number of drug repercussion and optimizes drug delivery process in outpatient pharmacy,and promotes safe drug use.

Objective To evaluate the efficacy of a sustained releasing mosquito larvicide package against larval breeding and its impact on water and plant,in order to provide a scientific evidence for its application in control and prevention of Dengue.Methods Guangzhou Center for Disease Control and Prevention was chosen as the test place.Twenty test sites were set up,2 bags of sustained releasing larvicides package,1 bag of sustained releasing larvicides package,3 g 1％ temephos granules and nothing were put into 4 glass bottles for each test site from July to December in 2014,respectively.The 4 glass bottles were called high dose (H) group,low dose (L)group,positive control (P) group and blank control (B) group,respectively.The 4 groups were observed at intervals of 10 days for 19 times.Environmental air temperature,turbidity of water,number of larvae and damage of plant were recorded.And 5 test sites were selected to collect water specimen.The chemical oxygen demand,ammonia nitrogen concentration and temephos concentration of water specimen were detected.Results The larval breeding rates were 0 (0/380),1.1％ (4/380),0.8％ (3/380) and 63.4％ (241/380),damage rates of plant were 5.0％ (19/380),5.5％ (21/380),4.7％ (18/380),4.7％ (18/380) and turbidty rates of water were 24.5％ (93/380),19.7％ (75/380),33.4％ (127/380) and 20.3％ (77/380) in H,L,P and B groups,respectively.Statistically significant differences were seen in larval breeding rate and turbidity rate of water between different groups (x2 =823.565,24.715,all P ＜ 0.05),but they were not seen in damage rate of plant (x2 =0.332,P ＞ 0.05).The temephos concentrations were 1.24,0.78 and 2.33 mg/L in H,L and P groups,respectively.Statistically significant differences were seen in temephos concentration between different groups (H =35.426,P ＜ 0.01),but they were not seen in chemical oxygen demand and ammonia nitrogen concentration (H =0.239,0.013,all P ＞ 0.05).Conclusions The sustained releasing package of mosquito larvicide makes less pollution to water and has no impact on water turbidity.Moreover,it doesn't damage the aquatic plant.The efficacy of the sustained releasing package of mosquito larvicide could effectively prevent mosquito larval breeding in Dengue epidemic period.

Objective To evaluate the safety and clinical efficacy of stereotactic body radiation therapy (SBRT) for lung cancer.Methods A retrospective analysis was performed on 200 patients with primary non-small cell lung cancer (NSCLC)(118 patients) or solitary pulmonary metastasis (82 patients) who underwent SBRT in Zhejiang Cancer Hospital from January 2012 to September 2015.The 80% isodose line covered 95% of the planning target volume,and the 100% isodose line covered 100% of the internal gross tumor volume.The fractional dose was 4.0-18.0 Gy daily or every other day,and the biologically equivalent dose ranged from 40.0 to 151.2 Gy (median 100 Gy).Results All patients completed treatment.The follow-up rate was 96.0%.The complete response and partial response rates were 14.8%(17/115) and 65.2%(75/115) for the primary tumor group,versus 25%(19/77) and 38%(29/77) for the metastasis group.The incidence rates of grade Ⅱ and Ⅲ acute radiation pneumonitis were 4.7% and 3.1%,respectively.The median follow-up was 14.9 months.The 1-and 2-year local control rates were 95.7% and 84.3% for the primary tumor group,versus 92% and 73% for the metastasis group.The 1-and 2-year overall survival rates were 94.5% and 92.0% for the primary tumor group,versus 85% and 62% for the metastasis group.Conclusions SBRT is a safe and effective treatment for early primary NSCLC and solitary pulmonary metastasis,resulting in high 1-and 2-year local control and overall survival rates and low rate of complications.

BACKGROUNDVon Hippel-Lindau (VHL) disease is a hereditary tumor disorder caused by mutations or deletions of the VHL gene. Few studies have documented the clinical phenotype and genetic basis of the occurrence of VHL disease in China. This study armed to present clinical and genetic analyses of VHL within a five-generation VHL family from Northwestern China, and summarize the VHL mutations and clinical characteristics of Chinese families with VHL according to previous studies.

METHODSAn epidemiological investigation of family members was done to collect the general information. A retrospective study of clinical VHL cases was launched to collect the relative clinical data. Genetic linkage and haplotype analysis were used to make sure the linkage of VHL to disease in this family. The VHL gene screening was performed by directly analyzing DNA sequence output. At last, we summarized the VHL gene mutation in China by the literature review.

RESULTSA five-generation North-western Chinese family afflicted with VHL disease was traced in this research. The family consisted of 38 living family members, of whom nine were affected. The individuals afflicted with VHL exhibited multi-organ tumors that included pheochromocytomas (8), central nervous system hemangioblastomas (3), pancreatic endocrine tumors (2), pancreatic cysts (3), renal cysts (4), and paragangliomas (2). A linkage analysis resulted in a high maximal LOD score of 8.26 (theta = 0.0) for the marker D3S1263, which is in the same chromosome region as VHL. Sequence analysis resulted in the identification of a functional C>T transition mutation (c. 499 C>T, p.R167W) located in exon 3 of the 167 th codon of VHL. All affected individuals shared this mutation, whereas the unaffected family members and an additional 100 unrelated healthy individuals did not. To date, 49 mutations have been associated with this disease in Chinese populations. The most frequent VHL mutations in China are p.S65 W, p.N78 S, p.R161Q and p.R167 W.

CONCLUSIONSThe results supported the notion that the genomic sequence that corresponds to the 167 th residue of VHL is a mutational hotspot. Further research is needed to clarify the molecular role of VHL in the development of organ-specific tumors.

Adolescent ; Adult ; Asian Continental Ancestry Group ; China ; Female ; Haplotypes ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Pedigree ; Retrospective Studies ; Von Hippel-Lindau Tumor Suppressor Protein ; genetics ; Young Adult ; von Hippel-Lindau Disease ; diagnosis ; genetics