A major impedance to neuronal regeneration after peripheral nerve injury(PNI)is the activation of various programmed cell death mechanisms in the dorsal root ganglion.Ferroptosis is a form of pro-grammed cell death distinguished by imbalance in iron and thiol metabolism,leading to lethal lipid peroxidation.However,the molecular mechanisms of ferroptosis in the context of PNI and nerve regeneration remain unclear.Ferroportin(Fpn),the only known mammalian nonheme iron export protein,plays a pivotal part in inhibiting ferroptosis by maintaining intracellular iron homeostasis.Here,we explored in vitro and in vivo the involvement of Fpn in neuronal ferroptosis.We first delineated that reactive oxygen species at the injury site induces neuronal ferroptosis by increasing intracellular iron via accelerated UBA52-driven ubiquitination and degradation of Fpn,and stimulation of lipid peroxidation.Early administration of the potent arterial vasodilator,hydralazine(HYD),decreases the ubiquitination of Fpn after PNI by binding to UBA52,leading to suppression of neuronal cell death and significant ac-celeration of axon regeneration and motor function recovery.HYD targeting of ferroptosis is a promising strategy for clinical management of PNI.

Objective: To design the proficiency testing (PT) project (No. NIFDC-PT-183) for assays of bismuth potassium citrate capsules and organize to assess the proficiency of complexometric titration in laboratories, and provide some technical analyses and advices.
Methods: Two groups of samples with different concentration were prepared. The uniformity was evaluated with one-way analysis of variance and the stability was confirmed with t-test, whose results all conformed the requirements. The samples with three combinations were randomly distributed to 279 laboratories. The determination was performed according to the assays of bismuth potassium citrate capsules in Volume Ⅱ of the Chinese Pharmacopoeia 2015. The median value and normalized interquartile range (NIQR) of robust statistical analysis was adopted and Z-scores were used to evaluate the results from each of laboratories.
Results: Among 279 laboratories, 240 laboratories results were satisfactory, 23 were questionable, and the other 16 were unsatisfied. The satisfaction rate was 86.0%.
Conclusion: The overall capacity of national laboratories for assays of bismuth potassium citrate capsules is good while a portion of participants require further improvement.

Objective:To compare the clinical efficacy of the H-Loop knotless double-row technique and the suture bridge technique in repairing L-shaped rotator cuff tears under arthroscopy.Methods:A retrospective analysis was performed on 58 patients with L-shaped rotator cuff injuries who underwent arthroscopic repair at Sun Yat-sen Memorial Hospital, Sun Yat-sen University, between January 2019 and December 2021. The H-Loop knotless double-row technique was used in 16 cases (8 males and 8 females, mean age 63.69±8.78 years), while the suture bridge technique was used in 42 cases (24 males and 18 females, mean age 61.02±7.02 years). The American Shoulder and Elbow Surgeons (ASES) score, University of California Los Angeles Shoulder Score (UCLA), Simple Shoulder Test (SST), shoulder range of motion, and muscle strength were evaluated and compared between the two groups one year after surgery.Results:The follow-up period was 12.81±0.98 months for the H-Loop group and 13.29±0.94 months for the suture bridge group. No significant differences were found between the groups in terms of age, sex, dominant hand, preoperative symptom duration, tear shape, tear size, or long head tendon amputation (P>0.05). The operative time was significantly shorter in the H-Loop group 67.50±16.02 minutes compared to the suture bridge group 76.67±13.19 minutes ( t=2.234, P=0.031). Additionally, the number of anchors used was significantly lower in the H-Loop group 2.00±0 compared to the suture bridge group 4.14±0.35 ( t=16.573, P<0.001). The ASES scores increased significantly in both groups: from 57.44±15.91 to 92.00±4.41 in the H-Loop group and from 58.21±16.58 to 87.71±6.19 in the suture bridge group ( F=53.439, P<0.001; F=72.511, P<0.001). Similarly, the UCLA scores improved from 20.63±3.79 to 31.56±3.65 in the H-Loop group and from 20.83±5.78 to 30.36±4.71 in the suture bridge group ( F=57.788, P<0.001; F=50.043, P<0.001). The Constant-Murley scores also showed significant improvement: from 68.50±15.31 to 87.5±8.70 in the H-Loop group and from 66.21±16.51 to 86.33±9.14 in the suture bridge group ( F=6.733, P<0.001; F=30.173, P<0.001). SST scores increased from 6.38±3.76 to 9.06±2.59 in the H-Loop group and from 6.55±3.31 to 9.17±2.45 in the suture bridge group ( F=2.847, P<0.001; F=11.096, P<0.001). The shoulder flexion range of motion increased from 158.75°±21.25° to 178.75°±47.07° in the H-Loop group and from 139.29°±45.12° to 179.76°±3.42° in the suture bridge group ( t=3.814, P=0.002; t=5.877, P<0.001). Shoulder abduction motion increased from 145°±45.46° to 178.75°±3.42° in the H-Loop group and from 135.24°±47.07° to 179.76°±1.54° in the suture bridge group ( t=2.952, P=0.001; t=6.185, P<0.001). Muscle strength improved from 53.36±25.21 N to 73.69±24.09 N in the H-Loop group and from 43.31±24.49 N to 61.8±30.07 N in the suture bridge group ( t=4.916, P<0.001; t=5.623, P<0.001). The ASES score at one year post-surgery was significantly higher in the H-Loop group 92.00±4.41 compared to the suture bridge group 87.71±6.19 ( t=2.529, P=0.014). There were no significant differences in UCLA scores, Constant-Murley scores, SST scores, shoulder motion, or muscle strength between the groups ( P>0.05). Conclusion:The H-Loop technique provides a good early curative effect. Compared to the traditional suture bridge technique, the H-Loop technique offers a higher early postoperative ASES score, shorter operative time, and fewer anchors required.

Hepatocellular carcinoma （HCC） has emerged as a significant public health concern， posing a serious threat to the lives and health of residents in China. Furthermore， the incidence and mortality rates of HCC are notably higher in males than in females. Androgen receptors （AR） can contribute to the occurrence of male-specific cancers such as prostate cancer， suggesting a potential link to the increased susceptibility of males to HCC. Elucidating the cancer-promoting mechanism of AR and developing specific targeted interventions are effective ways to advance tertiary prevention of HCC and improve patient prognosis. This paper reviews the relevant evidence of AR’s role in promoting the occurrence and development of HCC， summarizes relevant mechanisms discovered to date， including promoting the stemness of HCC cells， altering the immune microenvironment， regulating key signaling pathways， inducing glycolysis in hepatocellular carcinoma， and synergizing with hepatitis B virus to promote HCC. Additionally， research directions for targeted interventions in HCC through AR-related signaling pathways are discussed.

Ear, Inner/diagnostic imaging* ; Temporal Bone/diagnostic imaging* ; Tomography, X-Ray Computed/methods*

Objective:To study the different factors affecting platelet production post transplantation of hematopoietic stem cells (HSCs) isolated from different sources in order to explore novel options for treating platelet depletion following HSCs transplantation.Methods:HSCs and their downstream derivatives including myeloid and lymphoid cells (i.e., collective of mononuclear cells (MNCs)), were isolated from E14.5 fetal liver (FL) and bone marrow (BM) of 8-week-old mice by Ficoll separation technique. These cells were subsequently transplanted into the tibia bone marrow cavity of recipient mice post lethal myeloablative treatment in order to construct the FL-MNCs and BM-MNCs transplantation mouse model. Routine blood indices were examined in these recipient mice. The chimeric rate of donor cells in recipient peripheral blood cells were determined by flow cytometry. Different groups of cells involved in platelet reconstruction were analyzed. CD41 +megakaryocytes were sorted from fetal liver or bone marrow using magnetic beads, which were then induced to differentiate into platelets in an in vitro assay . Quantitative RT-PCR was used to detect the expression of platelet-related genes in CD41 +megakaryocytes from the two sources. Results:Both the FL-MNCs and the BM-MNCs transplantation groups resumed normal hematopoiesis at the 4th week after transplantation, and the blood cells of the recipient mice were largely replaced by the donor cells. Compared with the mice transplanted with BM-MNCs, the platelet level of mice transplanted with FL-MNCs recovered faster and were maintained at a higher level. At week 4, the PLT level of the FL-MNCs group was (1.45±0.37)×10 12/L, and of the BM-MNCs group was (1.22±0.24)×10 12/L, P<0.05. The FL-MNCs contain a higher proportion of hematopoietic stem cells (Lin -Sca-1 +c-Kit +)(7.60%±1.40%) compared to the BM-MNCs (1.10%±0.46%), P<0.01; the proportion of the megakaryocyte progenitor cells (Lin -Sca-1 -c-Kit +CD41 +CD150 +) and mature megakaryocyte cells (CD41 +CD42b +), also differ significantly between the FL-MNCs (3.05%±0.22%, 1.60%±0.06%, respectively) and the BM-MNCs (0.15%±0.02%, 0.87%±0.11%, respectively) groups, both P<0.01. In vitro functional studies showed that FL-MNCs-CD41 +megakaryocytes could produce proplatelet-like cells more quickly after induction, with proplatelet-like cells formation on day 3 and significant platelet-like particle formation on day 5, in contrast to bone marrow-derived BM-MNCs-CD41 +megakaryocytes that failed to form proplatelet-like cell on day 5. In addition, FL-MNCs-CD41 +cells expressed higher levels of platelet-related genes, Mpl (3.25-fold), Fog1 (3-fold), and Gata1 (1.5-fold) ( P<0.05). Conclusion:Compared with the BM-MNCs group, the FL-MNCs transplantation group appears to have a more efficient platelet implantation effect in the HSCs transplantation recipient in vivo , as well as a higher platelet differentiation rate in vitro. This might be related to a higher proportion of megakaryocytes and higher expression levels of genes such as Mpl, Fog1, and Gata1 that could be important for platelet formation in FL-MNCs-CD41 +cells. Further exploration of the specific functions of these genes and the characteristics of the different proportions of the donor cells will provide valuable clues for the future treatment of platelets reconstitution after HSCs transplantation clinically.

The mammalian target of rapamycin (mTOR) pathway is abnormally activated in lung cancer. However, the anti-lung cancer effect of mTOR inhibitors as monotherapy is modest. Here, we identified that ginsenoside Rh2, an active component of Panax ginseng C. A. Mey., enhanced the anti-cancer effect of the mTOR inhibitor everolimus both in vitro and in vivo. Moreover, ginsenoside Rh2 alleviated the hepatic fat accumulation caused by everolimus in xenograft nude mice models. The combination of everolimus and ginsenoside Rh2 (labeled Eve-Rh2) induced caspase-independent cell death and cytoplasmic vacuolation in lung cancer cells, indicating that Eve-Rh2 prevented tumor progression by triggering paraptosis. Eve-Rh2 up-regulated the expression of c-MYC in cancer cells as well as tumor tissues. The increased c-MYC mediated the accumulation of tribbles homolog 3 (TRIB3)/P62⁺ aggresomes and consequently triggered paraptosis, bypassing the classical c-MYC/MAX pathway. Our study offers a potential effective and safe strategy for the treatment of lung cancer. Moreover, we have identified a new mechanism of TRIB3/P62⁺ aggresomes-triggered paraptosis and revealed a unique function of c-MYC.

Background/Aims: This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniforms were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B.vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

OBJECTIVES: To explore and analyze the epidemic features of coronavirus disease 2019 (COVID-19) in Hunan Province from January 21, 2020 to March 14, 2020, as well as to investigate the COVID-19 epidemics in each city of Hunan Province. METHODS: The epidemic data was obtained from the official website of Hunan Province's Health Commission. The data of each city of Hunan Province was analyzed separately. Spatial distribution of cumulative confirmed COVID-19 patients and the cumulative occurrence rate was drawn by ArcGIS software for each city in Hunan Province. Some regional indexes were also compared with that in the whole country. RESULTS: The first patient was diagnosed in January 21, sustained patient growth reached its plateau in around February 17. Up to March 14, the cumulative confirmed COVID-19 patients stopped at 1 018. The cumulative occurrence rate of COVID-19 patients was 0.48 per 0.1 million person. The number of cumulative severe patients was 150 and the number of cumulative dead patients was 4. The mortality rate (0.39%) and the cure rate (99.6%) in Hunan Province was significantly lower and higher respectively than the corresponding average rate in the whole country (0.90% and 96.2%, Hubei excluded). The first 3 cities in numbers of the confirmed patients were Changsha, Yueyang, and Shaoyang. While sorted by the cumulative occurrence rate, the first 3 cities in incidence were Changsha, Yueyang, and Zhuzhou. CONCLUSIONS The epidemic of COVID-19 spread out smoothly in Hunan Province. The cities in Hunan Province implement anti-disease strategies based on specific situations on their own and keep the epidemic in the range of controllable.
Betacoronavirus ; China ; epidemiology ; Cities ; epidemiology ; Coronavirus Infections ; epidemiology ; mortality ; Humans ; Pandemics ; Pneumonia, Viral ; epidemiology ; mortality

The role of 5-hydroxytryptamine (5-HT) has attracted more and more attention in the development of tumor. In addition to the synthesis of 5-HT by enterochromaffin cells, some tumor cells and immune cells can also secrete 5-HT, and there are different 5-HT receptors on the surface of these cells. 5-HT plays multiple biological effects through activating different receptors. 5-HT promotes the proliferation and invasion of tumor and induces the angiogenesis of tumor tissues through activating its corresponding receptors, such as 5-HT1D, and so on. Furthermore, various 5-HT receptors are expressed on the surface of immune cells. On the one hand, physiological doses of 5-HT promote the proliferation and secretion of immune cells. On the other hand, pathologic 5-HT has an effect on inducing the differentiation of immune cells in the direction of immunosuppression, thus participating in the occurrence and development of tumor.