Far-Infrared Therapy Based on Graphene Ameliorates High-Fat Diet-Induced Anxiety-Like Behavior in Obese Mice via Alleviating Intestinal Barrier Damage and Neuroinflammation.

The consumption of a high-fat diet (HFD) has been implicated in the etiology of obesity and various neuropsychiatric disturbances, including anxiety and depression. Compelling evidence suggests that far-infrared ray (FIR) possesses beneficial effects on emotional disorders. However, the efficacy of FIR therapy in addressing HFD-induced anxiety and the underlying mechanisms remain to be elucidated. Here, we postulate that FIR emitted from a graphene-based therapeutic device may mitigate HFD-induced anxiety behaviors. The graphene-FIR modify the gut microbiota in HFD-mice, particularly by an enriched abundance of beneficial bacteria Clostridiaceae and Erysipelotrichaceae, coupled with a diminution of harmful bacteria Lachnospiraceae, Anaerovoracaceae, Holdemania and Marvinbryantia. Graphene-FIR also improved intestinal barrier function, as evidenced by the augmented expression of the tight junction protein occludin and G protein-coupled receptor 43 (GPR43). In serum level, we observed the decreased free fatty acids (FFA), lipopolysaccharides (LPS), diamine oxidase (DAO) and D-lactate, and increased the glucagon-like peptide-2 (GLP-2) levels in graphene-FIR mice. Simultaneously, inflammatory cytokines IL-6, IL-1ß, and TNF-α manifested a decrease subsequent to graphene-FIR treatment in both peripheral and central system. Notably, graphene-FIR inhibited over expression of astrocytes and microglia. We further noticed that the elevated the BDNF and decreased TLR4 and NF-κB expression in graphene-FIR group. Overall, our study reveals that graphene-FIR rescued HFD-induced anxiety via improving the intestine permeability and the integrity of blood-brain barrier, and reduced inflammatory response by down regulating TLR4/NF-κB inflammatory pathway.

Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models: A Cross-sectional Study in Rural Guangxi / 生物医学与环境科学（英文）

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 ( P interactions 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.

Acute stress reaction, depression anxiety stress, and job withdrawal behavior in non-frontline pediatric nurses during the pandemic: a cross-sectional study.

Backgrounds: The COVID-19 pandemic has brought an unprecedented healthy crisis to people worldwide. It is crucial to assess the psychological status of non-frontline nurses. More attention to the mental and physical health of non-frontline nurses during a public health emergency is necessary for a full understanding of the implications. Therefore, this study aims to investigate the factors that influence the acute stress reaction of non-frontline pediatric nurses during the COVID-19 pandemic. Methods: This study aimed to explore factors associated with acute stress reactions of non-frontline pediatric nurses in Hunan province during the COVID-19 pandemic. This was a cross-sectional design. Five hundred eighteen pediatric nurses from Hunan province, China, completed the Stanford Acute Stress Reaction Questionnaire (SASRQ), Depression Anxiety Stress Scales-21 (DASS-21), and Job Withdrawal Behavior Scales (JWB). Multiple linear regression analyses and Pearson's correlation were used to analyze the results. Results: The mean scores of DASS-21, JWB, SASRQ were 1.443 ± 0.500, 1.601 ± 0.544, and 1.858 ± 0.805, respectively. Stress, anxiety, depression (three sub-dimensions of DASS-21), JWB, monthly income and department were the major predictive factors for SASRQ (Adjusted R2 = 0.579, p < 0.001). Pearson's correlation showed that the mean score of SASRQ was positively correlated with JWB, DASS-21, and all its dimensions (p < 0.01). Conclusion: The study indicated that the SASRQ was greater with higher levels of DASS-21 and JWB. It revealed an acute stress reaction in non-frontline pediatric nurses and recommends more focus on the factors influencing the SASRQ.

Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China.

BACKGROUND: Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China. METHODS: A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL. RESULTS: A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level (all p < 0.05). No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group (hazard ratio [HR] = 11.1, 95% confidence interval [CI] = 1.3-93.2). After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results (HR = 10.1, 95% CI = 1.2-84.1). 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons. CONCLUSIONS: Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China.

Activated Carbon nanoparticles Loaded with Metformin for Effective Against Hepatocellular Cancer Stem Cells.

Introduction: Hepatocellular cancer stem cells (CSCs) play crucial roles in hepatocellular cancer initiation, development, relapse, and metastasis. Therefore, eradication of this cell population is a primary objective in hepatocellular cancer therapy. We prepared a nanodrug delivery system with activated carbon nanoparticles (ACNP) as carriers and metformin (MET) as drug (ACNP-MET), which was able to selectively eliminate hepatocellular CSCs and thereby increase the effects of MET on hepatocellular cancers. Methods: ACNP were prepared by ball milling and deposition in distilled water. Suspension of ACNP and MET was mixed and the best ratio of ACNP and MET was determined based on the isothermal adsorption formula. Hepatocellular CSCs were identified as CD133+ cells and cultured in serum-free medium. We investigated the effects of ACNP-MET on hepatocellular CSCs, including the inhibitory effects, the targeting efficiency, self-renewal capacity, and the sphere-forming capacity of hepatocellular CSCs. Next, we evaluated the therapeutic efficacy of ACNP-MET by using in vivo relapsed tumor models of hepatocellular CSCs. Results: The ACNP have a similar size, a regular spherical shape and a smooth surface. The optimal ratio for adsorption was MET: ACNP=1:4. ACNP-MET could target and inhibit the proliferation of CD133+ population and decrease mammosphere formation and renewal of CD133+ population in vitro and in vivo. Conclusion: These results not only suggest that nanodrug delivery system increased the effects of MET, but also shed light on the mechanisms of the therapeutic effects of MET and ACNP-MET on hepatocellular cancers. ACNP, as a good nano-carrier, could strengthen the effect of MET by carrying drugs to the micro-environment of hepatocellular CSCs.

Network pharmacology and pharmacological evaluation for deciphering novel indication of Sishen Wan in insomnia treatment.

BACKGROUND: Insomnia is the most frequent sleep disorder worldwide and is a prominent risk factor for mental and physical health deterioration. The clinical application of common pharmacological treatments for insomnia is far from satisfactory due to their various adverse effects. In recent years, drugs developed from natural herbs have become potential alternative therapies for insomnia. Sishen Wan (SSW), a traditional Chinese medicine (TCM) used for centuries to treat diarrheal disease, consists of multiple neurologically active herbs with sleep-regulating potential that may have therapeutic effects on insomnia. However, its hypnotic and sleep-regulating effects have not been evaluated in clinical practice or laboratory experiments. PURPOSE: To investigate the anti-insomnia effects of SSW and explore its possible mechanisms using preclinical models. STUDY DESIGN AND METHODS: The sedative effect of the SSW formula was investigated using network pharmacology analysis that was validated using various pharmacological approaches, including the evaluation of locomotor activity (LMA), pentobarbital-induced sleep time, and electroencephalography/electromyogram (EEG/EMG)-based sleep profiling in normal rats. Several animal models of insomnia, including sleep deprivation, serotonin depletion, and cage-changing models, have been used to further assess the anti-insomnia effects of SSW. Furthermore, the potential underlying mechanisms of action of SSW were predicted using bioinformatics methods and verified using in vivo and in silico experiments. RESULTS: The results showed that SSW reduced LMA and prolonged pentobarbital-induced sleep time in a dose-dependent manner, which was consistent with the increase in non-rapid eye movement (NREM) sleep in normal rats, indicating a solid sedative effect. In animal models of insomnia, SSW alleviated sleep disturbance by increasing NREM sleep time, shortening NREM sleep latency, and inhibiting sleep fragmentation, suggesting a possible curative effect of SSW on insomnia. Finally, through functional enrichment analysis and in vivo and in silico experiments, 5-HT1A was identified as the key target of the anti-insomnia effect of SSW. Moreover, (S)-propranolol, nuciferine, zizyphusine, and N,N-dimethyl-5-methoxytryptamine may be the active compounds of SSW responsible for its anti-insomnia effect. CONCLUSION: This study extended the possible indication scope for SSW, which provides a potential therapeutic TCM that may be used for insomnia treatment, as well as a reference scheme for the discovery of novel indications of TCM.

Drug resistance and genomic characteristics of Salmonella enterica serovar London from clinical and food sources in Hangzhou City from 2017 to 2021 / 中华预防医学杂志

Objective: To analyze the drug resistance and genomic characteristics of Salmonella enterica serovar London isolated from clinical and food sources in Hangzhou City from 2017 to 2021. Methods: A total of 91 Salmonella enterica serovar London strains isolated from Hangzhou City from 2017 to 2021 were analyzed for drug susceptibility, pulsed field gel electrophoresis (PFGE) typing and whole genome sequencing. Multilocus sequence typing (MLST), core genome multilocus sequence typing (cgMLST) and detection of drug resistance genes were performed by using the sequencing data. Phylogenetic analysis was conducted to compare the 91 genomes from Hangzhou City with 347 genomes from public databases. Results: No significant difference in the drug resistance rate was observed between clinical strains and food strains to 18 drugs in Hangzhou City(all P>0.05), and the multidrug resistance (MDR) rate was 75.8% (69/91). Most strains were resistant to 7 drug classes simultaneously. One strain was resistant to Polymyxin E as well as positive for mcr-1.1, and 50.5% (46/91) of the strains were resistant to Azithromycin and were positive for mph(A). All 91 Salmonella enterica serovar London strains were ST155, which were subdivided into 44 molecular types by PFGE and 82 types by cgMLST. Phylogenetic analysis showed that most strains from Hangzhou City (83/91) were clustered together, and a small number of human isolates from Europe, North America and pork isolates from Hubei and Shenzhen were mixed in the cluster. Other strains from Hangzhou City (8/91) were closely related to strains from Europe, America and Southeast Asia. Strains isolated from pork were the most closely related to clinical strains. Conclusion: The epidemic of Salmonella enterica serovar London in Hangzhou City is mainly caused by the spread of ST155 strains, which is mainly transmitted locally. At the same time, cross-region transmission to Europe, North America, Southeast Asia, and other provinces and cities in China may also occur. There is no significant difference in the drug resistance rate between clinical strains and food strains, and a high level of MDR is found in the strains. Clinical infection of Salmonella enterica serovar London may be closely related to pork consumption in Hangzhou City.

Discussion on application of mean gamma index to Compass 3D dose verification in target area receiving 50% of prescribed dose / 中华放射医学与防护杂志

Objective:To explore the value of using the mean gamma index (GI) in targer area receiving 50% prescribed dose as reference in VMAT planned dose verification through model-based dose calculation and measurement-based dose reconstruction.Methods:Based on Compass dose verificantion system, the VMAT plans for 70 patients were validated using two method. The mean GI and passing rate in target area receiving 50% of prescribed dose area for each validation plan were obtained to evaluate its application value in dose validation. First, plan information obtained by TPS calculation was input into the Compass system for performing independent dose calculation based on the accelerator data model, and obtain a three-dimensional dose based on the independent model calculation. The planned fluence measured for each patient′s treatment plan on the accelerator was reconstructed through the Compass system to obtain a three-dimensional dose based on measurement reconstruction. The three-dimensional dose obtained by the two method were compared with the three-dimensional dose calculated by TPS.Results:Combined with the gamma criteria of 3%/3 mm in the error setting condition of GI analysis, the mean GI in the area receiving 50% of prescribed dose was evaluated. GI≤0.4 was classified as PASS, 0.4 < GI ≤ 0.6 as being clinically acceptable, and GI > 0.6 as FAIL. The VMAT planned dose verification for 70 patients showed that the model-based independent calculation was in a better agreement with the TPS calculation. The GI values were all < 0.6: GI≤0.4 for 67 patients and 0.4 <GI≤ 0.6 for the other 3 patients, with gamma passing rate larger than 92%. The in- vivo measurement-based reconstructed 3D dose are slightly lesser than the model-based planed result ; theGI values were all < 0.6: GI ≤0.4 for 35 patients and 0.4 < GI ≤ 0.6 for other 35 patients, with gamma pass rate larger than 88%, of which gamma passing rate > 90% for 88 patients and < 90% for other 2, all meeting the requirements of clinical dose verification. The model-based independent dose verification is better than the measurement-based reconstructed dose verificantion, and the difference is statistically significant ( t=15.20, 10.71, P < 0.05). Conclusions:The mean GI in target area receiving 50% of prescribed dose can be used as a reference to judge the operatability of clinical plan in clinical dose verification. The mean GI value, in combination with the comprehensive result of gamma passing rate, is more convincing to evaluate dose verification. A combination of model-based dose verification, despite time-saving and labor-saving, and the measurement-based dose verification could become a reliable dose verification method for clinical application.

Application of typical tasks-based mind mapping in nursing teaching for children with autism spectrum disorder / 中华医学教育探索杂志

Objective:To explore the application of typical tasks-based mind mapping in nursing teaching for children with autism spectrum disorder (ASD).Methods:A total of 102 nursing students who were involved in the nursing of children with ASD in Hunan Children's Hospital were selected and divided into control group and observation group according to the teaching methods. Fifty-one students in the control group were provided with conventional teaching, while 51 students in the observation group were provided with typical tasks-based mind mapping teaching. The students in the two groups were assessed for performance, self-directed learning ability score, and overall literacy at completion of the nursing course. SPSS 22.0 was used for the t test. Results:The scores of theoretical examination[(92.34±4.07) vs. (89.92±3.61)], nursing note writing[(91.07±3.84) vs. (88.60±3.59)], and operational examination[(90.47±2.98) vs. (88.52±2.73)] were significantly higher among students in the observation group than among those in the control group ( P<0.05); after the internship, students in the two groups had significantly increased scores in interpersonal relationships, learning awareness, learning strategies, learning behaviors, and learning evaluation, and the observation group had better performance than the control group in the above indices ( P<0.05); after the internship, students in the two groups had significantly increased scores in problem solving, interpersonal communication, critical thinking, and self-leadership, and the observation group had better performance than the control group in the above indices ( P<0.05). Conclusion:The application of typical tasks-based mind mapping in nursing teaching for children with ASD can improve nursing students' academic performance, enhance their self-directed learning, and improve their overall literacy.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Solid Tumors With Cold Agglutinins:Report of Two Cases and Literature Review / 中国医学科学院学报

Cold agglutinins(CA),autoantibodies against the antigen I or i on the surface of red blood cells,are mainly of IgM class,and the majority have κ light chains.They can lead to red blood cell agglutination at decreased body temperature and are usually associated with infections,drug reactions,autoimmune diseases,and hematological malignancies.However,solid tumors with CA are rare.We reported two cases of CA in the peripheral blood of patients with solid tumors.Peripheral complete blood cell count of the patients at admission showed reduced erythrocyte count and hematocrit,mismatching between erythrocyte count and hemoglobin,abnormally elevated levels of mean corpuscular hemoglobin and mean cell hemoglobin concentration.Peripheral blood smear showed erythrocyte aggregation.After the sample was preheated at 37 ℃ for 30 min,the reversibility of red blood cell aggregation was observed,and the erythrocyte parameters were corrected.

Treadmill exercise alleviates neuropathic pain by regulating mitophagy of the anterior cingulate cortex in rats / 生理学报

This study aimed to investigate the effect of treadmill exercise on neuropathic pain and to determine whether mitophagy of the anterior cingulate cortex (ACC) contributes to exercise-mediated amelioration of neuropathic pain. Chronic constriction injury of the sciatic nerve (CCI) was used to establish a neuropathic pain model in Sprague-Dawley (SD) rats. Von-Frey filaments were used to assess the mechanical paw withdrawal threshold (PWT), and a thermal radiation meter was used to assess the thermal paw withdrawal latency (PWL) in rats. qPCR was used to evaluate the mRNA levels of Pink1, Parkin, Fundc1, and Bnip3. Western blot was used to evaluate the protein levels of PINK1 and PARKIN. To determine the impact of the mitophagy inducer carbonyl cyanide m-chlorophenylhydrazone (CCCP) on pain behaviors in CCI rats, 24 SD rats were randomly divided into CCI drug control group (CCI+Veh group), CCI+CCCP low-dose group (CCI+CCCP0.25), CCI+CCCP medium-dose group (CCI+CCCP2.5), and CCI+CCCP high-dose group (CCI+CCCP5). Pain behaviors were assessed on 0, 1, 3, 5, and 7 days after modeling. To explore whether exercise regulates pain through mitophagy, 24 SD rats were divided into sham, CCI, and CCI+Exercise (CCI+Exe) groups. The rats in the CCI+Exe group underwent 4-week low-moderate treadmill training one week after modeling. The mechanical pain and thermal pain behaviors of the rats in each group were assessed on 0, 7, 14, 21, and 35 days after modeling. Western blot was used to detect the levels of the mitophagy-related proteins PINK1, PARKIN, LC3 II/LC3 I, and P62 in ACC tissues. Transmission electron microscopy was used to observe the ultrastructure of mitochondrial morphology in the ACC. The results showed that: (1) Compared with the sham group, the pain thresholds of the ipsilateral side of the CCI group decreased significantly (P < 0.001). Meanwhile, the mRNA and protein levels of Pink1 were significantly higher, and those of Parkin were lower in the CCI group (P < 0.05). (2) Compared with the CCI+Veh group, each CCCP-dose group showed higher mechanical and thermal pain thresholds, and the levels of PINK1 and LC3 II/LC3 I were elevated significantly (P < 0.05, P < 0.01). (3) The pain thresholds of the CCI+Exe group increased significantly compared with those of the CCI group after treadmill intervention (P < 0.001, P < 0.01). Compared with the CCI group, the protein levels of PINK1 and P62 were decreased (P < 0.001, P < 0.01), and the protein levels of PARKIN and LC3 II/LC3 I were increased in the CCI+Exe group (P < 0.01, P < 0.05). Rod-shaped mitochondria were observed in the ACC of CCI+Exe group, and there were little mitochondrial fragmentation, swelling, or vacuoles. The results suggest that the mitochondrial PINK1/PARKIN autophagy pathway is blocked in the ACC of neuropathic pain model rats. Treadmill exercise could restore mitochondrial homeostasis and relieve neuropathic pain via the PINK1/PARKIN pathway.

Xinyang Tablet attenuates chronic hypoxia-induced right ventricular remodeling via inhibiting cardiomyocytes apoptosis.

BACKGROUND: Hypoxia-induced pulmonary hypertension (HPH) is one of the fatal pathologies developed under hypobaric hypoxia and eventually leads to right ventricular (RV) remodeling and RV failure. Clinically, the mortality rate of RV failure caused by HPH is high and lacks effective drugs. Xinyang Tablet (XYT), a traditional Chinese medicine exhibits significant efficacy in the treatment of congestive heart failure and cardiac dysfunction. However, the effects of XYT on chronic hypoxia-induced RV failure are not clear. METHODS: The content of XYT was analyzed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). Sprague-Dawley (SD) rats were housed in a hypobaric chamber (equal to the parameter in altitude 5500 m) for 21 days to obtain the RV remodeling model. Electrocardiogram (ECG) and hemodynamic parameters were measured by iWorx Acquisition & Analysis System. Pathological morphological changes in the RV and pulmonary vessels were observed by H&E staining and Masson's trichrome staining. Myocardial apoptosis was tested by TUNEL assay. Protein expression levels of TNF-α, IL-6, Bax, Bcl-2, and caspase-3 in the RV and H9c2 cells were detected by western blot. Meanwhile, H9c2 cells were induced by CoCl2 to establish a hypoxia injury model to verify the protective effect and mechanisms of XYT. A CCK-8 assay was performed to determine the viability of H9c2 cells. CoCl2-induced apoptosis was detected by Annexin-FITC/PI flow cytometry and Hoechst 33,258 staining. RESULTS: XYT remarkably improved RV hemodynamic disorder and ECG parameters. XYT attenuated hypoxia-induced pathological injury in RV and pulmonary vessels. We also observed that XYT treatment decreased the expression levels of TNF-α, IL-6, Bax/Bcl-2 ratio, and the numbers of myocardial apoptosis in RV. In H9c2 myocardial hypoxia model, XYT protected H9c2 cells against Cobalt chloride (CoCl2)-induced apoptosis. We also found that XYT could antagonize CoCl2-induced apoptosis through upregulating Bcl-2, inhibiting Bax and caspase-3 expression. CONCLUSIONS: We concluded that XYT improved hypoxia-induced RV remodeling and protected against cardiac injury by inhibiting apoptosis pathway in vivo and vitro models, which may be a promising therapeutic strategy for clinical management of hypoxia-induced cardiac injury.

Case report and literature review: Treatment of multiple meningiomas combined with multiple unruptured aneurysms in a single operation.

Background: Although the incidence of a single meningioma or a single aneurysm is common, cases of multiple meningiomas combined with multiple aneurysms are rarely reported, and surgical treatment of the coexisting situation is also relatively uncommon. Case presentation: A 38-year-old male patient presented to the neurosurgery department of our center with a headache. Examination revealed only symptoms of headache. Laboratory tests showed only decreased total protein and albumin. Magnetic resonance imaging showed preoccupation with the frontal lobe and the right temple bone. Magnetic resonance angiography and digital subtraction angiography showed two aneurysms in the anterior communicating artery and right anterior cerebral artery. Based on a combination of the patient's history and imaging, we hypothesized that the patient was simultaneously suffering from meningioma and an aneurysm, and both of them are multiple. The patient underwent tumor resection and clipping procedure based on this hypothesis in one surgery. Intraoperative biopsy proved to be a meningioma. The patient was discharged on the 10th postoperative day, and a postoperative follow-up suggested no complications. Conclusion: Multiple meningiomas combined with multiple aneurysms are rare to be reported in the same patient. For those unruptured intracranial aneurysms (UIAs) located in the visual field of craniotomy prepared for brain tumorlike meningioma, it is possible to do the clipping as well. When the meningiomas are multiple, fitted with the surgical indication, and located in a position that cannot be treated in one surgery, this may lead to a two-stage operation, no matter where the UIAs are located.

The efficacy and safety of fractional lasers for alopecia in mono and adjunctive therapy: A systematic review and meta-analysis.

BACKGROUND: Hair loss is affecting over half of the population worldwide, leading to noticeable psychotic disorders in a considerable proportion of patients. The current treatments remain unpredictable and disappointing. OBJECTIVE: This study aimed to evaluate the efficacy and safety of fractional lasers compared with other conventional treatments as either mono or combined therapy in the treatment of alopecia. METHODS: We have conducted a thorough literature search in PubMed, Web of Science, Embase, Cochrane library, and China national knowledge infrastructure databases (from inception to February 9, 2022). Relevant clinical trials, mainly randomized controlled trials, were included, regardless of their comparisons. The Cochrane risk of bias assessment was used for quality appraisal. Outcomes were evaluated by efficiency rate, hair density, etc. RESULTS: Thirteen controlled clinical trials, including nine randomized controlled trials, with 606 patients were retrieved. As an individual therapy, the fractional laser is superior to any other therapy in total efficiency (RR = 1.58, 95% CI: 1.16-2.14, p = 0.003). When the fractional laser was applied in combined treatments, the result showed a significant difference (RR = 1.23, 95%CI: 1.02 to 1.49, P = 0.03) compared with other treatments. Although both mono and adjunctive groups were confirmed to be efficient, there were no statistical differences between the two of them (RR = 1.24, 95% CI: 0.87-1.77, p = 0.24). CONCLUSION: Our results showed that the fractional laser has a significant efficacy as either mono or adjuvant therapy. Further research and exploration of fractional lasers with larger sample sizes are required to confirm the efficiency and safety of this treatment.

Melatonin pretreatment prevents propofol-induced sleep disturbance by modulating circadian rhythm in rats.

Postoperative sleep disorder frequently occurs in patients after surgery. Sleep disturbance aggravates pain, anxiety, and delirium, which is an important risk factor for poor recovery. Circadian rhythm disorder induced by general anesthesia plays important role in postoperative sleep disorders. A large number of clinical studies have shown that various forms and duration of general anesthesia can lead to postoperative sleep disorders. In this study, the effect of prolonged propofol anesthesia on biological rhythm was comprehensively evaluated by wireless physiological telemetry system, and the therapeutic effect of exogenous melatonin pretreatment was further investigated. The results showed that prolonged propofol anesthesia had significant impacts on the circadian rhythm of sleep, body temperature, locomotor activity and endogenous melatonin secretion within 24 h following anesthesia, resulting in diminished oscillation amplitude. In hypothalamus, the expression of circadian factor PER and CRY were inhibited by propofol, possibly through activation of CAMK-CREB signaling pathway. Post-translational factors GSK-3ß, SIRT1, AMPK were also involved in the regulation of circadian factors after propofol anesthesia. Melatonin pretreatment could restore circadian rhythm process by regulating circadian factor expression through post-translational modulation and prohibit the over-synthesis of melatonin in pineal gland. This study verified the effects of anesthetics on circadian rhythm and further evaluated the potential therapeutic effect of melatonin on postoperative circadian rhythm and sleep disorders.

Ferroptosis in laryngeal squamous cell carcinoma and its regulation by M2 macrophage-derived exosomes / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate ferroptosis in laryngeal squamous cell carcinoma (LSCC) and its regulation by M2 macrophage-derived exosomes. Methods: LSCC and adjacent noncancerous tissue samples were collected from 32 patients treated in the Department of Otorhinolaryngology, Head and Neck Surgery of the Second Affiliated Hospital of Harbin between September 2018 and April 2021, including 26 males and 6 females, aged 43-79 years. The expressions of ferroptosis marker glutathione peroxidase 4(GPX4) in LSCC and adjacent noncancerous tissues were detected by immunohistochemistry and reverse transcriptase-polymerase chain reaction(RT-PCR). The correlations between GPX4 expression and clinicopathological factors in LSCC were analyzed. Biological changes of TU212 cells after treated with ferroptosis-induced agent erastin were detected by transmission electron microscope, cell counting kit-8(CCK-8), clone test, reactive oxygen species(ROS), malondialdehyde(MDA), glutathione(GSH), JC-1, RT-PCR and western blot. Exosomes were isolated from the supernatant of M0/M2 macrophages (M0-exos/M2-exos) and co-incubated with erastin-treated TU212 cells to detect the change of ferroptosis in cells of each group. The data were analyzed by SPSS software of version19.0. Results: GPX4 expression in LSCC tissues was significantly higher than that in adjacent noncancerous tissues (2.04±0.65 vs. 0.99±0.09, F=30.36, P<0.001), and was closely related to T stage and clinical stage (Ⅰ-Ⅱvs.Ⅲ-Ⅳ: 1.75±0.39 vs. 2.18±0.71, F=2.25, P<0.05; T1-2 vs. T3-4: 1.71±0.42 vs. 2.20±0.69, F=2.06, P<0.05). In TU212 cells treated with erastin, mitochondrial crest became smaller, membrane density increased, proliferation rate decreased, intracellular ROS level increased, mitochondrial membrane potential depolarized, GSH content decreased, intracellular MDA level increased and expressions of GPX4 mRNA and protein decreased. Change of M0 into M2 macrophages was induced by IL-4 stimulation. When erastin-treated TU212 cells were incubated with M2-exos, cell proliferation was partially restored and GPX4 expression was enhanced, and also with the recoveries of levels of ROS, MDA and GSH (all P<0.05). Conclusions: Ferroptosis is one of the cell death ways of LSCC. M2-exos may inhibit ferroptosis of LSCC cells.

Serological Response in Lung Transplant Recipients after Two Doses of SARS-CoV-2 mRNA Vaccines

The immunological effectiveness of SARS-CoV-2 mRNA vaccines in lung transplant (LT) recipients is largely unknown. Thus, we assessed the effect of Pfizer-BioNTech and Moderna mRNA vaccines two-dose (2D) regimen on humoral responses in immunocompromised lung transplant (LT) recipients. About 25% (18/73) of SARS-CoV-2 uninfected-LT patients generated positive spike-IgG response following 2D of vaccines, with 36% (9/25) in the Moderna cohort and only 19% (9/48) in the Pfizer cohort. 2D in LT patients elicited significantly lesser median IgGSP response (1.7 AU/mL, 95% CI: 0.6-7.5 AU/mL) compared to non-transplanted, uninfected naive subjects (14209 AU/mL, 95% CI: 11261-18836 AU/mL) (p<0.0001). In LT patients, Moderna-evoked seropositivity trend was higher by 23-fold than Pfizer. 2D COVID-19 vaccination elicits a dampened serological response in LT patients. Whether assessing other arms of host immunity combined with higher vaccine dose can better capture and elicit improved immunogenicity in this immunocompromised population warrants investigation.

A study on the causes of operative failures after microwave ablation for primary hyperparathyroidism.

OBJECTIVE: To summarize the occurrence of operative failures after microwave ablation (MWA) in patients with primary hyperparathyroidism (pHPT), analyze the possible reasons, and explore strategies for preventing and managing these situations. METHODS: This retrospective study reviewed 91 pHPT patients who underwent MWA from April 2015 to November 2019. A cure was defined as the reestablishment of normal calcium homeostasis lasting a minimum of 6 months. An operative failure was defined as a failure to normalize serum intact parathyroid hormone (iPTH) and/or calcium levels at 6 months or longer. Patients who encountered operative failures were compared with patients who were successfully cured. RESULTS: Eighty-eight pHPT patients, consisting of 29 men and 59 women, were finally enrolled. The median follow-up duration was 15.9 months (IQR, 6.1-31.5 months). Seventy-eight patients (78/88, 88.6%) were cured. Ten (10/88, 11.4%) patients experienced operative failure, including 9 persistent pHPT (10.2%) and 1 (1.1%) recurrent pHPT. Small parathyroid nodules (maximum diameter < 0.6 cm) and incomplete ablation were the two key factors leading to operative failure. Of the 9 patients with a maximum nodule diameter less than 0.6 cm, 77.8% (7/9) of them encountered operative failure. CONCLUSION: Operative failure occurred in 11.4% of the pHPT patients who underwent MWA. The possibility of operative failure was increased when the maximum diameter of parathyroid nodule was less than 0.6 cm. Complete ablation could help avoid operative failure. KEY POINTS: • Failed to ablate the target lesion and incomplete ablation were the key factors attributed to operative failures. • When the maximum diameter of the parathyroid nodules is less than 0.6 cm, the possibility of operative failure was higher.