Aim To study the main active components and potential mechanism of selenshenzhi prescription a-gainst esophageal cancer by network pharmacology and in vivo and in vitro experiments.Methods The com-mon target was extracted from TCMSP,OMIM and GeneCards databases,and the PPI network was con-structed using STRING database.DAVID database was used for GO and KEGG enrichment analysis,and a network was constructed based on STRING and DAVID database for in vivo and in vitro experimental verifica-tion.Results Prediction results showed that a total of 100 active ingredients and 749 related targets were ob-tained,and 168 common targets were obtained between selenoshenzhi recipe and esophageal cancer,which were involved in the PI3K-AKT signaling pathway and proteoglycan signaling pathways in cancer.Selenshenz-hi prescription was used to conduct preliminary verifi-cation of related targets for human esophageal cancer EC9706 based on in vitro experiments.The results showed that selenshenzhi prescription could significantly inhibit the proliferation of esophageal cancer cells and induce the apoptosis of EC9706 through the expression of Bax,Bcl-2,caspase-3 and other key apoptotic pro-teins.Lastly,the core target and pathway of selensh-enzhi prescription were preliminically verified based on in vivo animal experiments on nude mice with esopha-geal cancer.The results showed that selenshenzhi pre-scription could significantly inhibit tumor proliferation,promote tumor cell apoptosis,and induce tumor apop-tosis by regulating the expression of key proteins on PI3K/AKT signaling pathway.Conclusions Selensh-enzhi prescription can control the occurrence and de-velopment of esophageal cancer through the synergistic effect of multi-components,multi-targets and multi-pathways,and provide a theoretical basis for further clinical investigation of the mechanism of selenshenzhi prescription in the treatment of esophageal cancer in the future.

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.
Male ; Mice ; Animals ; Phosphatidylinositol 3-Kinases/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Liver Glycogen ; Yang Deficiency/drug therapy* ; Yin Deficiency/drug therapy* ; Kidney ; Body Weight

OBJECTIVE: This study was aimed at investigating the carrier rate of, and molecular variation in, α- and β-globin gene mutations in Hunan Province. METHODS: We recruited 25,946 individuals attending premarital screening from 42 districts and counties in all 14 cities of Hunan Province. Hematological screening was performed, and molecular parameters were assessed. RESULTS: The overall carrier rate of thalassemia was 7.1%, including 4.83% for α-thalassemia, 2.15% for β-thalassemia, and 0.12% for both α- and β-thalassemia. The highest carrier rate of thalassemia was in Yongzhou (14.57%). The most abundant genotype of α-thalassemia and β-thalassemia was -α ^3.7/αα (50.23%) and β ^IVS-II-654/β ^N (28.23%), respectively. Four α-globin mutations [CD108 (ACC>AAC), CAP +29 (G>C), Hb Agrinio and Hb Cervantes] and six β-globin mutations [CAP +8 (C>T), IVS-II-848 (C>T), -56 (G>C), beta nt-77 (G>C), codon 20/21 (-TGGA) and Hb Knossos] had not previously been identified in China. Furthermore, this study provides the first report of the carrier rates of abnormal hemoglobin variants and α-globin triplication in Hunan Province, which were 0.49% and 1.99%, respectively. CONCLUSION Our study demonstrates the high complexity and diversity of thalassemia gene mutations in the Hunan population. The results should facilitate genetic counselling and the prevention of severe thalassemia in this region.
Humans ; beta-Thalassemia/genetics* ; alpha-Thalassemia/genetics* ; Hemoglobinopathies/genetics* ; China/epidemiology* ; High-Throughput Nucleotide Sequencing

Humans ; Child ; Nontuberculous Mycobacteria ; Lung Diseases

Objective: To investigate the response characteristics of patients with locally advanced/metastatic non-squamous non-small cell lung cancer (nsq-NSCLC) treated with tislelizumab in combination with chemotherapy in the first line. Methods: Patients with nsq-NSCLC who achieved complete or partial remission after treatment with tislelizumab in combination with chemotherapy or chemotherapy alone in the RATIONALE 304 study, as assessed by an independent review board, were selected to analyze the response characteristics and safety profile of the responders. Time to response (TTR) was defined as the time from randomization to the achievement of first objective response. Depth of response (DpR) was defined as the maximum percentage of tumor shrinkage compared with the sum of the baseline target lesion length diameters. Results: As of January 23, 2020, 128 patients treated with tislelizumab in combination with chemotherapy achieved objective tumor response (responders), representing 57.4%(128/223) of the intention-to-treat population, with a TTR of 5.1 to 33.3 weeks and a median TTR of 7.9 weeks. Of the responders (128), 50.8%(65) achieved first remission at the first efficacy assessment (week 6), 31.3%(40) at the second efficacy assessment (week 12), and 18.0%(23) at the third and subsequent tumor assessments. The percentages of responders who achieved a depth of tumor response of 30% to <50%, 50% to <70% and 70% to 100% were 45.3%(58/128), 28.1%(36/128) and 26.6%(34/128), respectively, with median progression-free survival (PFS) of 9.0 months (95% CI: 7.7 to 9.9 months), 11.5 months (95% CI: 7.7 months to not reached) and not reached (95% CI: 11.8 months to not estimable), respectively. Tislelizumab plus chemotherapy were generally well tolerated in responders with similar safety profile to the overall safety population. Conclusion: Among responders to tislelizumab in combination with chemotherapy for nsq-NSCLC, 82.0%(105/128) achieves response within the first two tumor assessments (12 weeks) and 18.0%(23/128) achieves response at later (18 to 33 weeks) assessments, and there is a trend toward prolonged PFS in responders with deeper tumor response.
Humans ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Lung Neoplasms/pathology* ; Treatment Outcome

Objective: To explore the performance of a self-made venous-venous bypass (VVB) device for liver transplantation based on the principle of magnetic levitation drive. Methods: Experimental study was conducted from August 2020 to January 2022. Eight Bama minipigs underwent VVB of hepatic portal vein-femoral vein-internal jugular vein after occlusion of hepatic portal vein and inferior vena cava. The animals were divided into two groups according to the VVB devices used during VVB. A self-made VVB device was used in group A(n=5),and an imported VVB device was used in group B(n=3). The hemodynamic changes of the two groups of animals were compared at 6 time points including before vascular occlusion, during vascular occlusion, 30 minutes, 60 minutes, 90 minutes after the start of VVB, and 30 minutes after vascular opening. In addition,the changes of blood compatibility indexes,intestinal injury indexes,kidney injury indexes and internal environment indexes of the two groups of animals at each time point were compared. The independent samples t test was used for the quantitative data between the two groups with non-repeated measures,and the repeated measures analysis of variance was used for the quantitative data between the two groups with repeated measures. Results: During the VVB of the two devices,the venous drainage was sufficient,and the main manifestations were that the color of the intestine of the Bama miniature pig was ruddy, the peristalsis was normal, and the urine output was normal. There were no significant differences in hemodynamics,blood injure indexes,intestinal injury indexes,kidney injury indexes,neutropil gelatinase-associated lipocalin,and internal environment indexes(all P>0.05).The indexes at 30 minutes after vascular opening in the group A and the group B were as follows:mean arterial pressure were (71.0±7.7)mmHg(1 mmHg=0.133 kPa) and (74.0±8.7)mmHg,central venous pressure were (7.0±1.4)cmH₂O(1 cmH₂O=0.098 kPa) and (7.7±0.6)cmH₂O,heart rate were (131±10) beats/minutes and (132±8)beats/minutes; red blood cell count were (6.43±0.89)×10¹²/L and (6.32±0.58)×10¹²/L,hemoglobin were (108.4±5.9)g/L and (110.0±3.5)g/L,free hemoglobin were (78.28±3.96)mg/L and (78.08±4.54)mg/L; intestinal fatty acid binding protein were (2.27±0.49)μg/L and (2.40±0.78)μg/L;creatinine were (68.30±9.77)μmol/L and (79.90±26.91)μmol/L,blood urea nitrogen were (3.94±1.39)mmol/L and (3.45±0.65)mmol/L;neutropil gelatinase-associated lipocalin were (4.02±0.53) μg/L and (3.86±0.23)μg/L;pH value were 7.27±0.04 and 7.23±0.03,lactic acid were (6.18±2.62)mmol/L and (4.30±0.50)mmol/L,concentrations of Na⁺ were (136.3±3.0)mmol/L and (137.6±1.6) mmol/L,concentrations of K⁺ were (3.89±0.42) mmol/L and (3.98±0.17)mmol/L,concentrations of Ca²⁺ were (1.40±0.03)mmol/L and(1.40±0.04)mmol/L;all indexes in the two group had no differences(all P>0.05). Conclusion: The self-made venous bypass device can be safely and effectively applied to VVB of Bama minipigs,and achieves the same performance as the imported venous bypass device.
Animals ; Creatinine ; Fatty Acid-Binding Proteins ; Gelatinases ; Lactic Acid ; Lipocalins ; Liver Transplantation ; Magnetic Phenomena ; Portal Vein/surgery* ; Swine ; Swine, Miniature

OBJECTIVE: To observe the clinical effect of acupuncture on coronavirus disease 2019 (COVID-19) based on the conventional treatment. METHODS: A total of 35 patients with COVID-19 of mild or ordinary type were involved (3 cases dropped off). Acupuncture was applied on the basis of western medicine and Chinese materia medica treatment. Dazhui (GV 14), Fengchi (GB 20), Kongzui (LU 6), Hegu (LI 4), etc. were selected as the main acupoints, the supplementary acupoints and the reinforcing and reducing manipulations were selected according to syndrome differentiation. Acupuncture treatment was given once a day, 5 times a week. On day 3 and day 7 of acupuncture, relief condition of the main symptoms was observed. Before acupuncture and on day 3 and day 7 of acupuncture, efficacy evaluation scale of TCM on COVID-19 (efficacy evaluation scale) score was recorded. The effects of different intervention time of acupuncture on patients' hospitalization time were compared, the understanding of acupuncture treatment of patients discharged from hospital was recorded, the clinical efficacy and safety of acupuncture treatment were evaluated. RESULTS: On day 3 and day 7 of acupuncture, the symptoms of lung system and non lung system were both relieved; the scores of efficacy evaluation scale were both decreased compared before acupuncture (P<0.05), and the efficacy evaluation scale score of day 7 of acupuncture were lower than day 3 of acupuncture (P<0.05). The average hospitalization time of patients received early acupuncture was shorter than late acupuncture (P<0.05). The total effective rate was 84.4% (27/32) on day 7 of acupuncture, which was higher than 34.4% (11/32) on day 3 of acupuncture (P<0.05). During the acupuncture treatment, there were neither adverse reactions in patients nor occupational exposures in doctors. The patients generally believed that acupuncture could promote the recovery of COVID-19 and recommended acupuncture treatment. CONCLUSION On the basis of the conventional treatment, acupuncture can effectively relieve the clinical symptoms in patients with COVID-19, early intervention of acupuncture can accelerate the recovery process. Acupuncture has good safety, clinical compliance and recognition of patients.
Acupuncture Points ; Acupuncture Therapy ; COVID-19/therapy* ; Combined Modality Therapy ; Humans ; Treatment Outcome

Objective: To investigate the characteristics and comprehensive treatment of infected wounds in patients with iatrogenic Cushing's syndrome. Methods: A retrospective observational study was conducted. From May 2012 to December 2021, the data of 19 patients with iatrogenic Cushing's syndrome discharged from the Department of Burns and Plastic Surgery of the First Affiliated Hospital of Guangxi Medical University were collected, including 8 males and 11 females, aged 28-71 (56±11) years, with 12 cases of infected acute wounds and 7 cases of infected chronic wounds. The lesions were located in the limbs, perianal, and sacrococcygeal regions, with original infection ranging from 9 cm×5 cm to 85 cm×45 cm. After admission, the patients were performed with multidisciplinary assisted diagnosis and treatment, and the wounds were treated with debridement and vacuum sealing drainage, according to the size, severity of infection, suture tension, and bone and tendon tissue exposure of wounds, direct suture or autologous skin and/or artificial dermis and/or autologous tissue flap transplantation was selected for wound repair. The levels of cortisol and adrenocorticotropic hormone (ACTH) of patients at 8:00, 16:00, and 24:00 within 24 h after admission were counted. After admission, the number of operations, wound repair methods, and wound and skin/flap donor site healing of patients were recorded. During follow-up, the wounds were observed for recurrent infection. Results: The cortisol levels of 16 patients at 8:00, 16:00, and 24:00 within 24 h after admission were (130±54), (80±16), and (109±39) nmol/L, respectively, and ACTH levels were (7.2±2.8), (4.1±1.8), and (6.0±3.0) pg/mL, respectively; and the other 3 patients had no such statistical results. After admission, the number of surgical operation for patients was 3.4±0.9. The following methods were used for wound repair, including direct suturing in 4 cases and autologous skin and/or artificial dermis grafting in 9 cases, of which 2 cases underwent stage Ⅱ autologous skin grafting after artificial dermis grafting in stage Ⅰ, and 6 cases had pedicled retrograde island flap+autologous skin grafting. The wound healing was observed, showing that all directly sutured wounds healed well; the wounds in 6 cases of autologous skin and/or artificial dermis grafting healed well, and the wounds in 3 cases also healed well after the secondary skin grafting; the flaps in 4 cases survived well with the wounds in 2 cases with distal perforators flap arteries circumfluence obstacle of posterior leg healed after stage Ⅱ debridement and autologous skin grafting. The healing status of skin/flap donor sites was followed showing that the donor sites of medium-thickness skin grafts in the thigh of 4 cases were well healed after transplanted with autologous split-thickness grafts from scalp; the donor sites of medium-thickness skin grafts in 3 cases did not undergo split-thickness skin grafting, of which 2 cases had poor healing but healed well after secondary skin grafting 2 weeks after surgery; the donor sites of split-thickness skin grafts in the head of 2 patients healed well; and all donor sites of flaps healed well after autologous skin grafting. During follow-up of more than half a year, 3 gout patients were hospitalized again for surgical treatment due to gout stone rupture, 4 patients were hospitalized again for surgical treatment due to infection, and no recurrent infection was found in the rest of patients. Conclusions: The infected wounds in patients with iatrogenic Cushing's syndrome have poor ability to regenerate and are prone to repeated infection. Local wound treatment together with multidisciplinary comprehensive treatment should be performed to control infection and close wounds in a timely manner, so as to maximize the benefits of patients.
Adrenocorticotropic Hormone ; China ; Cushing Syndrome/surgery* ; Female ; Gout ; Humans ; Hydrocortisone ; Iatrogenic Disease ; Male ; Skin, Artificial ; Wound Infection

Objective: To explore the relationship between DNA methylation and occupational noise-induced hearing loss. Methods: A case-control study was conducted. People with hearing loss induced by occupational noise were recruited as the case group and those with normal hearing but still exposed to occupational noise were recruited as the control group. A total of 60 participants were included, of which 30 participants were in the case group and 30 in the control group. The methylation level was detected by 850k genome-wide DNA methylation chip technology. The significance of differential methylated position (DMP) was tested by R-packet 'Champ'. The differential methylated region (DMR) was analyzed by using Champ's Bumphunter algorithm. Cluster profiler was used to analyze the gene list for GO and KEGG pathway enrichment. Results: There was significant difference between two groups in binaural high-frequency average hearing threshold (P<0.05), but there was no significant difference in age, smoking, drinking, hypertension, physical exercise and cumulative noise exposure. The results of DMP and DMR analysis showed that 713875 sites were detected in the case group and the control group, and 439 methylation sites with significant difference, accounting for 0.06%; 650 regions were detected, and 72 methylation regions with significant differences, accounting for 11.08%. Compared with the control group, the results of GO enrichment analysis showed that the case group had statistically significant differences in four pathways: axogenesis of projection neurons in the central nervous system, neuronal development in the central nervous system, axogenesis of neurons in the central nervous system and neuronal differentiation in the central nervous system. KEGG enrichment analysis showed that there were significant differences in sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis pathway between the case group and the control group. Conclusion: The occurrence of occupational noise-induced hearing loss may be related to the regulation of gene expression related to axogenesis of projection neurons in the central nervous system, development of neurons in the central nervous system, axogenesis of neurons in the central nervous system, differentiation of neurons in the central nervous system, sphingolipid metabolism, aldosterone synthesis and secretion, primary bile acid biosynthesis and gene methylation related to metabolism.
Aldosterone ; Bile Acids and Salts ; Case-Control Studies ; DNA Methylation ; Hearing Loss, Noise-Induced/genetics* ; Humans ; Noise, Occupational/adverse effects* ; Occupational Diseases ; Occupational Exposure ; Sphingolipids

The novel coronavirus disease (COVID-19) pandemic is emerging as a global health threat and shows a higher risk for men than women. Thus far, the studies on andrological consequences of COVID-19 are limited. To ascertain the consequences of COVID-19 on sperm parameters after recovery, we recruited 41 reproductive-aged male patients who had recovered from COVID-19, and analyzed their semen parameters and serum sex hormones at a median time of 56 days after hospital discharge. For longitudinal analysis, a second sampling was obtained from 22 of the 41 patients after a median time interval of 29 days from first sampling. Compared with controls who had not suffered from COVID-19, the total sperm count, sperm concentration, and percentages of motile and progressively motile spermatozoa in the patients were significantly lower at first sampling, while sperm vitality and morphology were not affected. The total sperm count, sperm concentration, and number of motile spermatozoa per ejaculate were significantly increased and the percentage of morphologically abnormal sperm was reduced at the second sampling compared with those at first in the 22 patients examined. Though there were higher prolactin and lower progesterone levels in patients at first sampling than those in controls, no significant alterations were detected for any sex hormones examined over time following COVID-19 recovery in the 22 patients. Although it should be interpreted carefully, these findings indicate an adverse but potentially reversible consequence of COVID-19 on sperm quality.
Adult ; Asthenozoospermia/virology* ; COVID-19/physiopathology* ; China ; Gonadal Steroid Hormones/blood* ; Humans ; Male ; Progesterone/blood* ; Prolactin/blood* ; SARS-CoV-2 ; Semen/physiology* ; Semen Analysis ; Sperm Count ; Sperm Motility ; Spermatozoa/physiology* ; Time Factors