OBJECTIVE: To evaluate clinical effect of transcutaneous acupoint electrical stimlation (TEAS) on perioperative immune function and postoperative recovery in patients with total knee arthroplasty (TKA). METHODS: From November 2021 to July 2022, 80 patients with unilateral TKA were selected and divided into TEAS group and sham TEAS group according to different treatment methods. There were 40 patients in TEAS group, including 9 males and 31 females;aged from 61 to 79 years old with an average of (66.90±5.86) years old;body mass index (BMI) ranged from 19.53 to 30.47 kg·m^-2 with an average of (25.34±2.83) kg·m^-2;21 patients on the left side, 19 patients on the right side;according to American Society of Anesthesiologists (ASA), 30 patients with gradeⅡ, 10 patients with grade Ⅲ;TEAS were administered at the bilateral Hegu (LI4), Neiguan (PC6) and non-operative Zusanli (ST36) and Sanyinjiao (SP6) points from 30 min before anesthesia to the end of operation, the frequency was 2/10 Hz, current intensity was tolerable and/or muscle rhythmic twitches of limbs were performed. There were 40 patients in sham TEAS group, including 9 males and 31 females;aged from 60 to 80 years old with an average of (67.35±4.29) years old;27 patients on the left side and 13 patients on the right side;BMI ranged from 20.02 to 30.09 kg·m^-2 with an average of (25.02±2.23) kg·m^-2;28 patients with gradeⅡand 12 patients with grade Ⅲ according to ASA;Electrodes were attached to the same points without electrical stimulation. Percentage contents of 24 h CD3+, CD4+, CD8+ and NK cells, postoperative infection, incidence of nausea, vomiting, abdominal distension and pruritus within 48 h after surgery, the first time on the ground, length of hospital stay and quality of recovery-15 (QoR-15) score were compared between two groups. RESULTS: Compared with pseudoteas group, expressions of CD3+ and CD4+ T lymphocytes in TEAS group were significantly increased at 24 h after surgery (P<0.05). The incidence of nausea within 48 h after surgery and the time spent on the ground early after surgery were significantly decreased (P<0.05). There was no significant difference in postoperative secondary infection, adverse reactions such as vomiting, abdominal distension, pruritus and hospitalization days (P>0.05). CONCLUSION Percutaneous acupoint electrical stimulation could improve perioperative cellular immunity in patients with total knee replacement, alleviate immunosuppression, reduce incidence of postoperative adverse reactions, and promote early postoperative recovery.
Humans ; Male ; Female ; Aged ; Middle Aged ; Arthroplasty, Replacement, Knee ; Acupuncture Points ; Postoperative Period ; Transcutaneous Electric Nerve Stimulation/methods* ; Recovery of Function

Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.
Male ; Mice ; Animals ; Testis/metabolism* ; Ferroptosis ; Semen ; Oxidative Stress

Objective: To investigate the clinical efficacy of entecavir combined with Biejiajian pills and its influence on TCM syndrome scores during the treatment of chronic hepatitis B with hepatic fibrosis and blood stasis syndrome by prospective, randomized and controlled study. Methods: Patients with chronic hepatitis B with hepatic fibrosis and blood stasis syndrome were selected as the research subjects and randomly divided into a treatment group and a control group. Entecavir plus Biejiajian pills or entecavir plus a simulant of Biejiajian pills were given for 48 weeks. The changes in liver stiffness measurement (LSM) and TCM syndrome scores before and after treatment were compared between the two groups to analyze the correlation. The data between groups were analyzed by t-test/Wilcoxon rank sum test or χ(2) test. Pearson correlation coefficient was used to analyze the correlation between TCM syndrome scores and LSM values. Results: After 48 weeks of treatment, the LSM values of the two groups were significantly lower than those of the baseline (P < 0.001), liver fibrosis was significantly improved, and the LSM values of the treatment group were lower than those of the control group [(8.67 ± 4.60) kPa and (10.13 ± 4.43) kPa, t = -2.011, P = 0.049]. After 48 weeks of treatment, the TCM syndrome scores of the two groups were significantly reduced compared with the baseline (P < 0.001), and the clinical symptoms were significantly relieved, and the total effective rates of the improvement of the TCM syndrome scores in the two groups were 74.19% and 72.97%, respectively, but the differences between the groups were not statistically significant (χ(2) = 0.013, P = 0.910). Correlation analysis showed that there was no obvious trend between TCM syndrome scores and LSM values. There were no serious adverse reactions associated with the drug during the observation period of this study. Conclusion: Based on antiviral treatment with entecavir, regardless of whether it is combined with the Biejiajian pill, it can effectively reduce the LSM value, improve liver fibrosis, reduce TCM syndrome scores, and alleviate symptoms in patients with chronic hepatitis B with liver fibrosis and blood stasis syndrome. Compared with entecavir alone, the combined Biejia pill has greater efficacy in improving liver fibrosis and a favorable safety profile, meriting its implementation and widespread application.
Humans ; Antiviral Agents/therapeutic use* ; Hepatitis B, Chronic/drug therapy* ; Liver Cirrhosis/drug therapy* ; Prospective Studies ; Treatment Outcome

OBJECTIVE: To analyze the efficacy of Biejiajian Pill (BJJP) on intestinal microbiota in patients with hepatitis B cirrhosis/liver fibrosis, and explore its relationship with liver fibrosis. METHODS: This was a prospective, randomized double-blind controlled trial. Using the stratified block randomization method, 35 patients with hepatitis B liver cirrhosis/liver fibrosis were randomly assigned (1:1) to receive entecavir (0.5 mg/d) combined with BJJP (3 g/time, 3 times a day) or placebo (simulator as control, SC group, simulator 3 g/time, 3 times a day) for 48 weeks. Blood and stool samples were collected from patients at baseline and week 48 of treatment, respectively. Liver and renal functions as well as hematological indices were detected. Fecal samples were analyzed by 16S rDNA V3-V4 high-throughput sequencing, and intestinal microbiota changes in both groups before and after treatment were compared, and their correlations with liver fibrosis were analyzed. RESULTS: Compared with the SC group, there was no significant difference in liver function, renal function and hematology indices in the BJJP group, however, the improvement rate of liver fibrosis was higher in the BJJP group (94.4% vs. 64.7%, P=0.041). Principal coordinate analysis (PCoA) based on weighted Unifrac distance showed significant differences in intestinal microbiota community diversity before and after BJJP treatment (P<0.01 and P=0.003), respectively. After 48 weeks' treatment, the abundance levels of beneficial bacteria (Bifidobacteria, Lactobacillus, Faecalibacterium and Blautia) increased, whereas the abundance levels of potential pathogenic bacteria, including Escherichia coli, Bacteroides, Ruminococcus, Parabacteroides and Prevotella decreased, among which Ruminococcus and Parabacteroides were significantly positively correlated with degree of liver fibrosis (r=0.34, P=0.04; r=0.38, P=0.02), respectively. The microbiota in the SC group did not change significantly throughout the whole process of treatment. CONCLUSION BJJP had a certain regulatory effect on intestinal microbiota of patients with hepatitis B cirrhosis/liver fibrosis (ChiCTR1800016801).
Humans ; Gastrointestinal Microbiome ; Prospective Studies ; Liver Cirrhosis/drug therapy* ; Hepatitis B/drug therapy*

Objective: To explore the effects of three-dimensional (3D) bioprinting gelatin methacrylamide (GelMA) hydrogel loaded with nano silver on full-thickness skin defect wounds in rats. Methods: The experimental research method was adopted. The morphology, particle diameter, and distribution of silver nanoparticles in nano silver solution with different mass concentrations and the pore structure of silver-containing GelMA hydrogel with different final mass fractions of GelMA were observed by scanning electron microscope and the pore size was calculated. On treatment day 1, 3, 7, and 14, the concentration of nano silver released from the hydrogel containing GelMA with final mass fraction of 15% and nano silver with final mass concentration of 10 mg/L was detected by mass spectrometer. At 24 h of culture, the diameters of inhibition zone of GelMA hydrogel containing final mass concentration of 0 (no nano silver), 25, 50, and 100 mg/L nano silver against Staphylococcus aureus and Escherichia coli were detected. Fibroblasts (Fbs) and adipose stem cells (ASCs) were isolated respectively by enzymatic digestion using the discarded prepuce after circumcision from a 5-year-old healthy boy who was treated in the Department of Urology of the Second Affiliated Hospital of Zhejiang University School of Medicine in July 2020, and the discarded fat tissue after liposuction from a 23-year-old healthy woman who was treated in the Department of Plastic Surgery of the Hospital in July 2020. The Fbs were divided into blank control group (culture medium only), 2 mg/L nano sliver group, 5 mg/L nano sliver group, 10 mg/L nano sliver group, 25 mg/L nano sliver group, and 50 mg/L nano sliver group, which were added with the corresponding final mass concentrations of nano sliver solution, respectively. At 48 h of culture, the Fb proliferation viability was detected by cell counting kit 8 method. The Fbs were divided into 0 mg/L silver-containing GelMA hydrogel group, 10 mg/L silver-containing GelMA hydrogel group, 50 mg/L silver-containing GelMA hydrogel group, and 100 mg/L silver-containing GelMA hydrogel group and then were correspondingly treated. On culture day 1, 3, and 7, the Fb proliferation viability was detected as before. The ASCs were mixed into GelMA hydrogel and divided into 3D bioprinting group and non-printing group. On culture day 1, 3, and 7, the ASC proliferation viability was detected as before and cell growth was observed by live/dead cell fluorescence staining. The sample numbers in the above experiments were all 3. Four full-thickness skin defect wounds were produced on the back of 18 male Sprague-Dawley rats aged 4 to 6 weeks. The wounds were divided into hydrogel alone group, hydrogel/nano sliver group, hydrogel scaffold/nano sliver group, and hydrogel scaffold/nano sliver/ASC group, and transplanted with the corresponding scaffolds, respectively. On post injury day (PID) 4, 7, 14, and 21, the wound healing was observed and the wound healing rate was calculated (n=6). On PID 7 and 14, histopathological changes of wounds were observed by hematoxylin eosin staining (n=6). On PID 21, collagen deposition of wounds was observed by Masson staining (n=3). Data were statistically analyzed with one-way analysis of variance, analysis of variance for repeated measurement, Bonferroni correction, and independent sample t test. Results: The sliver nano particles in nano silver solution with different mass concentrations were all round, in scattered distribution and uniform in size. The silver-containing GelMA hydrogels with different final mass fractions of GelMA all showed pore structures of different sizes and interconnections. The pore size of silver-containing GelMA hydrogel with 10% final mass fraction was significantly larger than that of silver-containing GelMA hydrogels with 15% and 20% final mass fractions (with P values both below 0.05). On treatment day 1, 3, and 7, the concentration of nano silver released from silver-containing GelMA hydrogel in vitro showed a relatively flat trend. On treatment day 14, the concentration of released nano silver in vitro increased rapidly. At 24 h of culture, the diameters of inhibition zone of GelMA hydrogel containing 0, 25, 50, and 100 mg/L nano silver against Staphylococcus aureus and Escherichia coli were 0, 0, 0.7, and 2.1 mm and 0, 1.4, 3.2, and 3.3 mm, respectively. At 48 h of culture, the proliferation activity of Fbs in 2 mg/L nano silver group and 5 mg/L nano silver group was both significantly higher than that in blank control group (P<0.05), and the proliferation activity of Fbs in 10 mg/L nano silver group, 25 mg/L nano silver group, and 50 mg/L nano silver group was all significantly lower than that in blank control group (P<0.05). Compared with the that of Fbs in 0 mg/L silver-containing GelMA hydrogel group, the proliferation activity of Fbs in 50 mg/L silver-containing GelMA hydrogel group and 100 mg/L silver-containing GelMA hydrogel group was all significantly decreased on culture day 1 (P<0.05); the proliferation activity of Fbs in 50 mg/L silver-containing GelMA hydrogel group was significantly increased (P<0.05), while the proliferation activity of Fbs in 100 mg/L silver-containing GelMA hydrogel group was significantly decreased on culture day 3 (P<0.05); the proliferation activity of Fbs in 100 mg/L silver-containing GelMA hydrogel group was significantly decreased on culture day 7 (P<0.05). The proliferation activity of ASCs in 3D bioprinting group show no statistically significant differences to that in non-printing group on culture day 1 (P>0.05). The proliferation activity of ASCs in 3D bioprinting group was significantly higher than that in non-printing group on culture day 3 and 7 (with t values of 21.50 and 12.95, respectively, P<0.05). On culture day 1, the number of dead ASCs in 3D bioprinting group was slightly more than that in non-printing group. On culture day 3 and 5, the majority of ASCs in 3D bioprinting group and non-printing group were living cells. On PID 4, the wounds of rats in hydrogel alone group and hydrogel/nano sliver group had more exudation, and the wounds of rats in hydrogel scaffold/nano sliver group and hydrogel scaffold/nano sliver/ASC group were dry without obvious signs of infection. On PID 7, there was still a small amount of exudation on the wounds of rats in hydrogel alone group and hydrogel/nano sliver group, while the wounds of rats in hydrogel scaffold/nano sliver group and hydrogel scaffold/nano sliver/ASC group were dry and scabbed. On PID 14, the hydrogels on the wound surface of rats in the four groups all fell off. On PID 21, a small area of wounds remained unhealed in hydrogel alone group. On PID 4 and 7, the wound healing rates of rats in hydrogel scaffold/nano sliver/ASC group were significantly higher than those of the other three groups (P<0.05). On PID 14, the wound healing rate of rats in hydrogel scaffold/nano sliver/ASC group was significantly higher than the wound healing rates in hydrogel alone group and hydrogel/nano sliver group (all P<0.05). On PID 21, the wound healing rate of rats in hydrogel alone group was significantly lower than that in hydrogel scaffold/nano sliver/ASC group (P<0.05). On PID 7, the hydrogels on the wound surface of rats in the four groups remained in place; on PID 14, the hydrogel in hydrogel alone group was separated from the wounds of rats, while some hydrogels still existed in the new tissue of the wounds of rats in the other three groups. On PID 21, the collagen arrangement in the wounds of rats in hydrogel alone group was out of order, while the collagen arrangement in the wounds of rats in hydrogel/nano sliver group, and hydrogel scaffold/nano sliver/ASC group was relatively orderly. Conclusions: Silver-containing GelMA hydrogel has good biocompatibility and antibacterial properties. Its three-dimensional bioprinted double-layer structure can better integrate with new formed tissue in the full-thickness skin defect wounds in rats and promote wound healing.
Male ; Rats ; Animals ; Humans ; Hydrogels/pharmacology* ; Bioprinting ; Metal Nanoparticles ; Rats, Sprague-Dawley ; Silver/pharmacology* ; Soft Tissue Injuries ; Anti-Bacterial Agents

Objective: To investigate the clinicopathological characteristics and the survival of re-operated patients for persistent/recurrent papillary thyroid carcinoma (PTC) and risk factors for re-recurrence after the second operation. Method: A retrospective analysis of 69 cases underwent re-operation for persistent/recurrent PTC in Sichuan Cancer Hospital from January 2010 to December 2016 was performed. There were 21 males and 48 females, aged 14-85 (44.8) years old. According to the imaging after initial treatment, they were divided into a recurrence group (42 cases) and a persistent disease/residual group (27 cases). The positive rates of ipsilateral paratracheal lymph node metastases at re-operation were calculated and compared by chi-square test. Patients were divided into different subgroups according to potential risk factors for re-recurrence. Kaplan-Meier (K-M) method was used for survival analysis. Results: The positive rate of ipsilateral paratracheal lymph node metastasis in recurrence group (15/42, 35.7%) was significantly lower than that in the persistent disease/residual group (17/27, 63.0%) (χ²=4.91, P<0.05). The follow-up period after re-operation was 60-104 months, with a median of 66 months, and 8 patients were lost to follow-up. Permanent hypoparathyroidism occurred in 2 cases (2.9%) and permanent recurrent laryngeal nerve palsy in 1 case (1.4%). Twenty patients had structural recurrences and/or distant metastases. The 5-year disease-specific survival rate was 92.8% and the 5-year recurrence-free survival rate was 68.1%. Survival analysis was performed on risk factors such as age≥55 years old, recurrent tumor diameter ≥4 cm, number of positive lymph nodes ≥ 10, and obvious extracapsular invasion (ENE). Among them, age and diameter of recurrent tumor had significant influences on recurrence-free survival rate (χ² was 6.36, 8.17, respectively, both P values<0.05). There was a statistically significant difference in recurrence-free survival rates between ENE(+) group and ENE(-) group (χ²=5.52, P<0.05). Conclusion: For the re-operated patients due to persistence/ recurrence PTC, attention should be paid to protecting the parathyroid gland and recurrent laryngeal nerve during re-operation. Timely and effective postoperative follow-up for patients aged ≥ 55 years, with recurrent tumor diameter ≥ 4 cm and ENE(+), can significantly improve their prognoses.
Adult ; Carcinoma/pathology* ; Carcinoma, Papillary/surgery* ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neck Dissection ; Neoplasm Recurrence, Local/surgery* ; Prognosis ; Retrospective Studies ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/pathology* ; Thyroidectomy/adverse effects*

Aim To investigate the role of calcium-independent phospholipase A2(iPLA2)in calcium regu-lation of intrarenal artery smooth muscle contraction.Methods The method of measuring the tension of isolated arterioles was used to explore the effect of bromoenol lactone(BEL), a specific inhibitor of iPLA2, on the tension of the intrarenal arteries in mice induced by different calcium channels, and the laser confocal calcium measurement technology was used to investigate the effect of BEL on the intracellular calcium influx mediated by arachidonic acid-mediated calcium channels.Results The intrarenal artery concentration dependent contractile response induced by the vasoconstrictors phenylephrine and 5-hydroxy tryptamine was inhibited by BEL(P<0.01).The contraction curve induced by CaCl2 was also inhibited by BEL(P<0.05).In the calcium-free K-H solution incubated with nifedipine, the intrarenal artery vasoconstriction caused by the release of sarcoplasmic reticulum calcium and the calcium influx of the SOC channel induced by CaCl2 was inhibited by BEL(P<0.05).BEL significantly inhibited the external calcium influx mediated by the ARC channel of human aortic smooth muscle cell lines incubated with nifedipine(P<0.01).Conclusions iPLA2 mediates the contractile response of intrarenal arteries by regulating the functions of L-type calcium channels, sarcoplasmic reticulum calcium release, SOC channels and ARC channels.

OBJECTIVES: To explore the differential expression of messenger RNA (mRNA) in myocardial tissues of rats with sudden coronary death (SCD), and to provide ideas for the forensic identification of SCD. METHODS: The rat SCD model was established, and the transcriptome sequencing was performed by next-generation sequencing technology. Differentially expressed genes (DEGs) in myocardial tissues of SCD rats were screened by using the R package limma. A protein-protein interaction (PPI) network was constructed by using the STRING database and Cytoscape 3.8.2 on DEG, and hub genes were screened based on cytoHubba plug-in. Finally, the R package clusterProfiler was used to analyze the biological function and signal pathway enrichment of the selected DEG. RESULTS: A total of 177 DEGs were associated with SCD and were mainly involved in the renin-angiotensin system and PI3K-Akt signaling pathway. The genes including angiotensinogen (AGT), complement component 4a (C4a), Fos proto-oncogene (FOS) and others played key roles in the development of SCD. CONCLUSIONS Genes such as AGT, C4a, FOS and other genes are expected to be potential biomarkers for forensic identification of SCD. The study based on mRNA expression profile can provide a reference for forensic identification of SCD.
Rats ; Animals ; RNA, Messenger/genetics* ; Gene Regulatory Networks ; Gene Expression Profiling ; Phosphatidylinositol 3-Kinases/genetics* ; Biomarkers

AIM: To investigate long-term efficacy and safety of patients after excimer laser in situ keratomileusis(LASIK)surgery in 20a.METHODS: A retrospective study.Patients who underwent LASIK in our hospital from January 1998 to December 2001 were recruited. The patients were notified by telephone to the outpatient for follow-up. The collected data included demographic characteristics(gender and age), preoperative uncorrected distance visual acuity(UCVA)and best corrected visual acuity(BCVA), preoperative diopter, intraoperative corneal flap thickness and corneal stromal residual thickness(RST). The main indicators were long-term efficacy index, safety index, UCVA, BCVA, corneal thickness and axial length. The slit lamp, fundus and optical coherence tomography(OCT)examination were performed at the same time.RESULTS: A total of 95 patients(190 eyes)were recruited. At the final postoperative visit, there were 71 patients(142 eyes, 74.7%)had UCVA≥1.0, and 82 patients(164 eyes, 86.3%)had BCVA≥1.0. There were 2 eyes among them had bad BCVA(≤0.6)due to macular retinoschisis and glaucoma, respectively, while other patients' BCVA was 0.8. There was no significant correlation between the UCVA and BCVA of patients after surgery in 20a and the factors such as age at surgery, preoperative diopter and corneal thickness(P>0.05), but there was a negative correlation with the increase of axis length(rs=-0.32, -0.31, all P<0.05). UCVA and BCVA were positively correlated with corneal stromal residual thickness at the last postoperative follow-up(P<0.05). The safety and efficacy indexes of LASIK after surgery in 20a were 1.00±0.10 and 0.83±0.27, respectively. During the follow-up, no patients were found to have corneal ectasia and complications related to corneal flap, and no patients underwent secondary surgery. No patients with corneal dryness were found after silt lamp examination.CONCLUSION: LASIK after surgery in 20a shows good safety and efficacy.

The processing of Chinese medicine is a unique and dialectical treatment of traditional Chinese medicine in clinic.The processing theory of "leading vinegar-processing Chinese medicine into liver" is one of the traditional processing theories of Chinese medicine.The vinegar-processing Chinese medicine under the guidance of the processing theory typically reflects the characteristics of "reducing toxicity and enhancing efficacy" of the processing of Chinese medicine.This paper traced the origin and discussed the connotation of the traditional theory of "leading vinegar-processing Chinese medicine into liver".Combined with the research status of "lea-ding vinegar-processing Chinese medicine into liver", this paper explored the mechanism of "leading vinegar-processing Chinese medicine into liver" from the aspects of material basis, medicine effect, and traditional Chinese medicine(TCM) meridian, and analyzed the existing problems in the current research.This paper reviewed the modern study on reducing toxicity and enhancing efficacy of vinegar-processing Chinese medicine, and deeply explored the scientific connotation of the traditional processing theory of "leading vinegar-processing Chinese medicine into liver".At the same time, the research trend and idea of the effect mechanism of "leading vinegar-processing Chinese medicine into liver" based on the Quality markers(Q-Marker) of TCM, biological targets, and clinical prescriptions were put forward, providing references for the further study on "leading vinegar-processing Chinese medicine into liver".This paper also provided a scientific basis for the rational selection of processed products in TCM clinical practice.
Acetic Acid ; Biomarkers ; Drugs, Chinese Herbal ; Liver ; Medicine, Chinese Traditional ; Meridians