Objective To study the role of photobiomodulation(PBM)in promoting the repair of spinal cord injury(SCI)by regulating microglial cells.Methods Forty-five C57BL/6J mice were randomly divided into the sham operation(Sham)group,surgery(SCI)group and the treatment(SCI+PBM)group,with 15 mice in each.After laminectomy of the T10 vertebral body in the three groups of mice,the SCI group and the SCI+PBM group were used to construct the model of spinal cord hemisection.The SCI+PBM group received immediate PBM treatment after spinal cord injury,while the other two groups did not.On the 1st,3rd,7th,14th,21st and 28th days(D1,D3,D7,D14,D21,D28)after the operation,the Basso Mouse Scale(BMS)was used to assess the recovery of the hind limb motor function of the mice.On the 28th day post operatively,immunofluorescence was used to detect the changes of neurons in the areas of injury in the three groups of mice.Quantitative real-time PCR and Western blotting experiments were used to detect the phenotypic changes of BV2 cells under the interventions of PBM with inflammatory stimulation.Western blotting experiments were conducted to detect the effects of PBM on the nuclear factor kappa-B(NF-κB)pathway.Results On the 28th day after the operation,the results of the mouse motor assessment showed that the BMS scores and related behaviors of the mice in the SCI+PBM group were better than those of the mice in the SCI group(P＜0.05),and the neurons in the SCI+PBM group far outnumbered those in the SCI group(P＜0.05).The results of quantitative real-time PCR and Western blotting experiments showed that on the 14th day after the operation,PBM promoted the activation of M2-type microglial cells in vivo but inhibited the activation of M1-type microglial cells.In vitro experiments confirmed that PBM could promote the polarization of BV2 cells towards M2-type microglial cells.In addition,PBM inhibited the activation of the NF-κB pathway in injured spinal cords and in activated BV2 cells.Conclusion PBM can promote the repair of spinal cord injury in SCI mice by promoting microglial cells through inhibiting the NF-κB pathway.

Objective To explore the clinical effects and influencing factors of recombinant human growth hormone(rhGH)treatment in pediatric patients with growth hormone deficiency.Methods The study subjects were pediatric patients with growth hormone deficiency,all of whom received a combination therapy of stanozolol tablets 2 mg(qd)and 0.1 U·kg-1·d-1 of recombinant human growth hormone injection for a continuous period of one year.After one year,the patients were divided into active group and invalid group based on clinical outcomes.Comparisons were made between the two groups in terms of height,annual growth velocity(GV)and height standard deviation score(HtSDS)before and after treatment,and safety evaluations were conducted.Multivariate Logistic regression analysis was used to identify factors that influenced the treatment outcomes in pediatric patients with growth hormone deficiency.Results After one year of treatment,a total of 93 cases pediatric patients were included in the analysis,with 62 cases in the active group and 31 cases in the invalid group.The heights of the patients before and after treatment were(119.40±2.48)and(129.08±2.37)cm,respectively;the GV were(3.08±0.39)and(7.34±1.02)cm·year-1,respectively;the HtSDS were-2.45±0.49 and-1.68±0.35,respectively,with statistically significant differences observed for all comparisons(all P＜0.05).In the active and invalid groups,the proportions of patients with GV＜3.0 cm·year-1 before treatment were 32.26％and 58.06％,respectively;the proportions of patients with peak growth hormone(GH)levels＜5.0 ng·mL-1 before treatment were 30.65％and 54.84％,respectively;the average maternal heights were(158.83±5.76)and(155.48±6.58)cm,respectively,with statistically significant differences observed for all comparisons(all P＜0.05).The results of the Logistic regression model showed that GV＜3.0 cm·year-1 before treatment,peak GH levels＜5.0 ng·mL-1 before treatment,and a shorter maternal height were independent risk factors for poor treatment outcomes with rhGH in pediatric patients with growth hormone deficiency(all P＜0.05).No severe adverse reactions occurred during the treatment of any patient;seven patients experienced pain at the injection site,one patient had a slight increase in blood glucose,and five patients had mild decreased appetite.The total incidence of adverse drug reactions were 13.98％(13 cases/93 cases).Conclusion Treatment with rhGH for pediatric patients with growth hormone deficiency can significantly improve height development and has good safety,but it is influenced by factors such as growth velocity,peak GH levels,and maternal height.

As an indispensable trace element in the human body,copper plays an important role in various physiological and biochemical reactions.The dyshomeostasis of copper leads to the disorder of copper metabolism and the occurrence of related diseases.Cuproptosis,a newly proposed regulatory cell death mode,is different from the known apoptosis,pyroptosis,necroptosis,and ferroptosis.Recent studies have found that the dyshomeostasis of copper has been observed in a variety of cancers.Therefore,targeting copper for disease treatment may become a new strategy and a new idea.This article systematically summarizes the fundamental properties of copper,copper dyshomeostasis-related diseases (Menkes syndrome,Wilson's disease,and cancer) and their treatment,and reviews the research progress in cuproptosis.
Humans ; Copper/metabolism* ; Homeostasis ; Neoplasms/metabolism* ; Hepatolenticular Degeneration/metabolism* ; Menkes Kinky Hair Syndrome/metabolism*

Objective To explore the clinical effects and influencing factors of recombinant human growth hormone(rhGH)treatment in pediatric patients with growth hormone deficiency.Methods The study subjects were pediatric patients with growth hormone deficiency,all of whom received a combination therapy of stanozolol tablets 2 mg(qd)and 0.1 U·kg-1·d-1 of recombinant human growth hormone injection for a continuous period of one year.After one year,the patients were divided into active group and invalid group based on clinical outcomes.Comparisons were made between the two groups in terms of height,annual growth velocity(GV)and height standard deviation score(HtSDS)before and after treatment,and safety evaluations were conducted.Multivariate Logistic regression analysis was used to identify factors that influenced the treatment outcomes in pediatric patients with growth hormone deficiency.Results After one year of treatment,a total of 93 cases pediatric patients were included in the analysis,with 62 cases in the active group and 31 cases in the invalid group.The heights of the patients before and after treatment were(119.40±2.48)and(129.08±2.37)cm,respectively;the GV were(3.08±0.39)and(7.34±1.02)cm·year-1,respectively;the HtSDS were-2.45±0.49 and-1.68±0.35,respectively,with statistically significant differences observed for all comparisons(all P＜0.05).In the active and invalid groups,the proportions of patients with GV＜3.0 cm·year-1 before treatment were 32.26％and 58.06％,respectively;the proportions of patients with peak growth hormone(GH)levels＜5.0 ng·mL-1 before treatment were 30.65％and 54.84％,respectively;the average maternal heights were(158.83±5.76)and(155.48±6.58)cm,respectively,with statistically significant differences observed for all comparisons(all P＜0.05).The results of the Logistic regression model showed that GV＜3.0 cm·year-1 before treatment,peak GH levels＜5.0 ng·mL-1 before treatment,and a shorter maternal height were independent risk factors for poor treatment outcomes with rhGH in pediatric patients with growth hormone deficiency(all P＜0.05).No severe adverse reactions occurred during the treatment of any patient;seven patients experienced pain at the injection site,one patient had a slight increase in blood glucose,and five patients had mild decreased appetite.The total incidence of adverse drug reactions were 13.98％(13 cases/93 cases).Conclusion Treatment with rhGH for pediatric patients with growth hormone deficiency can significantly improve height development and has good safety,but it is influenced by factors such as growth velocity,peak GH levels,and maternal height.

Objective To analyze the risk of adverse drug events in pediatric clinical applications of tocilizumab versus inflixima.Methods Adverse event(AE)reporting data for tocilizumab versus infliximab in the U.S.Food and Drug Administration Adverse Event Reporting System database for the pediatric population from Q1 2013 to Q1 2023 were collected.AE risk signal mining was performed using the reporting odds ratio(ROR)method and the proportional reporting ratio(PRR)method.AEs were also classified and statistically analyzed according to the preferred system organ classification and preferred terminology(PT)of the International Dictionary of Medical Terminology.Results Data were extracted and cleaned to include 1 052 AE reports with 198 positive PT signals for tocilizumab as the suspected drug and 9 1 39 AE reports with 387 positive PT signals for infliximab as the suspected drug.The analyses suggested that the stronger positive risk signals for both drugs were focused on gastrointestinal disorders,infectious and invasive diseases,laboratory tests,musculoskeletal and connective tissue disorders,and blood,vascular,and lymphatic disorders.The risk signals for infliximab were focused on gastrointestinal disorders,infections,and infectious diseases,while the risk signals for tocilizumab were focused on the musculoskeletal muscle system.Conclusion Clinical use of both drugs in children has multi-system effects,tocilizumab may have effects on growth and development,and infliximab has effects on the gastrointestinal tract in children.

Congenital bilateral absence of the vas deferens (CBAVD) is observed in 1%-2% of males presenting with infertility and is clearly associated with cystic fibrosis transmembrane conductance regulator (CFTR) mutations. CFTR is one of the most well-known genes related to male fertility. The frequency of CFTR mutations or impaired CFTR expression is increased in men with nonobstructive azoospermia (NOA). CFTR mutations are highly polymorphic and have established ethnic specificity. Compared with F508Del in Caucasians, the p.G970D mutation is reported to be the most frequent CFTR mutation in Chinese patients with cystic fibrosis. However, whether p.G970D participates in male infertility remains unknown. Herein, a loss-of-function CFTR p.G970D missense mutation was identified in a patient with CBAVD and NOA. Subsequent retrospective analysis of 122 Chinese patients with CBAVD showed that the mutation is a common pathogenic mutation (4.1%, 5/122), excluding polymorphic sites. Furthermore, we generated model cell lines derived from mouse testes harboring the homozygous Cftr p.G965D mutation equivalent to the CFTR variant in patients. The Cftr p.G965D mutation may be lethal in spermatogonial stem cells and spermatogonia and affect the proliferation of spermatocytes and Sertoli cells. In spermatocyte GC-2(spd)ts (GC2) Cftr p.G965D cells, RNA splicing variants were detected and CFTR expression decreased, which may contribute to the phenotypes associated with impaired spermatogenesis. Thus, this study indicated that the CFTR p.G970D missense mutation might be a pathogenic mutation for CBAVD in Chinese males and associated with impaired spermatogenesis by affecting the proliferation of germ cells.
Humans ; Animals ; Mice ; Male ; Mutation, Missense ; Retrospective Studies ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Infertility, Male/genetics* ; Mutation ; Vas Deferens/abnormalities* ; Spermatogenesis/genetics*

OBJECTIVE: To evaluate the safety and effectiveness of Qishe Pill () on neck pain in real-world clinical practice. METHODS: A multi-center, prospective, observational surveillance in 8 hospitals across Shanghai was conducted. During patients receiving 4-week Qishe Pill medication, Visual Analogue Scale (VAS) and Neck Disability Index (NDI) assessments have been used to assess their pain and function, while safety monitoring have been observed after 2 and 4 weeks. RESULTS: Results from 2,023 patients (mean age 54.5 years) suggest that the drug exposure per unit of body mass was estimated at 3.41 ± 0.62 g/kg. About 8.5% (172/2,023) of all participants experienced adverse events (AEs), while 3.8% (78/2,023) of all participants experienced adverse reaction. The most common AEs were gastrointestinal events and respiratory events. The VAS score (pain) and NDI score (function) significantly decreased after 4-week treatment. An effect-quantitative analysis was also conducted to show that the normal clinical dosage may be consider as 3-4 g/kg, at which dosage the satisfactory pain-relief effect may achieve by 40-mm reduction in VAS. CONCLUSION These findings showed that patients with cervical radiculopathy who received Qishe Pill experienced significant improvement on pain and function. (Registration No. NCT01875562).

Objective:To summarize clinical characteristics of and treatment experience with patients with critical illnesses in a dermatological ward.Methods:All patients with serious or life-threatening conditions, who were hospitalized at the dermatological ward of the Second Xiangya Hospital of Central South University from July 9, 2011 to December 31, 2020, were collected, and their clinical data were retrospectively analyzed. Demographic characteristics, disease types and proportions, main complications, causes of serious or life-threatening conditions, important treatment measures and outcomes were summarized, and causes of death were also analyzed and discussed.Results:A total of 1 057 patients with critical illnesses were collected, with a male-to-female ratio of 1∶1.11, and 64.81% of them aged 18 to 65 years. The types of diseases mainly included drug eruptions (332 cases) , connective tissue diseases (226 cases) , bullous skin diseases (104 cases) , psoriasis (57 cases) , erythroderma (45 cases) , infectious skin diseases (67 cases) , etc. Among them, psoriasis (39 cases) and erythroderma (32 cases) mostly occurred in males, and connective tissue diseases (168 cases) mostly occurred in females. Common complications mainly involved infections, important organ damage or dysfunction, hypoalbuminemia, and fluid, electrolyte and acid-base imbalances. A total of 94 patients were diagnosed with life-threatening conditions, which were found to be mainly caused by primary skin diseases, hematologic abnormalities, respiratory failure, nervous system abnormalities, renal failure, sepsis, fluid, electrolyte and acid-base imbalances, etc. During the management of critical illnesses, 43 patients were treated with high-dose glucocorticoid pulse therapy, 264 were treated with gamma-globulin pulse therapy, 355 were transfused with other blood products, and 34 received special therapies such as hemoperfusion/immunoadsorption therapy, plasma exchange, dialysis, artificial liver support therapy; 42 patients were transferred to the intensive care unit (ICU) , 12 were transferred to the department of surgery for operations, and 12 were transferred to the department of obstetrics and gynecology for delivery or induction of labor. After treatment, 989 patients (93.57%) achieved improvement and were discharged. A total of 14 patients (1.32%) died, of whom 7 died of secondary sepsis, 2 died of severe pulmonary infections, 2 died of asphyxia caused by respiratory mucosa shedding-induced airway obstruction, the other 3 died of gastrointestinal hemorrhage, cerebral hemorrhage and neuropsychiatric systemic lupus erythematosus, respectively.Conclusions:Critical cases in the dermatological ward mainly suffered from serious skin diseases such as severe drug eruptions, connective tissue diseases and bullous skin diseases, as well as complications such as severe underlying diseases, severe organ dysfunction, sepsis or severe fluid, electrolyte and acid-base imbalances. In terms of treatment, it is of critical significance to make a clear diagnosis and assess the severity of disease as early as possible, monitor and prevent possible complications, and to consult with specialists in relevant disciplines in time.

Objective:To explore the feasibility, safety and effectiveness of anatomical partial lobectomy.Methods:The clinical data of 3 336 patients with lung nodules underwent anatomical partial lobectomy in our center from November 2013 to November 2019 were retrospectively analyzed. We set the safety margin distance according to the imaging feature of the lesion. The surgeons then anatomically detached the major vessels and bronchus in this region, resected the targeted lung tissue along the plane, and completed the resection of anatomical pulmonary lobe and clean and sampling of systemic lymph nodules.Results:A total of 668 cases were multiple nodules and 2 668 cases were solitary pulmonary nodules. According to the postoperative pathological results, 283 cases were benign, 1 197 cases were preinvasive lesions (including 38 cases of atypical adenomatous hyperplasia, 445 cases of adenocarcinoma in situ and 714 cases of minimally invasive adenocarcinoma), 1 713 cases were invasive adenocarcinoma, 73 cases were non-adenocarcinoma and 70 cases were metastatic carcinoma. Among 1 786 invasive primary lung cancers, 11 cases received preoperative neoadjuvant chemotherapy, and their postoperative pathologic diagnoses were stage ypIA. Other 1 775 cases who did not receive postoperative neoadjuvant treatment included 1 587 cases in stage ⅠA, 112 cases in stage ⅠB, 3 cases in stage ⅡA, 18 cases in stage ⅡB, 37 cases in stage ⅢA, 9 cases in stage ⅢB, 9 cases in stage Ⅳ. The average operation time was (127.3±55.3) minutes, and the mean postoperative hospital stay was (4.8±2.4) days. The incidence rate of complications (grade>2) was 1.1%(38/3 336), and no death occurred during 30 days after operation.Conclusion:Anatomic partial lobectomy has good clinical applicability, safety and effectiveness, which is worthy of clinical application and recommendation.

Slow freezing is the most commonly used technique for the cryopreservation of spermatozoa in clinical practice. However, it has been shown to have a negative impact on sperm function and structure. Vitrification as a successful alternative method has been proved to have better protective effects on human embryos, but vitrification of spermatozoa is still subject to low recovery rates. In this study, a modified vitrification method for native spermatozoa was developed. A total of 28 semen samples were included; each sample was divided into three equal parts and assigned to fresh, slow freezing, and vitrification groups. Sperm vitality, motility, morphology, DNA integrity, and acrosome reaction were assessed for each of the groups. The results showed that vitrification achieves better results for several sperm protection parameters than slow freezing; vitrification achieves a higher recovery rate (P < 0.05), motility (P <0.05), morphology (P <0.05), and curve line velocity (P <0.05) than slow freezing. Furthermore, DNA fragmentation was decreased (P <0.05) and better acrosome protection (P <0.05) was exhibited in the spermatozoa after vitrification. Principal component analysis of all sperm parameters revealed that the vitrification cluster was closer to the fresh cluster, indicating that spermatozoa are better preserved through vitrification. In conclusion, while both slow freezing and vitrification have negative effects on sperm function and structure, the vitrification protocol described here had a relatively better recovery rate (65.8%) and showed improved preservation of several sperm quality parameters compared with slow freezing.