The pathogenesis of chronic wound healing is complex. It is often difficult to heal due to a long course of disease， difficulty in treatment， and it seriously affects the quality of life in patients. The active ingredients， couplet medicinals， and compound formulas of traditional Chinese medicine （TCM） possess unique advantages in the treatment of chronic wound healing. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway is extremely critical in the treatment of chronic wound healing by regulating a series of biological processes， including cell apoptosis， angiogenesis， and inflammatory responses. This article reviews the relevant research on the regulation of the PI3K/Akt signaling pathway by TCM to promote chronic wound healing. It has been found that the active ingredients of TCM （such as geniposide， astragaloside， and ginsenosides， etc.）， and compound formulas （such as Chonghe ointment， Huanglian ointment， Shirun shaoshang ointment， etc.） mainly reduce inflammatory responses， promote angiogenesis， regulate cell autophagy， and accelerate wound healing by activating the PI3K/Akt signaling pathway； at the same time， there are also a few couplet medicinals（ such as Huangqi-Honghua） and compound formulas （such as Xiangpi Shengji ointment） that exert anti-inflammatory effects by inhibiting this signaling pathway， to promote wound healing.

Nonobstructive azoospermia (NOA), one of the most severe types of male infertility, etiology often remains unclear in most cases. Therefore, this study aimed to detect four biallelic detrimental variants (0.5%) in the minichromosome maintenance domain containing 2 ( MCMDC2 ) genes in 768 NOA patients by whole-exome sequencing (WES). Hematoxylin and eosin (H&E) demonstrated that MCMDC2 deleterious variants caused meiotic arrest in three patients (c.1360G>T, c.1956G>T, and c.685C>T) and hypospermatogenesis in one patient (c.94G>T), as further confirmed through immunofluorescence (IF) staining. The single-cell RNA sequencing data indicated that MCMDC2 was substantially expressed during spermatogenesis. The variants were confirmed as deleterious and responsible for patient infertility through bioinformatics and in vitro experimental analyses. The results revealed four MCMDC2 variants related to NOA, which contributes to the current perception of the function of MCMDC2 in male fertility and presents new perspectives on the genetic etiology of NOA.
Humans ; Male ; Azoospermia/genetics* ; Meiosis/genetics* ; Spermatogenesis/genetics* ; Adult ; Exome Sequencing ; Microtubule-Associated Proteins/genetics* ; Alleles ; Infertility, Male/genetics*

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

Objective To summarize the clinical experience of pulmonary lobectomy by uniportal video-assisted thoracoscope in parallel position.Methods The clinical data of 90 patients who underwent uniportal video-assisted thoracoscopic lobectomy in Zhongshan Hospital(Xiamen Branch),Fudan University were retrospectively analyzed.Among them,41 patients underwent lobectomy by uniportal thoracoscope in parallel position,and 49 patients underwent lobectomy by uniportal thoracoscope in non-parallel position.The perioperative related indicators of the two groups were compared.Results There was no significant statistical difference between the parallel uniportal thoracoscopic group and the non-parallel uniportal thoracoscopic group in terms of operation time[(135.2±18.1)min vs.(132.7±25.6)min],intraoperative blood loss[(100.1±27.2)mL vs.(117.3±33.5)mL],postperative extubation time[(3.0±0.7)d vs.(3.1±0.9)d],hospitalization time after operation[(4.3±1.3)d vs.(4.8±1.5)d]and relapse rate after surgery in 3 year(7.32%vs.10.20%).Conclusion Lobectomy by uniportal thoracoscope in parallel position was safe and feasible in technique.

Licorice-gypsum (gancao-shigao, GC-SG) drug pair was used as the research object, using supramolecular chemistry to explore the scientific connotation of combining herbal medicine GC with insoluble mineral medicine SG in clinical application of traditional Chinese medicine. ① The Tyndall effect, microscopic morphology and particle size of the single and co-decocted of GC and SG were observed, the paste content and conductivity were determined, and the interaction between GC and SG was detected by isothermal titration calorimetry (ITC) and infrared absorption spectroscopy (IR). ② Calcium chloride (CaCl₂), a soluble calcium salt of equal gypsum quality, was used instead of SG with GC for co-decocting to explore the effect of calcium salt content on the water decocting, and the characteristics were combined with the Tyndall effect, microscopic morphology, paste content and conductivity. ITC and IR techniques were used to detect the interaction between the two, and the interaction between them was detected by ITC and IR. The zeta potential and ultraviolet-visible spectrophotometry (UV-vis) of GC-SG and GC-CaCl₂ co-decoction were compared, and the inorganic and organic components in the co-decoction were detected by inductively coupled plasma optical emission spectrometer (ICP-OES) and high performance liquid chromatography (HPLC). The results showed: ① Compared with the liquid phase of single decoction, GC-SG co-decoction had more obvious Tyndall effect, and showed uniform spherical nanoparticles under electron microscope. Physical characterization results such as paste content and conductivity showed that co-decoction promoted the dissolution of each other's components; ITC and IR results showed that there was strong interaction between GC and SG, which preliminatively indicated that GC and SG co-decoction promoted the formation of uniform and stable supramolecular system of traditional Chinese medicine. ② When soluble calcium salt was used to substitute insoluble SG with GC for co-decocting, a stronger but astigmatic light path appeared than single decocting solution, the zeta potential was reduced, and a large number of accumulated polymers were formed. The results of paste content and conductivity showed that the dissolution of the co-decocting component was reduced than the single decocting component. ITC, UV-vis and IR results showed that there was interaction between GC with Ca²⁺ and SG. The formation of polysink indicated that a large amount of soluble calcium salt would destroy the stability of supramolecular Chinese medicine. The results of ICP-OES and HPLC showed that the glycyrrhizic acid (GA) content of the former lower than the latter, which was related to the formation of a large number of polycondensates with the increase of Ca²⁺ concentration and the decrease of the dissolution of GA and other active ingredients. This study indicates that the compatibility of GC and SG can form a uniform and stable supramolecular system of traditional Chinese medicine. Calcium salt, the main component of SG, is taken as the starting point. Excessive soluble Ca²⁺ can promote the aggregation of active ingredients such as GA, so as to reveal the scientific connotation of the compatibility of GC and SG, an insoluble mineral medicine.

Objective To investigate the effects of forsythinol(Fo)on the expression of matrix metalloproteinase-2(MMP2)in hepatoma cells through Janus kinase 2/signal transduction and transcriptional activator 3(JAK2/STAT3)signaling pathway.Methods SMMC-7721 cells were divided into experimental-L,-M,-H groups,control group,inhibitor group and activator group.The control group was added with equal volume dimethyl sulfoxide(DMSO);the experimental-L,-M,-H groups were treated with 50,200,500 μg·mL-1 Fo;and the inhibitor group was added with 50 μmol·L-1 JAK2/STAT3 inhibitor AG490 based on the experimental-M group.In the activator group,10 μmol·L-1 JAK2/STAT3 activator Broussonin E was added to the experimental-M group.Apoptosis was detected by deoxynucleotide terminal transferase-mediated dUTP notch end labeling(TUNEL);protein expression was detected by Western blot;real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect mRNA levels.Results The apoptosis rates of control group,experimental-M group,inhibitor group and activator group were(19.94±4.88)％,(27.04±5.27)％,(15.36±3.40)％and(46.66±7.89)％,respectively;the relative expression levels of phosphorylated JAK2 protein were 1.00±0.13,0.73±0.11,1.33±0.17 and 0.26±0.07,respectively;the relative expression levels of phosphorylated STAT3 protein were 1.00±0.12,0.27±0.04,0.88±0.13 and 0.12±0.04,respectively;the mRNA relative expression levels of MMP2 were 1.00±0.14,0.68±0.08,1.17±0.17 and 0.51±0.09,respectively.Compared with experimental-M group and control group,inhibitor group and activator group,there were statistically significant differences(P＜0.05,P＜0.001).Conclusion Fo promotes apoptosis of hepatocellular carcinoma cells,and its mechanism may be related to the effect of Fo on the expression of MMP2 by regulating JAK2-STAT3 signaling pathway.

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 (Pinteractions 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.

Objective To investigate the effects of Tuina targeting different body parts on the behaviors and gut microflora of rat models with valproic acid(VPA)-induced autistic spectrum disorder(ASD). Methods Twenty female Sprague Dawley(SD)rats with 12.5 d of pregnancy were randomly divided into VPA model group[intraperitoneal injection of VPA(600 mg/kg),n=15]and saline group(intraperitoneal injection of equal amount of normal saline,n=5).The offspring male rats injected with saline were secleted as control group.The offspring male rats injected with VPA were randomly divided into VPA,dorsal,and abdominal groups(n=7 in each group).On the 21st day after birth,three-chamber social test,open field test,and marble-burying test were carried out to observe the social abilities,anxiety behaviors,and stereotypi-cal behaviors of rats in the four groups.Rats in dorsal and abdominal groups underwent Tuina for 14 d,twice a day.On the 35th day,behavioral tests were conducted again,and in-testinal contents were taken for species composition and structural analysis,as well as mark-er and differential species analysis. Results(i)According to behavioral observations,compared with VPA group,the social and movement time in the central open field of rats in dorsal group increased significantly(P<0.05),and the number of buried marbles decreased markedly(P<0.01),indicating improve-ment on their social abilities,anxiety behaviors,and stereotypical behaviors as consequences of dorsal Tuina;and the number of buried marbles was reduced as well in abdominal group when compared with VPA group(P<0.05),suggesting the improvement on their stereotypi-cal behaviors following abdominal Tuina.In the marble-burying test,the number of marbles buried in dorsal group was less than in abdominal group,and the stereotypical behaviors were improved more significantly(P<0.05),and there were no significant differences in the three-chamber social and open field tests between the two groups(P>0.05).(ii)In accor-dance with intestinal microflora detection results,compared with VPA group,both dorsal and abdominal groups showed increased richness(P<0.05)and elevated diversity(P<0.05 in dorsal group and P<0.01 in abdominal group)in intestinal microflora.The results of differen-tial analysis indicated that at the phylum level,compared with VPA group,the relative abun-dance of Firmicutes in rats in abdominal group showed a significant reduction trend(P<0.05);at the genus level,compared with VPA group,the relative abundance of Lactobacillus in rats in dorsal and abdominal groups decreased significantly(P<0.05).Dorsal group also showed significant increase in the genus Blautia in the analysis of marker species compared with VPA group(P<0.05). Conclusion Tuina impacted the behavior and gut microflora structure of ASD model rats.Dorsal intervention had a significant effect on social abilities,anxiety behaviors,and stereo-typical behaviors of ASD model rats,while abdominal intervention only had an obvious effect on stereotypical behaviors.Both dorsal and abdominal interventions increased the richness and diversity of gut microflora of ASD model rats,with abdominal intervention improving the intestinal microbial diversity more significantly and resulting in a more uniform species dis-tribution.