Objective To investigate the clinical efficacy of tetrandrine tablets combined with celecoxib in treating knee osteoarthritis(KOA).Methods A total of 234 patients with KOA admitted and treated in this hospital from February 2022 to January 2024 served as the study subjects.According to the random num-ber table method,the patients were assigned into the single group and combination group,117 cases in each group.The single group was treated with celecoxib capsules,while the combination group was treated with tetrandrine tablets on the basis of the single group treatment.The Western Ontario and McMaster Universi-ties Osteoarthritis Index(WOMAC)score,Hospital for Special Surgery(HSS)score,visual analogue scale(VAS)score,inflammatory factor level,bone metabolism related indicators levels,clinical efficacy and adverse reactions before treatment(T0)and in 24 weeks after treatment(T1)were observed and compared between the two groups.Results At T1,the WOMAC score,VAS score,levels of interleukin-iβ(IL-1β),tumor necro-sis factor-α(TNF-α)and CTX-Ⅱ in the two groups were significantly decreased compared with those at T0,moreover the combination group was lower than the single group,and the differences were statistically signifi-cant(P＜0.001).The HSS score,serum osteoprotegerin(OPG)and fibroblast growth factor-2(FGF-2)lev-els in the two groups were significantly increased compared with those at T0,moreover the combination group was higher than the single group,and the differences were statistically significant(P＜0.001).At T1,the to-tal effective rate in the combination group was 89.74％,which was significantly higher than 77.78％in the single group,and the difference was statistically significant(P＜0.05).During the treatment period,the total incidence rate of adverse reactions in the combination group was 3.42％,which was significantly lower than 12.82％in the single group,and the difference was statistically significant(P＜0.05).Conclusion The clinical efficacy of tetrandrine tablets combined with celecoxib in treating KOA is prominent,it could effectively allevi-ate the joint pain,improve the inflammation and bone metabolism level of the patients,and has certain safety.

Objective: To investigate the effect of aloperine (Alo) on the proliferation , migration and invasion of gastric cancer cells. Methods: Human gastric cancer cell lines HGC⁃27 and AGS were treated with 0 , 100 , and tion. Flow cytometry was used to detect apoptosis. Scratch and Transwell migration assays were used to detect cell migration. Transwell invasion assay was used to detect cell invasion. Western blot was used to detect the expression of proteins related to proliferation , apoptosis , migration , invasion and Hippo pathway. Results: Compared with the control group , the cell viability , number of colony formation , cell migration and invasion were significantly reduced after 100 and 200 μmol/L Alo treatment , and the apoptosis rate significantly increased (P < 0. 05) . Additionally , the expressions of proliferating cell nuclear antigen (PCNA) , B -cell lymphoma/leukemia⁃2 protein (Bcl⁃2) , neural cadherin ( N⁃cadherin) , Vimentin , and transcriptional co⁃activator with PDZ⁃binding motif ( TAZ)were significantly reduced , whereas the expressions of Bcl⁃2 ⁃associated X protein (Bax) , phosphorylated yes⁃asso⁃ciated protein (p⁃YAP) , and large tumor suppressor 1/2 (LATS1/2) significantly increased (P < 0. 05) . Conclusion Alo inhibits the proliferation , migration and invasion of gastric cancer cells HGC⁃27 and AGS by regulating the Hippo signaling pathway.

Objective:To investigate the clinicopathological features of Erdheim-Chester disease (ECD) initially diagnosed at extraskeletal locations.Methods:Clinical and pathological data of four cases of ECD diagnosed initially in extraskeletal locations were collected at Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from January 2013 to June 2023. BRAF V600E gene was detected by reverse transcription polymerase chain reaction (RT-PCR). Pertinent literatures were reviewed.Results:Four ECD patients included two males and two females ranging in ages from 2 years 11 months to 69 years. The lesions located in the lung (two cases), central nervous system (one case), and the testicle (one case) were collected in the study. One patient had occasional fever at night, one had nausea and vomiting, and two were asymptomatic. Radiologically, the two pulmonary ECD showed diffuse ground-glass nodules in both lungs, and the lesions in central nervous system and testicle both showed solid masses. Microscopically, there were infiltration of foamy histiocyte-like cells and multinucleated giant cells in a fibrotic background, accompanied by varying amounts of lymphocytes and plasma cells. The infiltration of tumor cells in pulmonary ECD was mainly seen in the subpleural area, interlobular septa, and perivascular and peribronchiolar areas. The fibrosis was more pronounced in the pleura and interlobular septa, and less pronounced in the alveolar septa. Immunohistochemical staining showed that all tumor cells expressed CD68, CD163 and F a; one case showed S-100 expression; three cases were positive for BRAF V600E; all were negative for CD1α and Langerin. RT-PCR in all four cases showed BRAF V600E gene mutation. Conclusions:Extraskeletal ECD is often rare and occult, and could be easily misdiagnosed, requiring biopsy confirmation. The radiologic findings of pulmonary ECD is significantly different from other types of ECD, and the histopathological features of pronounced infiltration in the subpleura area, interlobular septa, perivascular and peribronchiolar areas can be helpful in the differential diagnosis from other pulmonary diseases. Detection of BRAF V600E gene mutation by RT-PCR and its expression by immunohistochemical staining are also helpful in the diagnosis.

ObjectiveTo introduce the Hr gene of spontaneously mutated SHJH^hr mice into BALB/cAShjh inbred mice with clear genetic background,and provide a basis for study on the molecular mechanism of Hr gene mutation-induced abnormal phenotype and the application of this model.Methods Using a backcross-intercross breeding method guided by phenotypic monitoring, mutant genes from SHJH^hr mice bred by spontaneous mutation were introduced into inbred BALB/cAShjh mice by homozygous mutation introgression, and the mice were bred into BALB/cA.Cg.SHJH^hr (abbreviated as C.Cg.SHJH^hr) mice after 10 generations. The genotypes of 90 single nucleotide polymorphism (SNP) detection sites were analyzed in C.Cg.SHJH^hr mice by multiplex PCR library construction followed by next generation sequencing. Then 14 biochemical locus marker genes were detected in C.Cg.SHJH^hr mice according to the method of GB/T 14927.1-2008. Finally, whole genome exon sequencing was utilized to detect the mutated genes in this mouse. ResultsFrom May 2018 to March 2022, a total of 10 generations of backcross-intercross were conducted to complete the construction of the C.Cg.SHJH^hr mouse line. Among the 90 SNPs loci detected, except for rs13484115 and rs13484116, all the other loci had the same genotype as the recipient mice BALB/cAShjh. The results of biochemical marker gene detection showed that all the 14 loci of the mouse were the same as those of the recipient mouse. Whole genome exon sequencing found that the mouse had 109 site mutations compared with the recipient mouse strain, including 71 synonymous mutations, 1 stopgain, 37 missense mutations, and 20 genes involved in protein sequence alterations (including the reported Hr gene). ConclusionC.Cg.SHJH^hr mice were created. Through exon sequencing and genetic analysis, three Hr mutated genes and associated mutated genes that mainly cause phenotypic variations were identified, which provides a basis for expanding the application of C.Cg.SHJH^hr mice in biomedical research.

Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%（44/57） vs. 41.4%（12/29），χ2=10.853， P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.

Objective:To explore the improvement rate of the cognitive function of computerized cognitive remediation therapy (CCRT) on patients with schizophrenia and the clinical effect of CCRT in patients with different levels of cognitive impairment.Methods:A random number table was used to divide 311 patients with schizophrenia into CCRT group ( n=196) and work and amusement therapy (WAT) group ( n=115). The independently developed CCRT and operational music and dance therapy were given for 12 weeks to two treatment groups respectively. All patients were assessed using the MATRICS Consensus Cognitive Battery (MCCB) before and after treatment. According to the total score of MCCB at baseline, the patient′s cognition function was divided into 4 levels: severe cognitive impairment, moderate cognitive impairment, mild cognitive impairment and normal cognitive function. According to the change of MCCB total score, the efficacy of the treatment was divided into 3 levels: no improvement (≤0 points), improvement (0-9.57 points), superior improvement (>9.57 points). The improvement rate of cognitive function between two treatment groups was compared. Results:In the CCRT group, there were 19 cases with superior improvement, 105 cases with improvement, and 46 cases with no improvement. In the WAT group, there were 7 cases with superior improvement, 39 cases with improvement, and 41 cases with no improvement. The improvement of cognitive function of CCRT group was better than that of WAT group, and the difference was statistically significant ( Z=2.978, P=0.003). The patients with serious cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group ( Z=1.860, P=0.032). The patients with moderate cognitive impairment in the CCRT group had a lower no improvement rate than those in the WAT ( Z=-1.817, P=0.035).The patients with mild cognitive impairment in the CCRT group had a lower no improvement rate ( Z=-3.294, P=0.001) and higher improvement rate and superior improvement rate ( Z=2.084, P=0.019; Z=1.969, P=0.025) than those in the WAT group. There was no statistically significant difference in improvement rate between patients with normal cognitive function in the CCRT group and in the WAT group ( P>0.05).The patients with improvement and superior improvement of cognition were combined as responder, and the two treatment groups were compared. The patients with mild cognitive impairment in the CCRT group had a higher improvement rate than those in the WAT group (77.2%（44/57） vs. 41.4%（12/29），χ2=10.853， P=0.001). However, for patients with serious and moderate cognitive impairment or with normal cognitive function at baseline, rates of improvement after treatment did not differ significantly between CCRT group and WAT group. According to Cohen′s d, the level of effect size in cognition improvement after CCRT treatment in patients with different cognitive dysfunction level was: mild cognitive impairment (0.59)>moderate cognitive impairment (0.48)>normal cognitive function (-0.12)>serious cognitive impairment (-0.24). Conclusions:Schizophrenic patients treated with CCRT had a higher improvement rate of cognitive function than those with WAT, and the improvement rate of cognitive function is higher in patients with mild cognitive impairment after CCRT treatment.

Objective To investigate the effects of transient receptor potential cation channel 6 (TRPC6) on the expression of nephrin, desmin and caspase 9 and on the apoptosis of podocytes in a mouse model of podocyte injury induced by TGF-β1.Methods Conditionally immortalized mouse podocytes were cultured in vitro and divided into four groups: control, TGF-β1 treatment, TGF-β1+PGPU6/GFP/Neo-TRPC6-mus-581 (TRPC6 knockdown) and TGF-β1+PGPU6/GFP/Neo-NC (negative control).Real-time RT-PCR and Western blot analysis were performed to detect the expression of nephrin, desmin and caspase 9 at mRNA and protein levels, respectively.Flow cytometry was used to analyze the apoptotic rate of podocytes.DAPI fluorescent staining was used to observe the morphological changes of apoptotic podocytes.Results Green fluorescent protein (GFP)-expressing podocytes at 48 hours after transfection were significantly more than those at 24 hours after transfection.The level of TRPC6 in mouse podocytes transfected with PGPU6/GFP/Neo-TRPC6-mus-581 was significantly decreased as compared with that of the control group (P<0.05).No significant difference in the expression of TRPC6 was observed between the negative control group and the control group.Compared with the control group, the TGF-β1 treatment group showed increased expression of desmin and caspase 9 at both mRNA and protein levels (P<0.01), but decreased expression of nephrin at mRNA and protein levels at 48 hours after TGF-β1 intervention (P<0.05).The up-regulated desmin and caspase 9 and the down-regulated nephrin induced by TGF-β1 could be inhibited by the means of TRPC6 knockdown.The apoptosis rate of podocytes in TGF-β1 treatment group was (14.0±2.1)%, while that in TRPC6 knockdown was (10.90±0.56)% (P<0.05).The apoptosis rate of podocytes in negative control group was higher than that in TGF-β1 treatment group (P>0.05).More apoptotic cells with typical morphological features of apoptosis were observed after exposure to TGF-β1 for 48 hours.Conclusion TGF-β1 could induce the apoptosis of podocytes, inhibit the expression of nephrin and enhance the expression of caspase 9 and desmin, the possible mechanisms of which may be related to TRPC6 signal pathway.These changes in TGF-β1-treated podocytes could be alleviated by inhibiting the expression of TRPC6, which might have a protective effect on podocyte injury.

Objective This study aims to explore the characteristics of gender and age in six different suicide methods in urban area of China. Methods We collected 548 suicides from Shanghai, Jinhua, Wuhan, Loudi and Duyun, and then analyzed the age and gender characteristics in each suicide method. Results In the age characteristics, the mean age for jumping and hanging was oldest (about 55 years old), followed by drowning and hanging (about 49 years old), oral intake poisoning was much younger (about 49 years old), while carbon monoxide poisoning was youngest (about 37 years old). In the gender differences, male were more than females in suicides by sharp object (52:24), hanging (67:33) and jumping (55:45), while females were more than males in suicides by drowning (58:42). Conclusion The age and gender difference was eminent in different suicide methods. Carbon monoxide poisoning was the youngest age group in suicides and males involved more than females in suicides by mechanical methods.

An aerosol formulation containing 7.5 mg of R-salbutamol sulfate was developed. The aerosol was nebulized with an air-jet nebulizer, and further assessed according to the new European Medicines Agency (EMA) guidelines. A breath simulator was used for studies of delivery rate and total amount of the active ingredient at volume of 3 mL. A next generation impactor (NGI) with a cooler was used for analysis of the particle size and in vitro lung deposition rate of the active ingredient at 5 °C. The anti-asthmatic efficacy of the aerosol formulation was assessed in guinea pigs with asthma evoked by intravenous injection of histamine compared with racemic salbutamol. Our results show that this aerosol formulation of R-salbutamol sulfate met all the requirements of the new EMA guidelines for nebulizer. The efficacy of a half-dose of R-salbutamol equaled that of a normal dose of racemic salbutamol.

Objective To investigate the causes of infant mortality and analyze the reasons of misdiagnosis and medical disputes,and to provide help for improving clinical diagnostic accuracy in future in order to decrease the infant mortality and prevent the occurrence of medical tangle.Methods To collect and reorganize the autopsy pathology reports of medical tangle of infant deaths in the autopsy files of the Pathology Department of Affiliated Hospital of Zunyi Medical College within 5 years from Jan.2008 to Dec.2012,and a total of 58 cases were collected,of whom 39 cases were male and 19 cases were female,and the ages of these cases ranged from 0 to 3 years old.Results In 5 years,the number of medical tangle of infant deaths were 8 cases,10 cases,10 cases,15 cases and 15 cases,respectively,which showed an increasing trend on the whole.Infant mortality showed a significant decrease with the increase of age,as the highest mortality was the baby,which accounted for 77.59％ (45/58 cases) of infant deaths.The most common cause of infant death was pneumonia,which accounted for 15.52％ (9/58 cases) of all diseases,and neonatal asphyxia was the top cause of newborn infant deaths (27.27％,6/22 cases).In the cases of misdiagnosis and missed diagnosis of infant deaths,the respiratory system disease was the most common disease (57.89％,22/38 cases).Conclusions Infant mortality decreased year by year in clinical medicine,but there was an upward trend of medical disputes in infant deaths.Various types of pneumonia was the most common cause of infant deaths,and it was also the main cause contributing to medical tangles of infant deaths.