1.Discovery of a novel thiophene carboxamide analogue as a highly potent and selective sphingomyelin synthase 2 inhibitor for dry eye disease therapy.
Jintong YANG ; Yiteng LU ; Kexin HU ; Xinchen ZHANG ; Wei WANG ; Deyong YE ; Mingguang MO ; Xin XIAO ; Xichen WAN ; Yuqing WU ; Shuxian ZHANG ; He HUANG ; Zhibei QU ; Yimin HU ; Yu CAO ; Jiaxu HONG ; Lu ZHOU
Acta Pharmaceutica Sinica B 2025;15(1):392-408
Dry eye disease (DED) is a prevalent and intractable ocular disease induced by a variety of causes. Elevated sphingomyelin (SM) levels and pro-inflammatory cytokines were detected on the ocular surface of DED patients, particularly in the meibomian glands. Sphingomyelin synthase 2 (SMS2), one of the proteins involved in SM synthesis, would light a novel way of developing a DED therapy strategy. Herein, we report the design and optimization of a series of novel thiophene carboxamide derivatives to afford 14l with an improved highly potent inhibitory activity on SM synthesis (IC50, SMS2 = 28 nmol/L). Moreover, 14l exhibited a notable protective effect of anti-inflammation and anti-apoptosis on human corneal epithelial cells (HCEC) under TNF-α-hyperosmotic stress conditions in vitro, with an acceptable ocular specific distribution (corneas and meibomian glands) and pharmacokinetics (PK) profiles (t 1/2, cornea = 1.11 h; t 1/2, meibomian glands = 4.32 h) in rats. Furthermore, 14l alleviated the dry eye symptoms including corneal fluorescein staining scores and tear secretion in a dose-dependent manner in mice. Mechanically, 14l reduced the mRNA expression of Tnf-α, Il-1β and Mmp-9 in corneas, as well as the proportion of very long chain SM in meibomian glands. Our findings provide a new strategy for DED therapy based on selective SMS2 inhibitors.
2.Application value of 3D printing auxiliary stent in laryngeal micro instrument operation
Dingyuan XU ; Xichen HUANG ; Xin MA ; Bin WANG ; Ke LÜ ; Li FU ; Dawei HAO ; Guangke WANG
China Journal of Endoscopy 2025;31(5):8-11
Objective To explore the effect of 3D printing auxiliary stent on the operation of laryngeal microsurgery instrument.Methods Auxiliary stent of suspension laryngoscope was design and 3D printed.30 standardized training residents as experimental participants were randomly divided into conventional group and auxiliary stent group(15 in each group).The pig's larynx was used as a specimen,and the vocal folds were marked with localized staining.Participants performed operation on the stained areas of the vocal folds under suspension laryngoscope(60 times of grasping in 1 h).The conventional group performed operation unaided;The auxiliary stent group performed operation with the auxiliary stent as a support.Two senior chief physicians scored the participants'stability and accuracy.Results The operational stability scale score of the conventional group and the auxiliary stent group were(5.03±4.33)and(8.99±3.42),respectively;The operation accuracy rates were 58.4%(526/900)and 78.9%(710/900),respectively.The operation accuracy rate,operation stability of the auxiliary stent group were significantly higher than those in the conventional group,and the differences were significant(P<0.01).Conclusion The auxiliary stent can significantly improve the stability and accuracy of operation,which has highly application value.
3.Molecular epidemiological investigation of main intestinalprotozoa infection in BALB/c mice
Yu ZHENG ; Xichen ZHANG ; Yao RONG ; Jianhua LI ; Pengtao GONG ; Xiaocen WANG ; Taotao YUE ; Xin LI ; Xu ZHANG ; Nan ZHANG
Chinese Journal of Veterinary Science 2025;45(3):514-518
To understand the infection status of main intestinal protozoa in BALB/c mice and pro-vide a basis for further control of intestinal protozoa infection.Five hundred and forty BALB/c mice provided by four domestic suppliers of BALB/c mice were detected for intestinal protozoa,in which 140 from supplier A,130 from supplier B,135 from supplier C,and 135 from supplier D,re-spectively.Fresh faecal samples were collected from each mouse separately to extract the genome and amplified by nested PCR based on primers for the 18S rRNA gene sequences of Pent-atrichomonas hominis(P.hominis)and Cryptosporidium tyzzeri(C.tyzzeri),and the 16S-like rRNA gene sequence of Tritrichomonas muris(T.muris)and sequenced.The results showed that the total intestinal protozoan infection rate was 7.1%(10/140)in 140 mice faecal samples provided by supplier A.Among them,the positivity rate of T.muris was 7.1%(10/140),C.tyzzeri was 2.1%(3/140),and P.hominis was 7.1%(10/140),the co-infection rate of two intestinal protozoa was 7.1%(10 mice:T.muris+P.hominis),and three intestinal protozoa was 2.1%(3 mice:T.muris+P.hominis+C.tyzzeri).The total intestinal protozoan infection rate in 135 mice faecal samples provided by supplier C was 7.4%,in which,7.4%(10/135)was positive for T.muris.There are no intestinal protozoa to be detected in 130 mice faecal samples from supplier B and 135 mice faecal samples from supplier D.The homology analysis showed that the homology of ampli-fied sequence of T.muris,P.hominis and C.tyzzeri was 98.52%,98.27%and 99.87%compared with published sequence of GenBank No:AY886846.1,GenBank No:AF156964.1 and GenBank No:KJ000486.1,which was clustered as an independent branch by phylogenetic analysis respec-tively.In conclusion,there are intestinal protozoan infection in BALB/c mice in some animal sup-pliers.The co-infections of more than 3 parasites such as T.muris,P.hominis and C.tyzzeri has been found.It will provide a basis for control of intestinal protozoa infection in BALB/c mice in the future.
4.Surface electromyogram assessment of effectiveness of anti-G straining maneuver of high performance fighter pilots
Jinghui YANG ; Baohui LI ; Yan XU ; Haixia WANG ; Zhao JIN ; Xichen GENG ; Hong WANG ; Xiaoyang WEI ; Ke JIANG ; Yifeng LI ; Lihui ZHANG ; Xiaoxue ZHANG ; Minghao YANG
Chinese Journal of Aerospace Medicine 2025;36(2):113-118
Objective:To evaluate the effectiveness of anti-G straining maneuver (AGSM) in pilots by surface electromyography (sEMG), and to explore the relationships between characteristics of sEMG and anti-G endurance in pilots.Methods:Thirty-eight male high-performance fighter pilots who completed the human centrifuge test at the Air Force Medical Center were selected. Among them, 25 completed the 8.0 G for 10 s anti-G endurance test and 13 completed the 9.0 G for 10 s anti-G endurance test. The sEMG tester was used to keep track of the changes of sEMG in rectus abdominis, rectus femoris, anterior tibial and gastrocnemius muscles while pilots were engaged in AGSM. The anti-G endurance was evaluated according to the changes of visual fields and consciousness. The pilots were divided into 3 groups: the good vision and consciousness group, peripheral visual field narrowing group and endurance endpoint group. The differences in the integral electromyogram (iEMG), mean power frequency (MPF) and muscle input rates between the 3 groups were investigated.Results:A total of 25 pilots completed the 8.0 G for 10 s anti-G endurance test. Among them, 8 (32.0%) were in the good vision and consciousness group, 13 (52.0%) in the peripheral visual field narrowing group and 4 (16.0%) reached the endurance endpoint. Among the 13 pilots who completed the 9.0 G for 10 s anti-G endurance test, 3 (23.1%) were in the good vision and consciousness group, 6 (46.1%) in the peripheral visual field narrowing group, and 4 (30.8%) in the endurance endpoint group. The results of sEMG showed that the iEMG values of the anterior tibialis muscle in pilots under the 9.0 G for 10 s load were significantly different across endurance groups ( H=7.54, P=0.023), and that the iEMG values of the tibialis anterior muscle in the good vision and consciousness group were higher than those in the endurance endpoint group ( P=0.036). The negative slopes of MPF for the rectus abdominis, rectus femoris, anterior tibialis, and gastrocnemius muscles were higher in the good vision and consciousness group than in the other 2 groups, but the differences were not statistically significant ( P>0.05). During the 8.0 G for 10 s anti-G endurance test, there were significant differences in lower limb muscle contribution rates between the 3 groups ( F=4.19, P=0.029). The endurance endpoint group exhibited a lower contribution rate than the good vision and consciousness group ( P=0.025). During the 9.0 G for 10 s anti-G endurance test, there were significant differences in tibialis anterior muscle contribution rates between the 3 groups ( F=4.16, P=0.049). The endurance endpoint group demonstrated a lower contribution rate than the good vision and consciousness group ( P=0.049). Conclusions:The full and balanced activation of abdominal muscles and lower limb muscles, especially the effective mobilization of calf muscles, plays a pivotal role in improving pilots′ AGSM efficiency in high G environments.
5.Molecular epidemiological investigation of main intestinalprotozoa infection in BALB/c mice
Yu ZHENG ; Xichen ZHANG ; Yao RONG ; Jianhua LI ; Pengtao GONG ; Xiaocen WANG ; Taotao YUE ; Xin LI ; Xu ZHANG ; Nan ZHANG
Chinese Journal of Veterinary Science 2025;45(3):514-518
To understand the infection status of main intestinal protozoa in BALB/c mice and pro-vide a basis for further control of intestinal protozoa infection.Five hundred and forty BALB/c mice provided by four domestic suppliers of BALB/c mice were detected for intestinal protozoa,in which 140 from supplier A,130 from supplier B,135 from supplier C,and 135 from supplier D,re-spectively.Fresh faecal samples were collected from each mouse separately to extract the genome and amplified by nested PCR based on primers for the 18S rRNA gene sequences of Pent-atrichomonas hominis(P.hominis)and Cryptosporidium tyzzeri(C.tyzzeri),and the 16S-like rRNA gene sequence of Tritrichomonas muris(T.muris)and sequenced.The results showed that the total intestinal protozoan infection rate was 7.1%(10/140)in 140 mice faecal samples provided by supplier A.Among them,the positivity rate of T.muris was 7.1%(10/140),C.tyzzeri was 2.1%(3/140),and P.hominis was 7.1%(10/140),the co-infection rate of two intestinal protozoa was 7.1%(10 mice:T.muris+P.hominis),and three intestinal protozoa was 2.1%(3 mice:T.muris+P.hominis+C.tyzzeri).The total intestinal protozoan infection rate in 135 mice faecal samples provided by supplier C was 7.4%,in which,7.4%(10/135)was positive for T.muris.There are no intestinal protozoa to be detected in 130 mice faecal samples from supplier B and 135 mice faecal samples from supplier D.The homology analysis showed that the homology of ampli-fied sequence of T.muris,P.hominis and C.tyzzeri was 98.52%,98.27%and 99.87%compared with published sequence of GenBank No:AY886846.1,GenBank No:AF156964.1 and GenBank No:KJ000486.1,which was clustered as an independent branch by phylogenetic analysis respec-tively.In conclusion,there are intestinal protozoan infection in BALB/c mice in some animal sup-pliers.The co-infections of more than 3 parasites such as T.muris,P.hominis and C.tyzzeri has been found.It will provide a basis for control of intestinal protozoa infection in BALB/c mice in the future.
6.Application value of 3D printing auxiliary stent in laryngeal micro instrument operation
Dingyuan XU ; Xichen HUANG ; Xin MA ; Bin WANG ; Ke LÜ ; Li FU ; Dawei HAO ; Guangke WANG
China Journal of Endoscopy 2025;31(5):8-11
Objective To explore the effect of 3D printing auxiliary stent on the operation of laryngeal microsurgery instrument.Methods Auxiliary stent of suspension laryngoscope was design and 3D printed.30 standardized training residents as experimental participants were randomly divided into conventional group and auxiliary stent group(15 in each group).The pig's larynx was used as a specimen,and the vocal folds were marked with localized staining.Participants performed operation on the stained areas of the vocal folds under suspension laryngoscope(60 times of grasping in 1 h).The conventional group performed operation unaided;The auxiliary stent group performed operation with the auxiliary stent as a support.Two senior chief physicians scored the participants'stability and accuracy.Results The operational stability scale score of the conventional group and the auxiliary stent group were(5.03±4.33)and(8.99±3.42),respectively;The operation accuracy rates were 58.4%(526/900)and 78.9%(710/900),respectively.The operation accuracy rate,operation stability of the auxiliary stent group were significantly higher than those in the conventional group,and the differences were significant(P<0.01).Conclusion The auxiliary stent can significantly improve the stability and accuracy of operation,which has highly application value.
7.Surface electromyogram assessment of effectiveness of anti-G straining maneuver of high performance fighter pilots
Jinghui YANG ; Baohui LI ; Yan XU ; Haixia WANG ; Zhao JIN ; Xichen GENG ; Hong WANG ; Xiaoyang WEI ; Ke JIANG ; Yifeng LI ; Lihui ZHANG ; Xiaoxue ZHANG ; Minghao YANG
Chinese Journal of Aerospace Medicine 2025;36(2):113-118
Objective:To evaluate the effectiveness of anti-G straining maneuver (AGSM) in pilots by surface electromyography (sEMG), and to explore the relationships between characteristics of sEMG and anti-G endurance in pilots.Methods:Thirty-eight male high-performance fighter pilots who completed the human centrifuge test at the Air Force Medical Center were selected. Among them, 25 completed the 8.0 G for 10 s anti-G endurance test and 13 completed the 9.0 G for 10 s anti-G endurance test. The sEMG tester was used to keep track of the changes of sEMG in rectus abdominis, rectus femoris, anterior tibial and gastrocnemius muscles while pilots were engaged in AGSM. The anti-G endurance was evaluated according to the changes of visual fields and consciousness. The pilots were divided into 3 groups: the good vision and consciousness group, peripheral visual field narrowing group and endurance endpoint group. The differences in the integral electromyogram (iEMG), mean power frequency (MPF) and muscle input rates between the 3 groups were investigated.Results:A total of 25 pilots completed the 8.0 G for 10 s anti-G endurance test. Among them, 8 (32.0%) were in the good vision and consciousness group, 13 (52.0%) in the peripheral visual field narrowing group and 4 (16.0%) reached the endurance endpoint. Among the 13 pilots who completed the 9.0 G for 10 s anti-G endurance test, 3 (23.1%) were in the good vision and consciousness group, 6 (46.1%) in the peripheral visual field narrowing group, and 4 (30.8%) in the endurance endpoint group. The results of sEMG showed that the iEMG values of the anterior tibialis muscle in pilots under the 9.0 G for 10 s load were significantly different across endurance groups ( H=7.54, P=0.023), and that the iEMG values of the tibialis anterior muscle in the good vision and consciousness group were higher than those in the endurance endpoint group ( P=0.036). The negative slopes of MPF for the rectus abdominis, rectus femoris, anterior tibialis, and gastrocnemius muscles were higher in the good vision and consciousness group than in the other 2 groups, but the differences were not statistically significant ( P>0.05). During the 8.0 G for 10 s anti-G endurance test, there were significant differences in lower limb muscle contribution rates between the 3 groups ( F=4.19, P=0.029). The endurance endpoint group exhibited a lower contribution rate than the good vision and consciousness group ( P=0.025). During the 9.0 G for 10 s anti-G endurance test, there were significant differences in tibialis anterior muscle contribution rates between the 3 groups ( F=4.16, P=0.049). The endurance endpoint group demonstrated a lower contribution rate than the good vision and consciousness group ( P=0.049). Conclusions:The full and balanced activation of abdominal muscles and lower limb muscles, especially the effective mobilization of calf muscles, plays a pivotal role in improving pilots′ AGSM efficiency in high G environments.
8.Relationship between three-dimensional measurement of acromion coverage and degenerative full-thickness rotator cuff tears
Gang WANG ; Xuren GAO ; Shang QIU ; Gen LI ; Xichen ZHANG
Chinese Journal of Tissue Engineering Research 2024;28(36):5773-5778
BACKGROUND:Acromion morphology is the most important external factor of degenerative rotator cuff tear,and studies on acromion morphology and acromion coverage have been continuing. OBJECTIVE:To investigate the coverage of acromion on rotator cuff tissue in three-dimensional space,measure coronal and sagittal parameters,and explore the relationship of acromial overhang,acromioglenoid angle and acromial coverage angle with degenerative full-thickness rotator cuff tears. METHODS:A total of 56 patients diagnosed with full-thickness rotator cuff tears by shoulder arthroscopic surgery or MRI in the Affiliated Hospital of Xuzhou Medical University from January 2022 to June 2023 were retrospectively collected as the tear group,while 48 patients with non-rotator cuff tear were included as the control group.Clinical data and chest CT data of the patients of the two groups were collected,and the shoulder blades of the patients were reconstructed using Mimics software.Acromial overhang,acromioglenoid angle and acromial coverage angle were measured in 3-matic software.The differences between the measurement parameters were compared between the two groups.Binary Logistic regression analysis and receiver operating characteristic curve analysis were performed to evaluate the ability of the measurement parameters to predict rotator cuff tear.It is generally believed that the parameter had good diagnostic value when the area under the receiver operating characteristic curve was greater than 0.8. RESULTS AND CONCLUSION:(1)The mean acromial overhang in patients with rotator cuff tears was greater than that in controls(P<0.001).The mean acromial coverage angle was also greater in patients with rotator cuff tears than in controls(P<0.001).There was no significant difference in the acromioglenoid angle between the two groups(P>0.05).(2)Binary Logistic regression analysis showed that acromial overhang and acromial coverage angle were both risk factors for rotator cuff tear(P<0.05).(3)Receiver operating characteristic curve analysis indicated that the areas under the curve of acromial overhang and acromial coverage angle were 0.725 and 0.865,respectively,and the optimal cutoff values were 36.15 mm and 60.65°.(4)The results showed that the acromial overhang and acromial coverage angle were greater in patients with rotator cuff tears than in patients without rotator cuff tears.Both were associated with degenerative full-thickness rotator cuff tears,and they could be used to predict rotator cuff tears,and the acromial coverage angle was more effective in predicting rotator cuff tears.
9.Efficacy evaluation of different anti-G physical training programs for pilots
Jinghui YANG ; Xichen GENG ; Minghao YANG ; Zhao JIN ; Baohui LI ; Jie YU ; Yuhang LIU ; Haixia WANG ; Xiaoyang WEI ; Ke JIANG ; Lihui ZHANG ; Yifeng LI ; Qianyun ZHU ; Xiaoxue ZHANG ; Yan XU
Space Medicine & Medical Engineering 2024;35(1):38-41
Objective To establish a scientific training program that takes into account both anaerobic and aerobic training for pilots,and to explore the appropriate ratio of aerobic and anaerobic training.Methods According to the physical examination standards for pilots,a total of 16 healthy subjects aged 18-24 were selected from two batches.The two batches of subjects were trained with different aerobic and anaerobic ratios.Training period was 3 months.The changes in cardiopulmonary function of the subjects before and after training were evaluated using the cardiopulmonary function exercise testing system(CPET),and the changes in anaerobic capacity were evaluated using changes in strength as an indicator.Results After training,the weight load of the subjects in the two training programs,including barbell squats,leg flexion and hard pull,and barbell under 10RM and 3RM,was significantly increased(P<0.001),and there was no statistically significant difference in anaerobic strength growth between the two groups.The results of CPET showed that the maximum load,maximum heart rate,and respiratory quotient in the two groups were significantly increased after than before the training(P<0.01).The maximum load(Experiment group 1:29.12±19.69,Experiment group 2:72.00±46.24)and respiratory quotient(Experiment grouop 1:0.11±0.09,Experiment group 2:0.28±0.16)of the subjects in experiment group 2 before and after training were greater than those in experiment group 1.The difference was statistically significant(P<0.05).Conclusion The anaerobic and aerobic capacities of the subjects in the experiment group 2 are effectively improved,indicating that ratio of aerobic and anaerobic of the training scheme is better.
10.Application of peer support services for caregivers of mental disorder patients
Xinhui YE ; Lei ZHU ; Xichen WANG ; Han LIU ; Yuming CHEN ; Ning MA ; Hao YAO
Journal of Clinical Medicine in Practice 2024;28(19):129-133
Objective To investigate the impact of a peer support model on the mental health of caregivers and the perceived social support and psychiatric symptoms of the mental disorder patients under their care. Methods Patients with mental disorders undergoing long-term community-based rehabilitation and their primary caregivers were recruited for this study. A total of 44 pairs of eligible patients and caregivers were selected based on a 1∶1 matching ratio. Systematic peer support activities were conducted exclusively for the caregivers. The General Health Questionnaire (GHQ) and the Symptom Checklist-90 (SCL-90) were administered before and after the intervention to assess the mental health status of caregivers. The Perceived Social Support Scale (PSSS) and the Brief Psychiatric Rating Scale (BPRS) were employed to evaluate the patients' perceived social support and psychiatric conditions before and after the intervention. Results A total of 44 valid questionnaires from caregivers and 42 from patients were collected. The GHQ score and the total scores, the number of positive item, positive total scores, and positive mean scores of and SCL-90 of caregivers were significantly lower after the intervention compared to pre-intervention (


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