BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

BACKGROUND:Arthroscopic anchor repair has become the main treatment method for rotator cuff tears at present.Among them,the insertion status of the anchor is a key factor in the success or failure of the operation.However,currently,the impact of the insertion depth of the anchor on the stress of the bone tunnel and the anchor under different bone density conditions remains unclear.OBJECTIVE:To explore the stress distribution of the bone tunnel and the anchor when the insertion depth of the anchor varies under different bone density conditions by using three-dimensional finite element analysis technology.METHODS:The CT image data of the humerus of volunteers were collected,and the models of the humerus and the anchor were constructed by using Mimics,3-Matic,and Solidworks software.In 3-Matic,holes with distances of 0,2,4,6,and 8 mm from the surface of the humerus were respectively created at the same position of the humerus and assembled with the anchor.In Mimics,values were assigned based on the CT gray value to obtain a model with normal bone mass(T value ≥-1.0).The parameters were changed to construct models with reduced bone mass(-2.5＜T value＜-1.0)and osteoporosis(T value＜-2.5).In each model,a 70 N pulling force was applied to the anchor along the direction tangent to the inner edge of the bone tunnel.The stress distribution and magnitude of the bone tunnel and the anchor when inserted at different depths under different bone density conditions were observed.RESULTS AND CONCLUSION:(1)When the insertion depth was the same,as the bone density decreased,the maximum equivalent stress of the anchor increased,while the maximum equivalent stress of the bone tunnel decreased.(2)When the bone density was the same,as the insertion depth of the anchor increased,the maximum equivalent stress of the anchor decreased.When the insertion depth was 4 mm,the stress of the bone tunnel was the smallest and the distribution was relatively uniform.The stress of the anchor was mainly distributed around the lower anchor hole and the proximal thread,and the stress of the bone tunnel was mainly at the part in contact with the proximal thread.The increase in the insertion depth would change the uniformity and pattern of the stress distribution,while the bone density had a relatively small impact on the stress distribution pattern.(3)It is concluded that the bone density of the humerus is crucial for the anchor repair of rotator cuff tears.It is recommended that clinicians measure the bone density of the greater tuberosity of the humerus before the operation.Excessive insertion depth of the anchor does not significantly increase its stability.Clinicians can conduct personalized preoperative assessments by using the finite element analysis method in combination with the actual situation of patients to achieve the best surgical results.

Objective:To explore the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis of pulmonary tuberculosis (PTB) combined with non-tuberculous mycobacterial pulmonary disease (NTM-PD), compare it with conventional pathogen detection methods, and analyze its clinical characteristics.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with PTB complicated by NTM-PD who were admitted to Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (Nanjing Second Hospital) from November 2021 to November 2023. All patients were diagnosed using bronchoalveolar lavage fluid (BALF) mNGS and compared with traditional culture methods. Data on patient demographics, clinical manifestations, imaging features, and treatment outcomes were collected to analyze the advantages and clinical significance of mNGS in diagnosis.Results:The positive detection rate of Mycobacterium tuberculosis by mNGS was 100% (72/72), significantly higher than that of traditional culture 27.8%(20/72). The diagnostic time of mNGS was significantly shorter (2 d vs. 45 - 60 d, P<0.001). The majority of patients were elderly (mean age: 55.92 years) and often had underlying structural lung diseases (e.g., bronchiectasis, COPD) or immunocompromised conditions (e.g., diabetes). The main clinical manifestations were cough (68.06%) and sputum production (52.78%). Imaging features included bronchiectasis (63.89%), nodular shadows (47.22%), and tree-in-bud signs (25.00%). After 6 months of follow-up, 73.8% of patients showed significant improvement in lung lesions, while 26.2% had no significant change or disease progression. Conclusions:mNGS demonstrates rapid and accurate diagnostic advantages for PTB combined with NTM-PD, significantly outperforming traditional culture methods, and provides critical support for precise clinical treatment.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.

AIM:To study the protective effect of transient receptor potential vanilic acid subtype 1(TRPV1)agonist capsaicin(CAP)on traumatic blood loss shock rats,and to further explore its possible mechanism by network pharmacology.METHODS:Forty-five SD rats were divided into 5 groups by random number table method:normal group,shock group,lactated Ringer's solution(LR)group,CAP pretreatment(single administration before shock)group,CAP pre-final administration(twice administration before and after shock)group,with 9 rats in each group for survival observation.Then 32 SD rats were divided into 4 groups according to the results of survival experiment:normal group,shock group,LR group,CAP pre-final administration group,with 8 rats in each group for blood pressure,hemodynamics,arterial blood gas,vascular reactivi-ty and hepaticand renal blood flow.At the same time,the potential mechanism of CAP in the treat-ment of traumatic hemorrhagic shock was investi-gated by network pharmacology.Furthermore,ap-ply the dataset to validate and analyse the diagnos-tic value of the hub genes.RESULTS:Rats in shock group died within hours of the completion of the shock model,and the mean survival time was 1.25(0.42,6.21)h.LR resuscitation could improve the survival of rats to some extent.The survival rate and survival time of rats in the CAP pretreatment group were slightly increased as compared with the LR group,while twice administration of CAP be-fore and after shock(CAP pre-final administration)resulted in better outcomes than LR resuscitation alone.Further results indicated that CAP pre-final administration significantly reduced the blood lac-tic acid level,improved the vasoconstrictive and di-astolic reactivity,and increased the liver and kidney blood flow of shock rats as compared with LR group.The improvement of hemodynamics and blood gas indexes in CAP group was slightly higher than LR group,but there was no statistical signifi-cance.A total of 37 genes related to CAP anti-trau-matic hemorrhage shock were obtained by net-work pharmacology.KEGG enrichment analysis showed that the Ca ion signaling pathway and Ras signaling pathway were significantly enriched.Vali-dation of the dataset showed that the expression levels of CXCR4,NF-kB1,GFPA and NTF3 hub gene were significantly different in the normal and shock groups,and that CXCR4 has a high diagnostic value for traumatic haemorrhagic shock.CONCLUSIONS:CAP,the TRPV1 agonist,significantly improved vas-cular function,increased organ blood flow,and cor-rected the lactic acidosis in rats with traumatic hemorrhagic shock,thus markedly improved the survival outcomes.The mechanism may be related to Ca ion signal pathway and Ras signal pathway.CXCR4,NF-kB1,GFPA and NTF3 may be having an important role in it.

Objective:To explore the application value of metagenomic next-generation sequencing (mNGS) in the diagnosis of pulmonary tuberculosis (PTB) combined with non-tuberculous mycobacterial pulmonary disease (NTM-PD), compare it with conventional pathogen detection methods, and analyze its clinical characteristics.Methods:A retrospective analysis was conducted on the clinical data of 72 patients with PTB complicated by NTM-PD who were admitted to Nanjing Hospital Affiliated to Nanjing University of Chinese Medicine (Nanjing Second Hospital) from November 2021 to November 2023. All patients were diagnosed using bronchoalveolar lavage fluid (BALF) mNGS and compared with traditional culture methods. Data on patient demographics, clinical manifestations, imaging features, and treatment outcomes were collected to analyze the advantages and clinical significance of mNGS in diagnosis.Results:The positive detection rate of Mycobacterium tuberculosis by mNGS was 100% (72/72), significantly higher than that of traditional culture 27.8%(20/72). The diagnostic time of mNGS was significantly shorter (2 d vs. 45 - 60 d, P<0.001). The majority of patients were elderly (mean age: 55.92 years) and often had underlying structural lung diseases (e.g., bronchiectasis, COPD) or immunocompromised conditions (e.g., diabetes). The main clinical manifestations were cough (68.06%) and sputum production (52.78%). Imaging features included bronchiectasis (63.89%), nodular shadows (47.22%), and tree-in-bud signs (25.00%). After 6 months of follow-up, 73.8% of patients showed significant improvement in lung lesions, while 26.2% had no significant change or disease progression. Conclusions:mNGS demonstrates rapid and accurate diagnostic advantages for PTB combined with NTM-PD, significantly outperforming traditional culture methods, and provides critical support for precise clinical treatment.

ObjectiveTo construct a quantitative prediction model of three indicators（moisture absorption rate， film thickness and coating weight gain） during the coating process of Vitamin C Yinqiao tablets（VCYT） by near-infrared spectroscopy（NIRS）， and to realize the endpoint judgment. MethodReal-time NIRS data of 4 batches of VCYT during the coating process were collected by diffuse reflection method. The coating method employed was the rolling coating method， and the samples were obtained at the spray stage from the coater's sampling port every 10 minutes， and 57 batches of samples（about 1 800 tablets） were collected at various coating times， the tablets were embedded in molten paraffin， cut longitudinally， and observed by stereomicroscope. The film thickness， with a target value of 38 μm， was then measured using Motic Images Advanced 3.2 software. Furthermore， the mositure absorption rate of samples， aiming for a target value of 3%， was determined in accordance with guiding principles for drug hygroscopicity testing in the 2020 edition of Chinese Pharmacopoeia， and 3 samples were randomly selected from each batch（10 tablets per batch）， and the coating weight gain was calculated（target value of 4%）. Partial least squares regression（PLSR） was used to construct a quantitative model of the 3 coating indicators， and the predicted values of the coating indicators were smoothed using the moving average method and used to determine the coating endpoints. ResultThe prediction determination coefficients（R_p²） for moisture absorption rate， film thickness and coating weight gain were 0.933 4， 0.932 6 and 0.965 9， the root mean square errors of prediction（RMSEP） were 0.163 5%， 1.870 9 μm and 0.240 3%， the relative percent deviations（RPD） were 3.711 0， 2.760 7 and 5.415 8， respectively. The results of the external validation set demonstrated that the real-time predicted values obtained by the models exhibited the same trend as the measured values， and the coating endpoint could be accurately predicted（with a prediction error of less than 7.32 min and a relative error of less than 5.63%）. ConclusionThe established NIRS model exhibits excellent predictive performance and can be used for quality control of VCYT during the coating process.

Objective:To investigate the role of m.4435A>G and YARS2 c.572G>T(p.G191V)mutations in the development of essential hypertension.Methods:A hypertensive patient with m.4435A>G and YARS2 p.G191V mutations was identified from previously collected mitochondrial genome and exon sequencing data.Clinical data were collected,and a molecular genetic study was conducted in the proband and his family members.Peripheral venous blood was collected,and immortalized lymphocyte lines constructed.The mitochondrial transfer RNA(tRNA),mitochondrial protein,adenosine triphosphate(ATP),mitochondrial membrane potential(MMP),and reactive oxygen species(ROS)in the constructed lymphocyte cell lines were measured.Results:Mitochondrial genome sequencing showed that all maternal members carried a highly conserved m.4435A>G mutation.The m.4435A>G mutation might affect the secondary structure and folding free energy of mitochondrial tRNA and change its stability,which may influence the anticodon ring structure.Compared with the control group,the cell lines carrying m.4435A>G and YARS2 p.G191V mutations had decreased mitochondrial tRNA homeostasis,mitochondrial protein expression,ATP production and MMP levels,as well as increased ROS levels(all P<0.05).Conclusion:The YARS2 p.G191V mutation aggravates the changes in mitochondrial translation and mitochondrial function caused by m.4435A>G through affecting the steady-state level of mitochondrial tRNA and further leads to cell dysfunction,indicating that YARS2 p.G191V and m.4435A>G mutations have a synergistic effect in this family and jointly participate in the occurrence and development of essential hypertension.