Objective:To explore the expression and mechanism of lncRNA MALAT1 in negative sputum for tuberculous bac-terium.Methods:Expression of lncRNA MALAT1 in peripheral blood mononuclear cells(PBMC)of patients with positive sputum bacteria(Positive group)and negative sputum bacteria(Negative group)and healthy volunteers(HC group)was detected by RT-PCR.ELISA was used to detect expression levels of TNF-α,IL-1β and IL-6 in plasma.Expression of lncRNA MALAT1 in mice macro-phages RAW264.7 was silenced by siRNA interference,and RAW264.7 cells were infected with mycobacterium tuberculosis(MTB)H37Rv.Cells were divided into four groups:Control group,Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group.Proliferation activity of RAW264.7 cells in each group was detected by CCK-8 method.The number of MTB in each group was detected by CFU.Expressions of TNF-α,IL-1β and IL-6 in supernatant of RAW264.7 cells were detected by ELISA.Results:Compared with HC group,expressions of lncRNA MALAT1 in PBMC,and TNF-α,IL-1β and IL-6 in plasma were significantly increased in Positive group and Negative group(P<0.01).Compared with Control group,expression level of lncRNA MALAT1,proliferation activity,CFU value,and concentrations of TNF-α,IL-1β and IL-6 in supernatant of Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group were significantly increased(P<0.05).Compared with MTB+si-NC group,the above detection indexes in MTB+si-MALAT1 group were significantly decreased(P<0.05),while there was no significant difference in Control+MTB group(P>0.05).Conclusion:The significantly increased expression of MALAT1 in patients with negative sputum for tuberculous bacterium is positively correlated with expression of plasma inflammatory factors,while the silence of MALAT1 expression can reduce MTB induced inflammatory response by inhibiting the proliferation and phagocytosis of MTB infected macrophages.

Objective:To explore the expression and mechanism of lncRNA MALAT1 in negative sputum for tuberculous bac-terium.Methods:Expression of lncRNA MALAT1 in peripheral blood mononuclear cells(PBMC)of patients with positive sputum bacteria(Positive group)and negative sputum bacteria(Negative group)and healthy volunteers(HC group)was detected by RT-PCR.ELISA was used to detect expression levels of TNF-α,IL-1β and IL-6 in plasma.Expression of lncRNA MALAT1 in mice macro-phages RAW264.7 was silenced by siRNA interference,and RAW264.7 cells were infected with mycobacterium tuberculosis(MTB)H37Rv.Cells were divided into four groups:Control group,Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group.Proliferation activity of RAW264.7 cells in each group was detected by CCK-8 method.The number of MTB in each group was detected by CFU.Expressions of TNF-α,IL-1β and IL-6 in supernatant of RAW264.7 cells were detected by ELISA.Results:Compared with HC group,expressions of lncRNA MALAT1 in PBMC,and TNF-α,IL-1β and IL-6 in plasma were significantly increased in Positive group and Negative group(P<0.01).Compared with Control group,expression level of lncRNA MALAT1,proliferation activity,CFU value,and concentrations of TNF-α,IL-1β and IL-6 in supernatant of Control+MTB group,MTB+si-NC group and MTB+si-MALAT1 group were significantly increased(P<0.05).Compared with MTB+si-NC group,the above detection indexes in MTB+si-MALAT1 group were significantly decreased(P<0.05),while there was no significant difference in Control+MTB group(P>0.05).Conclusion:The significantly increased expression of MALAT1 in patients with negative sputum for tuberculous bacterium is positively correlated with expression of plasma inflammatory factors,while the silence of MALAT1 expression can reduce MTB induced inflammatory response by inhibiting the proliferation and phagocytosis of MTB infected macrophages.

Pulmonary siderosis caused by iron and its compound dust is prone to misdiagnosis and underdiagnosis due to its insidious exposure pathways and non-specific imaging manifestations. This study analyzes the occupational histories and clinical data of six patients with occupational pulmonary siderosis diagnosed at Qingdao Central Hospital between January 2017 and December 2023, summarizes its characteristics, and evaluates the value of AI-assisted diagnosis. All six patients were male, with five being welders. The median dust exposure duration was 9.4 years, and the median latency period was 8.4 years. The main symptoms were chest tightness, cough, and shortness of breath. High-kilovolt chest radiographs were negative in four cases and showed thickened bronchovascular markings in two cases. High-resolution computed tomography (HRCT) revealed centrilobular nodules and tree-in-bud opacities in all cases. Pulmonary siderosis caused by iron and its compound dust is characterized by mild symptoms and a favorable prognosis. Comprehensive assessment and HRCT are crucial for early diagnosis. The development of AI models could enhance diagnostic recognition efficiency and promote precision diagnosis in the future.

AIM:To evaluate the clinical efficacy of lamellar keratectomy and corneal collagen crosslinking(LKCCC)in treating superficial fungal keratitis.METHODS: Retrospective analysis. Totally 79 patients(79 eyes)with superficial fungal keratitis who underwent LKCCC in our hospital from January 2014 to October 2023 were included. After admission, routine antifungal drug treatment for 7 d showed no obvious improvement or progressive aggravation. The maximum diameter of corneal lesions in all patients was ≤7 mm, the maximum depth was no more than 50% of the corneal thickness at the location, and the remaining healthy corneal thickness was ≥300 μm. The follow-up time was 90 to 112 d.RESULTS:Among the included 79 eyes, the lesions were located in the central region of the cornea in 6 eyes, in the paracentral region in 61 eyes, and in the peripheral region in 12 eyes. Hypopyon was observed in 5 cases. LKCCC was successfully administered in 79 eyes, cured in 76 eyes(96%), and failed in 3 eyes(4%). The healing time of corneal epithelium in 76 cured eyes was 3-15 d, of which 51 eyes(67%)healed within 7 d and 24 eyes(32%)healed within 3 d. The uncorrected visual acuity(UCVA)and best corrected visual acuity(BCVA)of 76 eyes of cured patients were statistically significant compared with those preoperatively(P<0.0167). Two of the 3 failed eyes were located at the edge of the lesion and recovered after re-keratectomy. One eye was located in the center of the lesion and recovered after being covered by bulbar conjunctival flap. At the last follow-up, no other complications were observed in all patients except superficial cloud and thinning of cornea.CONCLUSION:LKCCC is a rapid and effective treatment for superficial fungal keratitis and can be considered a new treatment option.

AIM: To assess the impact of optimized pulsed technology(OPT)on the morphological and functional changes of meibomian glands in patients with meibomian gland dysfunction(MGD).METHODS: This prospective case-control study enrolled 60 MGD patients(60 right eyes)treated at Weifang Eye Hospital from September 2023 to February 2024. Patients were categorized into mild, moderate, and severe groups based on the extent of meibomian gland loss, with 20 cases(20 eyes)per group. Treatments consisted of bilateral OPT combined with meibomian gland massages, administered biweekly over four sessions. Ocular surface function indicators including the ocular surface disease index(OSDI), corneal fluorescein staining(CFS), non-invasive average tear break-up time(NIBUTav), and non-invasive tear meniscus height(NITMH), as well as meibomian gland function parameters such as meibomian gland expressibility score(MGES)and meibomian gland secretion score(MGYSS)were observed and recorded before treatment and at 3 mo after final treatment. Cellular-level assessments using in vivo confocal microscopy(IVCM)examined meibomian gland acinar unit density(MGAUD), inflammatory cell density(ICD), meibomian gland acinar longest diameter(MGALD)and meibomian gland acinar shortest diameter(MGASD).RESULTS: At baseline, no significant differences were found in NITMH across groups(P>0.05). Statistical significance were observed in NIBUTav, MGES, MGYSS, MGAUD, MGALD, and MGASD(all P<0.05). Compared to the mild group, the moderate and severe groups showed significant differences in OSDI, CFS, and ICD(all P<0.05), though no significant differences existed between moderate and severe groups(all P>0.05). At 3 mo after treatment, all groups showed no significant differences in NITMH(all P>0.05). All parameters improved significantly in the mild group(all P<0.05); all indicators improved in the moderate group(P>0.05), except for MGASD before and after treatment(all P<0.05); significant improvements were noted in OSDI, CFS, and NIBUTav in the severe group(all P<0.05), while MGES and MGYSS did not differ significantly(all P>0.05). IVCM parameters(MGAUD, ICD, MGALD, and MGASD)showed no significant change in the severe group(all P>0.05).CONCLUSION:OPT effectively enhances various ocular surface functions and improves gland expressibility and secretion quality in mild to moderate MGD cases, while also positively impacting certain cellular parameters. In severe cases, where most acinar functions are lost and structural reversibility is limited, OPT can still mitigate MGD symptoms and decelerate disease progression.

Pulmonary siderosis caused by iron and its compound dust is prone to misdiagnosis and underdiagnosis due to its insidious exposure pathways and non-specific imaging manifestations. This study analyzes the occupational histories and clinical data of six patients with occupational pulmonary siderosis diagnosed at Qingdao Central Hospital between January 2017 and December 2023, summarizes its characteristics, and evaluates the value of AI-assisted diagnosis. All six patients were male, with five being welders. The median dust exposure duration was 9.4 years, and the median latency period was 8.4 years. The main symptoms were chest tightness, cough, and shortness of breath. High-kilovolt chest radiographs were negative in four cases and showed thickened bronchovascular markings in two cases. High-resolution computed tomography (HRCT) revealed centrilobular nodules and tree-in-bud opacities in all cases. Pulmonary siderosis caused by iron and its compound dust is characterized by mild symptoms and a favorable prognosis. Comprehensive assessment and HRCT are crucial for early diagnosis. The development of AI models could enhance diagnostic recognition efficiency and promote precision diagnosis in the future.

Objective:To investigate the effect and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) transplantation on testicular function in aging mice with oxidative damage.Methods:Totally 18 SPF grade C57BL/C male mice aged 6-8 weeks were randomly divided into 3 groups using a complete randomization method. In control group, mice were injected with an equal amount of physiological saline; in model group, mice were subcutaneous injected D-galactose into the neck and back for 9 consecutive weeks, on the 4th weekend of modeling, the mice were injected with physiological saline via the tail vein; in hUCMSCs group: mice were subcutaneous injected D-galactose into the neck and back for 9 consecutive weeks, on the 4th weekend of modeling, the mice were injected with hUCMSCs via the tail vein of each mouse. After 9 weeks, body weight and testicular weight of the three groups mice were measured and testicular index was calculated. The contents of testosterone, malondialdehyde (MDA) and superoxide dismutase (SOD) in serum and testicular tissue were detected by enzyme-linked immunosorbent assay (ELISA) method. Visual observation of testicular appearance, the histopathological changes of testis were observed by hematoxylin-eosin (HE) staining, and the expression of NF-E2-related factor 2 (Nrf2) signal transduction-related genes and proteins were detected by RT-PCR and Western blotting, respectively.Results:Compared with control group [(0.81±0.13)%], the testicular index of mice in model group [(0.64±0.05)%, P=0.006] was decreased. In model group, the volume of testis was reduced, the integrity of spermatogenic tubules was damaged, spermatogenic cells and sperm were reduced, and the interstitium was sparse. In model group, serum testosterone [(4.10±0.67) μg/L] and SOD [(48.87±6.40) U/mg Prot] were decreased compared with control group [(5.71±0.81) μg/L, P=0.002; (78.53±9.70) U/mg Prot, P=0.001], MDA [(1.11±0.19) nmol/mg Prot] was increased compared with control group [(0.77±0.07) nmol/mg Prot, P=0.001], Keap1 mRNA and protein expression were increased ( P=0.006, P=0.043). The expression levels of Nrf2, SOD and NQO1 mRNA were significantly lower than those in control group ( P=0.002, P<0.001, P=0.001), and the expression levels of Nrf2 and HO-1 protein were significantly lower than those in control group ( P=0.011, P=0.021). Compared with the model group, the testicular index [(0.79±0.03)%, P=0.010] increased in hUCMSCs group, and the tissue structure of testis was clear and complete, spermatogenic cells at all levels of spermatogenic tubules, spermatogenic cells and stromal cells were abundant. Compared with the model group, the content of dihydrotestosterone [(5.24±0.21) μg/L, P=0.028] in serum and SOD [(79.47±14.32) U/mg Prot, P=0.001] in testicular tissue increased in hUCMSCs group, while the content of MDA [(0.77±0.08) nmol/mg Prot, P=0.001] decreased, Nrf2, SOD and NQO1 mRNA expression levels increased ( P=0.024, P=0.037, P=0.005), Keap1 mRNA expression decreased ( P=0.044), Nrf2 and HO-1 proteins expression increased ( P=0.009, P=0.012), while Keap1 protein expression decreased ( P=0.035). There were no statistically significant differences in testicular index, serum testosterone, SOD and MDA between hUCMSCs group and control group (all P>0.05). Conclusion:hUCMSCs significantly improve testicular structure and function damage caused by oxidative damage in aging mice, and the mechanism of action is related to upregulating Nrf2 signaling and downstream antioxidant activity SOD and HO-1 protein expression, reducing Keap1 mediated Nrf2 degradation.

Objective:To investigate the effect and mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) transplantation on testicular function in aging mice with oxidative damage.Methods:Totally 18 SPF grade C57BL/C male mice aged 6-8 weeks were randomly divided into 3 groups using a complete randomization method. In control group, mice were injected with an equal amount of physiological saline; in model group, mice were subcutaneous injected D-galactose into the neck and back for 9 consecutive weeks, on the 4th weekend of modeling, the mice were injected with physiological saline via the tail vein; in hUCMSCs group: mice were subcutaneous injected D-galactose into the neck and back for 9 consecutive weeks, on the 4th weekend of modeling, the mice were injected with hUCMSCs via the tail vein of each mouse. After 9 weeks, body weight and testicular weight of the three groups mice were measured and testicular index was calculated. The contents of testosterone, malondialdehyde (MDA) and superoxide dismutase (SOD) in serum and testicular tissue were detected by enzyme-linked immunosorbent assay (ELISA) method. Visual observation of testicular appearance, the histopathological changes of testis were observed by hematoxylin-eosin (HE) staining, and the expression of NF-E2-related factor 2 (Nrf2) signal transduction-related genes and proteins were detected by RT-PCR and Western blotting, respectively.Results:Compared with control group [(0.81±0.13)%], the testicular index of mice in model group [(0.64±0.05)%, P=0.006] was decreased. In model group, the volume of testis was reduced, the integrity of spermatogenic tubules was damaged, spermatogenic cells and sperm were reduced, and the interstitium was sparse. In model group, serum testosterone [(4.10±0.67) μg/L] and SOD [(48.87±6.40) U/mg Prot] were decreased compared with control group [(5.71±0.81) μg/L, P=0.002; (78.53±9.70) U/mg Prot, P=0.001], MDA [(1.11±0.19) nmol/mg Prot] was increased compared with control group [(0.77±0.07) nmol/mg Prot, P=0.001], Keap1 mRNA and protein expression were increased ( P=0.006, P=0.043). The expression levels of Nrf2, SOD and NQO1 mRNA were significantly lower than those in control group ( P=0.002, P<0.001, P=0.001), and the expression levels of Nrf2 and HO-1 protein were significantly lower than those in control group ( P=0.011, P=0.021). Compared with the model group, the testicular index [(0.79±0.03)%, P=0.010] increased in hUCMSCs group, and the tissue structure of testis was clear and complete, spermatogenic cells at all levels of spermatogenic tubules, spermatogenic cells and stromal cells were abundant. Compared with the model group, the content of dihydrotestosterone [(5.24±0.21) μg/L, P=0.028] in serum and SOD [(79.47±14.32) U/mg Prot, P=0.001] in testicular tissue increased in hUCMSCs group, while the content of MDA [(0.77±0.08) nmol/mg Prot, P=0.001] decreased, Nrf2, SOD and NQO1 mRNA expression levels increased ( P=0.024, P=0.037, P=0.005), Keap1 mRNA expression decreased ( P=0.044), Nrf2 and HO-1 proteins expression increased ( P=0.009, P=0.012), while Keap1 protein expression decreased ( P=0.035). There were no statistically significant differences in testicular index, serum testosterone, SOD and MDA between hUCMSCs group and control group (all P>0.05). Conclusion:hUCMSCs significantly improve testicular structure and function damage caused by oxidative damage in aging mice, and the mechanism of action is related to upregulating Nrf2 signaling and downstream antioxidant activity SOD and HO-1 protein expression, reducing Keap1 mediated Nrf2 degradation.

Objective:To investigate the incidence, influencing factors, and clinical characteristics during hospitalization of small for gestational age (SGA) infants among very preterm infants (VPIs) in neonatal intensive care units (NICUs).Methods:This study was a multicenter cohort study. Clinical data of VPIs with gestational age<32 weeks admitted to 19 collaborative units from January 1, 2019 to December 31, 2022, were collected from the Neonatal Perinatal Collaborative Network of Suxinyun (SNPN) and analyzed. General characteristics, perinatal conditions, and clinical manifestations during hospitalization of SGA infants among the VPIs were analyzed using Chi-square test, Mann-Whitney U test, and multivariate logistic regression. Clinical characteristics of symmetric and asymmetric SGA infants with hospital stay >7 d were also analyzed. Results:(1) During the study period, a total of 5 045 VPIs were included, among which there were 346 large for gestational age (LGA) infants, 4 475 appropriate for gestational age (AGA) infants, and 224 SGA infants, with a SGA incidence of 4.4%. The incidence of SGA was significantly higher in VPIs born at 30-31 +6 gestational weeks than in those with gestational age<28 weeks and born at 28-29 +6 weeks [6.1% (145/2 380) vs. 3.0% (25/833) and 3.6% (54/1 486), χ 2=11.77 and 11.32, both P<0.001]. No significant difference in SGA incidence was found between VPIs with gestational age<28 weeks and those born at 28-29 +6 weeks ( χ 2=0.65, P=0.248). (2) Multivariate logistic regression analysis showed that multiple pregnancies, hypertensive disorders of pregnancy (HDP) and assisted reproductive technology (ART) were independent risk factors for the occurrence of SGA in VPIs [ OR values (95% CI): 1.94 (1.43-2.64), 7.06 (5.34-9.33), and 1.59 (1.14-2.23)], and there was a significant gender difference, with the incidence of SGA being significantly lower in males than in females ( OR=0.61, 95% CI: 0.46-0.81). (3) The body temperature of SGA infants on admission was lower than that of AGA infants [36.0 °C (35.5-36.5 °C) vs. 36.0 °C (35.8-36.5 °C), Z=-2.08, P=0.004]. Moreover, the fasting time, the duration of parenteral nutrition, and the length of hospital stay for SGA infants were longer [3 d (1-7 d) vs. 2 d (1-5 d), 24 d (16-34 d) vs. 19 d (13-29 d), and 47 d (37-61 d) vs. 42 d (30-58 d), Z=-4.13,-4.65, and -3.02, all P<0.05]. The incidence of feeding intolerance, hypoglycemia, neonatal parenteral nutrition-associated cholestasis, and extrauterine growth restriction (EUGR), and the rate of treatment withdrawal or death were also higher in SGA infants [69.8% (143/205) vs. 58.9% (2 450/4 157), 17.6% (36/205) vs. 7.0% (292/4 157), 13.7% (28/205) vs. 6.4% (265/4 157), 77.7% (159/205) vs. 55.2% (2 295/4 157), and 7.8% (16/205) vs. 3.9% (162/4 157), χ 2=9.49, 31.19, 16.54, 44.40, and 7.62, all P<0.05]. Among SGA infants with hospital stay >7 d, there were 111 cases (54.1%) of symmetric SGA and 94 cases (45.9%) of asymmetric SGA. Compared with symmetric SGA infants, asymmetric SGA infants had shorter body length [34 cm (32-36 cm) vs. 38 cm (36-40 cm), Z=-8.49] and lower Apgar score at 1 min [7 points (5-8 points) vs. 8 points (5-8 points), Z=-3.05]. Besides, the proportion of multiple pregnancies and the incidence of postnatal hypoglycemia were higher in asymmetric SGA cases [38.3% (36/94) vs. 21.6% (24/111), 24.5% (23/94) vs. 10.8% (12/111), χ 2=6.84 and 6.71, both P<0.05], while the incidence of feeding intolerance and EUGR during hospitalization was lower [61.7% (58/94) vs. 76.6% (85/111), 58.5% (55/94) vs. 79.3% (88/111), χ2=5.34 and 10.41, both P<0.05]. Conclusions:Multiple pregnancies, HDP, and ART can increase the risk of SGA in VPIs. SGA infants may have increased risks of parenteral nutrition-related problems and EUGR during hospitalization. Symmetric SGA infants are more likely to develop EUGR.

Objective To investigate whether activation of PI3K/AKT/mTOR pathway can reduce inflammation in acute pancreatitis(AP)rats.Methods SD rats were grouped into sham surgery group,model group,Gln group,and Gln+LY294002 group(PI3K/AKT/mTOR pathway inhibitors).Intra-abdominal pressure(IAP),ascites volume(AS),serum amylase(AMY),diamine oxidase(DAO),interleukin(IL-1β,IL-6),Tumor necrosis factor(TNF-α)were measured.The pathological change in pancreatic and small intestinal tissues was evaluated by microscopy;The expression of PI3K,Akt and mTOR genes and cytoplasm compact linking protein(ZO-1),compact linking protein(occludin-1),PI3K,Akt and mTOR in ileum of each group were detected.Results Compared with the sham surgery group,the IAP and AS,IL-1β,IL-6,TNF-α,AMY,DAO,and pathological injury scores of pancreas and small intestine in the model group were obviously increased;The expression of PI3K mRNA,Akt mRNA,mTOR mRNA,ZO-1,occludin-1,p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in rat ileum tissue significantly reduced(P＜0.05).Compared with the model group,the level of IAP and AS,IL-1β,IL-6,TNF-α,AMY,DAO and pathological injury scores of pancreas and small intestine in the Gln group were significantly reduced;The expression of PI3K mRNA,Akt mRNA,mTOR mRNA,ZO-1,occludin-1,p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in rat ileum tissue was significantly increased(P＜0.05);LY294002 could specifically reverse the therapeutic effect of Gln on acute pancreatitis in rats.Conclusions Acti-vation of PI3K/AKT/mTOR pathway may reduce inflammation and improve gastrointestinal function in rats with acute pancreatitis.