Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

Objective:To investigate the effects of sampling methods on pathological assessment of resected non-small cell lung cancer (NSCLC) specimen with tumor maximum diameter >3 cm after neoadjuvant therapy.Methods:NSCLC patients with a large tumor (diameter >3 cm) that were resected after neoadjuvant therapy from June 2020 to July 2023 were retrospectively collected in the Department of Pathology, Shanghai Pulmonary Hospital, Shanghai, China. Sampling methods of the tumor bed were performed in accordance with the international and Chinese experts recommendations for resection specimens following neoadjuvant therapy (recommended sampling method, RSM), and all remaining tumor bed lesions were completely sampled after recommended sampling (complete sampling method, CSM). The difference of pathological response assessment of residual viable tumor (RVT) between RSM and CSM was examined.Results:A total of 90 cases were identified and analyzed, including 39 cases of squamous cell carcinoma and 51 cases of adenocarcinoma, treated with neoadjuvant therapy including chemotherapy in 22 cases (24.4%), targeted therapy in 14 cases (15.6%), and chemoimmunotherapy in 54 cases (60.0%). There were 62 males and 28 females with an average age of (62.7±17.9) years. The average tumor maximum diameter was 4.3 cm (range, 3.1-8.0 cm). The average number of sampled blocks was 8 blocks (range, 5 to 16) and 15 blocks (range, 8 to 36) per case by RSM and CSM, respectively. According to the definition of major pathological response (MPR) in which RVT is ≤10%, the numbers of patients with MPR were 34 cases by RSM and 30 cases by CSM, respectively. Four cases showed inconsistent RVT between the two methods, including one case of squamous cell carcinoma and three cases of adenocarcinoma. The RVT of the four inconsistent cases was 7%, 7%, 5% and 9% (MPR by RSM), and 15%, 15%, 15% and 20% (non-MPR by CSM), respectively. The kappa values of MPR consistency evaluated by the two sampling methods were 0.893 for all cases, 0.906 for squamous cell carcinoma cases and 0.751 for adenocarcinoma cases. According to MPR cut-off of 65% for invasive primary adenocarcinoma, 24 cases and 20 cases achieved MPR by RSM and CSM, respectively. Of the four inconsistent cases, the RVT by RSM was 60% in three cases and 65% in one case (MPR), whereas the RVT by CSM was 70% in three cases and 75% in one case (non-MPR). The kappa value of the two sampling methods was 0.741.Conclusions:There is high consistency between RSM and CSM in the pathological assessment of post-treatment responses in resected NSCLC specimens with tumor maximum diameter larger than 3 cm. When the percentage of RVT cells is close to MPR, re-evaluation of the specimen is required and CSM may be necessary to accurately evaluate the degree of pathological remission, assist in clinical postoperative treatment, and predict patient prognosis.

ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.

Objective:To observe the effect of mirror threshold load training on respiration of persons with respiratory muscle fatigue after a cerebral hemorrhage.Methods:Fifty cerebral hemorrhage patients with respiratory muscle fatigue were randomly divided into an observation group and a control group, each of 25. In addition to routine rehabilitation training, the control group was given threshold load training of the respiratory muscles, while the observation group was provided with mirror threshold load training, twice a day in the morning and afternoon, 5 days a week for 4 weeks. Before the experiment and after 1, 2, 3 and 4 weeks of the treatment, everyone′s maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was recorded. Before and after the 4 weeks forced expiration volume in the first second (FEV1) was measured along with 25% of the forced expiration volume (FEF25), maximum sound time (MPT) and respiration rate (RR).Results:At each time point the MIP and MEP values of both groups were significantly better than those before the treatment. After 4 weeks the average MIP and MEP values of the observation group were significantly better than those of the control group. And after 4 weeks the FEV1, FEF25, MPT and RR values of both groups had also improved significantly, on average. All of the observation group′s averages except MPT were then significantly better than the control group′s averages.Conclusions:Mirror threshold load training of the respiratory muscles can significantly improve the respiration of persons with respiratory muscle fatigue after a cerebral hemorrhage. It is more effective than respiratory muscle threshold load training.

Objective:To investigate the clinical pathological features, immunophenotypes, diagnosis, and differential diagnosis of non-small cell lung carcinoma (NSCLC) with trophoblastic differentiation in males, and to improve the understanding of this rare disease.Methods:The clinical and pathological features of 16 NSCLC with trophoblastic differentiation in males diagnosed in Shanghai Pulmonary Hospital from January 2017 to December 2023 were retrospectively analyzed. Relevant literature was reviewed.Results:All 16 patients were male, with an onset median age of 66.5 (56.8, 68.8) years. They had no known personal history of cancer. Among the 8 resected NSCLC with trophoblastic differentiation, 3 showed concurrent lung adenocarcinoma, and 1 showed concurrent lung squamous cell carcinoma. Among the 10 patients who underwent serum β human chorionic gonadotropin (β-HCG) testing after the surgery or biopsy, 7 had significantly increased β-HCG. On gross examination, the tumors were hemorrhagic and necrotic, resembling a hematoma, with a medium texture, clear boundaries and no capsules. At low magnification, tumor cells were arranged in a nested or solid pattern. Those cells often showed massive bleeding, necrosis, and vascular infiltration. They were composed of two types of cells, namely cytotrophoblast and syncytiotrophoblast cells. At high magnification, the tumor cells showed large nuclei and hyperchromatia. They also had rich purple blue to bichromatic cytoplasm, eosinophilic nucleoli, and sometimes bizarre nuclei. The syncytiotrophoblast cells expressed β-HCG, CKpan, GATA3, CD10, and SALL4. Fourteen patients were followed up for 1-37 months. Two of them died, while three showed distant metastasis.Conclusions:NSCLC with trophoblastic differentiation in males is a rare and highly malignant tumor, poorly understood with difficulty in diagnosis. It requires comprehensive histological analysis in combination with clinical and imaging studies. Properly diagnosing this disease relies on recognition of its histopathological characteristics, including large areas of bleeding and necrosis, large and peculiar syncytial trophoblast cells, and varying degrees of β-HCG expression. It seems that β-HCG expression is very valuable for diagnosing this rare tumor.

Objective:To observe the effect of mirror threshold load training on respiration of persons with respiratory muscle fatigue after a cerebral hemorrhage.Methods:Fifty cerebral hemorrhage patients with respiratory muscle fatigue were randomly divided into an observation group and a control group, each of 25. In addition to routine rehabilitation training, the control group was given threshold load training of the respiratory muscles, while the observation group was provided with mirror threshold load training, twice a day in the morning and afternoon, 5 days a week for 4 weeks. Before the experiment and after 1, 2, 3 and 4 weeks of the treatment, everyone′s maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) was recorded. Before and after the 4 weeks forced expiration volume in the first second (FEV1) was measured along with 25% of the forced expiration volume (FEF25), maximum sound time (MPT) and respiration rate (RR).Results:At each time point the MIP and MEP values of both groups were significantly better than those before the treatment. After 4 weeks the average MIP and MEP values of the observation group were significantly better than those of the control group. And after 4 weeks the FEV1, FEF25, MPT and RR values of both groups had also improved significantly, on average. All of the observation group′s averages except MPT were then significantly better than the control group′s averages.Conclusions:Mirror threshold load training of the respiratory muscles can significantly improve the respiration of persons with respiratory muscle fatigue after a cerebral hemorrhage. It is more effective than respiratory muscle threshold load training.

Objective:To investigate the clinical pathological features, immunophenotypes, diagnosis, and differential diagnosis of non-small cell lung carcinoma (NSCLC) with trophoblastic differentiation in males, and to improve the understanding of this rare disease.Methods:The clinical and pathological features of 16 NSCLC with trophoblastic differentiation in males diagnosed in Shanghai Pulmonary Hospital from January 2017 to December 2023 were retrospectively analyzed. Relevant literature was reviewed.Results:All 16 patients were male, with an onset median age of 66.5 (56.8, 68.8) years. They had no known personal history of cancer. Among the 8 resected NSCLC with trophoblastic differentiation, 3 showed concurrent lung adenocarcinoma, and 1 showed concurrent lung squamous cell carcinoma. Among the 10 patients who underwent serum β human chorionic gonadotropin (β-HCG) testing after the surgery or biopsy, 7 had significantly increased β-HCG. On gross examination, the tumors were hemorrhagic and necrotic, resembling a hematoma, with a medium texture, clear boundaries and no capsules. At low magnification, tumor cells were arranged in a nested or solid pattern. Those cells often showed massive bleeding, necrosis, and vascular infiltration. They were composed of two types of cells, namely cytotrophoblast and syncytiotrophoblast cells. At high magnification, the tumor cells showed large nuclei and hyperchromatia. They also had rich purple blue to bichromatic cytoplasm, eosinophilic nucleoli, and sometimes bizarre nuclei. The syncytiotrophoblast cells expressed β-HCG, CKpan, GATA3, CD10, and SALL4. Fourteen patients were followed up for 1-37 months. Two of them died, while three showed distant metastasis.Conclusions:NSCLC with trophoblastic differentiation in males is a rare and highly malignant tumor, poorly understood with difficulty in diagnosis. It requires comprehensive histological analysis in combination with clinical and imaging studies. Properly diagnosing this disease relies on recognition of its histopathological characteristics, including large areas of bleeding and necrosis, large and peculiar syncytial trophoblast cells, and varying degrees of β-HCG expression. It seems that β-HCG expression is very valuable for diagnosing this rare tumor.

Objective:To investigate the effects of laparoscopic transabdominal preperitoneal repair (TAPP) and Lichtenstein surgery on postoperative early pain and mobility in patients with inguinal hernia.Methods:The retrospective cohort study was conducted. The clinical data of 184 pati-ents with unilateral inguinal hernia who were admitted to Shaanxi Provincial People's Hospital from June 2021 to December 2022 were collected. There were 152 males and 32 females, aged (64±8)years. Of the 184 patients, 92 cases undergoing TAPP were divided into the TAPP group, and 92 cases under-going Lichtenstein surgery were divided into the Lichtenstein group. Observation indicators: (1) surgical situations; (2) postoperative pain; (3) postoperative mobility. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Paired sample t test was used for comparison within group before and after surgery. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical situations. Total duration of hospital stay, duration of postoperative hospital stay, expense of hospitalization were 1.70(1.00,2.00)days, 1.00(1.00,1.00)days, 14 808(14 385,15 292)yuan in the TAPP group, versus 2.12(2.00,3.00)days, 1.42(1.00,2.00)days, 10 590(9802,11 362)yuan in the Lichtenstein group, showing significant differences in the above indicators between the two groups ( Z=-3.23, -4.07, -11.72, P<0.05). (2) Postoperative pain. Score of verbal rating scale (VRS) were 1.36±0.75 and 3.22±0.66 before surgery and at 20-22 hours after surgery in the TAPP group, versus 1.34±0.80 and 3.42±0.80 in the Lichtenstein group, showing significant differences within the two groups ( t=-29.15, -31.46, P<0.05). (3) Postoperative mobility. The time from getting up to standing bedside of patients before surgery and at 20-22 hours after surgery were (5.47±1.08)seconds and (7.94±2.23)seconds in the TAPP group, versus (5.87±1.13)seconds and (11.59±1.88)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-11.99, -15.64, -27.26, P<0.05). The time for hip flexion 90° of patients before surgery and at 20-22 hours after surgery were (0.74±0.32)seconds and (1.23±0.54)seconds in the TAPP group, versus (0.81±0.19)seconds and (1.97±0.69)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-8.11, -16.53, -17.81, P<0.05). The time for walking 10 meters of patients before surgery and at 20-22 hours after surgery were (10.30±1.53)seconds and (12.80±1.67)seconds in the TAPP group, versus (10.38±1.35)seconds and (18.35±1.69)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-22.44, -33.66, -32.46, P<0.05). The time for walking 20 meters of patients before surgery and at 20-22 hours after surgery were (17.87±2.89)seconds and (24.16±2.54)seconds in the TAPP group, versus (18.02±2.82)seconds and (32.64±2.56)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-22.55, -38.75, -34.59, P<0.05). Conclusion:Compared to Lichtenstein surgery, patients with TAPP experience faster recovery of mobility, earlier discharge, and higher expense of hospitalization.

Objective:To investigate the effects of laparoscopic transabdominal preperitoneal repair (TAPP) and Lichtenstein surgery on postoperative early pain and mobility in patients with inguinal hernia.Methods:The retrospective cohort study was conducted. The clinical data of 184 pati-ents with unilateral inguinal hernia who were admitted to Shaanxi Provincial People's Hospital from June 2021 to December 2022 were collected. There were 152 males and 32 females, aged (64±8)years. Of the 184 patients, 92 cases undergoing TAPP were divided into the TAPP group, and 92 cases under-going Lichtenstein surgery were divided into the Lichtenstein group. Observation indicators: (1) surgical situations; (2) postoperative pain; (3) postoperative mobility. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Paired sample t test was used for comparison within group before and after surgery. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Results:(1) Surgical situations. Total duration of hospital stay, duration of postoperative hospital stay, expense of hospitalization were 1.70(1.00,2.00)days, 1.00(1.00,1.00)days, 14 808(14 385,15 292)yuan in the TAPP group, versus 2.12(2.00,3.00)days, 1.42(1.00,2.00)days, 10 590(9802,11 362)yuan in the Lichtenstein group, showing significant differences in the above indicators between the two groups ( Z=-3.23, -4.07, -11.72, P<0.05). (2) Postoperative pain. Score of verbal rating scale (VRS) were 1.36±0.75 and 3.22±0.66 before surgery and at 20-22 hours after surgery in the TAPP group, versus 1.34±0.80 and 3.42±0.80 in the Lichtenstein group, showing significant differences within the two groups ( t=-29.15, -31.46, P<0.05). (3) Postoperative mobility. The time from getting up to standing bedside of patients before surgery and at 20-22 hours after surgery were (5.47±1.08)seconds and (7.94±2.23)seconds in the TAPP group, versus (5.87±1.13)seconds and (11.59±1.88)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-11.99, -15.64, -27.26, P<0.05). The time for hip flexion 90° of patients before surgery and at 20-22 hours after surgery were (0.74±0.32)seconds and (1.23±0.54)seconds in the TAPP group, versus (0.81±0.19)seconds and (1.97±0.69)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-8.11, -16.53, -17.81, P<0.05). The time for walking 10 meters of patients before surgery and at 20-22 hours after surgery were (10.30±1.53)seconds and (12.80±1.67)seconds in the TAPP group, versus (10.38±1.35)seconds and (18.35±1.69)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-22.44, -33.66, -32.46, P<0.05). The time for walking 20 meters of patients before surgery and at 20-22 hours after surgery were (17.87±2.89)seconds and (24.16±2.54)seconds in the TAPP group, versus (18.02±2.82)seconds and (32.64±2.56)seconds in the Lichtenstein group, showing a significant difference at 20-22 hours after surgery between the two groups and significant differences within the two groups ( t=-22.55, -38.75, -34.59, P<0.05). Conclusion:Compared to Lichtenstein surgery, patients with TAPP experience faster recovery of mobility, earlier discharge, and higher expense of hospitalization.

Background: s/Aims: Transmembrane 6 superfamily member 2 (TM6SF2) E167K variant is closely associated with the occurrence and development of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the role and mechanism of TM6SF2 E167K variant during MASLD progression are not yet fully understood. Methods: The Tm6sf2167K knock-in (KI) mice were subjected to high-fat diet (HFD). Hepatic lipid levels of Tm6sf2167K KI mice were detected by lipidomics analysis. Thin-layer chromatography (TLC) was used to measure the newly synthesized triglyceride (TG) and phosphatidylcholine (PC). Results: The TM6SF2 E167K variant significantly aggravated hepatic steatosis and injury in HFD-induced mice. Decreased polyunsaturated PC level and increased polyunsaturated TG level were found in liver tissue of HFDinduced Tm6sf2167K KI mice. Mechanistic studies demonstrated that the TM6SF2 E167K variant increased the interaction between TM6SF2 and PNPLA3, and impaired PNPLA3-mediated transfer of polyunsaturated fatty acids (PUFAs) from TG to PC. The TM6SF2 E167K variant increased the level of fatty acid-induced malondialdehyde and reactive oxygen species, and decreased fatty acid-downregulated cell membrane fluidity. Additionally, the TM6SF2 E167K variant decreased the level of hepatic PC containing C18:3, and dietary supplementation of PC containing C18:3 significantly attenuated the TM6SF2 E167K-induced hepatic steatosis and injury in HFD-fed mice. Conclusions The TM6SF2 E167K variant could promote its interaction with PNPLA3 and inhibit PNPLA3-mediated transfer of PUFAs from TG to PC, resulting in the hepatic steatosis and injury during MASLD progression. PC containing C18:3 could act as a potential therapeutic supplement for MASLD patients carrying the TM6SF2 E167K variant.