Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

Objective:To assess the prevalence of dentinal hypersensitivity (DH) and related factors in urban adults in China.Methods:The study was designed as an observational, cross-sectional epidemiological study carried out in adults aged 18-69 years old in seven cities (Beijing, Shanghai, Wuhan, Chengdu, Xi′an, Guangzhou, and Harbin) of China. The study was conducted from March 2021 to May 2023. Patients were required to complete a questionnaire regarding the subjects′ socio-economic factors, dietary behavior, oral health behavior and personal antecedent factors. DH was clinically diagnosed by judging whether the tooth cold air stimulation provoked DH or not, and recorded by investigator pain rating Schiff score. Compare the findings of six cities (Harbin excluded) with a similar study conducted in 2008.Results:In total, 11 622 subjects from seven cities in China participated the study. Fifty two point two percent (6 072/11 622) of subjects reported DH in questionnaire, 36.7% (4 266/11 622) of subjects reported experiencing DH in response to cold air stimulation for at least one study tooth. Risk factors including age, sex, city, toothbrush method and acid reflux showed marked associations with DH ( P<0.05). The prevalence of DH of urban residents in six cities (Harbin excluded) was 33.7% (3 335/9 882), higher than that in 2008 [29.7%(2 354/7 939)]. Conclusions:Overall, DH was common among urban adults in China and the prevalence increased in recent years. Better understanding of DH and its associated factors should be considered in its prevention and management by dental professionals.

Objective:To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing.Methods:From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed.Results:The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [ M ( Q1, Q3) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant ( P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups ( P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion:The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

Ten compounds were isolated and purified from the dichloromethane extract of stems of Ephedra intermedia by various chromatographic methods. Based on the analysis of physicochemical properties and spectral data, the structures of the ten compounds were identified as 1-allyl-3,4-dimethoxy-benzene-5-O-β-D-glucopyranoside (1), lyoniresinol (2), secoisolariciresinol (3), 4,3′,4′-trihydroxy-3-methoxylignan-9,9′-diyldiacetate (4), dehydroconiferyl alcohol (5), isocubebin (6), balanophonin B (7), sesquipinsapol B (8), crataegifin A (9), 1-(2-(4-hydroxy-3-methoxyphenyl)-3-(hydroxymethyl)-7-methoxy-2,3-dihydrobenzofuran-5-yl)ethan-1-one (10). Compound 1 is a new compound, named as 1-allyl-3,4-dimethhoxy-benzene-5-O-β-D-glucopyranosyl, compounds 2-10 are lignans and isolated from this plant for the first time. Compound 3, 4, 8 possess potentially anti-asthmatic activities.

A Clinical pharmacist was fully involved in the anticoagulation drug treatment management process of a 104-year-old patient with a large area of cerebral infarction combined with chronic kidney disease stage Ⅴ and secondary deep vein thrombosis.After the patient was diagnosed with deep vein thrombosis,the clinical pharmacist comprehensively analyzed the patient's super-advanced age,history of atrial fibrillation,large area of cerebral infarction,extremely poor kidney function,deep vein thrombosis,and high bleeding risk indicated by the HAS-BLED score.They worked with the clinical doctor to develop an individualized anticoagulation treatment strategy for the patient.At the beginning of the treatment,warfarin was given to the patient at a daily dose of 1.25 mg,and the patient's coagulation indicators and kidney function were dynamically rechecked.The patient's blood creatinine level did not show significant changes throughout the anticoagulation treatment process.On the 8th day of medication,the patient's INR was 2.47,and the clinical pharmacist suggested adjusting the Warfarin to an alternate-day dose of 1.25 mg and 0.625 mg.Subsequently,the patient's INR was 2.41,and the condition improved,leading to discharge.Throughout the anticoagulation drug management process,the clinical pharmacist participated in the clinical decision-making for anticoagulant drug selection,provided professional medication guidance,and pharmacological monitoring to ensure the safe clinical use of drugs for special populations.

Epilepsy is a chronic disease characterized by recurrent,sudden,and excessive synchronous discharge of neurons in the brain,leading to transient brain dysfunction,and inflammatory responses in specific regions within the central nervous system are common features of epilepsy.In recent years,there has been increasing evidence that endoplasmic reticulum stress is involved in the pathology of epilepsy,which activates the unfolded protein response,then regulate and control nuclear factor kappa-B(NF-κB),efficiently induces glial cell activation through the release of pro-inflammatory signals,in turn affects epileptogenesis and seizures by triggering neuroinflammation.This review focuses on the close link between endoplasmic reticulum stress and glial cell activation-mediated neuroinflammation in epilepsy pathology,aiming to provide insights for a deeper understanding of epilepsy.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:To investigate the occupational noise hazards in five machinery manufacturing enterprises, and to evaluate the individual noise reduction values and influencing factors of workers wearing hearing protection device (HPD) by individual fit testing.Methods:From November 2021 to January 2022, 5 machinery manufacturing enterprises in Bao'an District of Shenzhen were selected to conduct an occupational health survey to understand the noise exposure level of workers. The 3MTM E-A-RfitTM fitness test system was used to test the baseline individual sound attenuation value level (PAR) of the daily wear of the ear protecters for 485 workers in typical noise working positions. Workers whose PAR values could not meet the requirements of noise reduction at work were instructed to wear and repeated tests were conducted. PAR results of the workers before and after the intervention were collected and analyzed.Results:The noise workers who received the suitability test were mainly distributed in 24 types of work, the job noise exposure level was 80.2 dB (A) ~ 95.0 dB (A), and the job noise excess rate was 52.5% (138/263). The median baseline PAR [ M ( Q1, Q3) ] for 485 workers was 6.0 (0.0, 14.0) dB. The baseline PAR of male workers, those with more than 15 years of working experience, those with more than 15 years of using ear guards, those who considered ear guards comfortable to wear, those with college degree or above, and those exposed to noise level 90 dB (A) were higher, and the difference was statistically significant ( P<0.05). A total of 275 workers (56.7%) did not pass the baseline PAR test, and there was no statistically significant difference in the intervention rate of workers in different noise groups ( P>0.05). PAR in subjects who did not pass baseline after intervention increased from 0.0 (0.0, 3.0) dB to 15.0 (12.0, 18.2) dB. Conclusion:The workplace noise hazard of machinery manufacturing enterprises is serious, and there is a great difference between the baseline PAR and the nominal value of the hearing guard worn by the noise exposed workers. The intervention measures can effectively improve the protective effect of wearing ear protectors.

Humans ; Lymphoma, Large-Cell, Anaplastic ; Receptor Protein-Tyrosine Kinases ; Anaplastic Lymphoma Kinase ; Soft Tissue Neoplasms

Nowadays potential preclinical drugs for the treatment of nonalcoholic steatohepatitis (NASH) have failed to achieve expected therapeutic efficacy because the pathogenic mechanisms are underestimated. Inactive rhomboid protein 2 (IRHOM2), a promising target for treatment of inflammation-related diseases, contributes to deregulated hepatocyte metabolism-associated nonalcoholic steatohepatitis (NASH) progression. However, the molecular mechanism underlying Irhom2 regulation is still not completely understood. In this work, we identify the ubiquitin-specific protease 13 (USP13) as a critical and novel endogenous blocker of IRHOM2, and we also indicate that USP13 is an IRHOM2-interacting protein that catalyzes deubiquitination of Irhom2 in hepatocytes. Hepatocyte-specific loss of the Usp13 disrupts liver metabolic homeostasis, followed by glycometabolic disorder, lipid deposition, increased inflammation, and markedly promotes NASH development. Conversely, transgenic mice with Usp13 overexpression, lentivirus (LV)- or adeno-associated virus (AAV)-driven Usp13 gene therapeutics mitigates NASH in 3 models of rodent. Mechanistically, in response to metabolic stresses, USP13 directly interacts with IRHOM2 and removes its K63-linked ubiquitination induced by ubiquitin-conjugating enzyme E2N (UBC13), a ubiquitin E2 conjugating enzyme, and thus prevents its activation of downstream cascade pathway. USP13 is a potential treatment target for NASH therapy by targeting the Irhom2 signaling pathway.