ObjectiveTo analyze the impact of diabetes-related deaths on the probability of premature mortality and life expectancy in Minhang District of Shanghai from 2004 to 2023, and to provide reference data for the optimization of targeted prevention and control strategies. MethodsAll death cases involving diabetes among the registered residents of Minhang District from 2004 to 2023 were collected. The probability of premature mortality and life expectancy was computed using the abridged life table method. The average annual percent change (AAPC) was calculated with Joinpoint 4.9.0.0. The Arriaga decomposition method was employed for statistical analyses of the influence of cause-specific and age-specific mortality related to diabetes on life expectancy. ResultsThe total number of diabetes-related mortality, crude mortality, and standardized mortality for both males and females in Minhang District from 2004 to 2023 exhibited an increasing trend (P<0.001). The primary causes of death among diabetes-related cases were cardiovascular disease (37.68%), diabetes mellitus (31.95%), and malignant tumor (17.80%). From 2004 to 2023, probability of premature mortality to diabetes-related diseases demonstrated a rising trend (P<0.001), contrasting with the declining trend observed in the overall population (P=0.001). Males showed a significant upward trajectory (P<0.001), while females displayed a stable pattern. Among the diseases exerting considerable influence, cardiovascular disease and malignant tumor revealed a marked increase over time (P<0.001), whereas diabetes mellitus maintained a stable trend; both factors negatively impacted the reduction in probability of premature mortality. From 2004 to 2023, diabetes-related mortality reduced life expectancy among residents by an average of 1.22 years (-49.89%), indicating a negative impact; the reduction was 1.41 years in males and 0.90 years in females. The age groups exhibiting greater negative contributions differed by genders, namely males aged 50‒54 years and females aged 70‒74 years. Cardiovascular disease, diabetes mellitus, and malignant tumor contributed significantly to this decline (-0.46 years, -0.42 years, -0.20 years, respectively), with male experiencing higher negative contributions than females. ConclusionIn Minhang District, the rising mortality associated with diabetes-related diseases negatively impact both the reduction of the probability of premature mortality and the increase in life expectancy. This trend is primarily attributed to the rapid escalation of mortality and younger age demographic of male residents, which warrants significant attention. It is recommended that, based on the enhancement of case management, efforts should be directed towards the targeted prevention and control of risk factors and high-risk populations.

Objective:To analyze the distribution of human immunodeficiency virus 1（HIV-1）genotypes and antiretroviral drug resistance patterns among individuals infected with HIV and patients with acquired immunodeficiency syndrome（AIDS）in Fuyang，with the aim of informing the optimization of antiretroviral therapy strategies.Methods:Blood samples were collected from HIV/AIDS patients who failed antiviral treatment in Fuyang from 2023 to 2024，as well as newly reported HIV-infected individuals who were first diagnosed and did not receive antiviral treatment. The HIV-1 pol gene was amplified and sequenced. Genotypic resistance was assessed using the Stanford University HIV Drug Resistance Database，and analyses were conducted on HIV-1 subtypes and drug resistance-associated mutations.Results:A total of 571 HIV/AIDS patients were included in this study，comprising 320 newly reported HIV-infected individuals and 251 HIV/AIDS patients who failed antiviral treatment. Both groups were predominantly male，middle-aged and elderly individuals over 45 years old，and heterosexual contact was the primary transmission route. The most prevalent HIV-1 subtypes differed between groups：CRF07_BC（36.88%，118/320）dominated among newly reported HIV-infected patients，whereas subtype B（43.03%，108/251）was predominant in HIV/AIDS patients who failed antiviral treatment. The drug resistance rate was significantly lower in newly reported HIV-infected patients（15.63%，50/320）compared to the HIV/AIDS patients who failed antiviral treatment（38.25%，96/251； χ2=37.825， P<0.001）. Non-nucleoside reverse transcriptase inhibitors（NNRTIs）exhibited the highest resistance rates in both cohorts. Compared to newly reported HIV-infected patients，HIV/AIDS patients who failed antiviral treatment showed a significantly higher prevalence of drug resistance mutations（ P<0.001），with greater diversity in mutation patterns. Key resistance-associated mutation site demonstrated statistically significant differences in mutation rates between the two groups（ P<0.05）. The results of the molecular transmission network showed that the proportion of elderly people over 60 years old and patients with CRF07_BC and B subtypes was higher among the networked cases in the two groups of newly reported and antiviral treatment failure. Conclusion:The study revealed a diverse distribution of HIV-1 subtypes among HIV/AIDS patients in Fuyang. NNRTIs exhibited the most prominent resistance challenges，accompanied by diversified resistance mutation profiles. These findings highlight the need for enhanced surveillance of resistance to curb the spread of resistant strains and improve clinical outcomes.

Objective:To analyze the distribution of human immunodeficiency virus 1（HIV-1）genotypes and antiretroviral drug resistance patterns among individuals infected with HIV and patients with acquired immunodeficiency syndrome（AIDS）in Fuyang，with the aim of informing the optimization of antiretroviral therapy strategies.Methods:Blood samples were collected from HIV/AIDS patients who failed antiviral treatment in Fuyang from 2023 to 2024，as well as newly reported HIV-infected individuals who were first diagnosed and did not receive antiviral treatment. The HIV-1 pol gene was amplified and sequenced. Genotypic resistance was assessed using the Stanford University HIV Drug Resistance Database，and analyses were conducted on HIV-1 subtypes and drug resistance-associated mutations.Results:A total of 571 HIV/AIDS patients were included in this study，comprising 320 newly reported HIV-infected individuals and 251 HIV/AIDS patients who failed antiviral treatment. Both groups were predominantly male，middle-aged and elderly individuals over 45 years old，and heterosexual contact was the primary transmission route. The most prevalent HIV-1 subtypes differed between groups：CRF07_BC（36.88%，118/320）dominated among newly reported HIV-infected patients，whereas subtype B（43.03%，108/251）was predominant in HIV/AIDS patients who failed antiviral treatment. The drug resistance rate was significantly lower in newly reported HIV-infected patients（15.63%，50/320）compared to the HIV/AIDS patients who failed antiviral treatment（38.25%，96/251； χ2=37.825， P<0.001）. Non-nucleoside reverse transcriptase inhibitors（NNRTIs）exhibited the highest resistance rates in both cohorts. Compared to newly reported HIV-infected patients，HIV/AIDS patients who failed antiviral treatment showed a significantly higher prevalence of drug resistance mutations（ P<0.001），with greater diversity in mutation patterns. Key resistance-associated mutation site demonstrated statistically significant differences in mutation rates between the two groups（ P<0.05）. The results of the molecular transmission network showed that the proportion of elderly people over 60 years old and patients with CRF07_BC and B subtypes was higher among the networked cases in the two groups of newly reported and antiviral treatment failure. Conclusion:The study revealed a diverse distribution of HIV-1 subtypes among HIV/AIDS patients in Fuyang. NNRTIs exhibited the most prominent resistance challenges，accompanied by diversified resistance mutation profiles. These findings highlight the need for enhanced surveillance of resistance to curb the spread of resistant strains and improve clinical outcomes.

Objective To study the clinical efficacy and safety of disitamab vedotin(RC48)in the third-line and above third-line treatment of advanced gastric cancer.Methods The clinical data of 30 patients with advanced gastric cancer who had previously failed to receive at least two systemic chemotherapy regimens from August 2020 to August 2022 in Nantong Tumor Hospital were retrospectively analyzed.According to different treatment regimens,they were divided into RC48 group(n=15)and control group(chemotherapy/targeted/immune monotherapy)(n=15).The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and treatment-related adverse reactions were observed in the two groups.Results The median follow-up time was 7.5 months.The ORR of RC48 group and control group was 20%vs.0%(P=0.224),DCR was 53.3%vs.20%(P=0.128),mPFS was 4 months vs.3 months(P=0.479),mOS was 18 months vs.5 months(P=0.043).In terms of safety,the most common adverse reactions in the RC48 group and the control group were leukopenia and neutropenia.The overall incidence of adverse reactions in the two groups was compa-rable,and there were no fatal adverse events.Conclusion RC48 has a certain effect in the third-line and above third-line treatment of advanced gastric cancer,and patients are well tolerated.

ObjectiveTo elucidate the principles and methods of the Bayesian probabilistic linkage model， and to demonstrate the effect of applying the model in linking birth and death data. MethodsThrough the Shanghai birth and death registration system， data of 199 025 infants born in 2017 and 1 512 infants who died in 2017 and 2018 were collected. After cleaning the data， the data were divided into monthly blocks and fully linked. The Jaro-Winkler algorithm and Euclidean distance were employed to measure the similarity of fields for matching. A Bayesian probabilistic linkage model was constructed and the linking effect was evaluated using a confusion matrix. ResultsUsing the Bayesian probabilistic linkage model， the birth and death data of infants were effectively linked， revealing that 36.71% of infants who died in Shanghai were born outside the city， and the probability of infant death was 2.6‰. The confusion matrix of the test set showed a recall rate of 0.86， precision of 0.76， and an F-score of 0.81. ConclusionThe practical application of Bayesian probabilistic linkage demonstrates a good model performance， enabling the establishment of birth-death cohorts that more accurately reflect the true levels of infant mortality. Utilizing this technique to integrate data from different departments can effectively improve research efficiency in the field of public health.

Objective:To investigate the predictive value of the changes of platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) in the therapeutic efficacy of the neoadjuvant treatment for breast cancer.Methods:The clinical data of 72 breast cancer patients who received neoadjuvant therapy in Nantong Tumor Hospital between February 2020 and January 2022 were retrospectively analyzed and the changes of PLR and NLR before and after neoadjuvant therapy were also analyzed. The receiver operating characteristic (ROC) curves were used to assess the predictive value of PLR, NLR and their changes in pathological complete remission (pCR) after neoadjuvant therapy.Results:The area under the ROC curve of PLR and NLR before the treatment, the difference in PLR before and after the treatment (ΔPLR), the difference in NLR before and after the treatment (ΔNLR) in predicting pCR was 0.520, 0.505,0.724 and 0.686,and the corresponding cut-off value was 269.231, 2.559, -2.840 and -1.457; the patients were divided into high and low groups according to the cut-off values. NLR before the treatment was not correlated with clinicopathological characteristics (all P > 0.05),while PLR before the treatment was correlated with tumor size ( P = 0.029), and ΔPLR was correlated with progesterone receptor expression ( P = 0.025), human epidermal growth factor receptor 2 (HER2) expression ( P < 0.001), molecular subtype ( P < 0.001), N stage ( P = 0.002), clinical stage ( P = 0.002) and treatment modality ( P < 0.001). ΔNLR was associated with HER2 expression ( P = 0.002), molecular subtype ( P = 0.024), tumor size ( P = 0.007), neural invasion ( P = 0.006), N stage ( P = 0.006), clinical stage ( P = 0.016) and treatment modality ( P = 0.014). ΔPLR and ΔNLR were influencing factors for patients achieving pCR after neoadjuvant therapy (all P < 0.05). Conclusions:Stage Ⅲ invasive breast cancer patients with higher ΔPLR and ΔNLR after neoadjuvant therapy have better prognosis.

ObjectiveTo investigate the effect of Shengjiang Tonglong prescription hollow suppository on rats with prostate hyperplasia， and the effect of the proteins related to phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway in the prostate， thus exploring the mechanism of Shengjiang Tonglong prescription hollow suppository in the treatment of rats with prostate hyperplasia. MethodTen SD male rats were randomly selected from 60 SD male rats to form a sham operation control group， and the rest rats were subcutaneously injected with testosterone propionate for 4 consecutive weeks after castration to induce the rat model of prostatic hyperplasia. According to the random number table method， the 50 rats were randomly divided into a model group， a finasteride group （0.45 mg·kg^-1）， and three high， middle， and low-dose Shengjiang Tonglong prescription hollow suppository groups （3.98， 1.99， 0.99 g·kg^-1）， with ten rats in each group. After castration for 7 d， the sham operation control group and the model group used the blank hollow suppositories， and the finasteride group and the Shengjiang Tonglong prescription hollow suppository groups used the corresponding hollow suppositories. The drugs were given to the rats by anal plugs continuously for 28 d. The rats were then killed， and the prostate tissues were separated and weighed to observe the effects of drugs on the prostate index of rats in each group. The hematoxylin-eosin （HE） staining was used for the pathological observation of the prostate tissues. The level of dihydrotestosterone （DHT） was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of PI3K/Akt signaling pathway protein， B-cell lymphoma-2 （Bcl-2）， cysteine aspartate-specific protease-3 （Caspase-3）， Bcl-2-associated X protein （Bax）， and αB-crystallin （CRYAB） protein in the prostate tissues. ResultAs compared with the sham operation control group， the protein expression levels of prostate index， DHT level， CRYAB， Bcl-2， PI3K， and Akt in the model group were increased， and the protein expression levels of Caspase-3 and Bax were decreased （P<0.05， P<0.01）. As compared with the model group， the prostate index in the high-dose Shengjiang Tonglong prescription hollow suppository group was decreased （P<0.05）， and the level of DHT and the protein expression levels of CRYAB， Bcl-2， PI3K， and Akt in the prostate of the Shengjiang Tonglong prescription hollow suppository groups were decreased， and the protein expression levels of Caspase-3 and Bax were increased （P<0.05， P<0.01）. ConclusionShengjiang Tonglong prescription hollow suppository decreases the expression of CRYAB protein， negatively regulates the PI3K/Akt signaling pathway， down-regulates the level of DHT and the protein expression levels of Bcl-2， PI3K， and Akt， and up-regulates the protein expression levels of Caspase-3 and Bax， thereby inhibiting cell proliferation and promoting cell apoptosis， which plays a therapeutic role in the benign prostate hyperplasia （BPH）. The high-dose Shengjiang Tonglong prescription hollow suppository significantly improves prostatic hyperplasia in rats.

ObjectiveTo investigate the effect of Shengjiang Tonglong prescription hollow suppository on rats with prostate hyperplasia， and the effect of the proteins related to phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway in the prostate， thus exploring the mechanism of Shengjiang Tonglong prescription hollow suppository in the treatment of rats with prostate hyperplasia. MethodTen SD male rats were randomly selected from 60 SD male rats to form a sham operation control group， and the rest rats were subcutaneously injected with testosterone propionate for 4 consecutive weeks after castration to induce the rat model of prostatic hyperplasia. According to the random number table method， the 50 rats were randomly divided into a model group， a finasteride group （0.45 mg·kg^-1）， and three high， middle， and low-dose Shengjiang Tonglong prescription hollow suppository groups （3.98， 1.99， 0.99 g·kg^-1）， with ten rats in each group. After castration for 7 d， the sham operation control group and the model group used the blank hollow suppositories， and the finasteride group and the Shengjiang Tonglong prescription hollow suppository groups used the corresponding hollow suppositories. The drugs were given to the rats by anal plugs continuously for 28 d. The rats were then killed， and the prostate tissues were separated and weighed to observe the effects of drugs on the prostate index of rats in each group. The hematoxylin-eosin （HE） staining was used for the pathological observation of the prostate tissues. The level of dihydrotestosterone （DHT） was detected by enzyme-linked immunosorbent assay （ELISA）. Western blot was used to detect the expression levels of PI3K/Akt signaling pathway protein， B-cell lymphoma-2 （Bcl-2）， cysteine aspartate-specific protease-3 （Caspase-3）， Bcl-2-associated X protein （Bax）， and αB-crystallin （CRYAB） protein in the prostate tissues. ResultAs compared with the sham operation control group， the protein expression levels of prostate index， DHT level， CRYAB， Bcl-2， PI3K， and Akt in the model group were increased， and the protein expression levels of Caspase-3 and Bax were decreased （P<0.05， P<0.01）. As compared with the model group， the prostate index in the high-dose Shengjiang Tonglong prescription hollow suppository group was decreased （P<0.05）， and the level of DHT and the protein expression levels of CRYAB， Bcl-2， PI3K， and Akt in the prostate of the Shengjiang Tonglong prescription hollow suppository groups were decreased， and the protein expression levels of Caspase-3 and Bax were increased （P<0.05， P<0.01）. ConclusionShengjiang Tonglong prescription hollow suppository decreases the expression of CRYAB protein， negatively regulates the PI3K/Akt signaling pathway， down-regulates the level of DHT and the protein expression levels of Bcl-2， PI3K， and Akt， and up-regulates the protein expression levels of Caspase-3 and Bax， thereby inhibiting cell proliferation and promoting cell apoptosis， which plays a therapeutic role in the benign prostate hyperplasia （BPH）. The high-dose Shengjiang Tonglong prescription hollow suppository significantly improves prostatic hyperplasia in rats.

  Objective  This study aimed at describing the frequency of rare variants of monogenic cerebral small vessel diseases (CSVD) in a cohort of patients with CSVD, and to explore its clinical relevance.  Methods  This study included CSVD patients visiting the Neurology Department of Peking Union Medical College Hospital(PUMCH) from March 2017 to January 2022, collecting their demographic and clinical information and DNA samples for whole-exome sequencing. Descriptive analysis and statistical analysis were conducted exploring the differences between monogenic CSVD-related gene mutation carriers and noncarriers.  Results  A total of 292 patients were included, 51.03% of whom carried one or more rare variants of monogenic CSVD-related genes. The most common rare low-frequency variants were located in the NOTCH3 gene (70 patients, 23.97%), followed by HTRA1 and COL4A1/COL4A2 (22 patients, 7.53%) respectively. Among the subgroup of patients without a family history of stroke (n=176), the frequency of rare variants was as high as 47.16%. Compared with non-carriers, the carriers were diagnosed at a younger age (58.76±13.71 vs. 63.46±13.21, P=0.003). No difference was found in phenotypes among single-SNP carriers, multiple-SNPs carriers, and noncarriers.  Conclusions  The frequency of rare mutation of monogenic CSVD-related genes were relatively high in Chinese CSVD cohort. The most common rare variant was within the NOTCH3, followed by HTRA1 and COL4A1/COL4A2 genes. For CSVD patients of unknown causes, genetic screening should not be neglected even if there is not a family history of the disease.

ObjectiveTo analyze the changing trend of cerebrovascular disease burden in Minhang District of Shanghai from 1996 to 2021， and to provide scientific evidence for government to formulate targeted cerebrovascular disease prevention and control strategies. MethodsMortality， years of life lost（YLL）， years of lived with disability（YLD） and disability⁃adjusted life years（DALY） were used to evaluate the burden of cerebrovascular diseases in Minhang District. Joinpoint linear regression was used to analyze the trend of disease burden. ResultsFrom 1996 to 2021， the YLL rate of cerebrovascular diseases in Minhang District showed a downward trend （whole population： APC=-1.69%， t=-6.9， P<0.05）， The YLD rate of cerebrovascular diseases showed a slow upward trend （whole population： APC=1.17%， t=3.5， P<0.05）， The DALY rate of cerebrovascular diseases showed a downward trend， and fluctuated since 2003 （whole population： APC= -1.43%， t=-5.6， P<0.05）. The YLL rate of cerebrovascular diseases in men was higher than that in women， and the YLD rate of cerebrovascular diseases in women was higher than that in men. After 2014， the DALY of cerebrovascular diseases in men was higher than that in women. With the increase of age， the burden of cerebrovascular diseases increased， and the burden of disease increased significantly in the age group above 70. ConclusionThe burden of cerebrovascular diseases in Minhang District is at a high level， and there are differences in age， gender and other aspects. Measures such as screening， intervention and rehabilitation need to be improved to reduce disability and premature death caused by cerebrovascular diseases and to reduce the burden of cerebrovascular diseases on individuals， families and society.